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  1. Primary cutaneous T-cell lymphomas.

    PubMed

    Rosen, Steven T; Querfeld, Christiane

    2006-01-01

    Primary cutaneous T-cell lymphomas (CTCLs) encompass a clinically and biologically heterogeneous group of non-Hodgkin lymphomas (NHLs) defined by clonal proliferation of skin-homing malignant T lymphocytes and natural killer cells. They account for up to 75% to 80% of all cutaneous lymphomas. The current WHO-EORTC classification of cutaneous lymphomas with primary cutaneous manifestations lists 13 entities. The most common subtypes-mycosis fungoides, Sézary syndrome, primary cutaneous anaplastic large cell lymphoma, and lymphomatoid papulosis-which represent approximately 95% of CTCLs, will be discussed in the following review. Each entity has unique biological characteristics and clinical course. Topical and/or systemic therapies are employed based on the stage of the disease and the tempo of progression.

  2. Primary cutaneous smoldering adult T-cell leukemia/ lymphoma.

    PubMed

    Gittler, Julia; Martires, Kathryn; Terushkin, Vitaly; Brinster, Nooshin; Ramsay, David

    2016-12-15

    HTLV-1 is a virus that is endemic in southwesternJapan and the Caribbean and has been implicatedin the development of ATLL. ATLL, which is anuncommon malignant condition of peripheralT-lymphocytes, is characterized by four clinicalsubtypes, which include acute, lymphomatous,chronic, and smoldering types, that are based onLDH levels, calcium levels, and extent of organinvolvement. We present a 52-year- old woman withpruritic patches with scale on the buttocks and withtender, hyperpigmented macules and papules oftwo-years duration. Histopathologic examinationwas suggestive of mycosis fungoides, laboratoryresults showed HTLV-I and II, and the patient wasdiagnosed with primary cutaneous ATLL. We reviewthe literature on HTLV-1 and ATLL and specifically theprognosis of cutaneous ATLL. The literature suggeststhat a diagnosis of ATLL should be considered amongpatients of Caribbean origin or other endemicareas with skin lesions that suggest a cutaneousT-cell lymphoma, with clinicopathologic features ofmycosis fungoides. Differentiation between ATLLand cutaneous T-cell lymphoma is imperative as theyhave different prognoses and treatment approaches.

  3. Primary Cutaneous CD8+ T-cell Lymphoma, an Indolent and Locally Aggressive Form Mimicking Paronychia.

    PubMed

    Beggs, Sarah M; Friedman, Ben J; Kornreich, Davida; Okon, Lauren; Alpdogan, Onder; Shi, Wenyin; Sahu, Joya

    2017-09-28

    CD8 T-cell lymphomas comprise a wide spectrum of lymphomas, many which have yet to be formally classified. We present a case of a 43-year-old woman with an enlarging tumor distal to the distal interphalangeal joint of the fourth finger, compressing the underlying nail matrix. Magnetic resonance imaging showed bony involvement of the underlying distal phalanx. Histology showed a dense epidermotropic and pandermal infiltrate composed of medium-sized, uniformly pleomorphic lymphocytes with cleaved nuclei, which raised the possibility of primary cutaneous CD8 aggressive epidermotropic cytotoxic T-cell lymphoma. However, the patient's clinical photograph was inconsistent with this diagnosis. Other diagnoses, such as primary cutaneous acral CD8 T-cell lymphoma-a provisional entity, were also considered but did not capture all the features of this patient's lymphoma. We propose to classify this case as a primary cutaneous CD8 T-cell lymphoma, an indolent and locally aggressive form.

  4. Illness Perception in Primary Cutaneous T-cell Lymphomas: What Patients Believe About Their Disease.

    PubMed

    Eder, Johanna; Kammerstätter, Martina; Erhart, Friedrich; Mairhofer-Muri, Daniela; Trautinger, Franz

    2016-03-01

    There is currently no information available on illness perception in primary cutaneous T-cell lymphomas (CTCL). The aim of this study was therefore to gather initial information on disease understanding and interpretation in patients with CTCL. Consecutive patients from a hospital-based primary cutaneous lymphoma ward completed the Revised Illness Perception Questionnaire (IPQ-R) on 2 consecutive visits. A total of 24 patients with different variants of CTCL were included in the study. Patients experienced their condition as being long-lasting, but not fundamentally affecting their lives. Patients had poor belief in personal control, but strong belief in treatment control. They did not show a good understanding of their disease, and had a moderately negative emotional response to their illness. In conclusion, the IPQ-R provides a feasible and reproducible tool for measurement and better understanding of illness perception in patients with CTCL. Knowledge of patients' attitudes towards their disease should enable optimization of the patient-physician relationship and patient care.

  5. Long-term efficacy and safety of alemtuzumab in advanced primary cutaneous T-cell lymphomas.

    PubMed

    de Masson, A; Guitera, P; Brice, P; Moulonguet, I; Mouly, F; Bouaziz, J-D; Battistella, M; Madelaine, I; Roux, J; Ram-Wolff, C; Cayuela, J-M; Bachelez, H; Bensussan, A; Michel, L; Bagot, M

    2014-03-01

    Alemtuzumab has been proposed as salvage therapy for refractory cutaneous T-cell lymphomas (CTCLs). Long-term follow-up data are scarce. To assess the efficacy and safety of alemtuzumab in the treatment of advanced CTCL. A multicentre retrospective analysis was carried out of 39 patients with advanced CTCL treated with alemtuzumab between 2003 and 2013. Thirty-nine patients (median age 62 years, range 20-83) with Sézary syndrome (SS, n = 23) or advanced mycosis fungoides (MF, n = 16) received alemtuzumab 30 mg two to three times per week for a median duration of 12 weeks (range 1-35). Fifteen patients received maintenance therapy for a median duration of 24 weeks (range 6-277). Eleven patients (28%) had transformed disease (MF, n = 10; SS, n = 1). After a median follow-up of 24 months (range 0.3-124), eight patients (21%) were still alive. The overall response rate was 51% in the whole study group (partial response, n = 13; complete response, n = 7); 70% in patients with SS and 25% in patients with MF (P = 0.009). The median time to progression was 3.4 months (range 0.4-42). Six patients (15%; SS, n = 5; MF, n = 1) remained progression free for > 2 years (median 56 months, range 28-117). Five patients experienced cutaneous large T-cell transformation during alemtuzumab treatment and one patient developed primary cutaneous large B-cell lymphoma. Twenty-four patients (62%) had a grade three or higher infectious adverse event and 10 (26%) a haematological toxicity, which led to treatment discontinuation in 17 cases (44%) and death in two (5%). Alemtuzumab may induce long-term remission in SS but seems ineffective in MF and transformed CTCL. © 2014 British Association of Dermatologists.

  6. Adult T-cell leukemia/lymphoma: a case report of primary cutaneous tumoral type

    PubMed Central

    Lyra-da-Silva, Julia Ocampo; de Mello Gonzaga, Yung Bruno; de Melo Espíndola, Otávio; de Andrada-Serpa, Maria José; Dib, Cassio; Jeunon, Thiago

    2012-01-01

    Background: Adult T-cell leukemia/lymphoma (ATLL) is a distinctive peripheral T- lymphocytic malignancy associated with human T-cell lymphotropic virus type 1 (HTLV-1). It may closely resemble other skin lymphomas, particularly mycosis fungoides (MF). Case report: A 38-year-old woman presented some ellipsoid scaling patches lasting 18 months and developed a large tumoral lesion in the abdomen, which were previously diagnosed as MF. Although histopathologic and immunohistochemistry findings were in consonance with this diagnosis, the fast progression of the disease raised the suspicion that it could represent another type of T-cell lymphoma. The work-up revealed a positive anti-HTLV-1 serology and molecular studies confirmed the monoclonal integration of HTLV-1 provirus into neoplastic cells of the skin, but not into circulating lymphocytes. Extensive investigations were unable to demonstrate any systemic involvement. The final diagnosis was of primary cutaneous type of ATLL. The patient was submitted to a chemotherapy regimen with cyclophosphamide, doxorubicin, vincristine and prednisone, later to conjugated dexamethasone and surgical cytoreduction and then to a second line treatment with gemcitabine, resulting in partial response. A bone marrow heterologous transplantation was performed, but failed to achieve a sustained remission. Discussion: ATLL is a rare lymphoid malignancy in non-endemic HTLV-1 areas, the diagnosis of which could be missed if not highly suspected. In addition to the four subtypes of Shimoyama classification (acute, lymphomatous, chronic and smoldering), a fifth one denominated primary cutaneous and characterized by presence of lesions only in the skin had been proposed and is herein exemplified. PMID:23785591

  7. Cutaneous extranodal natural killer/T-cell lymphoma: a comparative clinicohistopathologic and survival outcome analysis of 45 cases according to the primary tumor site.

    PubMed

    Lee, Woo Jin; Jung, Joon Min; Won, Chong Hyun; Chang, Sung Eun; Choi, Jee Ho; Chan Moon, Kee; Park, Chan-Sik; Huh, Jooryung; Lee, Mi Woo

    2014-06-01

    Differences in survival outcomes and prognostic factors of cutaneous extranodal natural killer/T-cell lymphoma (ENKTL) depending on primary tumor site are currently unknown. We sought to analyze the clinicopathological features and survival outcomes of cutaneous ENKTL according to primary tumor site. In all, 45 patients with cutaneous ENKTL were classified with: (1) primary cutaneous ENKTL, or (2) nasal ENKTL with cutaneous involvement. Clinicopathologic features, survival outcomes, and prognostic factors were analyzed using patient's medical records. Survival outcomes were analyzed using the Kaplan-Meier method and compared using the log rank test. The Student t test, Fisher exact test, and linear by linear association test were used to analyze clinicopathologic differences between groups. Clinical manifestations of cutaneous ENKTL included solitary or multiple subcutaneous nodules and cellulitis or abscess-like lesions. Primary cutaneous ENKTL demonstrated a less aggressive clinical course and better survival outcomes. The extent of cutaneous lesions demonstrated a significant effect on the prognosis of primary cutaneous ENKTL, but not on nasal ENKTL with cutaneous involvement. The presence of nasal lesions in primary cutaneous ENKTL was associated with poor prognosis. This study used a retrospective design and included a small sample size. Although the clinicopathological features were similar regardless of subgroup, survival outcomes and prognostic factors differed depending on the primary tumor site of cutaneous ENKTL. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  8. [Multiple primary cutaneous plasmacytoma].

    PubMed

    Malissen, N; Fabre, C; Joujoux, J-M; Bourquard, P; Dandurand, M; Marque, M; Stoebner, P; Meunier, L

    2014-05-01

    Primary cutaneous plasmacytoma is a rare form of cutaneous B-cell lymphoma. A 51 year-old male with an unremarkable history gradually presented erythematous papulonodular lesions that had appeared gradually over the whole body throughout a two-year period and showing histologic and immunohistochemical features of cutaneous plasmacytoma. Staging investigations confirmed the primary character of the disease, and because of this and the absence of functional impairment, we opted for therapeutic abstention. No progression was noted after 4 years of regular monitoring. Primary cutaneous plasmacytoma (PCP) is characterized by clonal proliferation of plasma cells in skin. Multiple PCPs are extremely rare and to date have been treated in most cases by chemotherapy, either with or without radiotherapy. The prognosis is poor, with 2-year survival of only 25%. The present case is original, being the only one to our knowledge in which therapeutic abstention was followed by a lack of progression after 4 years of regular follow-up. Consequently, certain indolent forms of PCP do not warrant automatic institution of chemotherapy. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  9. Primary cutaneous aggressive epidermotropic cytotoxic T-cell lymphomas: reappraisal of a provisional entity in the 2016 WHO classification of cutaneous lymphomas.

    PubMed

    Guitart, Joan; Martinez-Escala, M Estela; Subtil, Antonio; Duvic, Madeleine; Pulitzer, Melissa P; Olsen, Elise A; Kim, Ellen; Rook, Alain H; Samimi, Sara S; Wood, Gary S; Girardi, Michael; Junkins-Hopkins, Jacqueline; Ivan, Doina S; Selim, M Angelica; Sable, Kimberly A; Virmani, Pooja; Pincus, Laura B; Tetzlaff, Michael T; Kim, Jinah; Kim, Youn H

    2017-05-01

    Primary cutaneous CD8-positive aggressive epidermotropic T-cell lymphoma is a rare and poorly characterized variant of cutaneous lymphoma still considered a provisional entity in the latest 2016 World Health Organization Classification of Cutaneous lymphomas. We sought to better characterize and provide diagnostic and therapeutic guidance of this rare cutaneous lymphoma. Thirty-four patients with a median age of 77 years (range 19-89 years) presented primarily with extensive annular necrotic plaques or tumor lesions with frequent mucous membrane involvement. The 5-year survival was 32% with a median survival of 12 months. A subset of 17 patients had a prodrome of chronic patches prior to the development of aggressive ulcerative lesions. We identified cases with lack of CD8 or αβ T-cell receptor expression yet with similar clinical and pathological presentation. Allogeneic stem cell transplantation provided partial or complete remissions in 5/6 patients. We recommend the term primary cutaneous aggressive epidermotropic cytotoxic T-cell lymphoma as this more broad designation better describes this clinical-pathologic presentation, which allows the inclusion of cases with CD8 negative and/or αβ/γδ T-cell receptor chain double-positive or double-negative expression. We have identified early skin signs of chronic patch/plaque lesions that are often misdiagnosed as eczema, psoriasis, or mycosis fungoides. Our experience confirms the poor prognosis of this entity and highlights the inefficacy of our standard therapies with the exception of allogeneic stem cell transplantation in selected cases.

  10. Methotrexate-associated primary cutaneous CD30-positive cutaneous T-cell lymphoproliferative disorder: a case illustration and a brief review

    PubMed Central

    Claudino, Wederson M; Gibson, Bradley; Tse, William; Krem, Maxwell; Grewal, Jaspreet

    2016-01-01

    Methotrexate (MTX) is a commonly used anti-metabolite agent. Increased risk of lymphoproliferative disorders (LPD) in patients with rheumatoid arthritis (RA) has been documented with the prolonged use of immunosuppressive medications such as MTX. This is thought to be the result of immune dysregulation and/or chronic immune stimulation. Most cases of LPDs regress following withdrawal of the offending immunosuppressive agent. We present an interesting and rare case of CD30 and EBV positive CD8 primary cutaneous anaplastic large cell lymphoma (PC-ALCL) in a 66-year-old African American woman. Patient had been on MTX for rheumatoid arthritis (RA) which was stopped after the patient was evaluated at our institution. Patient had an incredible response to stopping immunosuppression with spontaneous regression of skin lesions and disappearance of clonal malignant cell population as evidenced on serial biopsy specimens. Primary cutaneous CD30+ LPDs constitute about 30% of the primary cutaneous T-cell lymphomas (CTLs) and includes entities such as lymphomatoid papulosis (LyP), primary cutaneous anaplastic large cell lymphoma (PC-ALCL) and other CD30+ borderline LPDs. Histopathological criteria in addition to CD30 positivity is important for identification of these conditions. Treatment options include “wait and see”, phototherapy, radiotherapy, topical agents, systemic therapy and surgical resection. Prognosis is excellent and most cases resolve spontaneously on withdrawal of immunosuppression. Refractory cases may require aggressive local treatment or systemic therapy. Brentuximab Vedontin, an anti-CD30 antibody drug conjugate (ADC), may provide additional therapeutic option in refractory cases. PMID:27335685

  11. Hepatitis E Virus-Induced Primary Cutaneous CD30(+) T cell Lymphoproliferative Disorder.

    PubMed

    Mallet, Vincent; Bruneau, Julie; Zuber, Julien; Alanio, Cécile; Leclerc-Mercier, Stéphanie; Roque-Afonso, Anne-Marie; Kraft, Anke R M; Couronné, Lucile; Roulot, Dominique; Wedemeyer, Heiner; Albert, Matthew L; Hillon, Patrick; Laroche, Liliane; Pol, Stanislas; Hermine, Olivier

    2017-08-28

    Several types of unexplained extra-hepatic manifestations, including haematological disorders, have been reported in the context of hepatitis E virus (HEV) infection. However, the underlying mechanism(s) of these manifestations are unknown. We provide evidence that HEV has an extra-hepatic endothelial tropism that can engage cutaneous T cells towards clonality. A patient with a CD30(+) cutaneous T cell lymphoproliferative disorder (T-LPD) and biopsy-proven chronic HEV infection received 3 rounds of oral ribavirin treatment administered either without or with interferon and eventually achieved a sustained virological response (SVR). Pathological, virological and immunological investigations were carried out on biopsied skin lesion, and peripheral blood mononuclear cells between the 2nd and 3rd round of antiviral treatment and biopsied liver. Remission of T-LPD was observed upon antiviral treatment, and the patient remained in complete remission after achieving SVR. The T cell analysis showed large CD30(+) lymphocytes surrounding the blood vessels within the CD8(+) T cell infiltrate. HEV was detected within dermal microvascular endothelial cells using immunofluorescence staining, in situ hybridization and electron microscopy. Infiltrating T cells mostly comprised memory CD8(+) T-cells with a tissue-resident memory T cell phenotype. Overall, 98% of extracted T cells were CD8(+) T cells with a Vβ signature skewed towards Vβ4 and with an oligoclonal profile. T cell clones from T-LPD were more similar to T cells in the liver than T cells in the blood [odds ratio=4.55, (3.70-5.60), p<0.0001]. No somatic mutations were found in the T-LPD exomes. HEV has an extra-hepatic tissue tropism in humans, including dermal endothelium, and can induce CD30(+) T-LPD that is sensitive to antivirals. Hepatitis E virus (HEV) has an extra-hepatic tissue tropism and should be added to the list of viruses associated with lymphoproliferative disorders. As such, HEV should be part of the

  12. Cutaneous Richter Syndrome Mimicking Primary Cutaneous CD4-Positive Small/Medium T-cell Lymphoma: Case Report and Review of the Literature.

    PubMed

    Rito, Miguel; Cabeçadas, José; Costa Rosa, Joaninha; Cravo, Mariana; Robson, Alistair

    2017-09-12

    Richter syndrome represents the transformation of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma into an aggressive large B-cell lymphoma. Skin involvement is exceptionally rare, with <20 cases reported and its presence as the first presentation of CLL/small lymphocytic lymphoma, as an isolated skin lesion has never been described. Primary cutaneous CD4-positive small/medium T-cell lymphoma (CD4 PCSM-TCL) characteristically presents with a dense dermal infiltrate consisting primarily of small-/medium-sized pleomorphic T-cells and less than 30% large pleomorphic cells. A polymorphous reactive infiltrate composed of B-cells, histiocytes, plasma cells, and eosinophils is also found in differing proportions. Because of these morphological characteristics, the differential diagnosis includes not only other forms of cutaneous T-cell lymphomas but also B-cell lymphomas and reactive lymphoid infiltrates. We report a case of a cutaneous Richter syndrome as the initial manifestation of CLL, mimicking CD4 PCSM-TCL, in a 65-year-old apparently healthy asymptomatic man who presented with a solitary nodule in his arm. The objective of this study is to draw attention to this potential pitfall and describe this rare presentation.

  13. Primary cutaneous acral CD8 positive T-cell lymphoma with extra-cutaneous involvement: A long-standing case with an unexpected progression.

    PubMed

    Alberti-Violetti, Silvia; Fanoni, Daniele; Provasi, Matteo; Corti, Laura; Venegoni, Luigia; Berti, Emilio

    2017-08-10

    Primary cutaneous acral CD8+ T-cell lymphoma (acral CD8+ TCL) is a new provisional entity characterized by acral skin lesions and an indolent course. We describe an extraordinary case characterized by relapsed nodules with CD8+ cytotoxic infiltrates on the left ear. After 35 years, the skin lesions spread to other acral sites, and a mass with the same histological features as the other skin lesions appeared on the nose. Multiple courses of chemotherapy led to stable disease. Histological examinations carried out at different times showed the gradual transformation of the neoplastic cells with an increased proliferation index. Genomic analysis revealed losses in the regions harboring the genes involved in cell cycle control. This is the first case of an acral CD8+ TCL with a very long history of indolent nodular lesions progressing to extra-cutaneous sites. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Expression of helper T cell master regulators in inflammatory dermatoses and primary cutaneous T-cell lymphomas: diagnostic implications.

    PubMed

    Hsi, Andy C; Lee, Sena J; Rosman, Ilana S; Carson, Kenneth R; Kelley, Amanda; Viele, Valerie; Pang, Xiaofan; Musiek, Amy; Schaffer, András

    2015-01-01

    Mycosis fungoides (MF) is a neoplasm of skin-homing CD4(+) helper T (TH) lymphocytes with dysregulation of TH1 and TH2 immunity. Diagnosis of MF is challenging, as there is significant morphologic overlap with other dermatologic entities. We investigated diagnostic utility of TH1- and TH2-specific markers, T-bet, and GATA-3, respectively, in MF and its reactive and neoplastic mimics. Immunohistochemical staining for CD3/T-bet and CD3/GATA-3 was performed on inflammatory dermatoses (n = 56), MF (n = 37), Sezary syndrome (SS; n = 8), and cutaneous anaplastic large cell lymphoma (C-ALCL; n = 14). Inflammatory dermatoses showed epidermal T cells predominantly expressing GATA-3, except psoriasis, which exhibited a mixed GATA-3/T-bet staining. In contrast, neoplastic T cells in patch stage MF showed markedly increased T-bet positivity with minimal GATA-3 expression. Plaque stage MF had a mixed T-bet/GATA-3 phenotype, whereas tumor stage MF and SS exhibited diffuse GATA-3 expression. C-ALCL lacked significant staining for both markers. Sample size was relatively small. A predominance of T-bet(+) T cells in the epidermis support patch stage MF over dermatitis. A predominance of GATA-3(+) T cells in the dermis support CD30(+) MF with large cell transformation over C-ALCL. These stains do not allow distinction between dermatitis and cutaneous infiltrates of SS. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  15. Neurolymphomatosis in Primary Cutaneous CD4+ Pleomorphic Small/Medium-sized T-cell Lymphoma Mimicking Hansen's Disease.

    PubMed

    Khader, Anza; Vineetha, Mary; George, Mamatha; Manakkad, Shiny Padinjarayil; Balakrishnan, Sunitha; Rajan, Uma

    2017-01-01

    Neurolymphomatosis (NL) refers to nerve infiltration by neurotropic neoplastic cells in the setting of a known or an unknown hematological malignancy. It typically presents as painful or painless peripheral mononeuropathy, mononeuritis multiplex, polyneuropathy, polyradiculopathy, or cranial neuropathy. A 32-year-old male presented with a hyperpigmented hypoesthetic plaque over the anterolateral aspect of the right leg with thickening of the right common peroneal nerve and foot drop clinically diagnosed as Hansen's disease. Biopsy taken from skin showed infiltrates of pleomorphic small and medium sized lymphocytes in the dermis and subcutis. On immunohistochemistry, the cells were positive for CD3, CD4 and negative for CD8, CD20, and CD30. Ultrasonography-guided fine-needle aspiration of the thickened nerve showed infiltrates of atypical lymphoid cells. Based on these findings, a diagnosis of NL in primary cutaneous CD4+ pleomorphic small/medium-sized T-cell lymphoma was made. The disease responded to systemic chemotherapy and localized radiotherapy with no evidence of relapse during 3 years follow-up. NL in primary cutaneous CD4+ pleomorphic small/medium-sized T-cell lymphoma presenting with manifestations redolent of Hansen's disease is not described in available literature. This case also demonstrates the utility of fine needle aspiration of nerve, a minimally invasive procedure in the diagnosis of NL.

  16. An overview of cutaneous T cell lymphomas

    PubMed Central

    Bagherani, Nooshin; Smoller, Bruce R.

    2016-01-01

    Cutaneous T cell lymphomas (CTCLs) are a heterogeneous group of extranodal non-Hodgkin’s lymphomas that are characterized by a cutaneous infiltration of malignant monoclonal T lymphocytes. They typically afflict adults with a median age of 55 to 60 years, and the annual incidence is about 0.5 per 100,000. Mycosis fungoides, Sézary syndrome, and primary cutaneous peripheral T cell lymphomas not otherwise specified are the most important subtypes of CTCL. CTCL is a complicated concept in terms of etiopathogenesis, diagnosis, therapy, and prognosis. Herein, we summarize advances which have been achieved in these fields. PMID:27540476

  17. Allogeneic hematopoietic stem cell transplantation for primary cutaneous T cell lymphomas

    PubMed Central

    Paralkar, Vikram R.; Nasta, Sunita Dwivedy; Morrissey, Kelly; Smith, Jacqueline; Vassilev, Pavel; Martin, Mary Ellen; Goldstein, Steven C; Loren, Alison; Rook, Alain H.; Kim, Ellen J; Porter, David L

    2011-01-01

    Cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of non-Hodgkin lymphomas that are considered incurable. The role of allogeneic hematopoietic stem cell transplantation (HSCT) in the treatment of CTCL is not well defined but may provide potent graft-vs-lymphoma (GVL) activity independent of the conditioning therapy. We present outcomes of 12 extensively-pretreated patients with CTCL who underwent allogeneic HSCT using, most commonly, a reduced intensity conditioning (RIC) regimen. Median age at diagnosis of CTCL was 49 yrs, and median time to transplantation from diagnosis was 3.3 years. Transplant induced and maintained CR in 6 patients with active disease supporting the presence of a GVL effect. Transplant related mortality was low, and 42% of patients were alive and disease-free a median duration of 22 months after transplant. Two patients showed strong and direct evidence of a GVL effect with a direct response to withdrawal of immunosuppression or to donor leukocyte infusion (DLI). Our data show that HSCT can provide long-term disease control in patients with advanced CTCL otherwise refractory to immunotherapy and chemotherapy. PMID:22020023

  18. Lymphocytes infiltrating primary cutaneous neoplasms selectively express the cutaneous lymphocyte-associated antigen (CLA).

    PubMed Central

    Gelb, A. B.; Smoller, B. R.; Warnke, R. A.; Picker, L. J.

    1993-01-01

    The cutaneous lymphocyte-associated antigen (CLA) is the T-cell ligand for E-selectin and is involved in tissue selective migration of memory/effector T cells to chronic inflammatory sites in skin. Here, we examine the hypothesis that CLA is also involved in the local host immune response to cutaneous neoplasms. Eleven primary cutaneous melanomas, nine primary cutaneous squamous cell carcinomas, and 11 assorted neoplasms metastatic to cutaneous and noncutaneous sites were immunostained with anti-CLA (HECA-452), as well as antibodies directed against B cells (CD20), T/NK cells (CD43), and memory/effector T cells (CD45RO). Essentially all of the lymphocytes surrounding and infiltrating both the cutaneous and noncutaneous tumors were CD43+/CD20-, and most expressed the memory/effector marker CD45RO. CLA was expressed on 10 to 80% (mean: 50%) of T cells associated with primary cutaneous neoplasms (including both melanomas and squamous cell carcinomas) but was essentially absent from noncutaneous primaries (including those metastatic to dermis) and from cutaneous primaries metastatic to dermis or other sites. Overall, the results suggest that CLA+memory T cells are a major component of the local host immune response to cutaneous neoplasms and are likely recruited to the skin by site-specific rather than tumor-specific mechanisms. The lack of a CLA+T-cell response to dermal metastases suggests that epidermal involvement may be required to attract this subset. Images Figure 1 Figure 2 Figure 3 PMID:7684198

  19. Evaluation of follicular T-helper cells in primary cutaneous CD4+ small/medium pleomorphic T-cell lymphoma and dermatitis.

    PubMed

    Ally, Mina S; Prasad Hunasehally, Ranganna Y; Rodriguez-Justo, Manuel; Martin, Blanca; Verdolini, Roberto; Attard, Natalie; Child, Fiona; Attygalle, Ayoma; Whittaker, Sean; Morris, Stephen; Robson, Alistair

    2013-12-01

    CD4+ small/medium-sized pleomorphic T-cell lymphoma (SMPTCL) is a controversial primary cutaneous lymphoma, in which the candidate neoplastic cells express a follicular T-helper phenotype. We describe 16 cases of SMPTCL and compare expression of PD-1, CXCL-13 and ICOS in these tumors with 40 dermatitis cases. Histopathologic examination and immunocytochemistry were performed for 16 tumors and 40 assorted dermatitis cases. All but one patient presented with solitary lesions. Each biopsy revealed a dense nodular non-epitheliotropic infiltrate of atypical T-cells. Neoplastic cells were CD3+/CD4+/CD8(-)/CD30(-). Cutaneous recurrence occurred in one patient over a median follow up of 8 months (range 5-36). All tumors widely expressed PD-1 and ICOS to a lesser extent. CXCL-13 stained much fewer cells. Of the dermatitis cases, PD-1 (most numerous) and ICOS labeled lymphoid cells in all cases, albeit fewer than in the tumors, and CXCL-13 was negative in 32. A rosette pattern of PD-1 expression was identified in all the SMPTCL cases but not in dermatitis. There remains uncertainty about the appropriate nosological status of SMPTCL, which some authors consider to be a pseudolymphoma. However, this study suggests a significant difference in the prevalence and pattern of follicular T-helper cell markers between this tumor and lymphoid proliferations known to be reactive. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Primary cutaneous lymphomas: diagnosis and treatment

    PubMed Central

    Olek-Hrab, Karolina; Ruckemann-Dziurdzińska, Katarzyna

    2015-01-01

    Primary cutaneous lymphomas (CLs) are a heterogeneous group of lymphoproliferative neoplasms, with lymphatic proliferation limited to the skin with no involvement of lymph nodes, bone marrow or viscera at the diagnosis. Cutaneous lymphomas originate from mature T-lymphocytes (65% of all cases), mature B-lymphocytes (25%) or NK cells. Histopathological evaluation including immunophenotyping of the skin biopsy specimen is the basis of the diagnosis, which must be complemented with a precise staging of the disease and identification of prognostic factors, to allow for the choice of the best treatment method as well as for the evaluation of the treatment results. PMID:26759546

  1. Mast Cells Are Abundant in Primary Cutaneous T-Cell Lymphomas: Results from a Computer-Aided Quantitative Immunohistological Study

    PubMed Central

    Eder, Johanna; Rogojanu, Radu; Jerney, Waltraud; Erhart, Friedrich; Dohnal, Alexander; Kitzwögerer, Melitta; Steiner, Georg; Moser, Julia; Trautinger, Franz

    2016-01-01

    Background Mast cells (MC) are bone marrow derived haematopoetic cells playing a crucial role not only in immune response but also in the tumor microenvironment with protumorigenic and antitumorigenic functions. The role of MC in primary cutaneous T-cell lymphomas (CTCL), a heterogeneous group of non-Hodgkin lymphomas with initial presentation in the skin, is largely unknown. Objective To gain more accurate information about presence, number, distribution and state of activation (degranulated vs. non-degranulated) of MC in CTCL variants and clinical stages. Materials and Methods We established a novel computer-aided tissue analysis method on digitized skin sections. Immunohistochemistry with an anti-MC tryptase antibody was performed on 34 biopsies of different CTCL subtypes and on control skin samples. An algorithm for the automatic detection of the epidermis and of cell density based CTCL areas was developed. Cells were stratified as being within the CTCL infiltrate, in P1 (a surrounding area 0–30 μm away from CTCL), or in P2 (30–60 μm away from CTCL) area. Results We found high MC counts within CTCL infiltrates and P1 and a decreased MC number in the surrounding dermis P2. Higher MC numbers were found in MF compared to all other CTCL subgroups. Regarding different stages of MF, we found significantly higher mast cell counts in stages IA and IB than in stages IIA and IIB. Regarding MC densities, we found a higher density of MC in MF compared to all other CTCL subgroups. More MC were non-degranulated than degranulated. Conclusion Here for the first time an automated method for MC analysis on tissue sections and its use in CTCL is described. Eliminating error from investigator bias, the method allows for precise cell identification and counting. Our results provide new insights on MC distribution in CTCL reappraising their role in the pathophysiology of CTCL. PMID:27893746

  2. Indolent CD8-positive lymphoid proliferation of the ear: a distinct primary cutaneous T-cell lymphoma?

    PubMed

    Petrella, Tony; Maubec, Eve; Cornillet-Lefebvre, Pascale; Willemze, Rein; Pluot, Michel; Durlach, Anne; Marinho, Eduardo; Benhamou, Jean-Luc; Jansen, Patty; Robson, Alistair; Grange, Florent

    2007-12-01

    The authors report 4 cases of cutaneous lymphoproliferation unusual by their histology and their clinical presentation. Each presented with a history of a slow growing nodule on the ear. Despite the indolent clinical evolution, the histology suggested a high-grade lymphoma. All lesions consisted of a dense, diffuse proliferation of monomorphous medium-sized T cells throughout the dermis and subcutis. There was no epidermotropism and a grenz zone was clearly present in each case. The tumor cells displayed irregular blastlike nuclei, with small nucleoli and clear chromatin and had a CD3+, CD8+, CD4+, TIA1+, granzyme B(-)immunophenotype with a loss of other T-cell antigens. The 3 cases with available material for polymerase chain reaction studies displayed a monoclonal T-cell rearrangement of the T-cell receptor-gamma chain. These cases do not correspond to a recognized cutaneous T-cell lymphoma as described in the recent WHO/EORTC classification. The apparent striking propensity for the ear suggests that they might represent a specific entity. Further cases are needed to confirm this hypothesis. It is important for such indolent lesions to be known to avoid over treatment.

  3. Primary cutaneous CD4+ small to medium-size pleomorphic T-cell lymphoma in a 12-year-old girl.

    PubMed

    Volks, Natalie; Oschlies, Ilske; Cario, Gunnar; Weichenthal, Michael; Fölster-Holst, Regina

    2013-01-01

    Primary cutaneous CD4+ small to medium-size pleomorphic T-cell lymphoma (PCSM-TCL) is a rare disease that has been added as a provisional entity to the World Health Organization European Organization for Research and Treatment of Cancer (WHO-EORTC) classification of lymphomas with primary cutaneous manifestations. Patients commonly present with a solitary nodule or plaque on the head or upper trunk, but are usually otherwise in good health. The prognosis is favorable, but the optimal treatment has not been defined. Recent publications have described the expression of programmed death-1 in PCSM-TCL and T-cell pseudolymphoma, suggesting a diagnostic value of this marker in the differential diagnosis of PCSM-TCL in contrast to other types of cutaneous T-cell lymphoma. We present the case of a 12-year-old girl with a tumor of the right supraorbital area. She was treated as an outpatient four times with intralesional triamcinolone acetonide at intervals of 3 to 4 weeks. In addition to the case history, this report includes the clinical and histologic findings and a review of the current literature. © 2013 Wiley Periodicals, Inc.

  4. Primary cutaneous CD4 positive small/medium T-cell lymphoma with high proliferation index and CD30-positive large lymphoid cells.

    PubMed

    Zhang, Ling; Shao, Haipeng

    2013-08-01

    Primary cutaneous CD4 positive small/medium pleomorphic T-cell lymphoma (SMPTCL) represents a provisional subtype of primary cutaneous T-cell lymphoma with indolent clinical course. A few aggressive fatal cases with increased proliferation rate and few infiltrating CD8 positive T-cells have been reported. We describe a case of SMPTCL with an increased proliferation rate, admixed CD30-positive large lymphoid cells, and few infiltrating CD8 positive T-cells. The lymphoma cells were positive for CD3, CD4, CD2 and CD5, and negative for CD8. A subset of the lymphoma cells was positive for follicular helper T-cell markers bcl-6 and PD-1. There were approximately 20% CD30-positive large lymphoid cells, and Ki-67 showed a moderately high proliferation rate (~40%), mostly in the large lymphoid cells. CD8 infiltrating T-cells were few (<5%). The patient had an indolent disease with complete response to radiation therapy. To the best of our knowledge, this is the first reported case of SMPTCL with an increased proliferation rate and large CD30+ cells that followed an indolent clinical course. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Erythema multiforme-like lesions in primary cutaneous aggressive cytotoxic epidermotropic CD8+ T-cell lymphoma: A diagnostic and therapeutic challenge.

    PubMed

    Tomasini, Carlo; Novelli, Mauro; Fanoni, Daniele; Berti, Emilio F

    2017-10-01

    Primary cutaneous aggressive cytotoxic epidermotropic CD8+ T-cell lymphoma is an extremely rare, rapidly progressing, cutaneous lymphoma, with frequent systemic involvement and poor prognosis, that still represents a diagnostic and therapeutic challenge, especially in the early stage. Herein, we report a case of an elderly woman with a fulminant course, who at onset presented with clinical and pathological features mimicking erythema multiforme (EM) and treated with cyclosporine that led to rapid deterioration with fatal outcome 6 months after disease onset. Histopathology showed a lichenoid, epidermotropic and nodular, angiocentric, dermal and subcutaneous infiltrate of sF1, CD8+, CD45RA+ small to medium-sized atypical lymphoid cells, which strongly expressed cytotoxic markers. Monoclonal T-cell-γ receptor was clonally rearranged and array-CGH showed numerous chromosomal imbalances. This case evidences the clinical, pathological and therapeutic challenges involved in this tumor. The first biopsy showed an interface dermatitis-like pattern, revealing the deceptive features that early cutaneous infiltrates of this aggressive lymphoma may have. A high suspicion for aggressive CTCL and a low threshold for repeat biopsies should be maintained when faced with rapidly progressing and/or ulcerative EM-like lesions, especially if immunomodulatory therapy is being considered. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Primary cutaneous mucormycosis in trauma patients.

    PubMed

    Johnson, P C; Satterwhite, T K; Monheit, J E; Parks, D

    1987-04-01

    Primary cutaneous mucormycosis in trauma patients has been rarely reported. We describe three cases occurring in noncompromised hosts and review the literature. Prompt diagnosis and aggressive treatment with vigorous local care and appropriate antibiotics are recommended.

  7. The microenvironment in primary cutaneous melanoma with associated spontaneous tumor regression: evaluation for T-regulatory cells and the presence of an immunosuppressive microenvironment.

    PubMed

    Gray, Arielle; Grushchak, Solomiya; Mudaliar, Kumaran; Kliethermes, Stephanie; Carey, Kyle; Hutchens, Kelli A

    2017-04-01

    Spontaneous tumor regression, regression in the absence of therapeutic intervention, can be identified histologically in over 25% of primary cutaneous melanomas at initial diagnosis. A unique subset of T lymphocytes found in areas of regression can be histologically distinguished from tumor-infiltrating T lymphocytes (TIL) found in areas of tumor progression. We call this unique subset of T lymphocytes regression-associated T lymphocytes (RATs). The aim of this study is to determine the phenotype of lymphocytes and the density of specific cell types linked to immunosuppression in areas of tumor progression compared with areas of tumor regression. These specific cell types include T-regulatory cells (Tregs) and S100A9 cells. A total of 14 primary cutaneous melanomas with areas of progression and regression were used. Immunohistochemistry staining was used to identify CD4 cells, CD8 cells, Tregs, and S100A9 cells. Two independent observers manually counted three high-powered ×40 fields. There was no predominance of CD4 or CD8 T lymphocytes in either RATs or TIL. We identified a lower density of Tregs in RATs compared with TIL when using the FOXP3/CD4 Treg marker (P=0.04) and a marginal difference when using our second, confirmatory Treg marker, FOXP3/CD25 (P=0.11). We observed a lower density of S100A9 cells in RATs compared with TIL (P=0.002). There was an observable difference in the tumor microenvironments of RATs and TIL, with RATs having a significantly lower density of Tregs and S100A9 cells. We deduce that the absence of immunosuppression in areas of regression allows for a more robust immune response and thus effective eradication of tumor cells.

  8. Primary cutaneous adenoid carcinoma of the scalp.

    PubMed

    Keck, Meike; Ueberreiter, Klaus; Tanzella, Ursula; Doll, Dietrich; Krapohl, Björn Dirk

    2012-01-01

    Primary adenoid carcinoma are rare skin tumors. We present a 75-year-old female with this primary cutaneous tumor of the scalp with additional bone involvement. Wide scalp excision with bone enclosure, latissimus-dorsi-free-flap defect overage, and subsequent radiation slowed down the disease but could not prevent further skull infiltration.

  9. Primary Cutaneous Extranodal Natural Killer/T-Cell Lymphoma Misdiagnosed as Peripheral T-Cell Lymphoma: The Importance of Consultation/Referral and Inclusion of EBV In Situ Hybridization for Diagnosis.

    PubMed

    Win, Khin Than; Liau, Jau-Yu; Chen, Bo-Jung; Takata, Katsuyoshi; Chen, Chiao-Yun; Li, Chi-Cheng; Hsiao, Cheng-Hsiang; Chuang, Shih-Sung

    2016-02-01

    Primary cutaneous T-cell lymphomas (CTCL) are heterogenous extranodal non-Hodgkin lymphomas including a few distinct and provisional entities. Compared with the West, Asian populations have a relatively higher frequency of nonmycosis fungoides CTCL. Primary cutaneous extranodal natural killer/T-cell lymphoma (PC-ENKTL) is distinct from other CTCL by the presence of EBV association. In our recent retrospective Asian study of PC-ENKTL, we identified 5 cases initially misdiagnosed as various CTCL. We fully characterized these cases with immunohistochemistry, EBV in situ hybridization, and clonality study for T-cell receptor (TCR) γ-chain gene (TRG). The 5 patients included 3 males and 2 females with a median age of 45. All tumors were positive for EBER. Two cases were clonal for TRG gene rearrangement but without expression of βF1 or TCR-γ (TCR-silent T-cell origin), 1 tumor expressed TCR-γ (γδ T-cell origin), and the remaining 2 were polyclonal for TRG and negative for TCR expression (NK-cell origin). On the basis of the initial diagnoses (2 as peripheral T-cell lymphoma, unspecified, 2 as primary cutaneous anaplastic large-cell lymphoma, and 1 as subcutaneous panniculitis-like T-cell lymphoma), all patients received CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy with additional radiotherapy in 3. All patients experienced persistent disease or relapse despite treatment in a mean duration of 8.8 months (range, 1 to 12 mo). PC-ENKTL is rare and aggressive. These cases strongly demonstrate the importance of consultation/referral to experienced hematopathologists and the inclusion of EBER in the initial diagnostic work-up for patients with nonmycosis fungoides CTCL to avoid erroneous diagnosis and subsequent inadequate treatment of the patients.

  10. Primary cutaneous mucormycosis: guide to surgical management.

    PubMed

    Losee, Joseph E; Selber, Jesse; Vega, Stephen; Hall, Caroline; Scott, Glynis; Serletti, Joseph M

    2002-10-01

    Mucormycosis is the most acute, fulminate, and fatal of all fungal infections in humans. It presents most frequently in immunocompromised patients, but can occur in healthy patients in the presence of often-insignificant trauma. Surgical management of primary cutaneous mucormycosis is almost always required. Case reports of surgical treatment for primary cutaneous mucormycosis are reported in the literature; however, the extent of debridement required for cure is unclear and no uniform plan of treatment has been suggested. To date, no clinical guidelines exist to assist the clinician in the surgical management of this disease. This article reviews the literature, reports on two clinical cases, and submits clinical guidelines designed to assist the clinician in the surgical management of primary cutaneous mucormycosis. Because of the infrequent and potentially fatal nature of the diagnosis, a high index of suspicion and a low threshold for wound biopsy must be maintained. Wound cultures are grossly inadequate and should not be relied on for a false sense of security. It is recommended that, for the early diagnosis of cutaneous mucormycosis, chemotherapy and surgical debridement of grossly necrotic tissue be performed at the earliest possible time. The debrided wound is monitored for the resolution of surrounding erythema and induration before definitive reconstruction. In the case of delayed diagnosis and/or advanced or rapidly progressive disease, surgical debridement of all involved tissue, in addition to chemotherapy, is warranted.

  11. A case of a primary cutaneous plasmacytoma presenting in adolescence.

    PubMed

    Koletsa, Triantafyllia; Patsatsi, Aikaterini; Kostopoulos, Ioannis; Kartsios, Charalambos; Korantzis, Ioannis; Sotiriadis, Dimitrios

    2012-07-01

    Primary cutaneous plasmacytoma is defined as monoclonal proliferation of plasma cells that arises primarily in the skin without evidence of systemic disease. We present an extremely rare case of a young adult diagnosed with solitary plasmacytoma. A 20-year-old woman presented with a pruritic erythematosquamous indurated plaque on the inner aspect of her right thigh. She had undergone a biopsy 5 years ago, and under the diagnosis of Nekam disease, she was treated with topical steroids followed by intralesional injections of triamcinolone acetonide. A new skin biopsy revealed infiltration of the epidermis by small T lymphocytes while plasma cell accumulations were found in the dermis. Immunostains for light and heavy chains [kappa, lambda, immunoglobulin (Ig) G, IgA, and IgM] demonstrated IgG/κ monoclonality of the plasma cells. On molecular analysis, T-cell receptor and immunoglobulin heavy chain rearrangements were polyclonal. Serum protein electrophoresis, immunofixation, and quantitative assessment of serum Igs were normal. Bone marrow biopsy, skeletal survey, and body computed tomography scan were unremarkable. A diagnosis of primary solitary cutaneous plasmacytoma was made. The lesion was removed surgically, and the patient remains in remission up to now. Primary cutaneous plasmacytoma represents only 2%-4% of extramedullary plasmacytomas. The rarity and the nonspecific presentation of cutaneous plasmacytomas does not allow a definite clinical diagnosis. Only histopathology reveals the typical pattern of a dense monomorphic dermal plasmacytic infiltrate, whereas immunohistochemistry shows monoclonality of the neoplastic cells.

  12. Primary cutaneous histiocytoid carcinoma with distant metastasis.

    PubMed

    Philips, Rebecca; Langston, Leila; Hwang, Helena; Vandergriff, Travis; Trynosky, Tanya; Berlingeri-Ramos, Alma C

    2017-04-01

    Distinguishing primary cutaneous adnexal carcinoma from metastatic carcinoma of unknown primary can be a diagnostic challenge due to the frequent overlap of histologic and immunohistochemical features. A 58-year-old man presented with a tender, indurated plaque on axillary skin. Biopsy revealed infiltrating atypical cells throughout the dermis, without connection to the epidermis. Tumor cells had a histiocytoid appearance and displayed mild pleomorphism. The tumor was discohesive and had areas with a single file pattern. Signet ring cells were also present. Cells were reactive with CK7, CK5/6, p63, GATA3, GCDFP-15 and Her 2-neu. Additional studies were negative, including TTF-1, CDX2, E-cadherin, mammaglobin, estrogen receptor and progesterone receptor. Thorough clinical and radiologic evaluation failed to identify an occult primary extracutaneous malignancy; however, regional lymphadenopathy, widespread osteoblastic lesions and multiple subcentimeter liver hypodensities were noted. Considering the clinical and histopathologic features, the diagnosis of primary cutaneous histiocytoid carcinoma with distant metastasis was favored.

  13. Primary Cutaneous Histoplasmosis Masquerading as Lepromatous Leprosy

    PubMed Central

    Rani, Poonam; Aggarwal, Radhika; Kaushal, Seema

    2017-01-01

    Histoplasmosis is a genus of dimorphic fungi having various varieties of which the commonest one causing infection is Histoplasma capsulatum known to cause histoplasmosis. It has a varied disease spectrum ranging from an acute infection to chronic disease especially in lungs, disseminated disease and cutaneous disorder. Histoplasma capsulatum usually causes subclinical infection and serious infections only manifest in immunocompromised patients. Frank cases of infection are seen in pulmonary histoplasmosis. The spores of these organisms are seen to be strongly associated with droppings of birds and bats. A combination of these droppings and some soil types provide for an excellent environment for the proliferation of spores. Pulmonary histoplasmosis and disseminated disease are very common in AIDS patients and are a great cause of morbidity and mortality in these patients. Primary cutaneous histoplasmosis is very rare and occurs due to penetrating injuries. Once diagnosis is made, the lesions respond very well to oral itraconazole, fluconazole or amphotericicn B. We report a rare case of Cutaneous Histoplasmosis (CHP) in a 70-year-old male with complaints of multiple nodules all over his body in a HIV seronegative and otherwise immunocompetent patient. PMID:28273974

  14. Primary cutaneous mucormycosis in an immunocompetent patient.

    PubMed

    Paduraru, Mihai; Moreno-Sanz, Carlos; Olalla Gallardo, Jose Maria

    2016-08-16

    Mucormycosis is most common in immunocompromised patients, but it can also occur in healthy hosts, most frequently as primary cutaneous mucormycosis (PCM) and predominantly as a result of skin trauma. We present an uncommon case of PCM in a healthy, young man with no previous history of local trauma. Despite rapid progression of the infection, the patient was successfully treated through surgical intervention and by administering liposomal amphotericin B and posaconazole. He made a full recovery without the need for skin grafting. 2016 BMJ Publishing Group Ltd.

  15. Primary cutaneous blastoid mantle cell lymphoma-case report.

    PubMed

    Estrozi, Bruna; Sanches, José A; Varela, Paulo C S; Bacchi, Carlos E

    2009-06-01

    Mantle cell lymphoma (MCL) commonly involves extranodal sites, usually as a manifestation of disseminated disease. In rare cases, MCLs may arise as a primary tumor in the skin. Blastoid mantle cell lymphoma (BV-MCL) is a rare variant and has a more aggressive clinical course. The phenotype of BV-MCL is characterized as CD20+, CD5+, cyclin D1+, CD23-, and CD10-. Interphase fluorescence in situ hybridization shows a characteristic t(11;14) fusion pattern. We report a case of a BV-MCL arising in skin as primary cutaneous MCL with the characteristic immunophenotype and translocation.

  16. Primary Cutaneous Mantle Cell Lymphoma: A Case Report

    PubMed Central

    Mazzuoccolo, L. D.; Castro Perez, G. A.; Sorin, I.; Bravo, A. I.

    2013-01-01

    Primary cutaneous mantle cell lymphoma (MCL) is a rare cutaneous proliferation of naive pregerminal CD-5 positive B cells in the skin with no extracutaneous involvement. Overexpression of cyclin D1 is pathognomonic of this condition, and surgery and radiation therapy are the most common therapeutic options. In this case, we describe the clinical, histopathological, immunohistochemical, and molecular characteristics of a new case of primary cutaneous MCL. PMID:23762653

  17. Primary Cutaneous Aspergillosis in an Immunocompetent Patient

    PubMed Central

    Tahir, Chubado; Garbati, Musa; Nggada, Haruna A.; Yawe, Edith H. Terna; Abubakar, Auwal M.

    2011-01-01

    We present a 32-year-old woman with primary cutaneous aspergillosis and an apparently normal immune status. She is a dietitian who carried out research on Aspergillus contamination of palm oil over a six-month period, during which she apparently shaved her axillae and perineum using a safety razor blade. She presented with nodular lesions, which became extensive ulcers after an attempt at incision and drainage. Diagnosis was based on culture and histology. The patient was treated with itraconazole 200 mg twice a day, with surgical excision and a rhomboid flap cover of the axillae. She has remained disease-free five years after discharge. This highlights the likely benefits of a combination of surgical excision and drug therapy, in achieving a cure in this patient. PMID:22413053

  18. Primary Cutaneous Melanoma: An 18-Year Study

    PubMed Central

    Anger, Moris; Friedhofer, Henri; Fukutaki, Marina Fussae; Ferreira, Marcus Castro; Landman, Gilles

    2010-01-01

    BACKGROUND: Primary cutaneous melanoma still constitutes the main cause of skin cancer death in developed countries, and its incidence in recent years has been increasing in a steady, worrisome manner. OBJECTIVES: This study evaluated the clinical, epidemiological and demographic aspects of this disease, and correlated them with patient prognosis. METHODS: Using epidemiologic and clinical data, we analyzed 84 patients with mild to severe primary cutaneous melanoma treated between 1990 and 2007. Slides containing surgical specimens were analyzed, and new slides were made from archived paraffin sections when necessary. RESULTS: The melanoma incidence was higher in areas of sun exposure, with lesions commonly observed in the trunk for males, and lower limbs for females. In addition to Breslow’s thickness and ulceration (p = 0.043 and p < 0.001, respectively), the mitotic rate per mm2 also correlated with worse patient outcome (p = 0.0007). The sum of ulceration (0 when absent or 1 when present), the Breslow index (1 when <1 mm, 2 when >1 mm and <4 mm, 3 when >4 mm) and the mitotic index (0 when absent or 1 when ≥1 per mm2) allowed the establishment of a prognostic score: if the sum was equal to or over three, nearly all (91.7%) patients had systemic disease. The 5-year survival was approximately seventy percent. CONCLUSION: Because American Join Committee of Cancer Staging will update the classification of malignant tumors (TNM) staging in the near future, and introduce mitosis as a prognostic factor, our results show the importance of such a feature. Additional studies are necessary to confirm the importance of a prognostic score as proposed herein. PMID:20360915

  19. Detection of t(2;5)(p23;q35) translocation by reverse transcriptase polymerase chain reaction and in situ hybridization in CD30-positive primary cutaneous lymphoma and lymphomatoid papulosis.

    PubMed Central

    Beylot-Barry, M.; Lamant, L.; Vergier, B.; de Muret, A.; Fraitag, S.; Delord, B.; Dubus, P.; Vaillant, L.; Delaunay, M.; MacGrogan, G.; Beylot, C.; de Mascarel, A.; Delsol, G.; Merlio, J. P.

    1996-01-01

    The t(2;5) generates a chimeric NPM-ALK transcript encoded by the nucleophosmin NPM gene fused to the anaplastic lymphoma kinase gene ALK. Using a reverse transcriptase nested polymerase chain reaction assay we have detected NPM-ALK transcripts within CD30+ primary cutaneous lymphoma and lymphomatoid papulosis (LP). The t(2;5) was identified in 4 out of 9 CD30+ anaplastic lymphomas and in 1 out of 4 CD30+ pleomorphic lymphomas. Moreover, the t(2;5) was detected in 3 out of 10 LPs. All NPM-ALK-positive lymphomas and 1 NPM-ALK-positive LP exhibited a clonal rearrangement of the T cell receptor gamma-chain gene. The t(2;5) was detected in 2 cases of LP without other evidence for a clonal lymphoid population. To identify cells carrying the t(2;5) translocation, we used immunohistochemistry to detect the ALK-encoded p80 protein and in situ hybridization for the specific detection of NPM-ALK transcripts. Both p80 protein and NPM-ALK transcripts were expressed by anaplastic or large CD30+ lymphoma cells with positive NPM-ALK amplification. The presence of t(2;5) in a subset of CD30+ cutaneous lymphoma and LP may indicate a common pathogenesis with a subset of anaplastic nodal lymphoma. Images Figure 2 Figure 3 PMID:8701987

  20. Primary cutaneous extravertebral meningioma. Case report.

    PubMed

    Zaaroor, M; Borovich, B; Bassan, L; Doron, Y; Gruszkiewicz, J

    1984-05-01

    A case of cutaneous extravertebral meningioma is presented. It was diagnosed in infancy as a lumbar meningocele. Operation was initially refused but was subsequently demanded for cosmetic reasons. The findings were a very thick corrugated skin and a cutaneous meningioma connected by a fibrous tract to the dura mater. The presence of a fibrous stalk linking the tumor to the dura mater might have been the pathogenetic connection between the meningocele and cutaneous meningioma.

  1. Primary cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome): part I. Diagnosis: clinical and histopathologic features and new molecular and biologic markers.

    PubMed

    Jawed, Sarah I; Myskowski, Patricia L; Horwitz, Steven; Moskowitz, Alison; Querfeld, Christiane

    2014-02-01

    Mycosis fungoides (MF) and Sézary syndrome (SS) comprise approximately 53% of cutaneous lymphomas. Both MF and SS may clinically and histologically mimic benign skin conditions, posing a diagnostic challenge to the dermatologist. Precise clinicopathologic correlation is necessary to support a diagnosis, especially in the early stages of disease. In addition to the identification of histopathologic criteria, ancillary studies, including the identification of CD4(+) T cells with aberrant immunophenotypes and T-cell receptor gene rearrangements within skin lesions and peripheral blood are used to support the diagnosis. Recent studies evaluating the pathogenesis of MF have found that the skin microenvironment, including immune cells, such as dendritic cells and reactive cytotoxic and regulatory T cells, plays a crucial supporting role in MF. The skin-homing ability of malignant T cells is the result of chemokines, cytokines, adhesion molecules, and defective apoptosis, and is believed to play a role in disease pathogenesis and progression. In addition, recent studies have also suggested that MF and SS arise from distinct memory T cell subsets and advanced/erythrodermic MF and SS may be distinguished by identification of certain molecules, including Programmed-Death-1.

  2. [Primary cutaneous manifestation of Wegener's granulomatosis].

    PubMed

    Bramsiepe, I; Danz, B; Heine, R; Taube, K-M; Holzhausen, H-J; Marsch, W C; Fiedler, E

    2008-07-01

    A 57-year-old man was admitted with hemorrhagic papules and necrotising nodules on both elbows and upper legs. Recurrent arthralgia occurred. The skin biopsy showed a cutaneous necrotising vasculitis. Positive test results for c-ANCA and proteinase 3 antibodies and a slightly increased WBC and a mild proteinuria were noticeable. The diagnosis of an early systemic Wegener's granulomatosis was based on elevated proteinase 3-titres and cutaneous histologic findings as necrotising vasculitis and granulomatous inflammation. Treatment with prednisolone followed by methotrexate resolved the cutaneous symptoms and the arthralgia completely. Three months later the patient developed a progredient methotrexate toxicity caused by a glomerulonephritis. Wegener's granulomatosis should be considered if a cutaneous necrotising vasculitis is diagnosed. A cutaneous manifestation could be an early symptom. Methotrexate could be used for treatment of mild courses of Wegener's disease without renal involvement.

  3. Primary Cutaneous Chrysosporium Infection following Ear Piercing: A Case Report.

    PubMed

    Suchonwanit, Poonkiat; Chaiyabutr, Chayada; Vachiramon, Vasanop

    2015-01-01

    Chrysosporium is a large genus of saprophytic fungi that is commonly found in the soil. Infection caused by this organism is rare in humans and typically occurs in immunocompromised patients. Primary cutaneous Chrysosporium infection is relatively rare and has been reported in a heart transplant patient. The prognosis is usually favorable, but very poor in the setting of persistent profound immunosuppression. We herein report a case of primary cutaneous Chrysosporium infection following ear piercing in an immunocompetent patient. It is important for clinicians to consider this condition in patients with slow-onset skin and soft tissue infection following cutaneous injury, even in an immunocompetent setting.

  4. Primary cutaneous anaplastic large cell lymphoma masquerading as large pyogenic granuloma

    PubMed Central

    Bains, Anupama; Vedant, Deepak; Shanker, Vinay; Tegta, G. R.

    2016-01-01

    Primary cutaneous anaplastic large cell lymphoma (pcALCL) forms 9% of the cutaneous T-cell lymphomas. It usually presents as solitary reddish brown ulcerating nodule or indurated plaque. Sometimes, it mimics other dermatological diseases such as eczema, pyoderma gangrenosum, pyogenic granuloma, morphea, and squamous cell carcinoma. Our case presented with large pyogenic granuloma like lesion with regional lymphadenopathy. Since pcALCL is rare, one can misdiagnose such cases and therefore high index of suspicion is necessary. PMID:27990392

  5. Cutaneous T-cell lymphoma/leukemia.

    PubMed

    Siegel, R S; Kuzel, T M

    2000-04-01

    Effective treatment for cutaneous T-cell lymphomas (CTCL) requires an accurate and specific diagnosis based on the clinical presentation combined with evaluation of the histopathology, immunophenotyping, and gene rearrangement studies. Careful clinical and pathologic evaluation in centers familiar with the diverse forms of CTCL is most valuable for determining treatment options. The goals of treatment in mycosis fungoides (MF), which afflicts more than 50% of patients with CTCL, are the relief of symptoms and improvement in cosmetics. Despite some uncontrolled clinical trial results that have been reported to suggest "cures" in this disease, the general perception remains that this disease is not curable with standard therapies available today. Treatment is divided into topical (skin-directed) and systemic therapy. The most active systemic agent for the treatment of MF remains interferon-alpha, although many new modalities have recently been approved for the treatment of CTCL.

  6. Controversies in the management of the cutaneous T cell lymphomas.

    PubMed

    Zic, John A

    2009-01-01

    The primary cutaneous T cell lymphomas (CTCL) encompass all malignancies of the T cell where the skin is the primary organ of involvement. The diagnosis of a CTCL variant can be detoured by a number of obstacles including the slow evolution of the disease into a classic clinical and pathologic pattern. A realistic goal of early stage treatment is to reduce the likelihood of progression to a more advanced stage, not to achieve a cure. No studies have adequately compared the different systemic agents in patients with advanced CTCL so the clinician is left to act in the best interest of the patient with what evidence is available. When using the systemic agents, a "start low and go slow" strategy may offer patients several advantages. Dermatologists are uniquely trained to diagnose and to manage all but the most advanced stage patients with CTCL.

  7. A Literature Revision in Primary Cutaneous B-cell Lymphoma

    PubMed Central

    Selva, R La; Violetti, S Alberti; Delfino, C; Grandi, V; Cicchelli, S; Tomasini, C; Fierro, M T; Berti, E; Pimpinelli, N; Quaglino, P

    2017-01-01

    The term “Primary Cutaneous B-Cell Lymphoma” (PCBCL) comprehends a variety of lymphoproliferative disorders characterized by a clonal proliferation of B-cells primarily involving the skin. The absence of evident extra-cutaneous disease must be confirmed after six-month follow-up in order to exclude a nodal non-Hodgkin's lymphoma (NHL) with secondary cutaneous involvement, which may have a completely different clinical behavior and prognosis. In this article, we have summarized the clinico-pathological features of main types of PCBCL and we outline the guidelines for management based on a review of the available literature. PMID:28400634

  8. Primary Cutaneous Ewing Sarcoma: Report of a Case.

    PubMed

    Yuste, Veronica; Sierra, Elena; Ruano, David; Llamas-Velasco, Mar; Conde, Esther; Azorin, Daniel

    2015-01-01

    Primary cutaneous Ewing's sarcoma is a rare entity. Although the diagnosis may be very difficult, it can be confirmed through molecular biology. We present the case of a 13-years old male with a lesion in the sole of the right foot, characterized by a monomorphous proliferation of small, round and blue cells. The histology and molecular biology allowed us to perform the diagnosis of cutaneous Ewing's sarcoma. This neoplasm must be distinguished from other round cell tumors with cutaneous involvement. The prognosis and treatment of this rare disease will also be discussed.

  9. Review of Primary Cutaneous Mucinoses in Nonlupus Connective Tissue Diseases.

    PubMed

    Wong, Russell X; Chia, Justin C; Haber, Richard M

    2017-07-01

    Lichen myxedematosus is an idiopathic, cutaneous mucinosis with 2 clinicopathologic subsets. There is the generalised papular and sclerodermoid form, more properly termed scleromyxedema, and the localised papular form. We report the first case, to our knowledge, of lichen myxedematosus in association with rheumatoid arthritis as well as a case in association with dermatomyositis. An up-to-date literature review on cutaneous mucinoses and connective tissue diseases, excluding the common association of primary and secondary mucinoses with systemic lupus erythematosus, was also performed.

  10. Epidermodysplasia verruciformis after cutaneous T-cell lymphoma: Periungual presentation.

    PubMed

    Cutlan, Jonathan E; Rashid, Rashid M; Torres-Cabala, Carlos; Tyring, Stephen K; Thomas, Valencia

    2010-08-15

    Epidermodysplasia verruciformis (EV) has several clinical presentations and has been reported in various states of immune deregulation. We report the unique presentation of this disease as a pigmented periungual macule in a patient with a previous history of immune deregulation related to cutaneous lymphoma. A literature review did not reveal any previous reports of EV in patients with cutaneous T-cell lymphoma.

  11. Best practices in diagnostic immunohistochemistry: workup of cutaneous lymphoid lesions in the diagnosis of primary cutaneous lymphoma.

    PubMed

    Dewar, Rajan; Andea, Aleodor Alexandru; Guitart, Joan; Arber, Daniel A; Weiss, Lawrence M

    2015-03-01

    Primary cutaneous lymphoma is a common extranodal non-Hodgkin lymphoma. These lesions share common features with their nodal counterparts, but also have differences in morphology, unique clinical presentations, and immunohistochemical features. To review the 2008 World Health Organization (WHO) and 2005 consensus WHO-EORTC (European Organisation for Research and Treatment of Cancer) classifications, and address the immunohistochemical findings in the most common primary cutaneous T- and B-cell lymphomas. Since clonality testing is commonly used as an ancillary test in the evaluation of cutaneous lymphoma, a brief section in the use and pitfalls of clonality testing is included. The WHO and EORTC classification publications and the relevant recent literature were used to compile appropriate and practical guidelines in this review. The practice of dermatopathology and hematopathology varies widely. Thus, while this review provides an overview and guideline for the workup of lymphoid lesions of the skin, the practitioner should understand the importance of clinical correlation as well as appropriate utility of available resources (such as clonality testing) in arriving at a diagnosis in cutaneous lymphoid lesions.

  12. Primary cutaneous amebiasis with a fatal outcome.

    PubMed

    Al-Daraji, Wael Ismail; Husain, Ehab A; Ilyas, Mohammed; Robson, Alistair

    2008-08-01

    We report a fatal case of disseminated amebiasis in a young African woman, which initially presented with an ulcerated cutaneous lesion on the left flank. The causative organism was confirmed by examination of a wet drop preparation from the ulcer discharge and by skin biopsy. The patient was not immunosuppressed and was treated unsuccessfully with metronidazole. Postmortem examination revealed the presence of intestinal amebiasis complicated by a liver abscess.

  13. Cutaneous primary B-cell lymphomas: from diagnosis to treatment*

    PubMed Central

    Lima, Margarida

    2015-01-01

    Primary cutaneous B-cell lymphomas are a heterogeneous group of mature B-cells neoplasms with tropism for the skin, whose biology and clinical course differ significantly from the equivalent nodal lymphomas. The most indolent forms comprise the primary cutaneous marginal zone and follicle center B-cell lymphomas that despite the excellent prognosis have cutaneous recurrences very commonly. The most aggressive forms include the primary cutaneous large B-cell lymphomas, consisting in two major groups: the leg type, with poor prognosis, and others, the latter representing a heterogeneous group of lymphomas from which specific entities are supposed to be individualized over time, such as intravascular large B-cell lymphomas. Treatment may include surgical excision, radiotherapy, antibiotics, corticosteroids, interferon, monoclonal antibodies and chemotherapy, depending on the type of lymphoma and on the type and location of the skin lesions. In subtypes with good prognosis is contraindicated overtreatment and in those associated with a worse prognosis the recommended therapy relies on CHOP-like regimens associated with rituximab, assisted or not with local radiotherapy. We review the primary cutaneous B-cell lymphomas, remembering the diagnostic criteria, differential diagnosis, classification, and prognostic factors and presenting the available therapies. PMID:26560215

  14. Primary Cutaneous Coccidioidomycosis of the Eyelid: A Case Report.

    PubMed

    Dworak, Douglas P; Kapustiak, James; Ehklassi, Timothy A; Patrianakos, Thomas D

    2016-01-01

    A 33-year-old man presented with an ulcerated nodule on his left eyelid and eyebrow that was unresponsive to broad-spectrum antibiotics. Incisional biopsies were performed, and cultures were positive for Coccidioides immitis. An extensive work-up revealed no systemic involve ment of disseminated coccidioidomycosis. The patient was treated with oral itraconazole for 6 months with resolution of the lesion. Few cases of primary cutaneous coccidioidomycosis have been reported. The authors describe a primary cutaneous coccidioidomycosis lesion of the eyelid without disseminated disease.

  15. Primary Cutaneous Plasmacytosis: Masquerading as Hidradenitis Suppurativa

    PubMed Central

    Goyal, Tarang; Varshney, Anupam; Zawar, Vijay; Sharma, Veena

    2016-01-01

    Isolated cutaneous plasmacytosis (CP) is a rare entity with few cases reported in world literature. CP masquerading as hidradenitis suppurativa like presentation is a unique case with some features differentiating it clinically from it which were further confirmed by histopathology and immunostaining. Our case showed hyperplasia of mature plasma cells and polyclonal hypergammaglobulinemia, immunostaining for CD138 positivity and kappa: lambda ratio more than 3:1. Extensive clinical and laboratory investigations failed to reveal any underlying pathology, presence of any underlying disease accompanying the hypergammaglobulinemia and/or plasma cell proliferation. PMID:27057027

  16. Primary Cutaneous Lymphoma-Associated Pseudoepitheliomatous Hyperplasia Masquerading as Squamous Cell Carcinoma in a Young Adult.

    PubMed

    Ansari, Mahsa; Azmoodeh Ardalan, Farid; Najafi, Masoumeh; Goodarzi, Azadeh; Ghanadan, Alireza

    2015-12-01

    Primary cutaneous anaplastic large cell lymphoma is a T-cell malignancy with atypical CD30 positive lymphocytes. Pseudoepitheliomatous hyperplasia is an uncommon finding in primary cutaneous anaplastic large cell lymphoma, and may mimic squamous cell carcinoma as pseudomalignancy. Careful attention of a pathologist to correct diagnosis of pseudoepitheliomatous hyperplasia and its underlying causes will help physicians to avoid inappropriate management. Here, we present a 22-year-old man referred to our hospital with a solitary nodule persistent on his forearm which was diagnosed as squamous cell carcinoma in the first biopsy. The lesion recurred after two months and histopathologic and immunohistochemistry examination revealed anaplastic large cell lymphoma with florid pseudoepitheliomatous hyperplasia which masquerading as well-differentiated squamous cell carcinoma. Diagnosis of pseudoepitheliomatous hyperplasia must guide the pathologist to search for underlying causes, such as primary cutaneous lymphoma. Pseudoepitheliomatous hyperplasia may mimic squamous cell carcinoma and this can result in inappropriate diagnosis and management.

  17. New Targeted Treatments for Cutaneous T-cell Lymphomas

    PubMed Central

    Bagot, Martine

    2017-01-01

    Cutaneous T-cell lymphomas (CTCLs) represent a group of rare and heterogeneous diseases that are very difficult to treat at advanced stages. The development of monoclonal antibodies is a new hope for the treatment of these diseases. Alemtuzumab (Campath) is a humanized IgG1 kappa monoclonal antibody specific for CD52, an antigen expressed by most T and B lymphocytes. Alemtuzumab may frequently induce long-term remissions in patients with Sezary syndrome but high-dose treatments lead to severe cytopenia, immune depletion, and opportunistic infections. This treatment is less efficient in mycosis fungoides (MF). Brentuximab vedotin is a chimeric anti-CD30 monoclonal antibody conjugated to monomethyl auristatin E, a cytotoxic antitubulin agent. Brentuximab vedotin is a very interesting new treatment for advanced tumor MF, Sezary syndrome, and primary cutaneous CD30+ lymphoproliferative disorders. The main limiting adverse event is neurosensitive peripheral neuropathy. Mogamulizumab is a humanized anti-C-C chemokine receptor Type 4 monoclonal antibody with a defucosylated Fc region leading to increased antibody-dependent cellular cytotoxicity. Mogamulizumab is very efficient on aggressive peripheral T-cell lymphomas, particularly adult T-cell leukemia/lymphoma and CTCLs, especially on the blood component of tumor cells. The main limiting events are related to the concomitant depletion of regulatory T-cells. IPH4102 is a humanized monoclonal antibody that targets the immune receptor KIR3DL2/CD158k. Preclinical results with this antibody offer proofs of concept for the clinical development of IPH4102 to treat patients with advanced CTCL. PMID:28400633

  18. Primary cutaneous plasmablastic lymphoma revealing clinically unsuspected HIV infection*

    PubMed Central

    Marques, Silvio Alencar; Abbade, Luciana P. Fernandes; Guiotoku, Marcelo Massaki; Marques, Mariangela Esther Alencar

    2016-01-01

    Plasmablastic lymphoma is a rare subtype of diffuse large B-cell lymphoma more frequently diagnosed in immunosuppressed patients, mainly HIV-infected. Primary cutaneous plasmablastic lymphoma is extremely rare, and in this patient it was the first clinical manifestation of unsuspected HIV-infection. PMID:27579749

  19. Immunohistochemical and morphologic evaluation of primary cutaneous apocrine carcinomas and cutaneous metastases from ductal breast carcinoma.

    PubMed

    Fernandez-Flores, A

    2012-01-01

    The differential diagnosis between a primary cutaneous apocrine carcinoma (CAC) and a cutaneous metastasis from a breast carcinoma can be a very difficult task if it is only made on morphologic bases. Concerning adnexal tumors (in general), there have been many attempts to define an immunohistochemical panel, and while a definition is useful in certain respects, the series presented often times does not include examples of CAC. Other times, CAC seems to behave in an odd way in an immunohistochemical context; they behave differently than other adnexal tumors, and this in turn adds a grade of confusion to the differential diagnosis of a cutaneous metastasis. In the current study, we include seven cases of primary cutaneous apocrine tumors, including one carcinoma in situ, five infiltrating carcinomas, and one adenoma. Additionally, we examine the expression of estrogen receptors (ER), progesterone receptors (PR), and c-erbB-2. We also study myoepithelial markers, such as p63, D2-40, and SMA in them, as well as the pattern of expression of the following cytokeratins: CK7, CK8, CK18, CK19, CK5/6 and 34betaE12. On the other hand, we examine the expression of six immunohistochemical markers (ER, PR, p63, mammaglobin, CK5÷6 and D2-40) in 30 cases of cutaneous metastases from breast carcinoma, ductal type. None of our infiltrating primary CAC expressed ER or PR, while the cutaneous metastasis expressed the markers in 90% of the cases. D2-40 was expressed in 60% of the infiltrating CACs, while the metastases were either negative (93.33% of the cases) or positive with luminal reinforcement. Mammaglobin was a very useful marker, expressed by 66.66% of the metastases, and by only one CAC (and in less than 10% of the cells). None of the metastases were positive for p63, while 60% of the CAC expressed the marker. CK 5/6 was also expressed by a high percentage of our CACs (80%), while it was seen in only 6.66% of the metastases. We found SMA as a very useful tool in diagnosing

  20. Primary cutaneous aspergillosis and idiopathic bone marrow aplasia*

    PubMed Central

    Furlan, Karina Colossi; Pires, Mario Cezar; Kakizaki, Priscila; Chartuni, Juliana Cabral Nunes; Valente, Neusa Yuriko Sakai

    2016-01-01

    We describe the case of a 9-year-old boy with idiopathic bone marrow aplasia and severe neutropenia, who developed skin ulcers under cardiac monitoring electrodes. The diagnosis of primary cutaneous aspergillosis was made after the second biopsy and culture. Imaging investigation did not reveal internal fungal infection. The child was treated, but did not improve and died 3 months after admission. The report highlights and discusses the preventable risk of aspergillus skin infection in immunocompromised patients. PMID:27438213

  1. Low-Dose Palliative Radiotherapy for Cutaneous B- and T-Cell Lymphomas

    SciTech Connect

    Neelis, Karen J. Schimmel, Erik C.; Vermeer, Maarten H.; Senff, Nancy J.; Willemze, Rein; Noordijk, Evert M.

    2009-05-01

    Purpose: To determine the efficacy of low-dose palliative radiotherapy for both low-grade malignant cutaneous B-cell lymphomas (CBCLs) and cutaneous T-cell lymphomas (mycosis fungoides). Methods and Materials: A total of 18 patients with low-grade CBCL (10 primary cutaneous marginal zone B-cell and 8 primary cutaneous follicle center lymphomas) with 44 symptomatic plaques and tumors underwent low-dose (4 Gy in two fractions) local radiotherapy. A total of 31 patients with mycosis fungoides were treated at 82 symptomatic sites, initially with 4 Gy and later with 8 Gy in two fractions. Results: The complete response rate for CBCL lesions was 72%. Of the 44 B-cell lymphoma lesions, 13 were re-treated to the same site after a median of 6.3 months because of persistent (n = 8) or recurrent (n = 5) symptomatic disease. Of the mycosis fungoides patients treated with 4 Gy in two fractions (17 lesions), 70% failed to respond. Increasing the dose to 8 Gy in two fractions yielded a complete response rate of 92% (60 of 65 lesions). The patients in whom low-dose radiotherapy failed were retreated with 20 Gy in eight fractions. Conclusion: Our results have demonstrated that low-dose involved-field radiotherapy induces a high response rate in both CBCL and cutaneous T-cell lymphoma lesions without any toxicity. Therefore, this treatment is now our standard palliative treatment. At progression, it is safe and feasible to apply greater radiation doses.

  2. Primary cutaneous diffuse large B-cell lymphoma (PCDLBCL), leg-type and other: an update on morphology and treatment.

    PubMed

    Paulli, M; Lucioni, M; Maffi, A; Croci, G A; Nicola, M; Berti, E

    2012-12-01

    Primary cutaneous B-cell lymphoma (PCBCL) is an heterogeneous group of lymphoproliferative disorders, which account for 25-30% of all primary cutaneous lymphoma and include three main histotypes: 1) primary cutaneous marginal zone B-cell lymphoma (PCMZL); 2) primary cutaneous follicular center cell lymphoma (PCFCL); 3) primary cutaneous diffuse large B-cell lymphoma (DLBCL), leg type (PCDLBCL-LT). PCMZL and PCFCL are indolent lymphomas, with an excellent prognosis despite an high rate of cutaneous recurrences; in contrast, PCDLBCL-LT is clinically more aggressive and usually requires to be treated with multi-agent chemotherapy and anti-CD20 monoclonal antibodies. PCDLBCL-LT histologically consists of large round cells (centroblasts and immunoblasts), is characterized by strong bcl-2 expression, in the absence of t(14;18) translocation, and resembles the activated B-cell type of nodal DLBCL. Recently, the term primary cutaneous DLBCL-other (PCDLBCL-O) has been proposed to include diffuse lymphomas composed of large transformed B-cells that lack the typical features of PCDLBCL-LT and do not conform to the definition of PCFCL. Some clinical studies suggested that such cases have an indolent clinical course and may be treated in a conservative manner; however, data regarding the actual prognosis and clinical behaviour of these peculiar cases are still too limited. The spectrum of primary cutaneous DLBCL also encompasses some rare morphological variants, such as anaplastic or plasmablastic subtypes and T-cell rich B-cell lymphoma, and some recently described, exceedingly rare DLBCL subtypes, such as intravascular large B-cell lymphoma and EBV-associated large B-cell lymphoma of the elderly, which often present in the skin.

  3. Prevalence of Borrelia burgdorferi infection in a series of 98 primary cutaneous lymphomas.

    PubMed

    Ponzoni, Maurilio; Ferreri, Andrés J M; Mappa, Silvia; Pasini, Elisa; Govi, Silvia; Facchetti, Fabio; Fanoni, Daniele; Tucci, Alessandra; Vino, Arianna; Doglioni, Claudio; Berti, Emilio; Dolcetti, Riccardo

    2011-01-01

    Borrelia burgdorferi has been variably associated with different forms of primary cutaneous lymphoma. Differences in prevalence rates among reported studies could be a result of geographic variability or heterogeneity in the molecular approaches that have been employed. In the present study, we investigated the prevalence of Borrelia burgdorferi sensu lato DNA in diagnostic tissue samples from fresh cutaneous biopsies of 98 primary cutaneous lymphomas and 19 normal skin controls. Three different polymerase chain reaction (PCR) protocols targeting the hbb, flagellin, and Osp-A genes were used. Direct sequencing of both sense and antisense strands of purified PCR products confirmed the specificity of the amplified fragments. Sequence specificity was assessed using the Basic Local Alignment Search Tool, and MultAlin software was used to investigate the heterogeneity of target gene sequences across the different samples. Borrelia DNA was not detected in 19 controls, 23 cases of follicular lymphoma, 31 cases of extranodal marginal zone lymphoma, or 30 cases of mycosis fungoides. A single case of 14 diffuse large B-cell lymphoma cases was positive for B. burgdorferi. This study does not support a pathogenic role of B. burgdorferi in primary cutaneous B- and T-cell lymphomas from areas nonendemic for this microorganism and the consequent rationale for the adoption of antibiotic therapy in these patients.

  4. Prevalence of Borrelia Burgdorferi Infection in a Series of 98 Primary Cutaneous Lymphomas

    PubMed Central

    Ferreri, Andrés J. M.; Mappa, Silvia; Pasini, Elisa; Govi, Silvia; Facchetti, Fabio; Fanoni, Daniele; Tucci, Alessandra; Vino, Arianna; Doglioni, Claudio; Berti, Emilio; Dolcetti, Riccardo

    2011-01-01

    Borrelia burgdorferi has been variably associated with different forms of primary cutaneous lymphoma. Differences in prevalence rates among reported studies could be a result of geographic variability or heterogeneity in the molecular approaches that have been employed. In the present study, we investigated the prevalence of Borrelia burgdorferi sensu lato DNA in diagnostic tissue samples from fresh cutaneous biopsies of 98 primary cutaneous lymphomas and 19 normal skin controls. Three different polymerase chain reaction (PCR) protocols targeting the hbb, flagellin, and Osp-A genes were used. Direct sequencing of both sense and antisense strands of purified PCR products confirmed the specificity of the amplified fragments. Sequence specificity was assessed using the Basic Local Alignment Search Tool, and MultAlin software was used to investigate the heterogeneity of target gene sequences across the different samples. Borrelia DNA was not detected in 19 controls, 23 cases of follicular lymphoma, 31 cases of extranodal marginal zone lymphoma, or 30 cases of mycosis fungoides. A single case of 14 diffuse large B-cell lymphoma cases was positive for B. burgdorferi. This study does not support a pathogenic role of B. burgdorferi in primary cutaneous B- and T-cell lymphomas from areas nonendemic for this microorganism and the consequent rationale for the adoption of antibiotic therapy in these patients. PMID:22071292

  5. Melanomas of unknown primary have a mutation profile consistent with cutaneous sun-exposed melanoma.

    PubMed

    Dutton-Regester, Ken; Kakavand, Hojabr; Aoude, Lauren G; Stark, Mitchell S; Gartside, Michael G; Johansson, Peter; O'Connor, Linda; Lanagan, Cathy; Tembe, Varsha; Pupo, Gulietta M; Haydu, Lauren E; Schmidt, Christopher W; Mann, Graham J; Thompson, John F; Scolyer, Richard A; Hayward, Nicholas K

    2013-11-01

    Melanoma of unknown primary (MUP) is an uncommon phenomenon whereby patients present with metastatic disease without an evident primary site. To determine their likely site of origin, we combined exome sequencing from 33 MUPs to assess the total rate of somatic mutations and degree of UV mutagenesis. An independent cohort of 91 archival MUPs was also screened for 46 hot spot mutations highly prevalent in melanoma including BRAF, NRAS, KIT, GNAQ, and GNA11. Results showed that the majority of MUPs exhibited high somatic mutation rates, high ratios of C>T/G>A transitions, and a high rate of BRAF (45 of 101, 45%) and NRAS (32 of 101, 32%) mutations, collectively indicating a mutation profile consistent with cutaneous sun-exposed melanomas. These data suggest that a significant proportion of MUPs arise from regressed or unrecognized primary cutaneous melanomas or arise de novo in lymph nodes from nevus cells that have migrated from the skin.

  6. Primary cutaneous marginal zone lymphoma as a complication of radiation therapy: Case report and review.

    PubMed

    Breton, Anne-Laure; Poulalhon, Nicolas; Balme, Brigitte; Thomas, Luc; Dalle, Stéphane

    2010-12-15

    The occurrence of primary cutaneous B-cell lymphoma at the site of radiation therapy is exceptional. We report herein the case of a primary cutaneous marginal zone lymphoma arising at the site of radiotherapy for breast cancer. A seventy-year-old woman was diagnosed in 2005 with an invasive ductal carcinoma of the left breast, which was treated with surgery, adjuvant chemotherapy, and radiation therapy. Three years later she developed several cutaneous nodules on her left breast, followed by similar lesions on her back. Histologic, immunohistochemistry, and molecular findings were consistent with the diagnosis of cutaneous marginal zone lymphoma. Physical examination was otherwise negative, as well as mammography, total body CT, bone marrow biopsy, and Borrelia serology. To our knowledge, this is the first published case of primary cutaneous marginal zone lymphoma occurring at the site of radiotherapy. Cutaneous surveillance is proposed from the first year after irradiation in order to detect new primary malignancies, including this rare cutaneous neoplasm.

  7. Memory T cells in cutaneous leishmaniasis.

    PubMed

    Glennie, Nelson D; Scott, Phillip

    2016-11-01

    Leishmania causes a spectrum of diseases that range from self-healing to fatal infections. Control of leishmania is dependent upon generating CD4+ Th1 cells that produce IFNγ, leading to macrophage activation and killing of the intracellular parasites. Following resolution of the disease, short-lived effector T cells, as well as long-lived central memory T cells and skin resident memory T cells, are retained and able to mediate immunity to a secondary infection. However, there is no vaccine for leishmaniasis, and the drugs used to treat the disease can be toxic and ineffective. While a live infection generates immunity, a successful vaccine will depend upon generating memory T cells that can be maintained without the continued presence of parasites. Since both central memory and skin resident memory T cells are long-lived, they may be the appropriate targets for a leishmaniasis vaccine. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Hemophagocytic Lymphohistiocytosis in Association with Primary Cutaneous Anaplastic Large Cell Lymphoma

    PubMed Central

    Basheer, Aneesh; Padhi, Somanath; Nagarajan, Ramesh; Boopathy, Vinoth; Mookkappan, Sudhagar; Iqbal, Nayyar

    2014-01-01

    Hemophagocytic lymphohistiocytosis (HLH) has a well known association with lymphomas, especially of T cell origin. Prognosis of lymphoma associated HLH is very poor, especially in T cell lymphomas; and, therefore, early diagnosis might alter the outcome. Though association of HLH with systemic anaplastic large cell lymphoma (ALCL) is known, its occurrence in primary cutaneous ALCL (C-ALCL) is distinctly rare. We aim to describe a case of C-ALCL (anaplastic lymphoma kinase (ALK)−) in an elderly male who succumbed to the complication of associated HLH, which was possibly triggered by coexistent virus infection. We briefly present the literatures on lymphoma associated HLH and discuss the histopathological differentials of cutaneous CD30+ lymphoproliferative disorders. We do suggest that HLH may pose diagnostic challenges in the evaluation of an underlying lymphoma and hence warrants proper evaluation for the underlying etiologies and/or triggering factors. PMID:25405042

  9. Dose-Escalation Trial of Carfilzomib With and Without Romidepsin in Cutaneous T-Cell Lymphoma

    ClinicalTrials.gov

    2015-11-10

    Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IA Mycosis Fungoides/Sezary Syndrome; Stage IB Mycosis Fungoides/Sezary Syndrome; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IIA Mycosis Fungoides/Sezary Syndrome; Stage IIB Mycosis Fungoides/Sezary Syndrome; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IIIA Mycosis Fungoides/Sezary Syndrome; Stage IIIB Mycosis Fungoides/Sezary Syndrome; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IVA Mycosis Fungoides/Sezary Syndrome; Stage IVB Mycosis Fungoides/Sezary Syndrome

  10. Strategies for Treating Cutaneous T-Cell Lymphoma

    PubMed Central

    Heald, Peter

    2009-01-01

    In this article, the management of cutaneous T-cell lymphoma will be presented in terms of the strategies that guide treatment. With the strategies and goals in mind, treatment options to achieve a measurable goal will be presented. The treatments presented in this article are those utilized to reliably achieve a remission. If remission is not achieved, a patient’s management plan must be changed. The landmarks that help guide the therapy plan will be discussed. PMID:20729945

  11. Primary Cutaneous Actinomycosis along with the Surgical Scar on the Hand

    PubMed Central

    Niknezhad, Nasim; Bidari-Zerehpoush, Farahnaz; Niknezhad, Nakisa

    2016-01-01

    Primary cutaneous actinomycosis is a rare clinical form with variable presentation. The tumoral presentation of actinomycosis as pseudocarcinomatous or sarcomatous masses is completely rare. The management of cutaneous actinomycosis needs proper antibiotic treatment and surgical resection would not be adequate alone. Herein, we report a case of primary cutaneous actinomycosis on the dorsal surface of the hand as draining and infiltrated lesions along with the scar of previous tumor excision that had not received proper antibiotics after the surgery. PMID:27957360

  12. Primary cutaneous CD 30 (+) ALK (−) anaplastic large cell lymphoma with dermoscopic findings: a case report

    PubMed Central

    Uzuncakmak, Tugba K.; Akdeniz, Necmettin; Karadag, Ayse S.; Taskin, Secil; Zemheri, Ebru I.; Argenziano, Giuseppe

    2017-01-01

    Primary cutaneous CD 30 (+) anaplastic large cell lymphoma (PCALCL) is a rare and indolent type of cutaneous T cell lymphoma, which usually presents as an asymptomatic solitary firm nodule that rapidly grows and often ulcerates without any systemic involvement. A 64-year-old female presented to our outpatient clinic with a one-year history of multiple pink nodular lesions on the chest, back and gluteal regions. Dermoscopic examination of the nodular lesions revealed pink-to-yellow structureless areas and arborizing-to-polymorphous vessels. Histopathologic examination was consistent with CD30 (+) anaplastic large cell lymphoma. Systemic involvement was not detected. Local radiotherapy for large nodules and surgical excision for small nodules were performed. The large nodules had totally regressed after 10 sessions of radiotherapy. PMID:28243498

  13. Cutaneous metastasis from gastrointestinal adenocarcinoma of unknown primary origin.

    PubMed

    Junqueira, Ana Lucia Ariano; Corbett, Ana Maria França; Oliveira Filho, Jayme de; Nasser, Kassila da Rosa; Haddad, Natalie Nejem; Tebet, Ana Carolina Franco

    2015-01-01

    Cutaneous metastasis is a rare manifestation of visceral malignancies that indicates primarily advanced disease. Due to its low incidence and similarity to other cutaneous lesions, it is not uncommon to have a delayed diagnosis and a shortened prognosis. We describe the case of a patient who presented with a cutaneous nodule in the sternal region as a first sign of malignancy.

  14. Cutaneous metastasis from gastrointestinal adenocarcinoma of unknown primary origin*

    PubMed Central

    Junqueira, Ana Lucia Ariano; Corbett, Ana Maria França; de Oliveira Filho, Jayme; Nasser, Kassila da Rosa; Haddad, Natalie Nejem; Tebet, Ana Carolina Franco

    2015-01-01

    Cutaneous metastasis is a rare manifestation of visceral malignancies that indicates primarily advanced disease. Due to its low incidence and similarity to other cutaneous lesions, it is not uncommon to have a delayed diagnosis and a shortened prognosis. We describe the case of a patient who presented with a cutaneous nodule in the sternal region as a first sign of malignancy. PMID:26375228

  15. Menus for Managing Patients With Cutaneous T-Cell Lymphoma

    PubMed Central

    Poligone, Brian; Heald, Peter

    2013-01-01

    In the management of patients with cutaneous T-cell lymphoma (CTCL), there are numerous distinct therapy options. Each of these therapies is discussed in terms of when to use it, what factors limit the success of the treatment, and what to expect. A menu is defined as a list of items from which to choose. The treatments for CTCL are presented in various menus where they are options for a particular goal in a particular setting of CTCL. The best recognized clinical scenarios of CTCL are those recognized by the staging system: limited patch plaque (T1), disseminated patch plaque (T2), erythroderma (T4), and tumor (T3). Each phase of the disease will have the menu of therapy options presented for a given goal of management. PMID:22361286

  16. Primary Cutaneous Nocardiosis in a Patient With Nephrotic Syndrome

    PubMed Central

    Chen, Bing; Tang, Jin; Lu, Zeyuan; Wang, Niansong; Gao, Xuping; Wang, Feng

    2016-01-01

    Abstract Nocardia infection is not common in clinical practice and most cases occur as an opportunistic infection in immunocompromised patients. We report a case of primary cutaneous nocardiosis characterized by multiple subcutaneous abscesses due to Nocardia brasiliensis in a patient with nephrotic syndrome undergoing long-term corticosteroid therapy. The patient was diagnosed with nephrotic syndrome 9 months ago, and mesangial proliferative glomerulonephritis was confirmed by renal biopsy. Subsequently, his renal disease was stable under low-dose methylprednisolone (8 mg/d). All of the pus cultures, which were aspirated from 5 different complete abscesses, presented Nocardia. Gene sequencing confirmed that they were all N. brasiliensis. The patient was cured by surgical drainage and a combination of linezolid and Trimethoprim-Sulfamethoxazole. The case highlights that even during the period of maintenance therapy with low-dose corticosteroid agents, an opportunistic infection still could occur in patients with nephrotic syndrome. PMID:26817885

  17. Allogeneic stem cell transplantation for advanced cutaneous T-cell lymphomas: a study from the French Society of Bone Marrow Transplantation and French Study Group on Cutaneous Lymphomas.

    PubMed

    de Masson, Adèle; Beylot-Barry, Marie; Bouaziz, Jean-David; Peffault de Latour, Régis; Aubin, François; Garciaz, Sylvain; d'Incan, Michel; Dereure, Olivier; Dalle, Stéphane; Dompmartin, Anne; Suarez, Felipe; Battistella, Maxime; Vignon-Pennamen, Marie-Dominique; Rivet, Jacqueline; Adamski, Henri; Brice, Pauline; François, Sylvie; Lissandre, Séverine; Turlure, Pascal; Wierzbicka-Hainaut, Ewa; Brissot, Eolia; Dulery, Rémy; Servais, Sophie; Ravinet, Aurélie; Tabrizi, Reza; Ingen-Housz-Oro, Saskia; Joly, Pascal; Socié, Gérard; Bagot, Martine

    2014-03-01

    The treatment of advanced stage primary cutaneous T-cell lymphomas remains challenging. In particular, large-cell transformation of mycosis fungoides is associated with a median overall survival of two years for all stages taken together. Little is known regarding allogeneic hematopoietic stem cell transplantation in this context. We performed a multicenter retrospective analysis of 37 cases of advanced stage primary cutaneous T-cell lymphomas treated with allogeneic stem cell transplantation, including 20 (54%) transformed mycosis fungoides. Twenty-four patients (65%) had stage IV disease (for mycosis fungoides and Sézary syndrome) or disseminated nodal or visceral involvement (for non-epidermotropic primary cutaneous T-cell lymphomas). After a median follow up of 29 months, 19 patients experienced a relapse, leading to a 2-year cumulative incidence of relapse of 56% (95%CI: 0.38-0.74). Estimated 2-year overall survival was 57% (95%CI: 0.41-0.77) and progression-free survival 31% (95%CI: 0.19-0.53). Six of 19 patients with a post-transplant relapse achieved a subsequent complete remission after salvage therapy, with a median duration of 41 months. A weak residual tumor burden before transplantation was associated with increased progression-free survival (HR=0.3, 95%CI: 0.1-0.8; P=0.01). The use of antithymocyte globulin significantly reduced progression-free survival (HR=2.9, 95%CI: 1.3-6.2; P=0.01) but also transplant-related mortality (HR=10(-7), 95%CI: 4.10(-8)-2.10(-7); P<0.001) in univariate analysis. In multivariate analysis, the use of antithymocyte globulin was the only factor significantly associated with decreased progression-free survival (P=0.04). Allogeneic stem cell transplantation should be considered in advanced stage primary cutaneous T-cell lymphomas, including transformed mycosis fungoides.

  18. Rituximab in the treatment of primary cutaneous B-cell lymphoma: a review.

    PubMed

    Fernández-Guarino, M; Ortiz-Romero, P L; Fernández-Misa, R; Montalbán, C

    2014-06-01

    Rituximab is a chimeric mouse-human antibody that targets the CD20 antigen, which is found in both normal and neoplastic B cells. In recent years, it has been increasingly used to treat cutaneous B-cell lymphoma and is now considered an alternative to classic treatment (radiotherapy and surgery) of 2 types of indolent lymphoma, namely, primary cutaneous follicle center lymphoma and primary cutaneous marginal zone B-cell lymphoma. Rituximab is also administered as an alternative to polychemotherapy in the treatment of primary cutaneous large B-cell lymphoma, leg type. Its use as an alternative drug led to it being administered intralesionally, with beneficial effects. In the present article, we review the literature published on the use of rituximab to treat primary cutaneous B-cell lymphoma. Copyright © 2012 Elsevier España, S.L. and AEDV. All rights reserved.

  19. Primary cutaneous lymphomas: A clinical and histological study of 99 cases in Isfahan, Iran

    PubMed Central

    Naeini, Farahnaz Fatemi; Abtahi-Naeini, Bahareh; Pourazizi, Mohsen; Sadeghiyan, Hamidreza; Najafian, Jamshid

    2015-01-01

    Background: Primary cutaneous lymphomas (PCLs) represent a heterogeneous group of T- and B-cell lymphomas that present in the skin with no evidence of extracutaneous disease at the time of diagnosis. The aim of this study was to assess and report the epidemiological characteristics of PCLs in Isfahan, Isfahan Province, Iran – as a main province of Iran. Materials and Methods: A total of 99 patients were recruited over a recent 10-year period (2003-2013) with diagnosis of PCLs; the patients were classified according to the The World Health Organization/European Organization for Research and Treatment of Cancer (WHO-EORTC) criteria. Mean and standard deviations (SDs) were used to describe continuous data, numbers, and percentages for categorical data. Statistical significance was defined as P < 0.05. Results: The patients comprised 45 men and 54 women aged 5-80 years (median 36) at diagnosis. The male-to-female ratio was 1:1.2. Histological examination showed features of primary cutaneous B-cell lymphomas (PCBCLs) in four cases. The mean ± SD age in primary cutaneous T-cell lymphomas (PCTCLs) and PCBCLs was 37.9 ± 16.5 years and 39.7 ± 9.1 years, respectively (P = 0.72). The mean ± SD latent period between the time of diagnosis and initiation of skin lesions in men and women was 2.3 ± 4.1 years and 5.9 ± 10.1 years, respectively (P = 0.02). The most frequent subtypes were mycosis fungoides (MFs) (86.9%) followed by Sιzary syndrome (SS) (4%). Five patients died from PCL-related deaths. Conclusion: The distinguishing epidemiologic characteristics of PCL in Iran are the absence of a male predominance and a lower age of diagnosis. The study highlights the ethnic or regional variations in the clinicoepidemiological characteristics of PCLs. PMID:26759567

  20. Factors affecting patient outcome in primary cutaneous aspergillosis

    PubMed Central

    Tatara, Alexander M.; Mikos, Antonios G.; Kontoyiannis, Dimitrios P.

    2016-01-01

    Abstract Primary cutaneous aspergillosis (PCA) is an uncommon infection of the skin. There is a paucity of organized literature regarding this entity in regard to patient characteristics, associated Aspergillus species, and treatment modalities on outcome (disease recurrence, disease dissemination, and mortality). We reviewed all published reports of PCA from 1967 to 2015. Cases were deemed eligible if they included the following: patient baseline characteristics (age, sex, underlying condition), evidence of proven or probable PCA, primary treatment strategy, and outcome. We identified 130 eligible cases reported from 1967 to 2015. The patients were predominantly male (63.8%) with a mean age of 30.4 ± 22.1 years. Rates of PCA recurrence, dissemination, and mortality were 10.8%, 18.5%, and 31.5%, respectively. In half of the cases, there was an association with a foreign body. Seven different Aspergillus species were reported to cause PCA. Systemic antifungal therapy without surgery was the most common form of therapy (60% of cases). Disease dissemination was more common in patients with underlying systemic conditions and occurred on average 41.4 days after PCA diagnosis (range of 3–120 days). In a multivariate linear regression model of mortality including only patients with immunosuppressive conditions, dissemination and human immunodeficiency virus/acquired immune deficiency syndrome were statistically significantly associated with increased mortality. Nearly one-third of patients with PCA die with the disease. Dissemination and host status are critical in patient outcome. PMID:27367980

  1. Primary cutaneous mantle cell lymphoma of the leg with blastoid morphology and aberrant immunophenotype: a diagnostic challenge.

    PubMed

    Cesinaro, Anna Maria; Bettelli, Stefania; Maccio, Livia; Milani, Marina

    2014-02-01

    Mantle cell lymphoma rarely affects the skin and is usually a secondary involvement. The present case illustrates a primary cutaneous mantle cell lymphoma of the leg, with blastoid morphology and aberrant expression of CD10 and bcl-6, which was misinterpreted at the beginning as diffuse large B-cell lymphoma. A larger panel of immunohistochemical markers, including cyclin-D1, and molecular investigation showing the typical translocation (t11;14), pointed toward the correct diagnosis. Cutaneous diffuse B-cell lymphomas with unusual morphology should be interpreted cautiously, and the diagnosis made on the basis of an appropriate panel of antibodies and molecular studies.

  2. Human immunodeficiency virus-positive secondary syphilis mimicking cutaneous T-cell lymphoma.

    PubMed

    Yamashita, Michiko; Fujii, Yoshiyuki; Ozaki, Keiji; Urano, Yoshio; Iwasa, Masami; Nakamura, Shingen; Fujii, Shiro; Abe, Masahiro; Sato, Yasuharu; Yoshino, Tadashi

    2015-10-08

    Malignant syphilis or lues maligna is a severe form of secondary syphilis that was commonly reported in the pre-antibiotic era, and has now reemerged with the advent of the human immunodeficiency virus (HIV) epidemic. However, the characteristic histopathological findings of malignant syphilis remain controversial. The aim of this case report was to clarify the clinical and histopathological findings of HIV-positive malignant secondary syphilis. A Japanese man in his forties complained of fever, skin lesions, headache, and myalgia without lymphadenopathy during the previous 4 weeks. The skin lesions manifested as erythematous, nonhealing, ulcerated papules scattered on his trunk, extremities, palm, and face. Although the skin lesions were suspected to be cutaneous T-cell lymphomas on histological analyses, they lacked T-cell receptor Jγ rearrangement; moreover, immunohistochemical analyses confirmed the presence of spirochetes. The patient was administered antibiotics and anti-retroviral therapy, which dramatically improved the symptoms. On the basis of these observations of the skin lesions, we finally diagnosed the patient with HIV-associated secondary syphilis that mimicked cutaneous T-cell lymphoma. The patient's systemic CD4+ lymphocyte count was very low, and the infiltrate was almost exclusively composed of CD8+ atypical lymphocytes; therefore, the condition was easily misdiagnosed as cutaneous lymphoma. Although the abundance of plasma cells is a good indicator of malignant syphilis on skin histological analyses, in some cases, the plasma cell count may be very low. Therefore, a diagnosis of malignant secondary syphilis should be considered before making a diagnosis of primary cutaneous peripheral T-cell lymphoma or lymphoma associated with HIV infection.

  3. Primary cutaneous plasmacytoma occurring after pacemaker implantation and recurring in scar tissue.

    PubMed

    Li, Anthony; Chen, Alexander; Gallagher, Mark; Kaczmarek, Pawel; Tinwell, Brendan; Sneddon, James; Cliff, Sandeep

    2013-02-15

    Primary cutaneous plasmacytomas are rare and little is known about their treatment and progression. We describe for the first time the predilection of primary cutaneous plasmacytoma to occur in a scar or sites of trauma. We report an 89-year-old man who presented with a slowly expanding asymptomatic mass over his pacemaker implantation, 1 year after insertion. Further investigation ruled out multiple myeloma and histology confirmed it to be a cutaneous plasmacytoma. This was treated successfully by local radiotherapy after extraction of the pacemaker and implantation of a new pacemaker on the opposite side. The patient subsequently developed an additional cutaneous plasmacytoma over the new pacemaker site, followed by the development of progressive multiple myeloma. Primary cutaneous plasmacytoma can show predilection for sites of trauma or surgery. Surgical excision of the plasmocytoma and local radiotherapy may be a reasonable strategy in the first initially after pacemaker removal.

  4. Cutaneous amyloidosis associated with autoimmune hepatitis-primary biliary cirrhosis overlap syndrome.

    PubMed

    González-Moreno, Emmanuel I; Cámara-Lemarroy, Carlos R; Borjas-Almaguer, David O; Martínez-Cabriales, Sylvia A; Paz-Delgadillo, Jonathan; Gutiérrez-Udave, Rodrigo; Ayala-Cortés, Ana S; Ocampo-Candiani, Jorge; Cortéz-Hernández, Carlos A; Maldonado-Garza, Héctor J

    2015-01-01

    Cutaneous amyloidosis is a rare disease characterized by the deposition of amyloid in the dermis. It can be primary or secondary, depending on associated diseases. It has been linked to various autoimmune diseases, including primary biliary cirrhosis. We present the case of a patient with an autoimmune hepatitis-primary biliary cirrhosis overlap syndrome with concomitant cutaneous amyloidosis, a very unusual association, and discuss similar cases and possible pathophysiological implications.

  5. Radioimmunodetection of cutaneous T-cell lymphoma with 111In-labeled T101 monoclonal antibody

    SciTech Connect

    Carrasquillo, J.A.; Bunn, P.A. Jr.; Keenan, A.M.; Reynolds, J.C.; Schroff, R.W.; Foon, K.A.; Su, M.H.; Gazdar, A.F.; Mulshine, J.L.; Oldham, R.K.

    1986-09-11

    T101 monoclonal antibody recognizes a pan-T-cell antigen present on normal T cells and also found in high concentrations in cutaneous T-cell lymphoma. We used this antibody, radiolabeled with 111In, in gamma-camera imaging to detect sites of metastatic cutaneous T-cell lymphoma in 11 patients with advanced disease. In all patients, (/sup 111/In)T101 concentrated in pathologically or clinically detected nodes, including those in several previously unsuspected nodal regions. Concentrations (per gram of tissue) ranged from 0.01 to 0.03 percent of the injected dose and were consistently 10 to 100 times higher than previously reported on radioimmunodetection. Focal uptake was seen in skin tumors and heavily infiltrated erythroderma but not in skin plaques. The specificity of tumor targeting was documented by control studies with (/sup 111/In)chloride or (/sup 111/In)9.2.27 (anti-melanoma) monoclonal antibody. Increasing the T101 dose (1 to 50 mg) altered distribution in nontumor tissues. These studies suggest that imaging with (/sup 111/In)T101 may be of value in identifying sites of cutaneous T-cell lymphoma. In contrast to the targeting of solid tumors, the mechanism of localization appears to be related to binding to T cells, which can then carry the radioactivity to involved sites.

  6. Uncorrectable ptosis: primary cutaneous signet-ring cell carcinoma.

    PubMed

    Hansen, Mark S; Chi, Sulene L; Cummings, Thomas; Woodward, Julie A

    2013-09-14

    Primary cutaneous signet-ring cell carcinoma (PCSRCC) is a rare but aggressive tumor. Our case highlights a 60-year-old man who presented with eyelid ptosis, for which he underwent multiple surgical procedures over a 3-year period prior to referral to our clinic. These procedures were complicated by scarring, delayed healing, and poor cosmetic outcome. In addition, the patient was noted to develop progressive enophthalmos. These concerning signs led to a CT scan and subsequent eyelid biopsy, which revealed a diagnosis of PCSRCC. Further management has involved an MRI and orbitotomy with biopsy revealing widespread extension of the carcinoma. Exenteration was performed to reduce the likelihood of metastasis. There are few documented case reports of PCSRCC of the eyelid in the literature. Of the 33 published cases of PCSRCC, 27 cases involve the eyelids and the other 6 cases involve the axilla. The unique clinical features of this case will be discussed, in particular the presentation as ptosis, an otherwise commonplace complaint in the oculoplastics clinic. The surgical course and histopathologic findings will be presented. The literature regarding PCSRCC will be reviewed including demographics, management, and prognosis. Although rare, PCSRCC follows an aggressive course with characteristically delayed diagnosis. Early identification and treatment likely offer a better prognosis. Thus, description of the clinical presentation of this rare tumor may aid in recognition and earlier treatment.

  7. Primary cutaneous marginal zone B-cell lymphoma: clinical and histological aspects.

    PubMed

    Khaled, A; Sassi, S; Fazaa, B; Ben Hassouna, J; Ben Romdhane, K; Kamoun, M R

    2009-02-01

    According to the WHO-EORTC classification of cutaneous lymphomas, primary cutaneous marginal zone B-cell lymphoma are now well characterized. We report here a case of primary cutaneous marginal zone B-cell lymphoma in a 51 year-old man in which the diagnosis was made using both histology and immunopathology. The patient had no remarkable medical history, no history of either acute inflammation or insect bite, and presented with a 5 cm solitary asymptomatic erythematous firm, multinodular and infiltrated plaque on the back for 12 months. Histological examination and immunohistochemical study of a cutaneous biopsy provided a differential diagnosis between B cell lymphoma and lymphocytoma cutis. Full body work up revealed no signs of extracutaneous dissemination. The patient underwent surgical excision of the nodule. Histological examination showed a histological and immunophenotyping profile typical of primary cutaneous marginal zone B-cell lymphoma. The lesion was completely excised with clear margins and no recurrence occurred after a 12 month-follow-up period. Primary cutaneous marginal zone B-cell lymphoma are low-grade lymphomas that have an indolent course and a high tendency to recur. They should be differentiated from lymphocytoma cutis and from the other types of cutaneous B cell lymphomas that have a different course and prognosis.

  8. Cutaneous T-cell lymphoma with HTLV-I infection: clinical overlap with adult T-cell leukemia/lymphoma.

    PubMed

    Sakamoto, F H; Colleoni, G W B; Teixeira, S P; Yamamoto, M; Michalany, N S; Almeida, F A; Chiba, A K; Petri, V; Fernandes, M A; Pombo-de-Oliveira, M S

    2006-04-01

    Adult T-cell leukemia/lymphoma (ATLL) is a malignant proliferation of mature helper T lymphocytes,(1) and is caused by human T-lymphotropic virus type I (HTLV-I);(2) an HTLV-I infection endemic in the Caribbean, south-western Japan, South America and Africa.(3,4) Seroepidemiological studies suggest that it is also endemic in Brazil.(5) Although carriers of HTLV-I show polyclonal integration of virus in T lymphocytes, only patients with ATLL of various subtypes show monoclonal integration of HTLV-I in tumor cells.(6,7) Cutaneous T-cell lymphomas (CTCL) are a group of primary cutaneous lymphoproliferative diseases(8) with unknown etiology.(9) The two most common presentations of CTCL are mycosis fungoides (MF) and Sézary syndrome (SS).(10-13) However, both CTCL categories can easily resemble ATLL. Therefore, in HTLV-I endemic areas, differentiation between ATLL and CTCL must be performed, as they have different prognoses and treatment approaches.(14).

  9. Live rubella virus vaccine long-term persistence as an antigenic trigger of cutaneous granulomas in patients with primary immunodeficiency.

    PubMed

    Bodemer, C; Sauvage, V; Mahlaoui, N; Cheval, J; Couderc, T; Leclerc-Mercier, S; Debré, M; Pellier, I; Gagnieur, L; Fraitag, S; Fischer, A; Blanche, S; Lecuit, M; Eloit, M

    2014-10-01

    Granulomas may develop as a response to a local antigenic trigger, leading to the activation of macrophages and T-lymphocytes. Primary immunodeficiency (PID) is associated with the development of extensive cutaneous granulomas, whose aetiology remains unknown. We performed high-throughput sequencing of the transcriptome of cutaneous granuloma lesions on two consecutive index cases, and RT-PCR in a third consecutive patient. The RA27/3 vaccine strain of rubella virus-the core component of a universally used paediatric vaccine-was present in the cutaneous granuloma of these three consecutive PID patients. Controls included the healthy skin of two patients, non-granulomatous cutaneous lesions of patients with immunodeficiency, and skin biopsy samples of healthy individuals, and were negative. Expression of viral antigens was confirmed by immunofluorescence. Persistence of the rubella vaccine virus was also demonstrated in granuloma lesions sampled 4-5 years earlier. The persistence of the rubella virus vaccine strain in all three consecutive cutaneous granuloma patients with PID strongly suggests a causal relationship between rubella virus and granuloma in this setting.

  10. Role of obesity on the thickness of primary cutaneous melanoma.

    PubMed

    Skowron, F; Bérard, F; Balme, B; Maucort-Boulch, D

    2015-02-01

    Thick primary cutaneous melanoma (PCM) is associated with older age, male sex, being single, a low educational level, self-detection and general practice detection, nodular melanoma (NM) and acral lentiginous melanoma (ALM) types; and are found in the head-neck and lower limb locations. Obesity plays a direct role on melanoma tumour growth, as it has been shown in animal models, but its role in the thickness of PCM remains unknown. We investigated the impact of obesity on the thickness of invasive PCM. A cross-sectional study was performed in a prospective cohort for which we collected several clinical and histological data already known to be associated with thick PCM and the Body Mass Index from new cases of invasive PCM which were referred to the dermatology department in Valence. Four hundred and twenty-seven patients were studied. In an univariate analysis, thick PCM was associated with low educational level, obesity, identification by the patient or the general practitioner (GP), location on the cephalic extremity, in a non-visible area of the body, the NM and ALM type, and an ulceration. In a multivariate analysis, NM, ulceration, topography of the melanoma and identification of the melanoma by the patient or GP were significantly associated with thick melanoma. When including only clinical features in the model, low educational level, mode of melanoma identification and obesity were significantly associated with a risk of thick melanoma. Obesity is a clinical independent risk factor of thick PCM. For health policies, governments should pay greater attention to detect melanoma in obese patients. Our results encourage the basic research on tumoural growth mechanisms due to obesity in melanoma. © 2014 European Academy of Dermatology and Venereology.

  11. Primary Cutaneous Coccidioidomycosis Presenting as a Recurrent Preauricular Cyst.

    PubMed

    Rivard, Shayna C; Satter, Elizabeth

    2016-01-01

    A 31-year-old Filipino active duty marine presented with a 2-year history of a waxing and waning nodule on his left cheek that had been incised and drained on multiple occasions. The patient had no significant medical history other than a positive purified protein derivative test with negative chest x-ray finding treated with a 9-month course of isoniazid in 2010. He denied cough, fever, chills, night sweats, weight loss, joint/bone pain, or prior trauma to the area. On initial examination, there was a 1×1-cm erythematous indurated nodule associated with an overlying violaceous scar on his left preauricular cheek. Since the lesion was presumed to be an inflamed epidermal cyst, it was initially treated with 0.1 cc of interlesional triamcinolone acetonide (10 mg/cc). At 1-month follow-up, the lesion was slightly less indurated, but an excisional biopsy was performed to remove the residual nodule. The biopsy showed an essentially normal epidermis with focal dermal fibrosis below which were multiple collections of histiocytes and multinucleated giant cells surrounded by a dense lymphoplasmacytic infiltrate with numerous eosinophils (Figure 1). A few multinucleated giant cells contained large thick-walled spherules, some with endospores, consistent with Coccidioides immitis (Figure 2). Serological tests showed positive serum for C immitis IgG antibodies with low levels of complement-fixing antibodies (1:2). IgM antibodies were negative. Findings from chest x-ray and bone scan failed to reveal evidence of systemic disease. Although the infectious disease physician felt that the patient most likely had primary cutaneous coccidioidomycosis (PCC), since the duration of the infection was unknown and the patient was Filipino, thereby increasing his risk of dissemination, he was placed on a daily regimen of 400 mg of oral fluconazole until his complement fixation titers became undetectable.

  12. Silicon Phthalocyanine 4 and Photodynamic Therapy in Stage IA-IIA Cutaneous T-Cell Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2015-12-03

    Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IA Mycosis Fungoides/Sezary Syndrome; Stage IB Mycosis Fungoides/Sezary Syndrome; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IIA Mycosis Fungoides/Sezary Syndrome

  13. Cutaneous metastasis of ovarian carcinoma with shadow cells mimicking a primary pilomatrical neoplasm.

    PubMed

    Lalich, Daniel; Tawfik, Ossama; Chapman, Julia; Fraga, Garth

    2010-07-01

    Shadow cells are characteristic of pilomatricoma, although they have been described in other cutaneous and visceral neoplasms, particularly endometrioid adenocarcinomas of the female genital tract. We describe a metastasis of an ovarian endometrioid adenocarcinoma with shadow cells to the skin that was initially misinterpreted as a pilomatricoma. We compare the histology of the ovarian neoplasm to 21 pilomatricomas. This is the first reported case of a cutaneous metastasis of a visceral neoplasm mimicking a primary pilomatrical neoplasm.

  14. Primary cutaneous nocardiosis caused by Nocardia nova in a kidney transplant recipient.

    PubMed

    Kim, Young Keun; Oh, Jin-Rok; Choi, Hee Kyoung; Kim, Hyo Youl; Park, Soon Deok; Uh, Young

    2014-01-01

    Nocardia nova is a rare aetiological pathogen for cutaneous nocardiosis. To the best of our knowledge, this is the first case of N. nova primary cutaneous infection in a kidney transplant recipient. Identification was performed using 16S rRNA and secA1 gene sequence analyses. The patient was not treated successfully by antibiotics alone. Surgical debridement was required for successful treatment.

  15. Allogeneic stem cell transplantation for advanced cutaneous T-cell lymphomas: a study from the French Society of Bone Marrow Transplantation and French Study Group on Cutaneous Lymphomas

    PubMed Central

    de Masson, Adèle; Beylot-Barry, Marie; Bouaziz, Jean-David; de Latour, Régis Peffault; Aubin, François; Garciaz, Sylvain; d’Incan, Michel; Dereure, Olivier; Dalle, Stéphane; Dompmartin, Anne; Suarez, Felipe; Battistella, Maxime; Vignon-Pennamen, Marie-Dominique; Rivet, Jacqueline; Adamski, Henri; Brice, Pauline; François, Sylvie; Lissandre, Séverine; Turlure, Pascal; Wierzbicka-Hainaut, Ewa; Brissot, Eolia; Dulery, Rémy; Servais, Sophie; Ravinet, Aurélie; Tabrizi, Reza; Ingen-Housz-Oro, Saskia; Joly, Pascal; Socié, Gérard; Bagot, Martine

    2014-01-01

    The treatment of advanced stage primary cutaneous T-cell lymphomas remains challenging. In particular, large-cell transformation of mycosis fungoides is associated with a median overall survival of two years for all stages taken together. Little is known regarding allogeneic hematopoietic stem cell transplantation in this context. We performed a multicenter retrospective analysis of 37 cases of advanced stage primary cutaneous T-cell lymphomas treated with allogeneic stem cell transplantation, including 20 (54%) transformed mycosis fungoides. Twenty-four patients (65%) had stage IV disease (for mycosis fungoides and Sézary syndrome) or disseminated nodal or visceral involvement (for non-epidermotropic primary cutaneous T-cell lymphomas). After a median follow up of 29 months, 19 patients experienced a relapse, leading to a 2-year cumulative incidence of relapse of 56% (95%CI: 0.38–0.74). Estimated 2-year overall survival was 57% (95%CI: 0.41–0.77) and progression-free survival 31% (95%CI: 0.19–0.53). Six of 19 patients with a post-transplant relapse achieved a subsequent complete remission after salvage therapy, with a median duration of 41 months. A weak residual tumor burden before transplantation was associated with increased progression-free survival (HR=0.3, 95%CI: 0.1–0.8; P=0.01). The use of antithymocyte globulin significantly reduced progression-free survival (HR=2.9, 95%CI: 1.3–6.2; P=0.01) but also transplant-related mortality (HR=10−7, 95%CI: 4.10−8–2.10−7; P<0.001) in univariate analysis. In multivariate analysis, the use of antithymocyte globulin was the only factor significantly associated with decreased progression-free survival (P=0.04). Allogeneic stem cell transplantation should be considered in advanced stage primary cutaneous T-cell lymphomas, including transformed mycosis fungoides. PMID:24213148

  16. Choices in the treatment of cutaneous T-cell lymphoma.

    PubMed

    Hymes, Kenneth B

    2007-02-01

    Mycosis fungoides is responsive to treatment in the early stages; patients have a long duration of survival but are rarely cured of the disease. Therefore, patients require long-term, sequential therapies with as little toxicity as possible. In the early stages, skin-directed therapies, such as psoralen plus ultraviolet A in combination with retinoids or interferon, generally produce good, long-term responses. Once the disease progresses, systemic agents such as cytokines and retinoids are introduced. The cytokines provide a rational treatment approach for cutaneous T-cell lymphoma (CTCL) and produce good, long-lasting responses with few immunosuppressant effects. Denileukin diftitox (Ontak) has also been shown to produce good treatment effects, and its toxic effects can usually be controlled using prophylactic therapies. The synthetic retinoid bexarotene (Targretin) is taken orally and produces high response rates in CTCL, with a good long-term tolerability profile. Conventional systemic chemotherapies produce rapid responses and high response rates in CTCL, but these are generally of short duration and accompanied by myelosuppression and immunosuppression. Current treatment strategies therefore consist of the use of initial skin-directed therapies, with the addition of low-toxicity systemic biologic agents as the disease progresses; patients who do not respond to biologic agents should then receive conventional chemotherapies, starting with single agents and progressing to combination therapies.

  17. [Primary cutaneous mucormycosis. Report of a case in a HIV patient].

    PubMed

    Pérez-Uribe, Adriana; Molina de Soschin, Dora; Arenas, Roberto; Reyes, Miguel

    2005-06-01

    Primary cutaneous mucormycosis is an unusual mycotic infection associated to immunosupression. We present a 34 year-old woman with HIV infection with a necrotic primary mucormycosis of the skin associated to a venous catheter. She was treated with amphotericin B and surgical debridement.

  18. A Clinicopathological Analysis of Primary Cutaneous Lymphomas: A 6-year Observational Study at a Tertiary Care Center of South India

    PubMed Central

    Khader, Anza; Manakkad, Shiny Padinjarayil; Shaan, Mohammed; Pillai, Sarita Sasidharan; Riyaz, Najeeba; Manikoth, P Binitha; Kunnummel, Muhammed; Balakrishnan, Sunitha

    2016-01-01

    Background: Little data are available concerning clinical and pathological patterns of cutaneous lymphomas in India. Aim: To analyze the clinical and histopathological characteristics of cutaneous lymphomas in Indian patients Materials and Methods: This is a single-center, prospective, observational study carried out from January 1, 2010, to December 31, 2015. The patients underwent clinical examination, human T-cell lymphotropic virus-1 (HTLV-1) screening, skin biopsy with hematoxylin and eosin and immunohistochemistry staining. Results: Among 35 cases, 33 (94.3%) were T-cell, and 2 (5.7%) were B-cell lymphomas. The mean age was 52.66, and the male to female ratio was 2.5:1. The most common types of T-cell lymphomas included mycosis fungoides (MF) (57.1%) followed by adult T-cell lymphoma/leukemia (ATL) (17.1%). Primary cutaneous peripheral T-cell lymphoma not otherwise specified was diagnosed in 17.1% and anaplastic large cell lymphoma in 2.9%. The morphological types of MF included polymorphic, poikilodermatous, folliculotropic, hypopigmented, hyperpigmented, mixed, and purpuric. Skin manifestations of ATL included ulcerated plaques and erythroderma. Epidermotropism was very marked in ATL (83.3%) than in MF (70%). Larger Pautrier's microabscess was noted in ATL compared to smaller ones in MF. Markedly dense, diffuse infiltrate of atypical cells was noted in ATL in contrast to mild to moderate nodular or perivascular infiltrate in MF. ATL had an extremely poor prognosis. Limitations: Identification of DNA integration of HTLV-1 by Southern blot could not be analyzed, and the number of cases studied is limited. Conclusions: The study showed unique patterns of subtypes of cutaneous lymphomas in our country. Variations in the clinical pattern and histopathological analysis will help to differentiate T-cell lymphoma types which have prognostic implications. PMID:27904177

  19. Pruritus in cutaneous T-cell lymphomas: frequent, often severe and difficult to treat.

    PubMed

    Meyer, Nicolas; Paul, Carle; Misery, Laurent

    2010-01-01

    Pruritus has a well-known association with Hodgkin's disease and other nodal lymphomas; indeed it often reveals the disease. Pruritus is also an important symptom of cutaneous T-cell lymphomas. Lymphoma-associated itch is thus both frequent and severe, but its pathophysiology remains unclear. Few studies have evaluated the efficacy of therapeutic agents in the management of cutaneous T-cell lymphoma-related pruritus. The main objective of treatment remains disease control. Pruritus management is generally based on the physician's experience. Treatment is very difficult, especially in Sézary syndrome. We present here management strategies for cutaneous lymphoma-associated pruritus.

  20. Neurotropic T-cell lymphocytosis: a cutaneous expression of CLIPPERS.

    PubMed

    Smith, Annika; Matthews, Yasmin; Kossard, Steven; Turner, Jenny; Buckland, Michael E; Parratt, John

    2014-08-01

    Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory disease of the central nervous system that predominantly involves the pons and cerebellum and that improves with immunosuppressive treatment. Only recently described, the etiology is unknown, diagnosis is difficult and long-term neurological sequelae may occur without aggressive treatment. Herein, we describe a 59-year-old woman who presented with subcutaneous nodules affecting her face, trunk, limbs and an indurated annular erythematous lesion on her forearm. This was associated with marked dysesthesia of her skin, refractory to treatment. There was a 4-year history of dysequilibrium, vertigo, truncal and gait ataxia with progressive neurological symptoms. Skin biopsy of the annular nodular lesion showed a lymphohistiocytic infiltrate in dermis and subcutis with a striking lymphocyte-dominant infiltrate that was perineural and formed a nodular collection extending along a prominent subcutaneous nerve. Immunophenotyping indicated a marked predominance of T cells that were CD3 positive with a 2 : 1 CD4 : CD8 ratio. Scattered histiocytes were present but no well-formed granulomas or vasculitis. Magnetic resonance imaging studies showed changes in the pontine, brain stem and cerebellar region, which subsequently were defined as characteristic for CLIPPERS, but no brain biopsy was pursued. The marked neural skin symptoms and the cutaneous histopathological findings indicate that the skin may be an additional target organ in CLIPPERS, and the immune response may be directed against a common neural antigen. In radiologically typical CLIPPERS, identification of clinical skin lesions particularly subcutaneous nodules and biopsy may potentially form a basis for tissue diagnosis in this syndrome.

  1. Primary Cutaneous Angiosarcoma Mimicking Metastasis on 18F-FDG PET/CT in Woman With Cervix Cancer.

    PubMed

    Hwang, Jae Pil

    2017-09-01

    Primary cutaneous angiosarcoma is a rare vascular tumor usually affecting the whole body, and its hypermetabolic features on F-FDG PET/CT may be confused with those of infection, metastasis, or primary malignancy. This is a case report of a cutaneous angiosarcoma of the lower anterior abdomen showing increased FDG uptake on F-FDG PET/CT mimicking a cutaneous metastasis in an 84-year-old woman with cervical cancer.

  2. Primary Gangrenous Cutaneous Mold Infections in a Patient With Cancer and Neutropenia.

    PubMed

    Yacoub, Abraham; Soni, Kiran K; Mojica, Lysenia; Mai, Jane; Morano, Jamie; Cruse, C Wayne; Sandin, Ramon L; Nanjappa, Sowmya; Bohra, Chandrashekar; Gajanan, Ganesh; Greene, John N

    2016-07-01

    Opportunistic fungal infections caused by Aspergillus and Candida followed by infections with Fusarium, Rhizopus, Mucor, and Alternaria species are an important cause of morbidity and mortality in patients with hematological malignancies. Cutaneous mucormycosis infections are rare, and the incidence, outcomes, and factors associated with survival in the setting of hematological malignancies are not clear. A literature search was conducted for all cases of primary cutaneous mold infections in patients with hematological malignancy, of which 50 cases were found. Our case of a patient with a hematological malignancy who sustained a cat bite that in turn caused a primary cutaneous mold infection is also included. In the 51 cases identified, 66.7% were neutropenic upon presentation, and 54.9% were male with an average age of 32 years. Aspergillus species (33.3%) was the most cited followed by Rhizopus species (19.6%). Overall mortality rate was 29.4% and was observed more frequently in patients with neutropenia (60.0%) and without surgical intervention (73.3%). Survival rate was higher (35.3%) for cases utilizing both antifungal and surgical intervention. The antifungal agent with the highest survival rate was amphotericin B and its formulations (58.8%). Neutropenia within hematological malignancies demonstrate a risk for developing severe cutaneous fungal infections, of which primary cutaneous mucormycosis can carry significant mortality. Combination antifungal therapy and surgical debridement appears to be associated with higher survival outcomes and warrants further investigation.

  3. Primary cutaneous mucormycosis caused by Mucor irregularis in an elderly person.

    PubMed

    Yamaguchi, Sayaka; Okubo, Yuko; Katano, Azusa; Sano, Ayako; Uezato, Hiroshi; Takahashi, Kenzo

    2015-02-01

    Primary cutaneous mucormycosis is a rare but often lethal severe fungal infection, which usually occurs in immunocompromised patients. We report a case of primary cutaneous mucormycosis caused by Mucor irregularis in an elderly patient. Seven months after the surgical dissection of the involved skin, cutaneous mucormycosis recurred at the peripheral edge of the skin graft. Shortly subsequent to the administration of liposomal amphotericin B, the remaining skin lesion was excised again. M. irregularis is rarely but increasingly reported as a cause of mucormycosis in immunocompetent individuals, especially in Asian farmers. M. irregularis may be largely disseminated in the soils of Asia and thus the trivial trauma at the time of farm work may be a trigger for the onset. These cases tend to leave severe cosmetic damage even in healthy individuals, although the vital prognosis is not affected. © 2014 Japanese Dermatological Association.

  4. Treatment of Primary Cutaneous CD30+ Anaplastic Large-Cell Lymphoma With Radiation Therapy

    SciTech Connect

    Yu, James B.; McNiff, Jennifer M.; Lund, Molly W.; Wilson, Lynn D.

    2008-04-01

    Purpose: Primary cutaneous CD30+ anaplastic large-cell lymphoma (CALCL) is a relatively rare and indolent variant of cutaneous T-cell lymphoma (CTCL). This report examines the response of localized disease to radiation alone. Methods: The Yale Cancer Center records were examined, and all patients with CTCL from January 1, 2001, to September 1, 2006, evaluated in the Department of Therapeutic Radiology were identified. Only those patients with localized or single CALCL lesions, no clinical evidence or history of lymphomatoid papulosis, no history of other CTCLs, no history of other skin disorders, lack of lymph node involvement, unambiguous pathology reports, and treatment with radiation alone were included. Results: Eight patients were identified. Median age was 67 years, and gender was split evenly. Patients received radiation ranging from 34 to 44 Gy in 2-Gy fractions. Most patients (5 of 8) received 40 Gy, using 6 to 9 MeV electrons with 0.5 to 2 cm of bolus. All patients had a complete response. All patients were without evidence of disease at the most recent follow-up (median follow-up, 12 months). Radiation therapy was well tolerated, and the only recorded toxicity was Grade I to II dermatitis. Conclusions: Radiation therapy alone for localized CALCL is very well tolerated and clinical response is excellent. A dose of 40 Gy in 2-Gy fractions seems to be well tolerated and effective in inducing a complete response. Lower doses may be effective in achieving the same result, but data are not available. Longer follow-up is necessary before conclusions regarding durable disease-free survival can be made.

  5. Primary Cutaneous Mammary Analog Secretory Carcinoma With ETV6-NTRK3 Translocation.

    PubMed

    Amin, Sapna M; Beattie, Adam; Ling, Xia; Jennings, Lawrence J; Guitart, Joan

    2016-11-01

    Mammary analog secretory carcinoma (MASC) is a recently described tumor of the salivary glands named for its morphological and molecular similarity to secretory carcinoma of the breast. Many primary carcinomas arising from the adnexal glands also share similar morphology to those arising from the breast. Brandt et al first described primary cutaneous MASC in 2009 and since then only 2 other cases have been reported. Herein, we describe a long-standing mass on the arm of an otherwise healthy 40-year-old female. Histologic examination revealed a circumscribed but unencapsulated, nodular tumor composed of bland epithelial cells arranged in solid and microcystic growth patterns. The cells showed vacuolated cytoplasm and round to oval nuclei with vesicular chromatin. Intraluminal homogenous eosinophilic secretions were present. Mitotic figures were not identified. The tumor cells stained positive for CK8/18, CK7, and S100 but were negative for other markers performed, including estrogen receptor, progesterone receptor, HER2/neu, paired box 8 (PAX8), and thyroid transcription factor 1 (TTF1). As the patient clinically had no other masses or known carcinomas, a diagnosis of primary cutaneous MASC was rendered. The ETV6-NTRK3 fusion transcript was subsequently detected by reverse transcriptase polymerase chain reaction amplification, further supporting the diagnosis. We present this case to review the histologic features of MASC and highlight the importance of recognizing this lesion not only as a possible cutaneous metastasis but also as a primary cutaneous tumor.

  6. Absence of human T-lymphotropic virus type I in Japanese patients with cutaneous T-cell lymphoma.

    PubMed

    Kikuchi, A; Nishikawa, T; Ikeda, Y; Yamaguchi, K

    1997-03-01

    Cutaneous T-cell lymphoma (CTCL) is a disease entity characterized by a primary sporadic T-cell proliferation in the skin. Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus that causes adult T-cell leukemia/lymphoma. Recently, several authors have detected the HTLV-1 genome in genomic DNA from patients with CTCL and proposed a causal relation of HTLV-1 to CTCL. However, it remains controversial because these studies contain some problems in materials used to detect HTLV-1. We investigated both fresh and cultured T lymphocytes (128 specimens) derived from 50 Japanese patients with CTCL, where HTLV-1 is endemic, by using polymerase chain reaction with four sets of primers including gag, pol, env, and pX regions of HTLV-1 to elucidate the relationship between HTLV-1 and CTCL in Japan. However, none of the 128 DNA specimens revealed positive for HTLV-1 in contrast to the previous studies. We conclude that CTCL, which does not include HTLV-1, is present although the pathogenesis of CTCL may be different by areas or races.

  7. Solitary facial cutaneous metastasis as the primary presentation of a small renal cell carcinoma.

    PubMed

    Bjurlin, Marc A; Bhalani, Vishal; Jordan, Michael D; Hollowell, Courtney M P

    2010-12-01

    Renal cell carcinoma (RCC) has been well described for its frequency to metastasize. Cutaneous facial lesions as the primary presentation of RCC is, however, extremely rare. We present clinical, radiographic, and histologic images of a 40-year-old man who presented with a cutaneous facial lesion that was diagnosed as metastatic RCC after excisional biopsy. A subsequent computed tomography demonstrated a small mass (3.5 × 2.6 cm) in the midpole of the right kidney. Partial nephrectomy with histologic analysis confirmed RCC, clear cell type.

  8. Primary immunodeficiency update II: Syndromes associated with mucocutaneous candidiasis and non-infectious cutaneous manifestations

    PubMed Central

    Pichard, Dominique C.; Freeman, Alexandra F.; Cowen, Edward W.

    2015-01-01

    Several primary immunodeficiencies (PID) have recently been described which confer elevated risk of fungal infections as well as non-infectious cutaneous manifestations. In addition, immunological advances have provided new insights into our understanding of the pathophysiology of fungal infections in established PID. We reviewed PID that present with an eczematous dermatitis in Part I. In Part II, we will discuss updates on PID associated with fungal infections and their biological basis in PID as well as non-infectious cutaneous manifestations. PMID:26282795

  9. Primary cutaneous mucormycosis presenting as a giant plaque: uncommon presentation of a rare mycosis.

    PubMed

    Vinay, Keshavamurthy; Chandrasegaran, Ariganesh; Kanwar, Amrinder J; Saikia, Uma N; Kaur, Harsimran; Shivaprakash, M R; Dogra, Sunil

    2014-08-01

    Mucormycosis is an uncommon systemic mycosis affecting the immunocompromised individuals. It is usually caused by organisms of the genera Rhizopus and Mucor, although rarely other organisms have also been implicated. Mycoses due to these angioinvasive fungi have an acute onset, rapidly progressive course with high mortality rate. A rare and less well known is the chronic subtype of primary cutaneous mucormycosis (PCM). Herein, we report a case of PCM clinically presenting as a chronic, giant destructive plaque in a young immunocompetent male and coin the term chronic granulomatous mucormycosis. A clinicopathological classification for cutaneous mucormycosis is also proposed.

  10. Disseminated cryptococcosis manifested as a single tumor in an immunocompetent patient, similar to the cutaneous primary forms.

    PubMed

    Amaral, Danielle Mechereffe do; Rocha, Ritha de Cássia Capelato; Carneiro, Luiz Euribel Prestes; Vasconcelos, Dewton Moraes; Abreu, Marilda Aparecida Milanez Morgado de

    2016-01-01

    Cryptococcosis is a fungal infection caused by Cryptococcus neoformans that tends to affect immunocompromised individuals. The fungi are mostly acquired by inhalation, which leads to an initial pulmonary infection. Later, other organs - such as the central nervous system and the skin - can be affected by hematogenous spread. In addition, cutaneous contamination can occur by primary inoculation after injuries (primary cutaneous cryptococcosis), whose diagnosis is defined based on the absence of systemic involvement. The clinical presentation of cutaneous forms typically vary according to the infection mode. We report an unusual case of disseminated cryptococcosis in an immunocompetent patient with cutaneous lesions similar to those caused by primary inoculation. This clinical picture leads us to question the definition of primary cutaneous cryptococcosis established in the literature.

  11. Disseminated cryptococcosis manifested as a single tumor in an immunocompetent patient, similar to the cutaneous primary forms*

    PubMed Central

    do Amaral, Danielle Mechereffe; Rocha, Ritha de Cássia Capelato; Carneiro, Luiz Euribel Prestes; Vasconcelos, Dewton Moraes; de Abreu, Marilda Aparecida Milanez Morgado

    2016-01-01

    Cryptococcosis is a fungal infection caused by Cryptococcus neoformans that tends to affect immunocompromised individuals. The fungi are mostly acquired by inhalation, which leads to an initial pulmonary infection. Later, other organs - such as the central nervous system and the skin - can be affected by hematogenous spread. In addition, cutaneous contamination can occur by primary inoculation after injuries (primary cutaneous cryptococcosis), whose diagnosis is defined based on the absence of systemic involvement. The clinical presentation of cutaneous forms typically vary according to the infection mode. We report an unusual case of disseminated cryptococcosis in an immunocompetent patient with cutaneous lesions similar to those caused by primary inoculation. This clinical picture leads us to question the definition of primary cutaneous cryptococcosis established in the literature. PMID:28300886

  12. Primary cutaneous mucormycosis in an immunocompetent host: report of a case.

    PubMed

    Kumar, Arvind; Khilnani, Gopi C; Aggarwal, Sandeep; Kumar, Subodh; Banerjee, Uma; Xess, Immaculata

    2003-01-01

    Cutaneous mucormycosis is an uncommon disease and it usually affects immunocompromised, diabetic, and trauma patients with contaminated wounds or patients with underlying malignancies. It is very rare to find this disease in immunocompetent, nondiabetic patients. We herein report a case of primary cutaneous mucormycosis in an immunocompetent and nondiabetic patient. Our patient was a 50-year-old veterinary doctor. He was diagnosed to have cutaneous mucormycosis of the anterior abdominal wall, and was treated with multiple debridements of the wound and intravenous amphotericin B therapy. He received a total of 1000 mg of amphotericin B. A high index of clinical suspicion and early institution of therapy in the form of surgical debridements and antifungal drugs are required to achieve a successful outcome.

  13. [Update on surgical treatment of primary and metastatic cutaneous melanoma].

    PubMed

    Zuluaga-Sepúlveda, María Alejandra; Arellano-Mendoza, Ivonne; Ocampo-Candiani, Jorge

    2016-01-01

    Melanoma is a common cutaneous tumour. It is of great importance due to its increasing incidence and aggressive behaviour, with metastasis to lymph nodes and internal organs. When suspecting melanoma, excisional biopsy should be performed to obtain complete histological information in order to determine the adverse factors such as ulceration, mitosis rate, and Breslow depth, which influence preoperative staging and provide data for sentinel lymph biopsy decision making. The indicated management for melanoma is wide local excision, observing recommended and well-established excision margins, depending on Breslow depth and anatomical location of the tumour. Therapeutic lymphadenectomy is recommended for patients with clinically or radiologically positive lymph nodes. This article reviews surgical treatment of melanoma, adverse histological factors, sentinel lymph node biopsy, and radical lymphadenectomy. Details are presented on special situations in which management of melanoma is different due to the anatomical location (plantar, subungual, lentigo maligna), or pregnancy. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

  14. Biological and clinical significance of tryptophan-catabolizing enzymes in cutaneous T-cell lymphomas

    PubMed Central

    Maliniemi, Pilvi; Dettmer, Katja; Lipsanen, Tuomas; Jeskanen, Leila; Bessede, Alban; Oefner, Peter J.; Kadin, Marshall E.

    2017-01-01

    ABSTRACT Indoleamine 2,3-deoxygenase 1 (IDO1) induces immune tolerance in the tumor microenvironment (TME) and is recognized as a potential therapeutic target. We studied the expression of both IDO1 and the related tryptophan 2,3-dioxygenase (TDO) in several different subtypes of cutaneous T-cell lymphoma (CTCL), and evaluated the kynurenine (KYN) pathway in the local TME and in patient sera. Specimens from the total of 90 CTCL patients, including mycosis fungoides (MF, n = 37), lymphomatoid papulosis (LyP, n = 36), primary cutaneous anaplastic large cell lymphoma (pcALCL, n = 4), subcutaneous panniculitis-like T-cell lymphoma (SPTCL n = 13), and 10 patients with inflammatory lichen ruber planus (LRP), were analyzed by immunohistochemistry (IHC), immunofluorescence (IF), quantitative PCR, and/or liquid chromatography–tandem mass spectrometry (LC–MS/MS). Three CTCL cell lines also were studied. Expression of both IDO1 and TDO was upregulated in CTCL. In MF specimens and in the MF cell line MyLa2000, IDO1 expression exceeded that of TDO, whereas the opposite was true for LyP, ALCL, and corresponding Mac1/2A cell lines. The spectrum of IDO1-expressing cell types differed among CTCL subtypes and was reflected in the clinical behavior. In MF, SPTCL, and LyP, IDO1 was expressed by malignant cells and by CD33+ myeloid-derived suppressor cells, whereas in SPTCL CD163+ tumor-associated macrophages also expressed IDO1. Significantly elevated serum KYN/Trp ratios were found in patients with advanced stages of MF. Epacadostat, an IDO1 inhibitor, induced a clear decrease in KYN concentration in cell culture. These results show the importance of IDO1/TDO-induced immunosuppression in CTCL and emphasize its role as a new therapeutic target. PMID:28405495

  15. CD30+ Cutaneous T Cell Lymphoma: Response to Rotational Total Skin Electron Irradiation.

    PubMed

    Danish, Hasan H; Heumann, Thatcher R; Bradley, Kyle T; Switchenko, Jeffrey; Esiashvili, Natia; Lechowicz, Mary Jo; Flowers, Christopher R; Khan, Mohammad K

    2016-06-01

    Rotational total skin electron irradiation (RTSEI) is an effective therapy for cutaneous T cell lymphoma (CTCL). CD30 expression has been identified as a prognostic factor in CTCL. Therefore, we investigated CD30 status, treatment response, and survival in our cohort of patients with CTCL treated with RTSEI. Patients with CTCL treated with RTSEI (≥30 Gy) between 2000 and 2013 at our institution were identified, and clinical and pathologic data were retrospectively reviewed. Primary outcomes were complete clinical response (CCR; >90% reduction of skin disease burden), relapse-free survival (RFS), and overall survival (OS). Sixty-eight patients with CTCL treated with RTSEI were identified. Median age at diagnosis was 51 years with median follow-up of 61 months. Median OS was 76 months and median RFS was 11 months. Thirteen patients (19%) had CD30+ lymphocytes on initial pathology. In the CD30+ cohort, there were no T2, eight T3, and five T4 cases. In comparison, in the CD30- cohort, there were 18 T2, 29 T3, and 8 T4 cases (P = 0.01). Six weeks post-RTSEI, CCR was 85% in CD30+ and 81% in CD30- cases (P = 1). Six months post-RTSEI, CCR was 23% in CD30+ and 50% in CD30- cases (P = 0.083). RTSEI resulted in excellent CCR at 6 weeks in our cohort of patients with CTCL, with a median RFS of 11 months. We found CD30+ patients presented with significantly higher T stage at time of RTSEI and trended towards decreased CCR at 6 months post-RTSEI compared with the CD30- group.

  16. Aurora Kinase A Is Upregulated in Cutaneous T-Cell Lymphoma and Represents a Potential Therapeutic Target.

    PubMed

    Humme, Daniel; Haider, Ahmed; Möbs, Markus; Mitsui, Hiroshi; Suárez-Fariñas, Mayte; Ohmatsu, Hanako; Geilen, Cyprienne Isabell; Eberle, Jürgen; Krueger, James G; Beyer, Marc; Hummel, Michael; Anagnostopoulos, Ioannis; Sterry, Wolfram; Assaf, Chalid

    2015-09-01

    Cutaneous T-cell lymphomas (CTCLs) form a heterogeneous group of non-Hodgkin's lymphomas characterized by only poor prognosis in advanced stage. Despite significant progress made in the identification of novel genes and pathways involved in the pathogenesis of cutaneous lymphoma, the therapeutic value of these findings has still to be proven. Here, we demonstrate by gene expression arrays that Aurora kinase A is one of the highly overexpressed genes of the serine/threonine kinase in CTCL. The finding was confirmed by quantitative reverse transcriptase-PCR, western blotting, and immunohistochemistry in CTCL cell lines and primary patient samples. Moreover, treatment with a specific Aurora kinase A inhibitor blocks cell proliferation by inducing cell cycle arrest in G2 phase, as well as apoptosis in CTCL cell lines. These data provide a promising rationale for using Aurora kinase A inhibition as a therapeutic modality of CTCL.

  17. Clinicopathologic features of incident and subsequent tumors in patients with multiple primary cutaneous melanomas

    PubMed Central

    Murali, Rajmohan; Goumas, Chris; Kricker, Anne; From, Lynn; Busam, Klaus J.; Begg, Colin B.; Dwyer, Terence; Gruber, Stephen B.; Kanetsky, Peter A.; Orlow, Irene; Rosso, Stefano; Thomas, Nancy E.; Berwick, Marianne; Scolyer, Richard A.; Armstrong, Bruce K.

    2011-01-01

    Background 0.6–12.7% of patients with primary cutaneous melanoma will develop additional melanomas. Pathologic features of tumors in patients with multiple primary cutaneous melanomas have not been well described. In this large international multi-center case-control study, we compared the clinicopathologic features of a subsequent melanoma with the preceding (usually the first) melanoma in patients with multiple primary cutaneous melanomas, and with those of melanomas in patients with single primary cutaneous melanomas. Methods Multiple primary melanoma (cases) and single primary invasive melanoma (controls) patients from the Genes, Environment and Melanoma (GEM) study were included if their tumors were available for pathologic review and confirmed as melanoma. Clinicopathologic characteristics of invasive subsequent and first melanomas in cases and invasive single melanomas in controls were compared. Results 473 pairs comprising a subsequent and a first melanoma and 1989 single melanomas were reviewed. Forward stepwise regression modeling in 395 pairs with complete data showed that, compared to first melanomas, subsequent melanomas were: more commonly contiguous with a dysplastic nevus; more prevalent on the head/neck and legs than other sites; and thinner. Compared with single primary melanomas, subsequent melanomas were also more likely to be: associated with a contiguous dysplastic nevus; more prevalent on the head/neck and legs; and thinner. The same differences were observed when subsequent melanomas were compared with single melanomas. First melanomas were more likely than single melanomas to have associated solar elastosis and no observed mitoses. Conclusions Thinner subsequent than first melanomas suggest earlier diagnosis, perhaps due to closer clinical scrutiny. The association of subsequent melanomas with dysplastic nevi is consistent with the latter being risk factors or risk markers for melanoma. PMID:21913010

  18. The cutaneous vasoconstrictor response to venous stasis is normal in subjects with primary Raynaud's disease.

    PubMed

    Edwards, C M; Marshall, J M; Pugh, M

    1999-10-01

    In control subjects and in subjects with primary Raynaud's disease, sudden sound or a mild cool stimulus evokes the pattern of alerting response that includes cutaneous vasoconstriction but vasodilatation in forearm muscle. In control subjects, response habituates on repetition of these stimuli both within experimental sessions and over successive days. However, in subjects with primary Raynaud's disease, the cutaneous vasoconstriction and the muscle vasodilatation persist. We have now tested whether a similar disparity exists for the cutaneous vasoconstriction evoked by venous stasis, a response considered to be a veno-arteriolar reflex mediated by sympathetic fibers, but not requiring transmission through the spinal cord. In 10 subjects with primary Raynaud's disease and in 10 matched controls, a sphygmomanometer cuff on the left arm was inflated to 40 mm Hg for 2 minutes, five times on each of three experimental sessions on days 1, 3, and 5. Cutaneous red cell flux (RCF) was recorded from the pulp and dorsum of the left index finger by using a laser Doppler meter; digital vascular conductance (DCVC) was computed as RCF divided by arterial pressure. The first venous stasis, in session 1, evoked a decrease in pulp and dorsum DCVC in the control and primary Raynaud's subjects. There were no differences between the groups in the magnitudes or durations of these responses. Within session 1, the magnitude of the decrease in DCVC diminished on repetition of venous stasis in the dorsum in controls and in the pulp in primary Raynaud's subjects. We propose these effects reflected the similar reductions in baseline DCVC over time; there was no change in the duration of the responses. Repetition of venous stasis had similar effects in both groups of subjects within sessions 2 and 3. Further, judging from the mean of the responses evoked in each Session the decreases evoked in pulp and dorsum DCVC by venous stasis were fully consistent in magnitude and duration over the

  19. Reconstruction after wide excision of primary cutaneous melanomas: part II--the extremities.

    PubMed

    Moncrieff, Marc D; Thompson, John F; Quinn, Michael J; Stretch, Jonathan R

    2009-08-01

    The core principle in the management of primary cutaneous melanoma is wide surgical excision, but occasionally a balance is needed between adequately resecting a potentially curable lesion and minimising the functional deficit in manual dexterity or ambulation for the patient. A secondary but nonetheless increasingly important consideration in this location is the potential cosmetic deformity caused by wide excision of the melanoma. Thus, the reconstructive surgeon forms an integral part of a multidisciplinary team managing patients with melanoma by providing knowledge of a wide range of reconstructive techniques, including the advantages and limitations, and a comprehensive understanding of the local and regional anatomy. The primary aim of this article is to review the current literature and available evidence on reconstruction after wide excision of primary cutaneous melanoma of the extremities.

  20. STAT5 induces miR-21 expression in cutaneous T cell lymphoma

    PubMed Central

    Lindahl, Lise M.; Fredholm, Simon; Joseph, Claudine; Nielsen, Boye Schnack; Jønson, Lars; Willerslev-Olsen, Andreas; Gluud, Maria; Blümel, Edda; Petersen, David L.; Sibbesen, Nina; Hu, Tengpeng; Nastasi, Claudia; Krejsgaard, Thorbjørn; Jæhger, Ditte; Persson, Jenny L.; Mongan, Nigel; Wasik, Mariusz A.; Litvinov, Ivan V.; Sasseville, Denis; Koralov, Sergei B.; Bonefeld, Charlotte M.; Geisler, Carsten; Woetmann, Anders; Ralfkiaer, Elisabeth; Iversen, Lars; Odum, Niels

    2016-01-01

    In cutaneous T cell lymphomas (CTCL), miR-21 is aberrantly expressed in skin and peripheral blood and displays anti-apoptotic properties in malignant T cells. It is, however, unclear exactly which cells express miR-21 and what mechanisms regulate miR-21. Here, we demonstrate miR-21 expression in situ in both malignant and reactive lymphocytes as well as stromal cells. qRT-PCR analysis of 47 patients with mycosis fungoides (MF) and Sezary Syndrome (SS) confirmed an increased miR-21 expression that correlated with progressive disease. In cultured malignant T cells miR-21 expression was inhibited by Tofacitinib (CP-690550), a clinical-grade JAK3 inhibitor. Chromatin immunoprecipitation (ChIP) analysis showed direct binding of STAT5 to the miR-21 promoter. Cytokine starvation ex vivo triggered a decrease in miR-21 expression, whereas IL-2 induced an increased miR-21 expression in primary SS T cells and cultured cytokine-dependent SS cells (SeAx). siRNA-mediated depletion of STAT5 inhibited constitutive- and IL-2-induced miR-21 expression in cytokine-independent and dependent T cell lines, respectively. IL-15 and IL-2 were more potent than IL-21 in inducing miR-21 expression in the cytokine-dependent T cells. In conclusion, we provide first evidence that miR-21 is expressed in situ in CTCL skin lesions, induced by IL-2 and IL-15 cytokines, and is regulated by STAT5 in malignant T cells. Thus, our data provide novel evidence for a pathological role of IL-2Rg cytokines in promoting expression of the oncogenic miR-21 in CTCL. PMID:27329723

  1. Primary cutaneous tuberculosis in a 27-year-old medical intern from needle-stick injury: a case report.

    PubMed

    Karoney, Mercy Jelagat; Kaumbuki, Erastus Kanake; Koech, Mathew Kiptonui; Lelei, Lectary Kibor

    2015-01-01

    The authors report a case of cutaneous tuberculosis in a 27-year-old African male medical intern who contracted primary cutaneous from a needle-stick injury. Cultures of pus aspirated from the finger initially grew Staphylococcus aureus that led to a delay in the diagnosis.

  2. The Use of Interferons in the Treatment of Cutaneous T-Cell Lymphoma.

    PubMed

    Spaccarelli, Natalie; Rook, Alain H

    2015-10-01

    Interferons are polypeptides that naturally occur in the human body as a part of the innate immune response. By harnessing these immunomodulatory functions, synthetic interferons have shown efficacy in combating various diseases including cutaneous T-cell lymphoma. This article closely examines the qualities of interferon alfa and interferon gamma and the evidence behind their use in the 2 most common types of cutaneous T-cell lymphomas, namely, mycosis fungoides and Sézary syndrome. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Natural antibodies to the human T cell lymphoma virus in patients with cutaneous T cell lymphomas

    PubMed Central

    1981-01-01

    Sera from patients with cutaneous T cell lymphoma and leukemia were screened for the presence of natural antibody to the human T cell lymphoma (leukemia) virus, HTLVCR, using a solid-phase radioimmunoassay. Sera from two patients, including patient CR, from whose cultured T lymphoblastic cell line (HUT102), the retrovirus HTLVCR was isolated, reacted specifically with proteins of HTLVCR. Serum from patient CR also reacted specifically with proteins of HTLVMB, an independent but highly related retroviral isolate from a patient with Sezary T cell leukemia. The specificity for HTLVCR proteins was demonstrated by solid-phase immunocompetition assays and competition radioimmunoprecipitation assays. Analysis of radioimmunoprecipitates indicated that the natural antibodies were directed against HTLVCR core proteins with molecular weights of 24,000 and 19,000 (p24 and p19). Whereas the serum reactivities for HTLVCR proteins were shown to be highly specific, additional reactivities seen against proteins of animal retroviruses including GaLV, SSV, FeLV, and BaEV were clearly shown not to be viral specific but rather were due to reactivity with cellular antigens contaminating the viral preparations or with related antigens present in fetal calf serum. These results demonstrating natural antibodies to HTLVCR provide the first evidence for a specific antibody response to a retrovirus in humans. PMID:6973601

  4. Pagetoid reticulosis (epitheliotropic cutaneous T-cell lymphoma) in an adult alpaca (Vicugna pacos).

    PubMed

    Hasbach, Andrea E; Stern, Adam W

    2016-07-01

    A 9-year-old, intact female alpaca (Vicugna pacos) was presented for a second opinion with a 1-year history of nonpruritic, multifocal scaling and crusted cutaneous lesions, mainly involving skin on the face, axillae, and ventral abdomen. Clinical abnormalities were limited to the skin, and the alpaca was otherwise healthy. The initial veterinarian had examined the alpaca, found no evidence of ectoparasites with laboratory testing, and had tried several trial therapies including oral antibiotics, ivermectin, and topical use of betadine solution. At the time of presentation, the lesions had neither improved nor worsened with any attempted therapy, and multiple skin biopsies were collected. Histopathology and immunohistochemical staining findings were consistent with the pagetoid reticulosis type of cutaneous epitheliotropic T-cell lymphoma. Our report describes the clinical, histopathologic, and immunophenotypic features of pagetoid reticulosis epitheliotropic cutaneous T-cell lymphoma in an alpaca. © 2016 The Author(s).

  5. Primary cutaneous melanoma of the scalp: Patterns of recurrence.

    PubMed

    Sparks, David S; Read, Tavis; Lonne, Michael; Barbour, Andrew P; Wagels, Michael; Bayley, Gerard J; Smithers, B Mark

    2017-03-01

    Patients with primary melanoma of the scalp have been reported to have worse disease-related outcomes compared with other anatomical regions. There are few studies in the literature specifically addressing recurrence patterns and treatment outcomes for primary scalp melanoma as a discrete anatomical sub-region. We sought to identify key features adversely influencing disease control and survival and to clarify the role of resection plane, margin, and method of reconstruction in the management of this disease process. A retrospective clinical study of medical records was performed evaluating all patients with primary melanoma of the scalp treated at two hospitals in southeast Queensland between 2004 and 2014. A total of 107 patients were eligible for analysis. There were 46 recurrences in 38 patients in the cohort accounting for a recurrence rate of 35.5%. The local recurrence rate was 15.9% with 12 in-transit metastases after diagnosis. Regional and distant recurrence rates were 12.1% and 15%, respectively. At a median follow up of 30.5 months, disease-free survival was 47% and overall survival was also 47%. On multi-variate analysis, the deeper resection plane (sub-galeal) had a lower disease-free survival rate compared with the supra-galeal resection plane (P = 0.032). Our results support the hypothesis that primary scalp melanoma represents a unique aggressive subcategory with high rates of in-transit disease and poor disease-related and survival outcomes. There is a need for robust prospective comparative studies to address the significance of resection plane in the management of patients with scalp melanoma. © 2016 Wiley Periodicals, Inc.

  6. Increased NY-ESO-1 Expression and Reduced Infiltrating CD3+ T Cells in Cutaneous Melanoma

    PubMed Central

    Giavina-Bianchi, Mara; Giavina-Bianchi, Pedro; Sotto, Mirian Nacagami; Muzikansky, Alona; Kalil, Jorge; Festa-Neto, Cyro; Duncan, Lyn M.

    2015-01-01

    NY-ESO-1 is a cancer-testis antigen aberrantly expressed in melanomas, which may serve as a robust and specific target in immunotherapy. NY-ESO-1 antigen expression, tumor features, and the immune profile of tumor infiltrating lymphocytes were assessed in primary cutaneous melanoma. NY-ESO-1 protein was detected in 20% of invasive melanomas (16/79), rarely in in situ melanoma (1/10) and not in benign nevi (0/20). Marked intratumoral heterogeneity of NY-ESO-1 protein expression was observed. NY-ESO-1 expression was associated with increased primary tumor thickness (P = 0.007) and inversely correlated with superficial spreading melanoma (P < 0.02). NY-ESO-1 expression was also associated with reduced numbers and density of CD3+ tumor infiltrating lymphocytes (P = 0.017). When NY-ESO-1 protein was expressed, CD3+ T cells were less diffusely infiltrating the tumor and were more often arranged in small clusters (P = 0.010) or as isolated cells (P = 0.002) than in large clusters of more than five lymphocytes. No correlation of NY-ESO-1 expression with gender, age, tumor site, ulceration, lymph node sentinel status, or survival was observed. NY-ESO-1 expression in melanoma was associated with tumor progression, including increased tumor thickness, and with reduced tumor infiltrating lymphocytes. PMID:25954764

  7. Increased NY-ESO-1 expression and reduced infiltrating CD3+ T cells in cutaneous melanoma.

    PubMed

    Giavina-Bianchi, Mara; Giavina-Bianchi, Pedro; Sotto, Mirian Nacagami; Muzikansky, Alona; Kalil, Jorge; Festa-Neto, Cyro; Duncan, Lyn M

    2015-01-01

    NY-ESO-1 is a cancer-testis antigen aberrantly expressed in melanomas, which may serve as a robust and specific target in immunotherapy. NY-ESO-1 antigen expression, tumor features, and the immune profile of tumor infiltrating lymphocytes were assessed in primary cutaneous melanoma. NY-ESO-1 protein was detected in 20% of invasive melanomas (16/79), rarely in in situ melanoma (1/10) and not in benign nevi (0/20). Marked intratumoral heterogeneity of NY-ESO-1 protein expression was observed. NY-ESO-1 expression was associated with increased primary tumor thickness (P = 0.007) and inversely correlated with superficial spreading melanoma (P < 0.02). NY-ESO-1 expression was also associated with reduced numbers and density of CD3+ tumor infiltrating lymphocytes (P = 0.017). When NY-ESO-1 protein was expressed, CD3+ T cells were less diffusely infiltrating the tumor and were more often arranged in small clusters (P = 0.010) or as isolated cells (P = 0.002) than in large clusters of more than five lymphocytes. No correlation of NY-ESO-1 expression with gender, age, tumor site, ulceration, lymph node sentinel status, or survival was observed. NY-ESO-1 expression in melanoma was associated with tumor progression, including increased tumor thickness, and with reduced tumor infiltrating lymphocytes.

  8. Reticulospinal actions on primary afferent depolarization of cutaneous and muscle afferents in the isolated frog neuraxis.

    PubMed

    González, H; Jiménez, I; Rudomin, P

    1993-01-01

    The effects of the brainstem reticular formation on the intraspinal excitability of low threshold cutaneous and muscle afferents were studied in the frog neuraxis isolated together with the right hindlimb nerves. Stimulation of low threshold fibers (less than two times threshold) in cutaneous nerves produced short latency, negative field potentials in the ipsilateral dorsal neuropil (200-400 microns depth) that reversed to positivity at deeper regions (500-700 microns). Stimulation of low threshold fibers (less than two times threshold) in muscle nerves produced, instead, negative response that acquired their maximum amplitude in the ventral neuropil (700-900 microns depth). These electrophysiological findings suggest, in agreement with observations in the cat, that low threshold cutaneous and muscle afferents end at different sites in the spinal cord. Intraspinal microstimulation applied within the dorsal neuropil produced antidromic responses in low threshold cutaneous afferents that were increased in size following stimulation of the dorsal or ventral roots, as well as of the brainstem reticular formation. This increase in excitability is interpreted as being due to primary afferent depolarization (PAD) of the intraspinal terminals of cutaneous fibers. Antidromic responses recorded in muscle nerves following intraspinal stimulation within the ventral neuropil were also increased following conditioning stimulation of adjacent dorsal or ventral roots. However, stimulation of the bulbar reticular formation produced practically no changes in the antidromic responses, but was able to inhibit the PAD of low threshold muscle afferents elicited by stimulation of the dorsal or ventral roots. It is suggested that the PAD of low threshold cutaneous and muscle afferents is mediated by independent sets of interneurons. Reticulospinal fibers would have excitatory connections with the interneurons mediating the PAD of cutaneous fibers and inhibitory connections with the

  9. Brazilian guidelines for diagnosis, treatment and follow-up of primary cutaneous melanoma - Part II*

    PubMed Central

    Castro, Luiz Guilherme Martins; Bakos, Renato Marchiori; Duprat Neto, João Pedreira; Bittencourt, Flávia Vasques; Giacomo, Thais Helena Bello Di; Serpa, Sérgio Schrader; Messina, Maria Cristina de Lorenzo; Loureiro, Walter Refkalefsky; Macarenco, Ricardo Silvestre e Silva; Stolf, Hamilton Ometto; Gontijo, Gabriel

    2016-01-01

    The last Brazilian guidelines on melanoma were published in 2002. Development in diagnosis and treatment made updating necessary. The coordinators elaborated ten clinical questions, based on PICO system. A Medline search, according to specific MeSH terms for each of the 10 questions was performed and articles selected were classified from A to D according to level of scientific evidence. Based on the results, recommendations were defined and classified according to scientific strength. The present Guidelines were divided in two parts for editorial and publication reasons. In this second part, the following clinical questions were answered: 1) which patients with primary cutaneous melanoma benefit from sentinel lymph node biopsy? 2) Follow-up with body mapping is indicated for which patients? 3) Is preventive excision of acral nevi beneficious to patients? 4) Is preventive excision of giant congenital nevi beneficious to patients? 5) How should stages 0 and I primary cutaneous melanoma patients be followed? PMID:26982779

  10. Brazilian guidelines for diagnosis, treatment and follow-up of primary cutaneous melanoma - Part II.

    PubMed

    Castro, Luiz Guilherme Martins; Bakos, Renato Marchiori; Duprat Neto, João Pedreira; Bittencourt, Flávia Vasques; Di Giacomo, Thais Helena Bello; Serpa, Sérgio Schrader; Messina, Maria Cristina de Lorenzo; Loureiro, Walter Refkalefsky; Macarenco, Ricardo Silvestre e Silva; Stolf, Hamilton Ometto; Gontijo, Gabriel

    2016-01-01

    The last Brazilian guidelines on melanoma were published in 2002. Development in diagnosis and treatment made updating necessary. The coordinators elaborated ten clinical questions, based on PICO system. A Medline search, according to specific MeSH terms for each of the 10 questions was performed and articles selected were classified from A to D according to level of scientific evidence. Based on the results, recommendations were defined and classified according to scientific strength. The present Guidelines were divided in two parts for editorial and publication reasons. In this second part, the following clinical questions were answered: 1) which patients with primary cutaneous melanoma benefit from sentinel lymph node biopsy? 2) Follow-up with body mapping is indicated for which patients? 3) Is preventive excision of acral nevi beneficious to patients? 4) Is preventive excision of giant congenital nevi beneficious to patients? 5) How should stages 0 and I primary cutaneous melanoma patients be followed?

  11. Cutaneous manifestations of human T cell leukemia virus type I infection in an experimental model.

    PubMed

    Simpson, R M; Leno, M; Hubbard, B S; Kindt, T J

    1996-03-01

    Skin diseases ranging from infective dermatitis to cutaneous lymphoma have been associated with human T cell leukemia virus (HTLV) type I. A generalized exfoliative papillated dermatopathy occurred in a rabbit 20 months into a course of chronic HTLV-I infection. Biopsies revealed epidermotropic T cell infiltrates, including Sezary-like cells, that resulted in a pattern mimicking cutaneous T cell lymphoma. HTLV-I was isolated from affected skin, and virus expression was detected in cutaneous cultures. Sezary-like cells also occurred in circulation. Interleukin-2-independent lymphocyte cultures, established from blood exhibiting elevated CD8 T cell levels and CD25 expression, had polyclonal integration of provirus. The findings are similar to those in evolving adult T cell leukemia lymphoma and may represent a prelymphomatous change. The cutaneous lymphoproliferative lesion resulted from HTLV-I infection and further establishes the New Zealand White rabbit inoculated with the RH/K34 cell line as a suitable model for investigation of HTLV-I pathogenesis.

  12. Diagnostic microRNA profiling in cutaneous T-cell lymphoma (CTCL).

    PubMed

    Ralfkiaer, Ulrik; Hagedorn, Peter H; Bangsgaard, Nannie; Løvendorf, Marianne B; Ahler, Charlotte B; Svensson, Lars; Kopp, Katharina L; Vennegaard, Marie T; Lauenborg, Britt; Zibert, John R; Krejsgaard, Thorbjørn; Bonefeld, Charlotte M; Søkilde, Rolf; Gjerdrum, Lise M; Labuda, Tord; Mathiesen, Anne-Merete; Grønbæk, Kirsten; Wasik, Mariusz A; Sokolowska-Wojdylo, Malgorzata; Queille-Roussel, Catherine; Gniadecki, Robert; Ralfkiaer, Elisabeth; Geisler, Carsten; Litman, Thomas; Woetmann, Anders; Glue, Christian; Røpke, Mads A; Skov, Lone; Odum, Niels

    2011-11-24

    Cutaneous T-cell lymphomas (CTCLs) are the most frequent primary skin lymphomas. Nevertheless, diagnosis of early disease has proven difficult because of a clinical and histologic resemblance to benign inflammatory skin diseases. To address whether microRNA (miRNA) profiling can discriminate CTCL from benign inflammation, we studied miRNA expression levels in 198 patients with CTCL, peripheral T-cell lymphoma (PTL), and benign skin diseases (psoriasis and dermatitis). Using microarrays, we show that the most induced (miR-326, miR-663b, and miR-711) and repressed (miR-203 and miR-205) miRNAs distinguish CTCL from benign skin diseases with > 90% accuracy in a training set of 90 samples and a test set of 58 blinded samples. These miRNAs also distinguish malignant and benign lesions in an independent set of 50 patients with PTL and skin inflammation and in experimental human xenograft mouse models of psoriasis and CTCL. Quantitative (q)RT-PCR analysis of 103 patients with CTCL and benign skin disorders validates differential expression of 4 of the 5 miRNAs and confirms previous reports on miR-155 in CTCL. A qRT-PCR-based classifier consisting of miR-155, miR-203, and miR-205 distinguishes CTCL from benign disorders with high specificity and sensitivity, and with a classification accuracy of 95%, indicating that miRNAs have a high diagnostic potential in CTCL.

  13. CD30+ Primary Cutaneous Post-transplant Lymphoproliferative Disorder with Signet-ring Cell Features

    PubMed Central

    Malviya, Neeta; Wickless, Heather

    2016-01-01

    We report a case of primary cutaneous CD30+ post-transplant lymphoproliferative disorder with an uncommon finding of signet ring cell features in a heart transplant patient. The neoplastic cells were CD4 and CD30 positive, and negative for S-100, pancytokeratin, myeloperoxidase, and CD56. In situ hybridization for Epstein Barr Virus (EBV) was negative, even though the patient did have EBV viremia. PMID:27499836

  14. Cutaneous EBV-positive γδ T-cell lymphoma vs. extranodal NK/T-cell lymphoma: a case report and literature review.

    PubMed

    Yu, Wei-Wen; Hsieh, Pin-Pen; Chuang, Shih-Sung

    2013-03-01

    Primary cutaneous γδ T-cell lymphoma and extranodal natural killer (NK)/T-cell lymphoma (ENKTL), nasal type are two distinct lymphoma entities in the World Health Organization (WHO) classification. We report the case of an aggressive cutaneous lymphoma of γδ T-cell origin showing overlapping features of both lymphomas. A 78-year-old female presented with confluent erythematous plaques with ulcerations over her right thigh. Microscopically, section of the skin showed a diffuse dermal and subcutaneous lymphocytic infiltration with tumor necrosis and angioinvasion. The medium- to large-sized tumor cells expressed CD3, CD8, cytotoxic molecules and T-cell receptor (TCR)-γ but not CD4, CD20, CD30, CD56 or βF1. In situ hybridization for Epstein-Barr virus-encoded mRNA (EBER) was diffusely positive. Polymerase chain reaction-based clonality assay showed a clonal TCR-γ chain gene rearrangement. The features compatible with γδ T-cell lymphoma include dermal and subcutaneous involvements, cytotoxic phenotype, expression of TCR-γ, as well as an aggressive course. On the other hand, the diffuse EBER positivity, angioinvasion, tumor necrosis and cytotoxic phenotype may also fit in the diagnosis of an ENKTL of T-cell lineage. We review the literature on EBER-positive γδ T-cell lymphoma and discuss the diagnostic dilemma using the current WHO classification system.

  15. Toll receptor agonist therapy of skin cancer and cutaneous T-cell lymphoma.

    PubMed

    Huen, Auris O; Rook, Alain H

    2014-03-01

    The use of agents which exhibit the ability to potently activate the innate immune response has gained significant interest as therapeutics to treat cancer. We will review the history and the current applications of these agents to treat skin cancer and cutaneous T-cell lymphoma. Particular attention has been focused upon Toll-like receptor (TLR) agonists, including imidazoquinolines, which can trigger TLR 7 and TLR 8, and cytosine-phosphate-guanine (CpG) oligodeoxynucleotides, which activate TLR 9-expressing cells. Imiquimod, a TLR 7 agonist, has been found to be efficacious for basal cell and squamous cell cancers, as well as cutaneous T-cell lymphoma and lentigo maligna melanoma. CpGs have demonstrated efficacy for cutaneous T-cell lymphoma. Additional more potent compounds, including resiquimod, are presently in clinical trials for several types of skin cancers. TLR agonists that can activate the innate immune response have been used to treat a variety of skin cancers including basal cell cancer, squamous cell cancer, lentigo maligna melanoma and cutaneous T-cell lymphoma. Significant clinical efficacy has been observed for all of these conditions. It is anticipated that additional members of the TLR agonist family will be available in the clinic for the future treatment of skin cancers as well as other malignancies.

  16. Cutaneous Epitheliotropic T-Cell Lymphoma in a Marsh Rice Rat (Oryzomys palustris)

    PubMed Central

    Taylor, Bryan F; Bekkevold, Christine M; Aguirre, J Ignacio; Andrutis, Karl; Reinhard, Mary K

    2015-01-01

    Published reports of spontaneous neoplasia in marsh rice rats (Oryzomys palustris) are sparse. We report here a case of cutaneous epitheliotropic T-cell lymphoma in a 14-mo-old marsh rice rat that involved the ear pinnae, with dissemination to the liver and spleen. Histologically, the thickened ear pinnae showed diffuse infiltration of neoplastic lymphocytes into the epidermis, dermis, and adnexal skin structures, with Pautrier microaggregations present in the epidermis. In addition, neoplastic lymphocytes were observed infiltrating and disrupting the architecture of the liver and spleen. Neoplastic lymphocytes were strongly positive for the T-cell marker CD3 but were negative for the B-cell markers CD19 and CD20. These histologic and immunohistochemical features are consistent with an epitheliotropic T-cell lymphoma, as previously reported in other species, including humans. To our knowledge, this report represents the first published case of spontaneous cutaneous epitheliotropic T-cell lymphoma in a marsh rice rat. PMID:26473345

  17. Primary Cutaneous Carcinosarcoma of the Basal Cell Subtype Should Be Treated as a High-Risk Basal Cell Carcinoma.

    PubMed

    Bourgeault, Emilie; Alain, Jimmy; Gagné, Eric

    2015-01-01

    Cutaneous carcinosarcoma is a rare primary tumor of the skin, characterized by biphasic epithelial and mesenchymal differentiation. Due to the limited number of cases reported, there is no consensus regarding treatment and prognosis. Some authors suggest that cutaneous carcinosarcomas should be viewed as aggressive tumors, with ancillary imaging used to evaluate potential metastatic disease. Other reports demonstrate an indolent disease course, especially with epidermal-type cutaneous carcinosarcomas. We report a case of cutaneous carcinosarcoma, which we treated with electrodessication and curettage following a shave biopsy. The tumor had an epithelial component resembling a basal cell carcinoma and a fibrosarcomatous stroma. At 1-year follow-up, our patient did not show evidence of recurrence or metastasis. Our case suggests that a cutaneous carcinosarcoma with an epithelial component composed of basal cell carcinoma can be regarded as a high-risk nonmelanoma skin cancer. © The Author(s) 2015.

  18. Gangrenous cutaneous mucormycosis caused by Rhizopus oryzae: a case report and review of primary cutaneous mucormycosis in China over Past 20 years.

    PubMed

    Li, HouMin; Hwang, Sonia Kay; Zhou, Cheng; Du, Juan; Zhang, JianZhong

    2013-08-01

    Cutaneous mucormycosis is a rare opportunistic infection caused by zygomycetes that can be rapidly fatal if unrecognized. We describe the clinical, histopathological, fungal and molecular features of a case of gangrenous cutaneous mucormycosis. The patient presented with great necrosis on his right forearm at the site of detained intravenous cannula needle. He had type II diabetes and chronic renal insufficiency. KOH mount of black eschar showed many broad, aseptate fungal hyphae with right-angle branching. PAS staining of the tissue sample revealed similar broad hyphae in the dermis and cutis. Fungal culture and ITS sequence analysis identified this fungus as Rhizopus oryzae. As no organ involvement was detected, the patient was diagnosed with primary cutaneous mucormycosis. Considering the poor state of the patient, complete excision of the infectious tissue was performed without skin graft instead of amputation. At the same time, intravenous liposomal amphotericin B was given, starting from a small dosage and increased to a total dosage amount of 5.45 g. The wound recovered well with granulation. We emphasize that early recognition and prompt therapy including the control of the primary diseases were important. In this article, we also reviewed the features of primary cutaneous mucormycosis reported in China over the last 20 years.

  19. Update and Review on the Surgical Management of Primary Cutaneous Melanoma

    PubMed Central

    Niknam Leilabadi, Solmaz; Chen, Amie; Tsai, Stacy; Soundararajan, Vinaya; Silberman, Howard; Wong, Alex K.

    2014-01-01

    The surgical management of malignant melanoma historically called for wide excision of skin and subcutaneous tissue for any given lesion, but has evolved to be rationally-based on pathological staging. Breslow and Clark independently described level and thickness as determinant in prognosis and margin of excision. The American Joint Committee of Cancer (AJCC) in 1988 combined features from each of these histologic classifications, generating a new system, which is continuously updated and improved. The National Comprehensive Cancer Network (NCCN) has also combined several large randomized prospective trials to generate current guidelines for melanoma excision as well. In this article, we reviewed: (1) Breslow and Clark classifications, AJCC and NCCN guidelines, the World Health Organization’s 1988 study, and the Intergroup Melanoma Surgical Trial; (2) Experimental use of Mohs surgery for in situ melanoma; and (3) Surgical margins and utility and indications for sentinel lymph node biopsy (SLNB) and lymphadenectomy. Current guidelines for the surgical management of a primary melanoma of the skin is based on Breslow microstaging and call for cutaneous margins of resection of 0.5 cm for MIS, 1.0 cm for melanomas ≤1.0 mm thick, 1–2 cm for melanoma thickness of 1.01–2 mm, 2 cm margins for melanoma thickness of 2.01–4 mm, and 2 cm margins for melanomas >4 mm thick. Although the role of SLNB, CLND, and TLND continue to be studied, current recommendations include SLNB for Stage IB (includes T1b lesions ≤1.0 with the adverse features of ulceration or ≥1 mitoses/mm2) and Stage II melanomas. CLND is recommended when sentinel nodes contain metastatic deposits. PMID:27429273

  20. Cutaneous neurturin overexpression alters mechanical, thermal, and cold responsiveness in physiologically identified primary afferents.

    PubMed

    Jankowski, Michael P; Baumbauer, Kyle M; Wang, Ting; Albers, Kathryn M; Davis, Brian M; Koerber, H Richard

    2017-03-01

    Neurotrophic factors play an important role in the regulation of functional properties of sensory neurons under normal and pathological conditions. The GDNF family member neurturin is one such factor that has been linked to modulating responsiveness to peripheral stimuli. Neurturin binds to the GFRα2 receptor, a receptor found primarily in isolectin B4-expressing polymodal cutaneous nociceptors. Previous work has shown that knockout of GFRα2 alters heat, but not mechanical, responses in dissociated sensory neurons and reduces pain-related behaviors during the second phase of the formalin test. Research has also shown that overexpression of neurturin in basal keratinocytes increases behavioral responsiveness to mechanical stimulation and innocuous cooling of the skin without affecting noxious heat responses. Here we directly examined the impact of neurturin overexpression on cutaneous afferent function. We compared physiological responses of individual sensory neurons to mechanical and thermal stimulation of the skin, using an ex vivo skin-nerve-dorsal root ganglion-spinal cord preparation produced from neurturin-overexpressing (NRTN/OE) mice and wild-type littermate controls. We found that neurturin overexpression increases responsiveness to innocuous mechanical stimuli in A-fiber nociceptors, alters thermal responses in the polymodal subpopulation of C-fiber sensory neurons, and changes the relative numbers of mechanically sensitive but thermally insensitive C-fiber afferents. These results demonstrate the potential roles of different functional groups of sensory neurons in the behavioral changes observed in mice overexpressing cutaneous neurturin and highlight the importance of neurturin in regulating cutaneous afferent response properties.NEW & NOTEWORTHY GDNF family neurotrophic factors regulate the development and function of primary sensory neurons. Of these, neurturin has been shown to modulate mechanical and cooling sensitivity behaviorally. Here we show

  1. EXTRINSIC APOPTOTIC PATHWAYS: A NEW POTENTIAL “TARGET” FOR MORE SUFFICIENT THERAPY IN A CASE OF CUTANEOUS ANAPLASTIC LARGE CD30+ ALK–T-CELL LYMPHOMA

    PubMed Central

    Georgi, Tchernev; Carlos, Cardoso José; Lubomir, Arseniev; Hiroyuki, Okamoto

    2011-01-01

    The primary cutaneous T-cell lymphomas (CTCL) represent a clonal T-lymphocyte proliferation infiltrating the skin. CD30+T-cell lymphomas present clinically as nodules with a diameter between 1 and 15 cm, mostly in elderly patients. The role of the CD30 molecule in patients suffering from T-cell lymphomas is not completely clear yet. The signal transduction pathway which includes CD30 seems to play a key role in tumor progression. In certain forms of T-cellular lymphomas, the interaction between CD30/CD30-ligand is able to provoke apoptosis of the “tumor lymphocytes”. The modern conceptions of the pathogenesis of T-cell lymphomas include disorders in the pathways involved in programmed cellular death and disregulation in the expression of certain of its regulatory molecules. We are presenting an unusual case of a female patient with a primary cutaneous form of CD30+/ALK− anaplastic large T-cell lymphoma. Upon the introduction of systemic PUVA, (psoralen plus ultraviolet light radiation) combined with beam therapy, a complete remission could be noticed. Eight months later, we observed a local recurrence, which was overcome by CHOP chemotherapy (Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Vincristin (Oncovin®), Predniso(lo)n). Six months later, new cutaneous lesions had been noticed again. A new therapeutic hope for the patients with anaplastic large CTCL is actually based on the influence of the activity of the different apoptotic pathways. Death ligands, including tumor necrosis factor (TNF)-α, CD95L/FasL, and TRAIL, mediate also some important safeguard mechanisms against tumor growth in patients with CD30+ cutaneous anaplastic large T-cell lymphomas and critically contribute to lymphocyte homeostasis. PMID:21572802

  2. Natural course of cutaneous warts among primary schoolchildren: a prospective cohort study.

    PubMed

    Bruggink, Sjoerd C; Eekhof, Just A H; Egberts, Paulette F; van Blijswijk, Sophie C E; Assendelft, Willem J J; Gussekloo, Jacobijn

    2013-01-01

    Because cutaneous warts resolve spontaneously and available treatments often fail, family physicians and patients may consider a wait-and-see policy. We examined the natural course of cutaneous warts and treatment decisions in a prospective observational cohort of primary schoolchildren. We inspected the hands and feet of children aged 4 to 12 years from 3 Dutch primary schools for the presence of warts at baseline and after a mean follow-up of 15 months. Parental questionnaires at follow-up provided information on inconvenience caused by warts and any treatments used. Of the 1,134 eligible children, 1,099 (97%) participated, of whom 366 (33%) had cutaneous warts at baseline. Among these children with warts, loss to follow-up was 9% and the response rate to the parental questionnaires was 83%. The complete resolution rate was 52 per 100 person-years at risk (95% CI, 44-60). Younger age (hazard ratio = 1.1 per year decrease; 95% CI, 1.0-1.2) and non-Caucasian skin type (hazard ratio = 2.0; 95% CI, 1.3-2.9) increased the likelihood of resolution. During follow-up, 38% of children with warts at baseline treated their warts: 18% used over-the-counter treatment only, 15% used a family physician-provided treatment only, and 5% used both. Children were more likely to initiate treatment if the warts measured at least 1 cm in diameter (odds ratio = 3.2; 95% CI, 1.9-5.3) and especially if parents reported that the warts caused inconvenience (odds ratio = 38; 95% CI, 16-90). One-half of primary schoolchildren with warts will be free of warts within 1 year. Young age and non-Caucasian skin type enhance resolution. Children with large or inconvenient warts are more likely to start treatment. These findings will be useful in the process of shared decision making with parents and children.

  3. Diagnostic microRNA profiling in cutaneous T-cell lymphoma (CTCL)

    PubMed Central

    Ralfkiaer, Ulrik; Hagedorn, Peter H.; Bangsgaard, Nannie; Løvendorf, Marianne B.; Ahler, Charlotte B.; Svensson, Lars; Kopp, Katharina L.; Vennegaard, Marie T.; Lauenborg, Britt; Zibert, John R.; Krejsgaard, Thorbjørn; Bonefeld, Charlotte M.; Søkilde, Rolf; Gjerdrum, Lise M.; Labuda, Tord; Mathiesen, Anne-Merete; Grønbæk, Kirsten; Wasik, Mariusz A.; Sokolowska-Wojdylo, Malgorzata; Queille-Roussel, Catherine; Gniadecki, Robert; Ralfkiaer, Elisabeth; Geisler, Carsten; Litman, Thomas; Woetmann, Anders; Glue, Christian; Røpke, Mads A.; Skov, Lone

    2011-01-01

    Cutaneous T-cell lymphomas (CTCLs) are the most frequent primary skin lymphomas. Nevertheless, diagnosis of early disease has proven difficult because of a clinical and histologic resemblance to benign inflammatory skin diseases. To address whether microRNA (miRNA) profiling can discriminate CTCL from benign inflammation, we studied miRNA expression levels in 198 patients with CTCL, peripheral T-cell lymphoma (PTL), and benign skin diseases (psoriasis and dermatitis). Using microarrays, we show that the most induced (miR-326, miR-663b, and miR-711) and repressed (miR-203 and miR-205) miRNAs distinguish CTCL from benign skin diseases with > 90% accuracy in a training set of 90 samples and a test set of 58 blinded samples. These miRNAs also distinguish malignant and benign lesions in an independent set of 50 patients with PTL and skin inflammation and in experimental human xenograft mouse models of psoriasis and CTCL. Quantitative (q)RT-PCR analysis of 103 patients with CTCL and benign skin disorders validates differential expression of 4 of the 5 miRNAs and confirms previous reports on miR-155 in CTCL. A qRT-PCR–based classifier consisting of miR-155, miR-203, and miR-205 distinguishes CTCL from benign disorders with high specificity and sensitivity, and with a classification accuracy of 95%, indicating that miRNAs have a high diagnostic potential in CTCL. PMID:21865341

  4. Primary cutaneous cryptococcosis caused by Cryptococcus gattii in an immunocompetent host.

    PubMed

    Leão, Carlos Alberto; Ferreira-Paim, Kennio; Andrade-Silva, Leonardo; Mora, Delio Jose; da Silva, Paulo Roberto; Machado, Anna Silva; Neves, Priscila Freitas Das; Pena, Giovana Silva; Teixeira, Luciana Silva de Almeida; Silva-Vergara, Mario León

    2011-05-01

    This paper presents the case of a 75-year-old Brazilian man who developed inflammatory skin lesions with nodules and ulcerations on the right forearm after an injury caused by handling barbed-wire and Eucalyptus spp. logs. Histopathological assessment of the lesions showed granulomatous processes with yeasts similar to Cryptococcus spp. Tissue fragments yielded yeasts when cultured that were identified as Cryptococcus gattii VGII through biochemical reactions and URA5-RFLP genotype. No evidence of systemic involvement or any underlying immunosuppressive diseases were identified, which supported the diagnosis of primary cutaneous cryptococcosis. After 5 months on therapy with high fluconazole doses, the skin lesions had fully healed.

  5. Bacterial toxins fuel disease progression in cutaneous T-cell lymphoma.

    PubMed

    Willerslev-Olsen, Andreas; Krejsgaard, Thorbjørn; Lindahl, Lise M; Bonefeld, Charlotte Menne; Wasik, Mariusz A; Koralov, Sergei B; Geisler, Carsten; Kilian, Mogens; Iversen, Lars; Woetmann, Anders; Odum, Niels

    2013-08-14

    In patients with cutaneous T-cell lymphoma (CTCL) bacterial infections constitute a major clinical problem caused by compromised skin barrier and a progressive immunodeficiency. Indeed, the majority of patients with advanced disease die from infections with bacteria, e.g., Staphylococcus aureus. Bacterial toxins such as staphylococcal enterotoxins (SE) have long been suspected to be involved in the pathogenesis in CTCL. Here, we review links between bacterial infections and CTCL with focus on earlier studies addressing a direct role of SE on malignant T cells and recent data indicating novel indirect mechanisms involving SE- and cytokine-driven cross-talk between malignant- and non-malignant T cells.

  6. Primary cutaneous adenoid cystic carcinoma of the scalp with p16 expression: a case report and review of the literature.

    PubMed

    Morrison, Annie O; Gardner, Jerad M; Goldsmith, Stuart M; Parker, Douglas C

    2014-09-01

    Adenoid cystic carcinoma (ACC) is a rare carcinoma that typically arises in salivary glands but can also occur in other sites including skin. Primary salivary ACC is a locally aggressive tumor characterized by local recurrence and late metastasis. Primary cutaneous ACC is found predominately on the scalp and is more indolent than salivary ACC; and, despite a high incidence of local recurrence, metastases are exceedingly rare. A 62-year-old white male presented with a 6-mm mobile, blue-tinted nodule on the left mid scalp unchanged for several years. The histopathological findings of an excisional biopsy were diagnostic for a primary cutaneous ACC. Immunohistochemistry demonstrated focal positivity for p16. Primary cutaneous ACC is a rare malignancy that should be considered in the differential diagnosis of adnexal neoplasms and, when occurring on the head and neck, must be distinguished from cutaneous involvement by salivary ACC. The majority of reported salivary ACC with p16 protein expression were not positive for high-risk human papilloma virus by in situ hybridization. Immunostaining for p16 has previously been reported in salivary gland ACC. This is the first report in the English literature of p16 immunoexpression in primary cutaneous ACC.

  7. MULTICENTRIC T-CELL LYMPHOMA AND CUTANEOUS HEMANGIOSARCOMA IN A CAPTIVE CHEETAH (ACINONYX JUBATUS).

    PubMed

    Lindemann, Dana M; Carpenter, James W; Nietfeld, Jerome C; Gonzalez, Estehela; Hallman, Mackenzie; Hause, Ben M

    2015-12-01

    A 13-yr-old intact male cheetah (Acinonyx jubatus) presented for evaluation after a 4-mo history of intermittent lethargy and increased expiratory effort. The clinical signs were initially noted after the diagnosis and death of its 13-yr-old male sibling with solitary hepatic T-cell lymphoma. Physical examination findings included thin body condition, harsh lung sounds, peripheral lymphadenopathy, and a cutaneous mass on the right medial tarsus and scrotum. Excisional biopsies diagnosed well-differentiated cutaneous hemangiosarcomas. Thoracic radiographs revealed a cranial mediastinal mass. Complete blood count and serum biochemical analyses showed a leukocytosis with persistent lymphocytosis, progressive azotemia, and markedly elevated alkaline phosphatase. Because of the cheetah's declining quality of life, euthanasia was elected. Postmortem examination, histopathology, and immunohistochemical staining revealed multicentric T-cell lymphoma. Feline leukemia virus (FeLV) enzyme-linked immunosorbent assay, FeLV polymerase chain reaction (whole blood), and viral metagenomic analysis were negative. This is the first case of cutaneous hemangiosarcoma and multicentric T-cell lymphoma reported in a FeLV-negative cheetah.

  8. Modern Radiation Therapy for Primary Cutaneous Lymphomas: Field and Dose Guidelines From the International Lymphoma Radiation Oncology Group

    SciTech Connect

    Specht, Lena; Dabaja, Bouthaina; Illidge, Tim; Wilson, Lynn D.; Hoppe, Richard T.

    2015-05-01

    Primary cutaneous lymphomas are a heterogeneous group of diseases. They often remain localized, and they generally have a more indolent course and a better prognosis than lymphomas in other locations. They are highly radiosensitive, and radiation therapy is an important part of the treatment, either as the sole treatment or as part of a multimodality approach. Radiation therapy of primary cutaneous lymphomas requires the use of special techniques that form the focus of these guidelines. The International Lymphoma Radiation Oncology Group has developed these guidelines after multinational meetings and analysis of available evidence. The guidelines represent an agreed consensus view of the International Lymphoma Radiation Oncology Group steering committee on the use of radiation therapy in primary cutaneous lymphomas in the modern era.

  9. Total Skin Electron Therapy for Cutaneous T-Cell Lymphoma Using a Modern Dual-Field Rotational Technique

    SciTech Connect

    Heumann, Thatcher R.; Esiashvili, Natia; Parker, Sareeta; Switchenko, Jeffrey M.; Dhabbaan, Anees; Goodman, Michael; Lechowicz, Mary Jo; Flowers, Christopher R.; Khan, Mohammad K.

    2015-05-01

    Purpose: To report our experience with rotational total skin electron irradiation (RTSEI) in cutaneous T-cell lymphoma (CTCL), and to examine response by disease stage and race. Methods and Materials: We reviewed our outcomes for 68 CTCL patients who received RTSEI (≥30 Gy) from 2000 to 2013. Primary outcomes were complete clinical response (CCR), recurrence-free survival (RFS), and overall survival (OS). Using log–rank tests and Cox proportional hazards, OS and RFS were compared across tumor stages at time of RTSEI with further racial subgroup analysis. Results: Median age at diagnosis and at time of radiation was 52 and 56 years, respectively. Median follow-up was 5.1 years, 49% were African American, and 49% were female. At time of treatment, 18, 37, and 13 patients were T stage 2, 3, and 4, respectively. At 6 weeks after RTSEI, overall CCR was 82% (88%, 83%, and 69% for T2, T3, and T4, respectively). Median RFS was 11 months for all patients and 14, 10, and 12 months for stage T2, T3, and T4, respectively. Tumor stage was not associated with RFS or CCR. Maintenance therapy after RTSEI was associated with improved RFS in both crude and multivariable analysis, controlling for T stage. Median OS was 76 months (91 and 59 months for T3 and T4, respectively). With the exception of improved OS in African Americans compared with whites at stage T2, race was not associated with CCR, RFS, or OS. Conclusions: These results represent the largest RTSEI clinical outcomes study in the modern era using a dual-field rotational technique. Our observed response rates match or improve upon the standard set by previous outcome studies using conventional TSEI techniques, despite a large percentage of advanced CTCL lesions in our cohort. We found that clinical response after RTSEI did not seem to be affected by T stage or race.

  10. Total skin electron therapy for cutaneous T-cell lymphoma using a modern dual-field rotational technique.

    PubMed

    Heumann, Thatcher R; Esiashvili, Natia; Parker, Sareeta; Switchenko, Jeffrey M; Dhabbaan, Anees; Goodman, Michael; Lechowicz, Mary Jo; Flowers, Christopher R; Khan, Mohammad K

    2015-05-01

    To report our experience with rotational total skin electron irradiation (RTSEI) in cutaneous T-cell lymphoma (CTCL), and to examine response by disease stage and race. We reviewed our outcomes for 68 CTCL patients who received RTSEI (≥ 30 Gy) from 2000 to 2013. Primary outcomes were complete clinical response (CCR), recurrence-free survival (RFS), and overall survival (OS). Using log-rank tests and Cox proportional hazards, OS and RFS were compared across tumor stages at time of RTSEI with further racial subgroup analysis. Median age at diagnosis and at time of radiation was 52 and 56 years, respectively. Median follow-up was 5.1 years, 49% were African American, and 49% were female. At time of treatment, 18, 37, and 13 patients were T stage 2, 3, and 4, respectively. At 6 weeks after RTSEI, overall CCR was 82% (88%, 83%, and 69% for T2, T3, and T4, respectively). Median RFS was 11 months for all patients and 14, 10, and 12 months for stage T2, T3, and T4, respectively. Tumor stage was not associated with RFS or CCR. Maintenance therapy after RTSEI was associated with improved RFS in both crude and multivariable analysis, controlling for T stage. Median OS was 76 months (91 and 59 months for T3 and T4, respectively). With the exception of improved OS in African Americans compared with whites at stage T2, race was not associated with CCR, RFS, or OS. These results represent the largest RTSEI clinical outcomes study in the modern era using a dual-field rotational technique. Our observed response rates match or improve upon the standard set by previous outcome studies using conventional TSEI techniques, despite a large percentage of advanced CTCL lesions in our cohort. We found that clinical response after RTSEI did not seem to be affected by T stage or race. Published by Elsevier Inc.

  11. Total Skin Electron Therapy for Cutaneous T-Cell Lymphoma Using a Modern Dual-Field Rotational Technique

    PubMed Central

    Heumann, Thatcher R.; Esiashvili, Natia; Parker, Sareeta; Switchenko, Jeffrey M.; Dhabbaan, Anees; Goodman, Michael; Lechowicz, Mary Jo; Flowers, Christopher R.; Khan, Mohammad K.

    2016-01-01

    Purpose To report our experience with rotational total skin electron irradiation (RTSEI) in cutaneous T-cell lymphoma (CTCL), and to examine response by disease stage and race. Methods and Materials We reviewed our outcomes for 68 CTCL patients who received RTSEI (≥30 Gy) from 2000 to 2013. Primary outcomes were complete clinical response (CCR), recurrence-free survival (RFS), and overall survival (OS). Using log–rank tests and Cox proportional hazards, OS and RFS were compared across tumor stages at time of RTSEI with further racial subgroup analysis. Results Median age at diagnosis and at time of radiation was 52 and 56 years, respectively. Median follow-up was 5.1 years, 49% were African American, and 49% were female. At time of treatment, 18, 37, and 13 patients were T stage 2, 3, and 4, respectively. At 6 weeks after RTSEI, overall CCR was 82% (88%, 83%, and 69% for T2, T3, and T4, respectively). Median RFS was 11 months for all patients and 14, 10, and 12 months for stage T2, T3, and T4, respectively. Tumor stage was not associated with RFS or CCR. Maintenance therapy after RTSEI was associated with improved RFS in both crude and multivariable analysis, controlling for T stage. Median OS was 76 months (91 and 59 months for T3 and T4, respectively). With the exception of improved OS in African Americans compared with whites at stage T2, race was not associated with CCR, RFS, or OS. Conclusions These results represent the largest RTSEI clinical outcomes study in the modern era using a dual-field rotational technique. Our observed response rates match or improve upon the standard set by previous outcome studies using conventional TSEI techniques, despite a large percentage of advanced CTCL lesions in our cohort. We found that clinical response after RTSEI did not seem to be affected by T stage or race. PMID:25670538

  12. Cutaneous T-Cell Lymphoma: A Review with a Focus on Targeted Agents.

    PubMed

    Devata, Sumana; Wilcox, Ryan A

    2016-06-01

    Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of extranodal lymphomas involving the skin. Diagnosis of the two main subtypes of CTCL-mycosis fungoides (MF) and Sézary syndrome (SS)-is based on the International Society for Cutaneous Lymphomas/European Organization for Research and Treatment of Cancer (ISCL/EORTC) classification system, which utilizes clinical, histopathological, molecular biologic, and immunopathologic features. Risk stratification, based on TNMB (tumor, node, metastasis, and blood) staging, provides prognostic information, with limited-stage disease conferring the longest median overall survival. Skin-directed therapies are preferred in the management of limited-stage disease, whereas advanced-stage disease requires systemic therapies. As the mechanisms of CTCL pathogenesis are increasingly understood, new monoclonal antibodies, checkpoint inhibitors, immunomodulatory agents, and small molecules are under investigation and may provide additional therapeutic options for those with advanced CTCL. This review examines the current landscape of targeted therapies in the treatment of CTCLs.

  13. Somatostatin inhibits activation of dorsal cutaneous primary afferents induced by antidromic stimulation of primary afferents from an adjacent thoracic segment in the rat.

    PubMed

    Guo, Yuan; Yao, Fan-Rong; Cao, Dong-Yuan; Pickar, Joel G; Zhang, Qi; Wang, Hui-Sheng; Zhao, Yan

    2008-09-10

    To investigate the effect of somatostatin on the cross-excitation between adjacent primary afferent terminals in the rats, we recorded single unit activity from distal cut ends of dorsal cutaneous branches of the T10 and T12 spinal nerves in response to antidromic stimulation of the distal cut end of the T11 dorsal root in the presence and absence of somatostatin and its receptor antagonist applied to the receptive field of the recorded nerve. Afferent fibers were classified based upon their conduction velocity. Mean mechanical thresholds decreased and spontaneous discharge rates increased significantly in C and Adelta but not Abeta fibers of the T10 and T12 spinal nerves in both male and female rats following antidromic electrical stimulation (ADES) of the dorsal root from adjacent spinal segment (DRASS) indicating cross-excitation of thin fiber afferents. The cross-excitation was not significantly different between male and female rats. Microinjection of somatostatin into the receptive field of recorded units inhibited the cross-excitation. This inhibitory effect, in turn, was reversed by the somatostation receptor antagonist cyclo-somatostatin (c-SOM). Application of c-SOM alone followed by ADES of DRASS significantly decreased the mechanical thresholds and increased the discharge rates of C and Adelta fibers, indicating that endogenous release of somatostatin plays a tonic inhibitory role on the cross-excitation between peripheral nerves. These results suggest that somatostatin could inhibit the cross-excitation involved in peripheral hyperalgesia and have a peripheral analgesic effect.

  14. Primary localized cutaneous amyloidosis with lichen and poikiloderma-like lesions and an excellent response to systemic acitretin*

    PubMed Central

    MA, Han; Su, Xiangyang; Zhu, Guoxing; Yin, Songchao; Lu, Chun; Lai, Wei

    2016-01-01

    Primary localized cutaneous amyloidosis is a skin-limited amyloidosis that does not involve internal organs. It is clinically subclassified into 3 general categories and some rare variants. However, there is considerable overlap within the classification. Though there are a variety of therapeutic measures, the treatment is often unsatisfactory, particularly when the disease is severe and extensive. We describe a rare case of primary localized cutaneous amyloidosis with lichen and poikiloderma-like lesions that showed an excellent response to systemic acitretin. PMID:27828646

  15. Therapy-related myelodysplastic syndrome in a case of cutaneous adult T-cell lymphoma.

    PubMed

    Fukuda, Naofumi; Shinohara, Kenji; Ota, Ituro; Muraki, Kazuhiko; Shimohakamada, Yoko

    2002-01-01

    We report a case of therapy-related myelodysplastic syndrome (t-MDS) in adult T-cell lymphoma. A 69-year-old man suffered from cutaneous adult T-cell lymphoma, which was treated with radiation to the skin and combination chemotherapy of CHOP-V-MMV and VEPA-B. After 14 months of these therapies, anemia and thrombocytopenia appeared, and bone marrow aspiration smears showed immature myeloblasts, dysplastic erythroblasts, and micromegakaryocytes. Therapy-related MDS of refractory anemia with an excess of blasts was diagnosed. Cytogenetic study of the bone marrow cells showed 5q- and additional abnormalities. Rearrangement of the MLL gene was observed in the bone marrow cells. Mutations of N-ras codons at 12,13, and 61, p53 tumor suppressor gene, and monoclonal integration of human T-lymphotrophic virus -1 provirus DNA were not observed in the bone marrow cells. The patient died of pneumonia 21 months after diagnosis of cutaneous adult T-cell lymphoma.

  16. Inactivation of RUNX3/p46 Promotes Cutaneous T-Cell Lymphoma.

    PubMed

    Haider, Ahmed; Steininger, Anne; Ullmann, Reinhard; Hummel, Michael; Dimitrova, Lora; Beyer, Marc; Vandersee, Staffan; Lenze, Dido; Sterry, Wolfram; Assaf, Chalid; Möbs, Markus

    2016-11-01

    The key role of RUNX3 in physiological T-cell differentiation has been extensively documented. However, information on its relevance for the development of human T-cell lymphomas or leukemias is scarce. Here, we show that alterations of RUNX3 by either heterozygous deletion or methylation of its distal promoter can be observed in the tumor cells of 15 of 21 (71%) patients suffering from Sézary syndrome, an aggressive variant of cutaneous T-cell lymphoma. As a consequence, mRNA levels of RUNX3/p46, the isoform controlled by the distal promoter, are significantly lower in Sézary syndrome tumor cells. Re-expression of RUNX3/p46 reduces cell viability and promotes apoptosis in a RUNX3/p46(low) cell line of cutaneous T-cell lymphoma. Based on this, we present evidence that RUNX3 can act as a tumor suppressor in a human T-cell malignancy and suggest that this effect is predominantly mediated through transcripts from its distal promoter, in particular RUNX3/p46.

  17. Canine epitheliotropic cutaneous T-cell lymphoma: an investigation of T-cell receptor immunophenotype, lesion topography and molecular clonality.

    PubMed

    Moore, Peter F; Affolter, Verena K; Graham, Petra S; Hirt, Barbara

    2009-10-01

    Canine epitheliotropic cutaneous T-cell lymphoma (CTCL) is a spontaneous neoplasm of the skin and mucous membranes of aged dogs. The WHO classification of tumours of haematopoietic and lymphoid tissues in human beings recognizes three forms of cutaneous epitheliotropic CTCL: mycosis fungoides (MF), Sézary syndrome and pagetoid reticulosis. In this series of dogs (n = 56), there were 39 cases of MF, 16 cases of pagetoid reticulosis and a single case of Sézary syndrome. Epitheliotropic T cells in CTCL lesions expressed CD8 in 44 of 55 dogs (80%) assessed; neither CD4 nor CD8 was expressed in the remainder. This contrasts with human MF in which alphabeta T-cell receptors (TCR) and CD4 are dominantly expressed. Molecular clonality assessment of canine epitheliotropic CTCL utilizing PCR primers specific for canine TCR gamma (TCRG) was performed. Of the 45 canine cases assessed, TCRG monoclonality was detected in 36 cases (80%). TCR typing of canine epitheliotropic CTCL revealed that TCRgammadelta was expressed in 60% of cases, including all cases of canine pagetoid reticulosis assessed. Either muco-cutaneous junctions or tissues of the oral cavity were the sites of lesions in 32 dogs (57%) with epitheliotropic CTCL. Analysis of the topography of lesions revealed an association with TCR type. If epitheliotropic CTCL lesions occurred in both locations, T cells were more likely to express TCRgammadelta (gammadelta : alphabeta = 2.0). These data establish that canine skin trafficking T cells have a far wider range than previously thought; this includes tongue, gingival, buccal and palatine mucosae.

  18. Global transcriptome analysis and enhancer landscape of human primary T follicular helper and T effector lymphocytes

    PubMed Central

    Weinstein, Jason S.; Lezon-Geyda, Kimberly; Maksimova, Yelena; Craft, Samuel; Zhang, Yaoping; Su, Mack; Schulz, Vincent P.

    2014-01-01

    T follicular helper (Tfh) cells are a subset of CD4+ T helper cells that migrate into germinal centers and promote B-cell maturation into memory B and plasma cells. Tfh cells are necessary for promotion of protective humoral immunity following pathogen challenge, but when aberrantly regulated, drive pathogenic antibody formation in autoimmunity and undergo neoplastic transformation in angioimmunoblastic T-cell lymphoma and other primary cutaneous T-cell lymphomas. Limited information is available on the expression and regulation of genes in human Tfh cells. Using a fluorescence-activated cell sorting–based strategy, we obtained primary Tfh and non-Tfh T effector cells from tonsils and prepared genome-wide maps of active, intermediate, and poised enhancers determined by chromatin immunoprecipitation–sequencing, with parallel transcriptome analyses determined by RNA sequencing. Tfh cell enhancers were enriched near genes highly expressed in lymphoid cells or involved in lymphoid cell function, with many mapping to sites previously associated with autoimmune disease in genome-wide association studies. A group of active enhancers unique to Tfh cells associated with differentially expressed genes was identified. Fragments from these regions directed expression in reporter gene assays. These data provide a significant resource for studies of T lymphocyte development and differentiation and normal and perturbed Tfh cell function. PMID:25331115

  19. Thin and thick primary cutaneous melanomas reveal distinct patterns of somatic copy number alterations

    PubMed Central

    Apollo, Alessandro; Pescucci, Chiara; Licastro, Danilo; Urso, Carmelo; Gerlini, Gianni; Borgognoni, Lorenzo; Luzzatto, Lucio; Stecca, Barbara

    2016-01-01

    Cutaneous melanoma is one of the most aggressive type of skin tumor. Early stage melanoma can be often cured by surgery; therefore current management guidelines dictate a different approach for thin (<1mm) versus thick (>4mm) melanomas. We have carried out whole-exome sequencing in 5 thin and 5 thick fresh-frozen primary cutaneous melanomas. Unsupervised hierarchical clustering analysis of somatic copy number alterations (SCNAs) identified two groups corresponding to thin and thick melanomas. The most striking difference between them was the much greater abundance of SCNAs in thick melanomas, whereas mutation frequency did not significantly change between the two groups. We found novel mutations and focal SCNAs in genes that are embryonic regulators of axon guidance, predominantly in thick melanomas. Analysis of publicly available microarray datasets provided further support for a potential role of Ephrin receptors in melanoma progression. In addition, we have identified a set of SCNAs, including amplification of BRAF and ofthe epigenetic modifier EZH2, that are specific for the group of thick melanomas that developed metastasis during the follow-up. Our data suggest that mutations occur early during melanoma development, whereas SCNAs might be involved in melanoma progression. PMID:27095580

  20. Efficacy of Topical Timolol as Primary Monotherapy in Cutaneous Facial Infantile Hemangiomas.

    PubMed

    Ng, Zhi Yang; Kang, Gavin Chun-Wui; Chang, Chun-Shin; Por, Yong Chen

    2016-09-01

    Recent studies have shown that infantile hemangiomas (IHs) undergo a rapid growth phase between 5.5 and 7.5 weeks of life and do not usually proliferate beyond 6 months; growth thereafter is usually proportionate to the child's growth. This review assesses the evidence for topical timolol as primary monotherapy for cutaneous facial IHs before 12 months of age, and to determine the differences in outcome between early (before 6 months) and late initiation (after 6 months) of timolol. A review of English language articles published up to November 2015 was performed using selected key words. Articles identified were further reviewed for relevance. The full text of studies included for final analysis was perused to include pertinent patient details, treatment protocol with timolol, complications (if any) reported, and response to treatment. Four studies met the inclusion criteria. In children before 12 months of age, the efficacy of topical timolol for the treatment of cutaneous facial IHs in achieving clinically significant improvement as defined by a standardized Global Assessment Score score of 3 and above ranged from 47% to 88%. One study also showed that IH regression was greater in patients started on timolol before 6 months of age compared with those started later (P <0.05). Topical timolol initiated in children before 12 months of age appears to be safe and clinically effective. There was insufficient data for detailed analysis of outcomes in patients who commenced treatment before and after 6 months of age.

  1. Fatal primary cutaneous cryptococcosis: case report and review of published literature.

    PubMed

    Liu, Y; Qunpeng, H; Shutian, X; Honglang, X

    2016-11-01

    Cryptococcus is an opportunistic yeast with a worldwide distribution that primarily causes significant infections in immunocompromised individuals, generally by affecting the respiratory tract. But primary cutaneous cryptococcosis (PCC) without systemic infection is rare. We report a case of PCC in a patient with nephrotic syndrome. The 23-year-old man developed severe necrotising cellulitis on both the anterior and posterior of his trunk following a massage. He had been treated with systemic corticosteroids over 20 months for nephrotic syndrome. A skin biopsy of the wound area revealed cutaneous vasculitis and chronic inflammation with yeast-like organisms. Periodic acid-Schiff (PAS) staining indicated that the structures were consistent with Cryptococcus. A Cryptococcus neoformans infection was confirmed by culture. Azole therapy was begun, and the skin ulcers gradually stopped disseminating. However, the patient died following continuous capillary haemorrhage on the 22 day since admission. Cryptococcus is crucial to be considered in the differential diagnosis of subcutaneous necrosis in any patient on immunosuppressive therapy.

  2. Analysis of the BRAF V600E mutation in primary cutaneous melanoma.

    PubMed

    Inumaru, J S S; Gordo, K I F; Fraga Junior, A C; Silva, A M T C; Leal, C B Q S; Ayres, F M; Wastowski, I J; Borges, N F; Saddi, V A

    2014-01-22

    BRAF V600E is the most common mutation in cutaneous melanomas, and has been described in 30-72% of such cases. This mutation results in the substitution of valine for glutamic acid at position 600 of the BRAF protein, which consequently becomes constitutively activated. The present study investigated the BRAF V600E mutation frequency and its clinical implications in a group of 77 primary cutaneous melanoma patients treated in a cancer reference center in Brazil. Mutation analysis was accomplished by polymerase chain reaction, restriction fragment length polymorphism, and automated DNA sequencing. The chi-squared and Fischer exact tests were used for comparative analyses. The BRAF V600E mutation was detected in 54/77 (70.1%) melanoma subjects. However, no statistically significant association was found between the presence of the mutation and clinical or prognostic parameters. Our results demonstrated that the BRAF V600E mutation is a common event in melanomas, representing an important molecular target for novel therapeutic approaches in such tumors.

  3. Natural Course of Cutaneous Warts Among Primary Schoolchildren: A Prospective Cohort Study

    PubMed Central

    Bruggink, Sjoerd C.; Eekhof, Just A. H.; Egberts, Paulette F.; van Blijswijk, Sophie C. E.; Assendelft, Willem J. J.; Gussekloo, Jacobijn

    2013-01-01

    PURPOSE Because cutaneous warts resolve spontaneously and available treatments often fail, family physicians and patients may consider a wait-and-see policy. We examined the natural course of cutaneous warts and treatment decisions in a prospective observational cohort of primary schoolchildren. METHODS We inspected the hands and feet of children aged 4 to 12 years from 3 Dutch primary schools for the presence of warts at baseline and after a mean follow-up of 15 months. Parental questionnaires at follow-up provided information on inconvenience caused by warts and any treatments used. RESULTS Of the 1,134 eligible children, 1,099 (97%) participated, of whom 366 (33%) had cutaneous warts at baseline. Among these children with warts, loss to follow-up was 9% and the response rate to the parental questionnaires was 83%. The complete resolution rate was 52 per 100 person-years at risk (95% CI, 44–60). Younger age (hazard ratio = 1.1 per year decrease; 95% CI, 1.0–1.2) and non-Caucasian skin type (hazard ratio = 2.0; 95% CI, 1.3–2.9) increased the likelihood of resolution. During follow-up, 38% of children with warts at baseline treated their warts: 18% used over-the-counter treatment only, 15% used a family physician–provided treatment only, and 5% used both. Children were more likely to initiate treatment if the warts measured at least 1 cm in diameter (odds ratio = 3.2; 95% CI, 1.9–5.3) and especially if parents reported that the warts caused inconvenience (odds ratio = 38; 95% CI, 16–90). CONCLUSIONS One-half of primary schoolchildren with warts will be free of warts within 1 year. Young age and non-Caucasian skin type enhance resolution. Children with large or inconvenient warts are more likely to start treatment. These findings will be useful in the process of shared decision making with parents and children. PMID:24019275

  4. Early migration of cutaneous lymphocyte-associated antigen (CLA) positive T cells into evolving psoriatic plaques.

    PubMed

    Davison, S C; Ballsdon, A; Allen, M H; Barker, J N

    2001-08-01

    The majority of T cells in lesional psoriatic skin express the skin homing receptor, cutaneous lymphocyte-associated antigen (CLA). We investigated whether this reflects the selective migration of CLA positive cells into evolving psoriatic plaques, consistent with an important role in disease onset, or whether this occurs in the context of an established cutaneous inflammatory response. We identified the advancing edge of plaques in 16 patients with chronic plaque psoriasis using scanning laser Doppler fluxmetry, and performed immunohistochemical analysis of i) lesional psoriatic skin, ii) clinically normal skin immediately in front of the advancing plaque edge, and iii) uninvolved skin distant from the plaque edge. The T-cell infiltrate was characterized using monoclonal antibodies to CD3, CLA and the integrin alphaEbeta7, which is associated with the retention of lymphocytes at mucosal sites. Epithelial proliferation was assessed using a monoclonal antibody to the nuclear proliferation marker Ki67. There was enrichment of CLA positive T cells in evolving psoriatic skin compared to distant, uninvolved skin (mean CLA positive 75.9% vs 47.8%; P<0.003). This accumulation of CLA positive cells occurred before epidermal hyperproliferation was evident, suggesting that this population of cells plays an important, early role in disease pathogenesis. Established lesional psoriatic skin contained a mixed infiltrate of CLA positive (mean 53.2%) and alphaEbeta7 positive (mean 18.2%) cells, suggesting less tissue-specific T-cell infiltration, although an additional, specific role for alphaEbeta7 in cutaneous inflammation cannot be excluded. Furthermore, this study has highlighted scanning laser Doppler fluxmetry as a useful investigative tool, permitting analysis of the earliest and therefore potentially most important changes in psoriatic plaque formation.

  5. Overview of cutaneous T-cell lymphoma: prognostic factors and novel therapeutic approaches.

    PubMed

    Foss, Francine

    2003-01-01

    The cutaneous T-cell lymphomas (CTCL) comprise a heterogeneous group of entities. The WHO classification distinguishes indolent low-risk entities, including mycosis fungoides/Sézary syndrome (MF/SS), from aggressive entities, including peripheral T-cell lymphoma and its variants and HTLV-1 associated acute T-cell leukemia/lymphoma. Mycosis fungoides represents the most benign of the cutaneous T-cell lymphomas, with 10-year relative survival ranging from 100% to 41%, depending on the degree of skin involvement. Probability of progression to extracutaneous disease within 20 years of diagnosis can be up to 40%, depending on stage. Treatment strategies for early stage CTCL include topical therapies with or without interferon-alpha or oral agents, while advanced stage patients often progress and are treated with chemotherapy and novel agents. Multiagent cytotoxic regimens are palliative with no demonstrated survival benefit. Among the novel therapies for CTCL is bexarotene, a retinoid X-receptor (RXR)-selective agonist, which has demonstrated efficacy in advanced refractory CTCL. Other novel agents include the interleukin (IL)-2 fusion toxin (ONTAK), pentostatin (a potent adenosine deaminase inhibitor), histone deacetylase inhibitors such as depsipeptide, NF-kappaB inhibitors, cytokine receptor antagonists, immunomodulatory therapies and allogeneic stem cell therapy. The value of new therapeutic approaches to CTCL urgently needs to be assessed.

  6. Malignant T cells secrete galectins and induce epidermal hyperproliferation and disorganized stratification in a skin model of cutaneous T-cell lymphoma.

    PubMed

    Thode, Christenze; Woetmann, Anders; Wandall, Hans H; Carlsson, Michael C; Qvortrup, Klaus; Kauczok, Claudia S; Wobser, Marion; Printzlau, Andreas; Ødum, Niels; Dabelsteen, Sally

    2015-01-01

    Cutaneous T-cell lymphomas (CTCLs) are the most common primary skin lymphomas, which are characterized by an accumulation of malignant T cells in the skin. The early lesion resembles both clinically and histologically benign inflammatory disorders and also presents with hyperproliferative epidermis and T-cell infiltration. Despite considerable progress in understanding the molecular mechanisms involved in the malignant transformation of T cells, the causes of the morphological and histopathological features of the disease are largely unknown. We used an organotypic model of CTCL to show that malignant T cells through the secretion of galectin-1 and -3 stimulate vigorous growth of keratinocytes. In parallel, malignant T cells induce disorganized keratinocyte stratification, resembling the early hyperproliferative stage of CTCL. We also observed a loss of attachment between the epithelial and mesenchymal compartments. In addition, hyperproliferation was followed by a downregulation of differentiation markers, such as keratin 10 and involucrin, and a decrease in barrier formation. In conclusion, we provide evidence that malignant T cells orchestrate the histopathological epidermal changes seen in CTCL.

  7. Staphylococcal enterotoxin A (SEA) stimulates STAT3 activation and IL-17 expression in cutaneous T-cell lymphoma

    PubMed Central

    Willerslev-Olsen, Andreas; Krejsgaard, Thorbjørn; Lindahl, Lise M.; Litvinov, Ivan V.; Fredholm, Simon; Petersen, David L.; Nastasi, Claudia; Gniadecki, Robert; Mongan, Nigel P.; Sasseville, Denis; Wasik, Mariusz A.; Bonefeld, Charlotte M.; Geisler, Carsten; Woetmann, Anders; Iversen, Lars; Kilian, Mogens; Koralov, Sergei B.

    2016-01-01

    Cutaneous T-cell lymphoma (CTCL) is characterized by proliferation of malignant T cells in a chronic inflammatory environment. With disease progression, bacteria colonize the compromised skin barrier and half of CTCL patients die of infection rather than from direct organ involvement by the malignancy. Clinical data indicate that bacteria play a direct role in disease progression, but little is known about the mechanisms involved. Here, we demonstrate that bacterial isolates containing staphylococcal enterotoxin A (SEA) from the affected skin of CTCL patients, as well as recombinant SEA, stimulate activation of signal transducer and activator of transcription 3 (STAT3) and upregulation of interleukin (IL)-17 in immortalized and primary patient–derived malignant and nonmalignant T cells. Importantly, SEA induces STAT3 activation and IL-17 expression in malignant T cells when cocultured with nonmalignant T cells, indicating an indirect mode of action. In accordance, malignant T cells expressing an SEA-nonresponsive T-cell receptor variable region β chain are nonresponsive to SEA in monoculture but display strong STAT3 activation and IL-17 expression in cocultures with SEA-responsive nonmalignant T cells. The response is induced via IL-2 receptor common γ chain cytokines and a Janus kinase 3 (JAK3)-dependent pathway in malignant T cells, and blocked by tofacitinib, a clinical-grade JAK3 inhibitor. In conclusion, we demonstrate that SEA induces cell cross talk–dependent activation of STAT3 and expression of IL-17 in malignant T cells, suggesting a mechanism whereby SEA-producing bacteria promote activation of an established oncogenic pathway previously implicated in carcinogenesis. PMID:26738536

  8. Primary Cutaneous Mucormycosis Caused by Rhizopus oryzae: A Case Report and Review of Literature.

    PubMed

    Rodríguez-Lobato, Erika; Ramírez-Hobak, Lourdes; Aquino-Matus, Jorge E; Ramírez-Hinojosa, Juan P; Lozano-Fernández, Víctor H; Xicohtencatl-Cortes, Juan; Hernández-Castro, Rigoberto; Arenas, Roberto

    2017-04-01

    Mucormycosis is an invasive infection caused by opportunistic fungi. Rhizopus, Lichtheimia, Mucor and Rhizomucor are the most common isolated genera. Primary cutaneous mucormycosis is usually related to traumatic injuries, but immunocompromised cases are associated with underlying conditions such as diabetes mellitus and malignancies. The treatment of choice is surgical debridement and liposomal amphotericin B. We present a 40-year-old male with fever and a painful necrotic lesion on the middle back and history of poorly controlled diabetes mellitus. Rhizopus oryzae was isolated and identified using an internal transcribed spacer regions ITS1 and ITS2. An initial good response to treatment was observed; however, 7 days later a diabetic ketoacidosis due to poor adherence to treatment caused a lethal outcome.

  9. Impact of gender and primary tumor location on outcome of patients with cutaneous melanoma.

    PubMed

    S, Voinea; A, Blidaru; E, Panaitescu; A, Sandru

    2016-01-01

    Background. The survival of patients with cutaneous malignant melanoma (MM) depends on multiple factors whose role is continuously updated, as the molecular mechanisms underlying the disease progression are understood. This study intended to assess whether the patient's gender and tumor location affect the disease outcome. Methods. Between 2008 and 2012, 155 patients with cutaneous MM underwent various types of surgeries in our clinic. Patients were staged according to the 2009 TNM classification. There were 90 women and 65 men. Primary tumors were located as it follows head and neck region - 4.5%, limbs - 50.7% and trunk - 44.8%. The disease free and overall survival rates (DFS, OS) were estimated by using the Kaplan-Meier method. Results. Metastases developed in 52.3% of the males and 31.1% of the females (p=0.008). In univariate analysis, distant metastasis risk was significantly higher in men (p = 0.0472 for stage II patients and p = 0.0288 for stage III). In multivariate analysis, male gender almost doubled the risk of relapse (p = 0.044) and death (p = 0.022). Consequently, DFS and OS were significantly higher among females. Primary tumor location seemed to influence the melanoma spreading ability. Half of the trunk MM developed metastases while only a third of limbs MM did. The association between MM location and the recurrence risk was not random (p = 0.033). Conclusions. The patient gender represents an independent prognostic factor for both relapse and death. Although trunk MM had a significantly higher risk of metastasis than limbs MM, the location per se was not an independent prognostic factor for survival (p = 0.078). Abbreviations: MM = malignant melanoma, DFS = disease free survival, OS = overall survival, p = p value, AJCC = American Joint Commission on Cancer, CI = confidence interval.

  10. Systemic Review of Published Reports on Primary Cutaneous Cryptococcosis in Immunocompetent Patients.

    PubMed

    Du, Lin; Yang, Yali; Gu, Julin; Chen, Jianghan; Liao, Wanqing; Zhu, Yuanjie

    2015-08-01

    Primary cutaneous cryptococcosis (PCC) has been confirmed as a distinct clinical entity with secondary cutaneous cryptococcosis from systematic infection since 2003. Although it has been confirmed as a distinct clinical entity, little has progressed on PCC in immunocompetent hosts compared to their immunocompromised counterpart. We reviewed the literature on cases of PCC in immunocompetent patients from 2004 to 2014, and 21 cases from 16 reports were identified. Males are more likely to develop PCC infections, with a ratio of 17:4 male to female. These patients were found to be almost all senior population except for patients from Asia. Asymptomatic or moderate itching manifesting in a painful nodule is the most common presentation, although there is no typical clinical manifestation recorded. Upper limbs are the most common site of infection, accounting for 71.4 % of all patients. Of the 12 identified isolates, 6 strains are identified as C. neoformans, 5 as C. gattii, and 1 as C.laurentii. Fluconazole was used in 10 cases; however, only 80 % of the 10 cases could confirm that fluconazole was effective in clearing the infections. Interestingly although not approved as a treatment option, Itraconazole was effective in the seven cases it was used to treat cryptococcosis, with a dosage range of 100-400 mg/d and duration from 3 to 6 months. Even though the prognosis of these patients was generally good, more data are need to determine which antifungal azole is the better treatment option and whether primary skin infections could disseminate to systematic infection.

  11. Total scalp radiation using image-guided IMRT for progressive cutaneous T cell lymphoma.

    PubMed

    Samant, R S; Fox, G W; Gerig, L H; Montgomery, L A; Allan, D S

    2009-06-01

    Modern radiotherapy has advanced dramatically over the past decade and it is now possible to focus radiotherapy with extreme precision. This allows the radiation dose to be targeted to the area(s) of tumour while sparing adjacent normal tissues even in seemingly complicated and difficult parts of the body. The case report presented here will illustrate how it is possible to irradiate the entire scalp for extensive cutaneous T cell lymphoma while minimising radiotherapy to the underlying brain, orbits and other critical structures.

  12. Cutaneous immunosurveillance by self-renewing dermal γδ T cells

    PubMed Central

    Sumaria, Nital; Roediger, Ben; Qin, Jim; Pinto, Rachel; Cavanagh, Lois L.; Shklovskaya, Elena; Fazekas de St. Groth, Barbara; Triccas, James A.

    2011-01-01

    The presence of γδ T cell receptor (TCR)–expressing cells in the epidermis of mice, termed dendritic epidermal T cells (DETCs), is well established. Because of their strict epidermal localization, it is likely that DETCs primarily respond to epithelial stress, such as infections or the presence of transformed cells, whereas they may not participate directly in dermal immune responses. In this study, we describe a prominent population of resident dermal γδ T cells, which differ from DETCs in TCR usage, phenotype, and migratory behavior. Dermal γδ T cells are radioresistant, cycle in situ, and are partially depend on interleukin (IL)-7, but not IL-15, for their development and survival. During mycobacterial infection, dermal γδ T cells are the predominant dermal cells that produce IL-17. Absence of dermal γδ T cells is associated with decreased expansion in skin draining lymph nodes of CD4+ T cells specific for an immunodominant Mycobacterium tuberculosis epitope. Decreased CD4+ T cell expansion is related to a reduction in neutrophil recruitment to the skin and decreased BCG shuttling to draining lymph nodes. Thus, dermal γδ T cells are an important part of the resident cutaneous immunosurveillance program. Our data demonstrate functional specialization of T cells in distinct microcompartments of the skin. PMID:21339323

  13. Results of a Phase II Trial of Brentuximab Vedotin for CD30+ Cutaneous T-Cell Lymphoma and Lymphomatoid Papulosis

    PubMed Central

    Duvic, Madeleine; Tetzlaff, Michael T.; Gangar, Pamela; Clos, Audra L.; Sui, Dawen; Talpur, Rakhshandra

    2015-01-01

    Purpose Brentuximab vedotin, a monoclonal antibody (cAC10) conjugated to monomethyl auristatin E, targets CD30+ receptors. This phase II open-label trial was conducted to evaluate safety and efficacy in CD30+ cutaneous T-cell lymphomas. Patients and Methods Forty-eight patients with CD30+ lymphoproliferative disorders or mycosis fungoides (MF) received an infusion of 1.8 mg/kg every 21 days. Results Forty-eight evaluable patients (22 women and 26 men; median age, 59.5 years) had an overall response rate of 73% (95% CI, 60% to 86%; 35 of 48 patients) and complete response rate of 35% (95% CI, 22% to 49%; 17 of 48 patients). Fifteen (54%; 95% CI, 31% to 59%) of 28 patients with MF responded, independent of CD30 expression. In patients with MF/Sézary syndrome, the overall response rate was 50% (five of 10 patients) in patients with low CD30 expression (< 10%), 58% (seven of 12 patients) in patients with medium expression (10% to 50%), and 50% (three of six patients) in patients with high expression (≥ 50%). Time to response was 12 weeks (range, 3 to 39 weeks), and duration of response was 32 weeks (range, 3 to 93 weeks). All patients with lymphomatoid papulosis (n = 9) and primary cutaneous anaplastic T-cell lymphomas (n = 2) responded; time to response was 3 weeks (range, 3 to 9 weeks), and median duration of response was 26 weeks (range, 6 to 44 weeks). Soluble baseline CD30 levels were lowest in complete responders (P = .036). Grade 1 to 2 peripheral neuropathy was observed in 65% of patients (95% CI, 52% to 79%; 31 of 48 patients), is still ongoing in 55% of patients (95% CI, 41% to 69%; 17 of 31 patients), and resolved in 45% of patients (95% CI, 31% to 59%; 14 of 31 patients), with a median time to resolution of 41.5 weeks. Grade 3 to 4 events were neutropenia (n = 5), nausea (n = 2), chest pain (n = 2), deep vein thrombosis (n = 1), transaminitis (n = 1), and dehydration (n = 1). Dose reductions to 1.2 mg/kg were instituted as a result of grade 2 neuropathy

  14. Quantitative flow cytometric identification of aberrant T cell clusters in erythrodermic cutaneous T cell lymphoma. Implications for staging and prognosis.

    PubMed

    Horna, Pedro; Deaver, Darcie M; Qin, Dahui; Moscinski, Lynn C; Sotomayor, Eduardo M; Glass, L Frank; Sokol, Lubomir

    2014-05-01

    Assessment of peripheral blood tumour burden for staging of cutaneous T cells lymphoma is most often accomplished by flow cytometry (FC) using various non-standarised strategies. We report the results of calculating absolute Sezary cell counts (SCCs) by FC, based on the identification of aberrant T cell clusters on a virtual 6-dimensional space and independently of the expected immunophenotype (6D-FC SCC). 6D-FC SCCs were calculated on 65 peripheral blood specimens from 28 patients with erythrodermic cutaneous T cells lymphoma (stage III or IV). Comparisons were made with recommended FC strategies and correlations with overall mortality were studied. At first visit, 17 of 28 patients (61%) had 6D-FC SCCs meeting current criteria for Stage IV disease (≥1000 SC/μL); while only 2 patients (7%) met Stage IV criteria on other tissues. As defined by comprehensive staging using clinicomorphological criteria and 6D-FC SCCs, Stage IV disease identified a subgroup of patients with worse overall survival (p=0.0227). Residual non-aberrant CD4 T cells were markedly decreased in Stage IV disease (p=0.018). Among 65 specimens, discrepancies were observed between 6D-FC SCCs and usual FC thresholds for Stage IV disease, namely a CD4:CD8 ratio ≥10:1 (9 discrepancies, 14%), and ≥40% aberrant CD4 T cells (4 discrepancies, 6%). Surprisingly, 8 cases (12%) from 6 patients exhibited two distinctively separate clusters of aberrant CD4 T cells with different CD7 and/or CD26 expression. Visual 6-dimensional identification of aberrant T cell clusters by FC allows for the calculation of clinically significant SCCs. Simplified gating strategies and relative quantitative values might underestimate the immunophenotypical complexity of Sezary cells.

  15. New entity, definition and diagnostic criteria of cutaneous adult T-cell leukemia/lymphoma: human T-lymphotropic virus type 1 proviral DNA load can distinguish between cutaneous and smoldering types.

    PubMed

    Amano, Masahiro; Kurokawa, Motoki; Ogata, Katsumi; Itoh, Hiroshi; Kataoka, Hiroaki; Setoyama, Mitsuru

    2008-05-01

    Adult T-cell leukemia/lymphoma (ATLL) has been divided into four subtypes up to now: (i) acute; (ii) lymphoma; (iii) chronic; and (iv) smoldering. Skin lesion(s) may be present and the cases showing less than 5% abnormal T-lymphocytes in peripheral blood without involvement of other organs, have been classified as smoldering ATLL. However, this type of ATLL with skin manifestations had a worse prognosis than that without skin lesions. This study aimed to define and distinguish cutaneous ATLL lacking nodal lymphoma and leukemic change from smoldering ATLL. We propose an entity of cutaneous ATLL, which has less than 5% abnormal T lymphocyte in peripheral blood, a normal lymphocyte count (i.e. <4 x 10(9)/L), no hypercalcemia and lactate dehydrogenase values of up to 1.5 times the normal upper limit. At least one of the histologically proven skin lesions should be present accompanying monoclonal integration of human T-cell lymphotropic virus type 1 (HTLV-1) proviral DNA in the skin lesion. Blood samples were collected from 41 HTLV-1-infected patients, 21 asymptomatic carriers, 16 patients with cutaneous ATLL and four patients with smoldering ATLL. HTLV-1 proviral loads, soluble interleukin-2 receptors and other parameters were examined in each case. HTLV-1 proviral DNA loads in smoldering ATLL group are significantly higher than those in asymptomatic carrier and cutaneous ATLL group. Cutaneous ATLL may be a distinct entity that should be separated from smoldering ATLL clinically and virologically.

  16. DNA methylation Profiles in Primary Cutaneous Melanomas are Associated with Clinically Significant Pathologic Features

    PubMed Central

    Thomas, Nancy E.; Slater, Nathaniel A.; Edmiston, Sharon N.; Zhou, Xin; Kuan, Pei-Fen; Groben, Pamela A.; Carson, Craig C.; Hao, Honglin; Parrish, Eloise; Moschos, Stergios J.; Berwick, Marianne; Ollila, David W.; Conway, Kathleen

    2014-01-01

    Summary DNA methylation studies have elucidated a methylation signature distinguishing primary melanomas from benign nevi and provided new insights about genes that may be important in melanoma development. However, it is unclear whether methylation differences among primary melanomas are related to tumor pathologic features with known clinical significance. We utilized the Illumina Golden Gate Cancer Panel array to investigate the methylation profiles of 47 primary cutaneous melanomas. Array-wide methylation patterns revealed a positive association of methylation with Breslow thickness and mutated BRAF, a negative association with mitotic rate, and a weak association with ulceration. Hierarchical clustering on CpG sites exhibiting the most variable methylation (n=235) divided the melanoma samples into three clusters, including a highly-methylated cluster that was positively associated with Breslow thickness and an intermediately-methylated cluster associated with Breslow thickness and mitotic rate. Our findings provide support for the existence of methylation-defined subsets in melanomas, with increased methylation associated with Breslow thickness. PMID:24986547

  17. Primary cutaneous spindle cell B cell lymphoma: A report of three cases and review of the literature.

    PubMed

    Magro, Cynthia M; Momtahen, Shabnam

    2017-04-01

    Primary cutaneous spindle cell lymphoma is a rare variant of primary cutaneous B-cell lymphoma (PCBCL). Herein, we present 3 cases of primary cutaneous spindle cell B cell lymphoma, 2 males and one female (age range 66-76years). The patients presented with solitary skin lesions, distributed in the head and neck area and chest. The dominant cell size was in the intermediate to large cell size range. While the main cell type was a spindled one, other cells with a nuclear morphology quite typical for a centroblast were noted and as well careful inspection in the three cases revealed a focal residuum of germinal center-like structures. The spindled cells exhibited a B cell follicle center cell phenotype as revealed by expression of CD20, CD79a, BCL6, and CD10. BCL2 was negative in two cases and positive in one case. The proliferation index exceeded 80%. In one case the neoplastic cells were CD30 positive. Subsequent to a diagnosis in each case of follicle center cell lymphoma, the patients underwent complete excision with no known recurrence. In our review of the literature, a total of 42 other cases were reported showing a similar male predominance with the commonest sites of involvement being the head and neck area and upper back. Other than one patient who died of progressive disease due to treatment refusal and one patient who developed metastatic disease to the liver all patients are alive and well without recurrent or metastatic disease. In summation, our experience along with the reported cases suggest the categorization of primary cutaneous spindle cell B cell lymphoma as a variant of primary cutaneous indolent follicle center lymphoma. It is a neoplasm of middle aged to older adults with a predominance in males which can be treated locally in most cases whereby recurrent and metastatic disease following complete removal is uncommon.

  18. Preliminary clinical and pharmacologic investigation of photodynamic therapy with the silicon phthalocyanine photosensitizer pc 4 for primary or metastatic cutaneous cancers.

    PubMed

    Kinsella, Timothy James; Baron, Elma D; Colussi, Valdir C; Cooper, Kevin D; Hoppel, Charles L; Ingalls, Stephen T; Kenney, Malcolm E; Li, Xiaolin; Oleinick, Nancy L; Stevens, Seth R; Remick, Scot C

    2011-01-01

    Photodynamic therapy (PDT) for cutaneous malignancies has been found to be an effective treatment with a range of photosensitizers. The phthalocyanine Pc 4 was developed initially for PDT of primary or metastatic cancers in the skin. A Phase I trial was initiated to evaluate the safety and pharmacokinetic profiles of systemically administered Pc 4 followed by red light (Pc 4-PDT) in cutaneous malignancies. A dose-escalation study of Pc 4 (starting dose 0.135 mg/m(2)) at a fixed light fluence (135 J/cm(2) of 675-nm light) was initiated in patients with primary or metastatic cutaneous malignancies with the aim of establishing the maximum tolerated dose (MTD). Blood samples were taken at intervals over the first 60 h post-PDT for pharmacokinetic analysis, and patients were evaluated for toxicity and tumor response. A total of three patients (two females with breast cancer and one male with cutaneous T-cell lymphoma) were enrolled and treated over the dose range of 0.135 mg/m(2) (first dose level) to 0.54 mg/m(2) (third dose level). Grade 3 erythema within the photoirradiated area was induced in patient 2, and transient tumor regression in patient 3, in spite of the low photosensitizer doses. Pharmacokinetic observations fit a three-compartment exponential elimination model with an initial rapid distribution phase (∼0.2 h) and relatively long terminal elimination phase (∼28 h), Because of restrictive exclusion criteria and resultant poor accrual, the trial was closed before MTD could be reached. While the limited accrual to this initial Phase I study did not establish the MTD nor establish a complete pharmacokinetic and safety profile of intravenous Pc 4-PDT, these preliminary data support further Phase I testing of this new photosensitizer.

  19. Two Different Cell Populations Is an Important Clue for Diagnosis of Primary Cutaneous Adenoid Cystic Carcinoma: Immunohistochemical Study

    PubMed Central

    Alkan, Banu Ince; Karadeniz, Müjde; Bozdoğan, Nazan

    2017-01-01

    Primary cutaneous adenoid cystic carcinoma (PCACC) is a very rare malignancy. The differential diagnosis of PCACCs in pathology practice can be difficult and a group of primary and metastatic lesions, including adenoid basal cell carcinoma of the skin, should be considered in the differential diagnosis. Besides histomorphological clues, immunohistochemistry studies are very helpful in the differential diagnosis of PCACC. We report herein a case of PCACC with extensive immunohistochemical studies and review the literature from an immunohistochemistry perspective. PMID:28243477

  20. [Primary cutaneous malignant melanoma: retrospective studyfrom 1963 to 1997 at Hospital do Servidor Público Estadual de São Paulo].

    PubMed

    Criado, P R; Vasconcellos, C; Sittart, J A; Valente, N Y; Moura, B P; Barbosa, G L; Ichihara, C

    1999-01-01

    A retrospective study on the Primary Cutaneous Malignant Melanoma in the Hospital do Servidor Público Estadual de São Paulo (HSPE-SP) analyzing its distribution according to age, sex, race and cutaneous site. We studied 222 patients with Primary Cutaneous Malignant Melanoma as diagnosed at Hospital do Servidor Público Estadual de São Paulo, Brazil between the period from 1963 to 1997. A retrospective study was performed. Data were expressed as inance of caucasians (98.19%) over afro-americans (1.81) and of the female sex (69.36%) over the male sex (30.63%) was found. The predominant age on the occasion of the diagnosis was between 50 and 60 years for the women (25.32%) and between 60 and 69 years for the men (22.52%). The most frequent site of the cancer in men was the back region (29.41%) and in the lower members in the women (38.31%). The most frequent level of the tumor invasion (Clark) was IV (39.77%), and the average of tumor thickeness (Breslow) was < 0.75 mm (28.4%). A 5 years survival was observed in 73.3% of the patients. At our Hospital the incidence of Primary Cutaneous Malignant Melanoma has shown an increase in recent years; these results are compatible with the most recent international surveys.

  1. THERAPY-RELATED T/MYELOID MIXED PHENOTYPE ACUTE LEUKEMIA IN A PATIENT TREATED WITH CHEMOTHERAPY FOR CUTANEOUS DIFFUSE LARGE B CELL LYMPHOMA.

    PubMed

    Roberts, Evans; Oncale, Melody; Safah, Hana; Schmieg, John

    2016-01-01

    Mixed-phenotype acute leukemia is a rare form of leukemia that is associated with a poor prognosis. Most cases of mixed-phenotype acute leukemia are de novo. However, therapy-related mixed-phenotype acute leukemia can occur, and are often associated with exposure to topoisomerase-II inhibitors and alkylating agents. There are no known treatment guidelines for therapy-related mixed-phenotype acute leukemia. We present a patient with T/myeloid mixed-phenotype acute leukemia secondary to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone R-CHOP chemotherapy for primary cutaneous diffuse large B-cell lymphoma. The patient's leukemic cells express CD34, an immaturity marker, CD3, a T-cell marker, and myeloperoxidase, a myeloid marker, and her history of chemotherapy for previous lymphoma supports the diagnosis of therapy-related T/myeloid mixed phenotype acute leukemia. Clinicians should be aware that this entity could be associated with R-CHOP chemotherapy. Given the complexity in diagnosis, and lack of treatment guidelines, a further understanding of the pathological and genetic principles of therapy-related mixed-phenotype acute leukemia will assist in future efforts to treat and categorize these patients. Mixed phenotype acute leukemia is a rare entity that accounts for two to five percent of all acute leukemias. Therapy- related mixed phenotype acute leukemia is an exceedingly rare hematological neoplasm that accounts for less than one percent of acute leukemias. We describe a case of therapy-related T/myeloid mixed phenotype acute leukemia following rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone R-CHOP chemotherapy for primary cutaneous diffuse large B-cell lymphoma DLBCL. The patient is a 63-year-old female who presented with several cutaneous nodules diagnosed as primary cutaneous DLBCL. The patient received R-CHOP chemotherapy and achieved remission. She remained in remission for four years until she presented with

  2. An Attempt at a Molecular Prediction of Metastasis in Patients with Primary Cutaneous Melanoma

    PubMed Central

    Gschaider, Melanie; Neumann, Friederike; Peters, Bettina; Lenz, Florian; Cibena, Michael; Goiser, Malgorzata; Wolf, Ingrid; Wenzel, Jörg; Mauch, Cornelia; Schreiner, Wolfgang; Wagner, Stephan N.

    2012-01-01

    Background Current prognostic clinical and morphological parameters are insufficient to accurately predict metastasis in individual melanoma patients. Several studies have described gene expression signatures to predict survival or metastasis of primary melanoma patients, however the reproducibility among these studies is disappointingly low. Methodology/Principal Findings We followed extended REMARK/Gould Rothberg criteria to identify gene sets predictive for metastasis in patients with primary cutaneous melanoma. For class comparison, gene expression data from 116 patients with clinical stage I/II (no metastasis) and 72 with III/IV primary melanoma (with metastasis) at time of first diagnosis were used. Significance analysis of microarrays identified the top 50 differentially expressed genes. In an independent data set from a second cohort of 28 primary melanoma patients, these genes were analyzed by multivariate Cox regression analysis and leave-one-out cross validation for association with development of metastatic disease. In a multivariate Cox regression analysis, expression of the genes Ena/vasodilator-stimulated phosphoprotein-like (EVL) and CD24 antigen gave the best predictive value (p = 0.001; p = 0.017, respectively). A multivariate Cox proportional hazards model revealed these genes as a potential independent predictor, which may possibly add (both p = 0.01) to the predictive value of the most important morphological indicator, Breslow depth. Conclusion/Significance Combination of molecular with morphological information may potentially enable an improved prediction of metastasis in primary melanoma patients. A strength of the gene expression set is the small number of genes, which should allow easy reevaluation in independent data sets and adequately designed clinical trials. PMID:23166783

  3. Novel therapeutic strategies for cutaneous T-cell lymphoma in advanced stages.

    PubMed

    Kun, Lillian; Hernandez-Ilizaliturri, Francisco J; Reddy, Nishitha M

    2014-01-01

    The term cutaneous T-cell lymphoma (CTCL), introduced in 1975, was used to describe a spectrum of skin-based malignant tumors of T-cell origin. Immunological studies identified the complex interaction of cytokines released from infiltrating accessory or malignant cells and how such cytokines aid in the maintenance and proliferation of malignant cells. Though the etiology remains unknown, an association with rare retrovirus in some cases has been described. The mainstay of therapy has been to control the cutaneous presentation with topical therapies in patients with early limited-stage disease. However, a significant number of patients develop refractory disease to skin-directed therapies with or without clinical progression to advanced stages requiring systemic therapy. Over the last two decades a wide number of novel agents such as monoclonal antibodies, small molecule inhibitors, and chemotherapy agents have been developed and are used in patients with advanced disease or those who have exhausted topical treatment options and/or radiation. In this contribution we review the results of clinical studies evaluating emerging therapeutic strategies for patients with CTCL that had developed from ongoing translational research programs focused on understanding the biology of different subtypes of CTCL and identifying disease-specific biomarkers suitable for targeting.

  4. Optimal excision margins for primary cutaneous melanoma: a systematic review and meta-analysis

    PubMed Central

    Haigh, Philip I.; DiFronzo, L. Andrew; McCready, David R.

    2003-01-01

    Objective To determine in patients with localized primary melanoma of the trunk or extremities the optimal excision margin that achieves the highest disease-free survival and overall survival and the lowest local recurrence rate. Data sources Trials comparing 2 different excision margins were identified by searching MEDLINE from 1966 to May 2002 using the term “melanoma,” subheading “surgery,” and limiting the search to human studies and randomized controlled trials (RCTs). Additional studies were found using the MeSH term “surgical procedures, operative,” combining with “melanoma,” and limiting to human studies. We searched EMBASE and the Cochrane Library in May 2002 using similar terminology. No language restriction was applied. Study selection We selected studies for the overview using the following inclusion criteria: design — an RCT with wide excision versus narrower excision (margin width was not specified a priori); population — adult patients (> 18 yr) with cutaneous melanoma of the trunk or extremities without evidence of metastasis; intervention — surgical excision of the primary melanoma; and outcomes — at least 1 of overall survival, disease-free survival, local recurrence, wound complications and necessity for skin grafting. Data extraction Information was abstracted for each outcome reported in the studies, and results were pooled by consensus. Statistical analysis was performed using RevMan 4.1 (The Cochrane Collaboration) software program. Relative risk and risk difference were reported with 95% confidence intervals. The number needed to harm was calculated for the need for skin grafting by taking the inverse of the risk difference. Data synthesis Three trials and their follow-up studies met the inclusion criteria and included 2087 adults with localized cutaneous melanoma of the trunk or extremities. No statistically significant differences were found between wide surgical excision (margins ranging from 3–5 cm) and narrower

  5. Optimal excision margins for primary cutaneous melanoma: a systematic review and meta-analysis.

    PubMed

    Haigh, Philip I; DiFronzo, L Andrew; McCready, David R

    2003-12-01

    To determine in patients with localized primary melanoma of the trunk or extremities the optimal excision margin that achieves the highest disease-free survival and overall survival and the lowest local recurrence rate. Trials comparing 2 different excision margins were identified by searching MEDLINE from 1966 to May 2002 using the term "melanoma," subheading "surgery," and limiting the search to human studies and randomized controlled trials (RCTs). Additional studies were found using the MeSH term "surgical procedures, operative," combining with "melanoma," and limiting to human studies. We searched EMBASE and the Cochrane Library in May 2002 using similar terminology. No language restriction was applied. We selected studies for the overview using the following inclusion criteria: design--an RCT with wide excision versus narrower excision (margin width was not specified a priori); population--adult patients (> 18 yr) with cutaneous melanoma of the trunk or extremities without evidence of metastasis; intervention--surgical excision of the primary melanoma; and outcomes--at least 1 of overall survival, disease-free survival, local recurrence, wound complications and necessity for skin grafting. Information was abstracted for each outcome reported in the studies, and results were pooled by consensus. Statistical analysis was performed using RevMan 4.1 (The Cochrane Collaboration) software program. Relative risk and risk difference were reported with 95% confidence intervals. The number needed to harm was calculated for the need for skin grafting by taking the inverse of the risk difference. Three trials and their follow-up studies met the inclusion criteria and included 2087 adults with localized cutaneous melanoma of the trunk or extremities. No statistically significant differences were found between wide surgical excision (margins ranging from 3-5 cm) and narrower surgical excision (margins ranging from 1-2 cm) with respect to mortality, disease-free survival or

  6. Role of infectious agents in cutaneous T-cell lymphoma: facts and controversies.

    PubMed

    Mirvish, Judah J; Pomerantz, Rebecca G; Falo, Louis D; Geskin, Larisa J

    2013-01-01

    The etiology of cutaneous T-cell lymphoma (CTCL) remains unknown, with potential infectious causes having been explored. This contribution evaluates the evidence suggesting an infectious etiology and pathogenesis of the disease, characterizes the relationships between various specific pathogens and CTCL, and discusses some of the difficulties in establishing a causal link between infectious agents and CTCL carcinogenesis. Researchers have evaluated CTCL specimens for evidence of infection with a variety of agents, including human T-lymphotropic virus, Epstein-Barr virus, human herpesvirus-8, and Staphylococcus aureus, although other pathogens also have been detected in CTCL. Although there is significant evidence implicating one or more infectious agents in CTCL, studies to date have not linked definitively any pathogen to disease development, and various studies have yielded conflicting results.

  7. Cutaneous T cell lymphoma complicating severe atopic dermatitis. Is making a diagnosis the main challenge?

    PubMed

    Meyer, Nicolas; Mazereeuw-Hautier, Juliette; Launay, François; Lamant, Laurence; Paul, Carle

    2009-01-01

    The association between severe long-term atopic dermatitis (AD) and the risk of skin lymphoma is still a matter of debate, since epidemiological studies have shown contradictory results. We report 2 cases of patients with a documented history of severe longstanding atopic disease, who had never been treated with topical or systemic calcineurin inhibitors, and who developed a cytotoxic cutaneous T cell lymphoma (CTCL). For these 2 patients, clinical manifestations preceded the diagnosis of CTCL. The diagnosis was based on histological findings and molecular analysis of the T cell receptor (TCR) clonality. These cases illustrate the difficulty in diagnosing CTCL in patients with severe AD and extensive inflammatory skin lesions. The transition between severe AD and CTCL is progressive; histological findings and molecular evidence of TCR clonality are detected after the clinical changes. These 2 cases lend further support to the hypothesis of an association between severe long-term AD and CTCL. Copyright (c) 2008 S. Karger AG, Basel.

  8. Successful Treatment of Primary Cutaneous Mucormycosis Complicating Anti-TNF Therapy with a Combination of Surgical Debridement and Oral Posaconazole.

    PubMed

    Camargo, Jose F; Yakoub, Danny; Cho-Vega, Jeong Hee

    2015-10-01

    Lipid formulations of amphotericin B remain the first-line antifungal therapy for invasive mucormycosis. Posaconazole is an alternative for salvage therapy, but its use as primary therapy is not recommended due to the paucity of clinical data. Here we describe the case of a 57-year-old diabetic woman receiving etanercept and prednisone for the treatment of psoriatic arthritis who developed primary cutaneous mucormycosis after a minor gardening injury. Infection was successfully treated with aggressive surgical debridement followed by a 6-week course of the new delayed-release tablet formulation of posaconazole and temporary withholding of anti-TNF treatment. Primary antifungal therapy with posaconazole can be considered in selected cases of cutaneous mucormycosis.

  9. The role of human T-cell lymphotropic viruses (HTLV-I and II) in cutaneous T-cell lymphomas.

    PubMed

    Zucker-Franklin, D; Pancake, B A

    1994-09-01

    Although an association between the human T cell lymphotropic viruses (HTLV-I and II) and cutaneous T cell lymphoma (CTCL) has long been suspected, only a minor fraction of patients with this disease have antibodies to the viral structural proteins. However, the consistent finding of HTLV-like particles in cultures of peripheral blood mononuclear cells (PBMC) from such patients has prompted a continued effort to find evidence linking the virus to this disease. Capitalizing on the increased sensitivity afforded by combining PCR amplification with detection by Southern blot hybridization, it became possible to demonstrate HTLV tax and/or pol proviral sequences in freshly isolated PBMC of most patients with mycosis fungoides. These observations suggest a possible role of the virus in the pathogenesis of CTCL, and may impact on diagnostic and therapeutic measures in the future.

  10. Hydroa Vacciniforme-Like EBV-Positive Cutaneous T-Cell Lymphoma, First Report of 2 Cases in Ecuador.

    PubMed

    Montalvo, Nelson; Redrobán, Ligia

    2016-05-01

    Hydroa vacciniforme-like cutaneous lymphoma is a very rare Epstein-Barr virus positive peripheral T-cell lymphoma affecting Asian and Hispanic children and young adults with a defective cytotoxic immune response to EBV predisposing to the development of the disease. We report on 2 Ecuadorian patients with papulovesicular and ulcerated crusted lesions on the face, upper and lower extremities and abdomen, with aggressive clinical course and, in one case, a fatal outcome. The histological and molecular profiles (immunohistochemistry and in situ hybridization) established a diagnosis of hydroa vacciniforme-like Epstein-Barr virus-encoded small RNAs + cutaneous T-cell lymphoma in both cases.

  11. Indium-111 T101 monoclonal antibody is superior to iodine-131 T101 in imaging of cutaneous T-cell lymphoma

    SciTech Connect

    Carrasquillo, J.A.; Mulshine, J.L.; Bunn, P.A. Jr.; Reynolds, J.C.; Foon, K.A.; Schroff, R.W.; Perentesis, P.; Steis, R.G.; Keenan, A.M.; Horowitz, M.

    1987-03-01

    We have reported that (/sup 111/In)T101 is highly effective in the detection of cutaneous T-cell lymphoma (CTCL) in nodal and cutaneous (erythroderma and tumor) sites. This study compares the biodistribution of (/sup 131/I)T101 (1 to 7.1 mg, 2 mCi) in four patients with CTCL; two of these patients also received (/sup 111/In)T101 (1 mg, 5 mCi). There was rapid clearance of (/sup 131/I)T101 from whole-body, spleen, liver, and bone marrow, with evidence of loss of /sup 131/I tracer from the T101. Lymph node uptake was minimal in three of four patients, and there was no localization in skin lesions. This contrasted with (/sup 111/In)T101 where there was prolonged retention of activity in these organs and excellent uptake in skin tumors, erythroderma, and lymph nodes. The study showed that (/sup 131/I)T101 was suboptimal for imaging CTCL patients and demonstrates that the isotope or labeling method can dramatically alter the apparent biodistribution and tumor targeting of a given monoclonal antibody.

  12. Proteomic Approaches to Biomarker Discovery in Cutaneous T-Cell Lymphoma

    PubMed Central

    Papagheorghe, Laura Maria Lucia; Lisievici, Cristina

    2016-01-01

    Cutaneous T-cell lymphoma (CTCL) is the most frequently encountered type of skin lymphoma in humans. CTCL encompasses multiple variants, but the most common types are mycosis fungoides (MF) and Sezary syndrome (SS). While most cases of MF run a mild course over a period of many years, other subtypes of CTCL are very aggressive. The rapidly expanding fields of proteomics and genomics have not only helped increase knowledge concerning the carcinogenesis and tumor biology of CTCL but also led to the discovery of novel markers for targeted therapy. Although multiple biomarkers linked to CTCL have been known for a relatively long time (e.g., CD25, CD45, CD45RA, and CD45R0), compared to other cancers (lymphoma, melanoma, colon carcinoma, head and neck cancer, renal cancer, and cutaneous B-cell lymphoma), information about the antigenicity of CTCL remains relatively limited and no dependable protein marker for CTCL has been discovered. Considering the aggressive nature of some types of CTCL, it is necessary to identify circulating molecules that can help in the early diagnosis, differentiation from inflammatory skin diseases (psoriasis, nummular eczema), and aid in predicting the prognosis and evolution of this pathology. This review aims to bring together some of the information concerning protein markers linked to CTCL, in an effort to further the understanding of the convolute processes involved in this complex pathology. PMID:27821903

  13. MicroRNA expression profiling and DNA methylation signature for deregulated microRNA in cutaneous T-cell lymphoma.

    PubMed

    Sandoval, Juan; Díaz-Lagares, Angel; Salgado, Rocío; Servitje, Octavio; Climent, Fina; Ortiz-Romero, Pablo L; Pérez-Ferriols, Amparo; Garcia-Muret, Maria P; Estrach, Teresa; Garcia, Mar; Nonell, Lara; Esteller, Manel; Pujol, Ramon M; Espinet, Blanca; Gallardo, Fernando

    2015-04-01

    MicroRNAs usually regulate gene expression negatively, and aberrant expression has been involved in the development of several types of cancers. Microarray profiling of microRNA expression was performed to define a microRNA signature in a series of mycosis fungoides tumor stage (MFt, n=21) and CD30+ primary cutaneous anaplastic large cell lymphoma (CD30+ cALCL, n=11) samples in comparison with inflammatory dermatoses (ID, n=5). Supervised clustering confirmed a distinctive microRNA profile for cutaneous T-cell lymphoma (CTCL) with respect to ID. A 40 microRNA signature was found in MFt including upregulated onco-microRNAs (miR-146a, miR-142-3p/5p, miR-21, miR-181a/b, and miR-155) and downregulated tumor-suppressor microRNAs (miR-200ab/429 cluster, miR-10b, miR-193b, miR-141/200c, and miR-23b/27b). Regarding CD30+ cALCL, 39 differentially expressed microRNAs were identified. Particularly, overexpression of miR-155, miR-21, or miR-142-3p/5p and downregulation of the miR-141/200c clusters were observed. DNA methylation in microRNA gene promoters, as expression regulatory mechanism for deregulated microRNAs, was analyzed using Infinium 450K array and approximately one-third of the differentially expressed microRNAs showed significant DNA methylation differences. Two different microRNA methylation signatures for MFt and CD30+ cALCL were found. Correlation analysis showed an inverse relationship for microRNA promoter methylation and microRNA expression. These results reveal a subgroup-specific epigenetically regulated microRNA signatures for MFt and CD30+ cALCL patients.

  14. Treatment and outcomes for primary cutaneous extramedullary plasmacytoma: a case series

    PubMed Central

    Tsang, D.S.; Le, L.W.; Kukreti, V.; Sun, A.

    2016-01-01

    Background Primary cutaneous plasmacytoma (pcp) is a rare disease, with few studies to guide therapy. Our primary study objective was to define treatments used for pcp; a secondary objective was to describe outcomes of patients, including disease recurrence and death. Methods An institutional cancer registry was used to identify cases for retrospective chart review. In a systematic review, treatments for, and outcomes of, all known cases of pcp were described. Results Three eligible cases identified at our institution; each patient had a solitary pcp. The systematic review identified 66 patients. Radiotherapy was the most commonly used primary treatment modality (31% of all patients; 42% for patients with solitary lesions), followed by surgery (28% of all patients; 36% for patients with solitary lesions). Median survival for all patients was 10.4 years [95% ci: 4.3 years to not reached], with a trend toward a decreased risk of death with solitary lesions compared with multiple lesions (hazard ratio: 0.37; 95% ci: 0.13 to 1.08; p = 0.059). For patients with solitary lesions, the median and recurrence-free survivals were, respectively, 17.0 years (95% ci: 1.7 years to not reached) and 11.0 years (95% ci: 2 years to not reached); for patients with multiple lesions, they were 4.3 years (95% ci: 1.3 to not reached) and 1.4 years (95% ci: 0.6 years to not reached). Disease recurrence, including progression to multiple myeloma, was the most common cause of death. Conclusions Compared with patients having multiple pcp lesions, those presenting with a single pcp lesion might experience longer overall survival. Local therapy (radiation or surgery) is a reasonable curative treatment for a solitary pcp lesion. PMID:28050154

  15. Small Cell Variant of T-Cell Prolymphocytic Leukemia with Acquired Palmoplantar Keratoderma and Cutaneous Infiltration.

    PubMed

    Al-Musalhi, Buthaina; Shehata, Nancy; Billick, Robin

    2016-01-01

    T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive post-thymic malignancy that is characterized by the proliferation of small- to medium- sized prolymphocytes. The classic clinical features of T-PLL are lymphocytosis, lymphadenopathy, hepatosplenomegaly, and skin lesions. Skin involvement varies clinically from diffuse infiltrated erythema. Infiltration is localized to the face and ears, nodules, and erythroderma. We present a case of small cell variant of T-PLL in a patient who presented with unusual cutaneous manifestations of acquired palmoplantar keratoderma (PPK) followed by diffuse erythematous infiltrated papules and plaques involving the trunk. When the etiology of acquired PPK is not clear, the physician should consider the possibility of an underlying malignant disease. In this case, the diagnosis of T-PLL was subsequently confirmed by laboratory and cytological findings, as well as by the immunophenotyping of leukemic cells in skin biopsy. Since paraneoplastic acquired PPK may be the initial evident sign of malignancy, the physician's awareness of this manifestation may be crucial for early diagnosis and treatment. Our case emphasizes the importance of accurate evaluation of skin lesions and early skin biopsy in the diagnosis of some hematological malignancies.

  16. Head and neck cutaneous squamous cell carcinoma metastatic to cervical sublevel IIb lymph nodes occurred from primary sites involving the auricle and adjacent neck.

    PubMed

    Maher, Nigel Gordon; Hoffman, Gary Russell

    2014-03-01

    Neck dissections that include sublevel IIb increase the risk of postoperative shoulder dysfunction. The purpose of this investigation was to document the incidence of level IIb metastatic lymphatic spread in a group of patients undergoing neck dissection as part of the surgical management of cutaneous squamous cell carcinoma of the head and neck. A retrospective review of the pathology records taken from 1 surgeon from June 2006 through June 2013 was carried out. The predictor variable was the primary tumor site. The outcome variable was the metastatic nodal involvement according to neck level and sublevel. Secondary variables included T stage, pathologist, tumor depth, and the presence of perineural, perilymphatic, and perivascular invasion. Data analyses were by descriptive statistics. Thirty-six patients with a total of 40 neck dissections met the inclusion criteria. The average primary site tumor depth was 14.7 mm, and there were 16 cases of poorly differentiated squamous cell carcinoma. Sublevel IIb was involved in 7.5% of cases, all of which occurred from lateralized primary sites of the head and neck. Cutaneous squamous cell carcinoma arising from the auricle and neck sites adjacent to sublevel IIb may have increased risk of metastatic involvement of sublevel IIb nodes. Further studies with larger numbers are required to determine the risk of metastasis to sublevel IIb from midline sites of the face. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

  17. Canine cutaneous epitheliotropic lymphoma (mycosis fungoides) is a proliferative disorder of CD8+ T cells.

    PubMed Central

    Moore, P. F.; Olivry, T.; Naydan, D.

    1994-01-01

    Canine epitheliotropic lymphoma (mycosis fungoides [MF]) is a spontaneous neoplasm of skin and mucous membranes that occurs in old dogs (mean age 11 years) and has no breed predilection. The lesions evolve from a patch-plaque stage with prominent epitheliotropism into a tumor stage in which distant metastasis is observed. Unlike human MF, epitheliotropism of the lymphoid infiltrate is still prominent in tumor stage lesions. Tropism of the lymphoid infiltrate for adnexal structures, especially hair follicles and apocrine sweat glands, was marked in all clinical stages of canine MF. Twenty-three cases of MF were subjected to extensive immunophenotypic analysis in which reagents specific for canine leukocyte antigens and fresh frozen tissue sections of the canine lesions were used. Canine MF proved to be a T cell lymphoma in which the epitheliotropic lymphocytes consistently expressed CD3 (22 cases) and CD8 (19 cases); CD3+CD4-CD8- lymphocytes predominated in the remaining 4 cases. In this regard, canine MF clearly differed from human MF in which a CD4 immunophenotype predominates in the T cell infiltrate. Lack of expression of CD45RA by epitheliotropic T cells and intense expression of a beta 1 integrin (VLA-4-like) suggested that T cells in canine MF belonged to the memory subpopulation, as has been suggested for T cells in human MF. Pan-T cell antigen loss or discordant expression also proved useful as phenotypic indicators of neoplasia in canine MF. Loss of CD5 was observed in epitheliotropic T cells in 63% of cases. Discordance of neoplastic T cell Thy-1 expression was frequently observed between epithelial and dermal or submucosal compartments. We conclude that canine MF still represents a useful spontaneous animal disease model of human cutaneous T cell lymphoma, despite the immunophenotypic differences, which may reflect operational differences between human and canine skin-associated lymphoid tissue. Images Figure 1 Figure 2 Figure 3 Figure 5 Figure 6 Figure

  18. Underuse of wide excision for primary cutaneous melanoma in the United States.

    PubMed

    Haigh, Philip I; Urbach, David R

    2004-11-01

    Three randomized trials support wide excision (WEX) for primary cutaneous melanoma. The objective was to evaluate WEX use for melanoma in the United States. Patients with localized melanoma were identified from the Surveillance, Epidemiology and End Results database between 1988 and 1997. Associations between predictor variables and WEX compared to biopsy alone were evaluated using logistic regression. Of 8,268 patients identified, 74.9 per cent had WEX, whereas 25.1 per cent had biopsy alone. WEX use peaked in 1990 at 81.6 per cent and was lowest in 1995 at 69.8 per cent. Overall, WEX use decreased over time. WEX use was independently associated with Breslow thickness (odds ratio [OR] per 1-mm depth of invasion 1.4, 95 per cent confidence interval [CI] 1.3, 1.5), and was inversely related to patient age (OR per 10 years of age 0.93; 95% CI 0.90, 0.96). As compared with the time period 1988 to 1990, WEX use declined during 1991 to 1993 (OR 0.71, 95% CI 0.60-0.83) and from 1994 to 1997 (OR 0.65; 95% CI 0.57-0.75). Many patients with localized melanoma undergo biopsy alone without a WEX. Use of WEX is associated with thicker melanomas and younger patients. Use of WEX has decreased over time, despite results from three randomized trials supporting its use.

  19. Treatment of primary cutaneous amyloidosis with laser: a review of the literature.

    PubMed

    Al Yahya, Rand S

    2016-07-01

    Primary cutaneous amyloidosis (PCA) is a condition characterized by tissue deposition of misfolded proteins. PCA can present in different forms, namely macular, lichen, and nodular amyloidosis. These lesions can be of cosmetic concern and are difficult to treat. Many therapeutic modalities have been suggested for the treatment of PCA, with variable efficacy, including topical and systemic medications, phototherapy, electrodessication, dermabrasion, cryosurgery, and lasers. Over the past decade, several studies have reported successful treatment of PCA with different types of lasers; however, a review of these studies has never been reported in the dermatologic literature. The aim of this study was to review the efficacy and safety of lasers in the treatment of PCA. A search of the National Library of Medicine's PubMed Database was performed. Studies were considered for inclusion based on their relevance, and specific data were extracted from all included studies. Eleven studies, comprising 64 patients, were included in this review. Significant improvements were observed in macular and lichen amyloidosis patients treated with carbon dioxide laser in two studies, while a number of case series and case reports showed good results with other types of laser in the treatment of PCA. This review was limited by the lack of large double-blinded randomized controlled trials and the overall small sample size. Laser treatment is a promising option in the treatment of PCA. Future randomized controlled trials are needed to compare the efficacy of different types of lasers and to select the best parameters for different types of PCA.

  20. Chemokine receptor expression by leukemic T cells of cutaneous T-cell lymphoma: clinical and histopathological correlations.

    PubMed

    Capriotti, Elisabetta; Vonderheid, Eric C; Thoburn, Christopher J; Bright, Emilie C; Hess, Allan D

    2007-12-01

    Chemokine receptors expressed by normal and neoplastic lymphocytes provide an important mechanism for cells to traffic into the skin and skin-associated lymph nodes. The goal of this study was to correlate chemokine receptor and CD62L expression by circulating neoplastic T cells with the clinical and pathological findings of the leukemic phase of cutaneous T-cell lymphoma, primarily Sézary syndrome (SS). Chemokine receptor mRNA transcripts were found in the majority of leukemic cells for CCR1, CCR4, CCR7, CCR10, CXCR3, and CD62L and in 20-50% of the samples for CXCR5. In patients with SS, relatively high expression levels of CCR7 and CCR10 by circulating neoplastic T cells correlated with epidermotropism, CXCR5 expression correlated with density of the dermal infiltrate, and CD62L correlated with extent of lymphadenopathy. Of note, CXCR5 expression and a dense dermal infiltrate correlated with a poor prognosis. The chemokine receptor profile supports the concept that neoplastic T cells are central memory T cells, and that CCR10 and CD62L play a fundamental role respectively in epidermotropism and lymphadenopathy that is observed in SS.

  1. [Primary cutaneous aspergillosis complicated with invasive aspergillosis in an extremely preterm infant: case report and literature review].

    PubMed

    Stock, C; Veyrier, M; Magnin-Verschelde, S; Duband, S; Lavocat, M-P; Teyssier, G; Berthelot, P

    2010-10-01

    Aspergillus is a ubiquitous fungus that can cause primary cutaneous aspergillosis in extremely low-birth-weight (ELBW) neonates, then be invasive and lead to death. ELBW neonates are particularly at risk because of decreased qualitative immune defenses and defects in the skin barrier. Broad-spectrum antimicrobial therapy and corticosteroids, often used in these patients, contribute to increased risk. We present a fatal case of primary cutaneous aspergillosis complicated with invasive aspergillosis, confirmed by autopsy, in an ELBW infant. The source of contamination was probably non-sterile disposable latex gloves used for neonatal care. The early recognition of this source led to its eviction for other hospitalized ELBW infants and no outbreak was observed.

  2. Optical perception for detection of cutaneous T-cell lymphoma by multi-spectral imaging

    NASA Astrophysics Data System (ADS)

    Hsiao, Yu-Ping; Wang, Hsiang-Chen; Chen, Shih-Hua; Tsai, Chung-Hung; Yang, Jen-Hung

    2014-12-01

    In this study, the spectrum of each picture element of the patient’s skin image was obtained by multi-spectral imaging technology. Spectra of normal or pathological skin were collected from 15 patients. Principal component analysis and principal component scores of skin spectra were employed to distinguish the spectral characteristics with different diseases. Finally, skin regions with suspected cutaneous T-cell lymphoma (CTCL) lesions were successfully predicted by evaluation and classification of the spectra of pathological skin. The sensitivity and specificity of this technique were 89.65% and 95.18% after the analysis of about 109 patients. The probability of atopic dermatitis and psoriasis patients misinterpreted as CTCL were 5.56% and 4.54%, respectively.

  3. Growth dynamics and cyclin expression in cutaneous T-cell lymphoma cell lines

    PubMed Central

    Biskup, Edyta; Manfé, Valentina; Kamstrup, Maria R.; Gniadecki, Robert

    2010-01-01

    We have investigated cell growth dynamics and cyclins B1 and E expression in cell lines derived from mycosis fungoides (MyLa), Sézary syndrome (SeAx), and CD30+ lympho-proliferative diseases (Mac1, Mac2a, JK). Mac1 and Mac2a had the highest growth rate (doubling time 18–28 h, >90% cycling cells) whereas SeAx was proliferating slowly (doubling time 55 h, approximately 35% cycling cells). Expression of cyclin B1 correlated positively with doubling time whereas expression of cyclin E was unscheduled and constant across the investigated cell lines. All cell lines exhibited high expression of PCNA. Thus, we concluded that cyclin B1 could be used for rapid screening of cell proliferation in malignant lymphocytes derived from cutaneous T-cell lymphoma. PMID:25386244

  4. BRAFV600E protein expression in primary cutaneous malignant melanomas and paired metastases.

    PubMed

    Eriksson, Hanna; Zebary, Abdlsattar; Vassilaki, Ismini; Omholt, Katarina; Ghaderi, Mehran; Hansson, Johan

    2015-04-01

    BRAFV600E mutations are present in approximately 50% of cutaneous malignant melanomas (CMMs). The use of BRAFV600E mutation-specific monoclonal antibody VE1 immunohistochemical analysis may facilitate rapid detection of BRAFV600E mutations in CMMs and demonstrate heterogeneity among tumors. To characterize the pattern of BRAFV600E protein expression in primary CMMs with matched metastases and to analyze the use of VE1 immunohistochemical analysis in clinical practice using formalin-fixed, paraffin-embedded tumor tissue. In this retrospective cohort study performed at Karolinska University Hospital from September 2012 to September 2013, we examined CMMs (124 primary tumors and 76 metastases) with VE1 immunohistochemical analysis, and results were compared with DNA mutation analyses. Determination of intratumoral and intertumoral heterogeneity as well as the sensitivity and specificity of VE1 immunohistochemical analysis. Positive staining results with the VE1 antibody were detected in 94 of 200 tumors (47.0%). In general, VE1 staining was homogeneous. However, VE1 staining intensity varied among the primary tumors and corresponding metastases in 63 of 135 tumors (46.7%), but a change of mutational status based on DNA analysis was found in only 4 matched tumors (3.0%). Discordant findings between DNA mutation analysis and immunohistochemical analysis were observed in 12 tumors. The overall sensitivity and specificity of VE1 immunohistochemical analysis were 96.7% and 94.5%, respectively. A comparable sensitivity was obtained for primary and metastatic CMMs. The specificity was lower among primary CMMs (92.4%) compared with metastases (98.0%). We found VE1 immunohistochemical analysis to be a useful and rapid assay for BRAFV600E mutations that may contribute to the detection of intratumoral and intertumoral heterogenetic subclones. Tumors with positive results, including strong staining, should be expedited for confirmatory BRAF mutation testing. If this test result

  5. Neutrophils are dispensable in the modulation of T cell immunity against cutaneous HSV-1 infection

    PubMed Central

    Hor, Jyh Liang; Heath, William R.; Mueller, Scott N.

    2017-01-01

    Neutrophils rapidly infiltrate sites of inflammation during peripheral infection or tissue injury. In addition to their well described roles as pro-inflammatory phagocytes responsible for pathogen clearance, recent studies have demonstrated a broader functional repertoire including mediating crosstalk between innate and adaptive arms of the immune system. Specifically, neutrophils have been proposed to mediate antigen transport to lymph nodes (LN) to modulate T cell priming and to influence T cell migration to infected tissues. Using a mouse model of cutaneous herpes simplex virus type 1 (HSV-1) infection we explored potential contributions of neutrophils toward anti-viral immunity. While a transient, early influx of neutrophils was triggered by dermal scarification, we did not detect migration of neutrophils from the skin to LN. Furthermore, despite recruitment of neutrophils into LN from the blood, priming and expansion of CD4+ and CD8+ T cells was unaffected following neutrophil depletion. Finally, we found that neutrophils were dispensable for the migration of effector T cells into infected skin. Our study suggests that the immunomodulatory roles of neutrophils toward adaptive immunity may be context-dependent, and are likely determined by the type of pathogen and anatomical site of infection. PMID:28112242

  6. CD20-Positive nodal natural killer/T-cell lymphoma with cutaneous involvement.

    PubMed

    Tsai, Yi-Chiun; Chen, Chi-Kuan; Wu, Yu-Hung

    2015-09-01

    CD20-positive natural killer (NK)/T-cell lymphoma is extremely rare. We describe a case of a CD20-positive nodal NK/T-cell lymphoma with cutaneous involvement in a 32-year-old man. The patient presented with fever, night sweats, right inguinal lymphadenopathy and multiple violaceous to erythematous nodules and plaques on the back and bilateral legs. Immunohistochemical analysis showed diffusely and strongly positive staining for CD3, CD3 epsilon, CD43, CD56, TIA-1 and CD20 but negative staining for other B-cell markers, including CD79a and PAX-5 and T-cell markers CD5 and CD7. The tumor cell nuclei were diffusely positive for Epstein-Barr virus-encoded RNA in situ hybridization. A partial clinical response was observed after chemotherapy, indicated by the decreased size of the lymph nodes and skin lesions. It is a diagnostic challenge to deal with lymphoma cells that present with the surface proteins of both T- and B-cells.

  7. Malignant inflammation in cutaneous T-cell lymphoma-a hostile takeover.

    PubMed

    Krejsgaard, Thorbjørn; Lindahl, Lise M; Mongan, Nigel P; Wasik, Mariusz A; Litvinov, Ivan V; Iversen, Lars; Langhoff, Erik; Woetmann, Anders; Odum, Niels

    2017-04-01

    Cutaneous T-cell lymphomas (CTCL) are characterized by the presence of chronically inflamed skin lesions containing malignant T cells. Early disease presents as limited skin patches or plaques and exhibits an indolent behavior. For many patients, the disease never progresses beyond this stage, but in approximately one third of patients, the disease becomes progressive, and the skin lesions start to expand and evolve. Eventually, overt tumors develop and the malignant T cells may disseminate to the blood, lymph nodes, bone marrow, and visceral organs, often with a fatal outcome. The transition from early indolent to progressive and advanced disease is accompanied by a significant shift in the nature of the tumor-associated inflammation. This shift does not appear to be an epiphenomenon but rather a critical step in disease progression. Emerging evidence supports that the malignant T cells take control of the inflammatory environment, suppressing cellular immunity and anti-tumor responses while promoting a chronic inflammatory milieu that fuels their own expansion. Here, we review the inflammatory changes associated with disease progression in CTCL and point to their wider relevance in other cancer contexts. We further define the term "malignant inflammation" as a pro-tumorigenic inflammatory environment orchestrated by the tumor cells and discuss some of the mechanisms driving the development of malignant inflammation in CTCL.

  8. Reduced Intensity Conditioning Before Partially Matched Donor Stem Cell Transplant in Treating Patients With Advanced Cutaneous T Cell Lymphoma

    ClinicalTrials.gov

    2016-10-19

    Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides and Sezary Syndrome; Stage IIB Mycosis Fungoides and Sezary Syndrome; Stage IIIA Mycosis Fungoides and Sezary Syndrome; Stage IIIB Mycosis Fungoides and Sezary Syndrome; Stage IVA Mycosis Fungoides and Sezary Syndrome; Stage IVB Mycosis Fungoides and Sezary Syndrome

  9. Detection of Chlamydophila pneumoniae and human herpesvirus 8 in primary cutaneous anaplastic large-cell lymphoma: a case report.

    PubMed

    Borghi, Alessandro; Caselli, Elisabetta; Di Luca, Dario; Sebastiani, Adolfo; Perri, Paolo; Seraceni, Silva; Contini, Carlo; Virgili, Annarosa

    2013-10-07

    The etiology of primary cutaneous anaplastic large-cell CD30+ lymphoma is largely unknown, and although an infectious involvement has been suspected, the implication of infectious agents in its pathogenesis is still unclear. We report the case of a HIV-negative patient referred to our hospital with a rapidly enlarging skin tumor on her upper eyelid. Surgical excision was performed and histological analysis evidenced a primary cutaneous anaplastic large-cell lymphoma. Due to the ocular localization and to the prominent angiogenic component of the lesion, molecular analyses for the detection of Chlamydophila pneumoniae and HHV8 were performed, revealing the presence of an infection by both pathogens in surgical biopsy and in peripheral blood mononuclear cells. These findings suggest for the first time a possible association of C. pneumoniae and/or HHV8 infection, or both together, with primary cutaneous anaplastic large-cell lymphoma in non-immunocompromised and HIV-negative subjects. This potential pathogenic association, if confirmed, could provide potential indications for future therapy.

  10. Detection of Chlamydophila pneumoniae and human herpesvirus 8 in primary cutaneous anaplastic large-cell lymphoma: a case report

    PubMed Central

    2013-01-01

    Background The etiology of primary cutaneous anaplastic large-cell CD30+ lymphoma is largely unknown, and although an infectious involvement has been suspected, the implication of infectious agents in its pathogenesis is still unclear. Findings We report the case of a HIV-negative patient referred to our hospital with a rapidly enlarging skin tumor on her upper eyelid. Surgical excision was performed and histological analysis evidenced a primary cutaneous anaplastic large-cell lymphoma. Due to the ocular localization and to the prominent angiogenic component of the lesion, molecular analyses for the detection of Chlamydophila pneumoniae and HHV8 were performed, revealing the presence of an infection by both pathogens in surgical biopsy and in peripheral blood mononuclear cells. Conclusions These findings suggest for the first time a possible association of C. pneumoniae and/or HHV8 infection, or both together, with primary cutaneous anaplastic large-cell lymphoma in non-immunocompromised and HIV-negative subjects. This potential pathogenic association, if confirmed, could provide potential indications for future therapy. PMID:24099147

  11. Primary cutaneous apocrine gland carcinoma from areolar tissue in a male patient with gynecomastia: a case report.

    PubMed

    Seo, Kyung-Jin; Kim, Jae-Jun

    2015-09-08

    Primary cutaneous apocrine gland carcinoma, which is a type of sweat gland carcinoma, is an extremely rare type of cancer. Clinical courses of this type of cancer usually progress slowly but can, occasionally, be associated with rapid progression. This case report describes a 53-year-old Korean man with primary cutaneous apocrine gland carcinoma that arose from an apocrine gland in the areola tissue. The patient visited our hospital because of a large, painful chest wall mass beneath the right nipple. The mass had been present for more than eight years but had grown rapidly over the past few months. The patient was initially diagnosed with a benign cystic mass, and we performed a wide excision with a clear margin and without lymph node dissection. The mass was a well-encapsulated cystic lesion that contained old blood material, and there was no invasion into the surrounding tissue. The final pathology showed that the mass was a primary cutaneous apocrine gland carcinoma that arose from the areola apocrine sweat gland, not from the breast parenchymal tissue. Herein, we report an extremely rare chest wall mass unfamiliar to thoracic surgeons.

  12. Direct intralymphatic injection of radiolabeled sup 111 In-T101 in patients with cutaneous T-cell lymphoma

    SciTech Connect

    Mulshine, J.L.; Carrasquillo, J.A.; Weinstein, J.N.; Keenan, A.M.; Reynolds, J.C.; Herdt, J.; Bunn, P.A.; Sausville, E.; Eddy, J.; Cotelingam, J.D. )

    1991-01-15

    Direct intralymphatic administration of radiolabeled monoclonal antibody in targeting antigen-bearing lymphoma cells in regional lymph nodes of patients with cutaneous T-cell lymphoma was evaluated. Seven consecutive patients undergoing staging lymphangiography received intralymphatic infusions of {sup 111}In-T101 to evaluate lymph node involvement. This procedure was accomplished without significant complication. The {sup 111}In-T101 rapidly distributed throughout the regional lymphatic compartment and passed into the systemic circulation. Tumor-bearing sites in the inguinal-femoral lymph nodes retained from 0.42 to 4.8% of the injected dose of radiolabeled antibody. Three patients were upstaged to Stage IVA based on tumor involvement found after radiolymphoscintigraphy-directed biopsy of groin lymph nodes, selected because of intense radioactivity by gamma camera imaging. Compared with previously reported s.c. antibody administration, there was a marked reduction in the radioactive exposure of normal tissues at the injection sites in the lower extremities. Direct intralymphatic delivery of {sup 111}In-T101 appears to be a feasible, efficient method for delivering therapeutic doses of radiolabeled antibody.

  13. Ubiquitin-specific protease 2 decreases p53-dependent apoptosis in cutaneous T-cell lymphoma.

    PubMed

    Wei, Tianling; Biskup, Edyta; Gjerdrum, Lise Mette Rahbek; Niazi, Omid; Ødum, Niels; Gniadecki, Robert

    2016-07-26

    Treatment of advanced cutaneous T-cell lymphomas (CTCL) is challenging because they are resistant to conventional chemotherapy. USP2 has been shown to promote resistance to chemotherapeutic agents in several cancer models.We show here USP2 is expressed in quiescent and activated T-cells and its expression is 50% lower in CTCL cell lines (MyLa2000, SeAx and Hut-78) than in normal T-cells. USP2 is expressed in neoplastic cells in early, plaque-stage mycosis fungoides (MF) and is downregulated in advanced tumor stages. Upon treatment with psoralen with UVA (PUVA) or a p53 activator, nutlin3a, USP2 expression is significantly increased in MyLa2000 (p53wt/wt), but not in SeAx (p53mut) or Hut-78 (p53-/-). USP2 knockdown decreases MyLa2000 cell viability after PUVA by 50% but not Hut-78, suggesting that the function of USP2 in CTCL cells is p53-dependent. Furthermore, USP2 knockdown results in a decreased Mdm2 expression and upregulation of p53. Taken together, our findings suggest that USP2 stabilizes Mdm2 which antagonizes pro-apoptotic activity of p53 and possibly contributes to therapeutic resistance in CTCL.

  14. Ubiquitin-specific protease 2 decreases p53-dependent apoptosis in cutaneous T-cell lymphoma

    PubMed Central

    Wei, Tianling; Biskup, Edyta; Rahbek Gjerdrum, Lise Mette; Niazi, Omid; Ødum, Niels; Gniadecki, Robert

    2016-01-01

    Treatment of advanced cutaneous T-cell lymphomas (CTCL) is challenging because they are resistant to conventional chemotherapy. USP2 has been shown to promote resistance to chemotherapeutic agents in several cancer models. We show here USP2 is expressed in quiescent and activated T-cells and its expression is 50% lower in CTCL cell lines (MyLa2000, SeAx and Hut-78) than in normal T-cells. USP2 is expressed in neoplastic cells in early, plaque-stage mycosis fungoides (MF) and is downregulated in advanced tumor stages. Upon treatment with psoralen with UVA (PUVA) or a p53 activator, nutlin3a, USP2 expression is significantly increased in MyLa2000 (p53wt/wt), but not in SeAx (p53mut) or Hut-78 (p53−/−). USP2 knockdown decreases MyLa2000 cell viability after PUVA by 50% but not Hut-78, suggesting that the function of USP2 in CTCL cells is p53-dependent. Furthermore, USP2 knockdown results in a decreased Mdm2 expression and upregulation of p53. Taken together, our findings suggest that USP2 stabilizes Mdm2 which antagonizes pro-apoptotic activity of p53 and possibly contributes to therapeutic resistance in CTCL. PMID:27351221

  15. The role of human T cell lymphotropic virus type I tax in the development of cutaneous T cell lymphoma.

    PubMed

    Zucker-Franklin, D

    2001-09-01

    Although it has been well established that the human T cell lymphotropic virus type I (HTLV-I) causes adult T cell leukemia/lymphoma (ATLL) in regions of the world where this virus is endemic, its role in the pathogenesis of cutaneous T cell lymphoma (CTCL) in the Western world has been less well established. Most patients with CTCL are negative for antibodies to the structural proteins of HTLV-I, and thus a causative role for this virus is usually dismissed. However, the Tax sequence of HTLV-I has been found in the peripheral blood mononuclear cells of practically all patients with CTCL. Such patients express Tax mRNA and have antibodies to p40Tax, the protein encoded by this sequence. Sequence analysis of a 159-bp region of Tax extracted from CTCL cells proved to be homologous with the same region prepared from a cell line infected with prototypic HTLV-I. By in situ PCR, Tax has been demonstrated in the lymphocytes infiltrating the skin as well as in the keratinocytes of such patients. Apart from the pathophysiologic and clinical interest of these studies, these observations may have therapeutic implications. In vitro, the proliferation of HTLV-I-transformed cells can be inhibited by antisense to HTLV-I Tax. Since Tax has not been identified in the normal human genome, antisense to Tax deserves serious consideration as a treatment modality for patients whose cells have been demonstrated to harborTax.

  16. Tumor Cell Adhesion As a Risk Factor for Sentinel Lymph Node Metastasis in Primary Cutaneous Melanoma

    PubMed Central

    Meves, Alexander; Nikolova, Ekaterina; Heim, Joel B.; Squirewell, Edwin J.; Cappel, Mark A.; Pittelkow, Mark R.; Otley, Clark C.; Behrendt, Nille; Saunte, Ditte M.; Lock-Andersen, Jorgen; Schenck, Louis A.; Weaver, Amy L.; Suman, Vera J.

    2015-01-01

    Purpose Less than 20% of patients with melanoma who undergo sentinel lymph node (SLN) biopsy based on American Society of Clinical Oncology/Society of Surgical Oncology recommendations are SLN positive. We present a multi-institutional study to discover new molecular risk factors associated with SLN positivity in thin and intermediate-thickness melanoma. Patients and Methods Gene clusters with functional roles in melanoma metastasis were discovered by next-generation sequencing and validated by quantitative polymerase chain reaction using a discovery set of 73 benign nevi, 76 primary cutaneous melanoma, and 11 in-transit melanoma metastases. We then used polymerase chain reaction to quantify gene expression in a model development cohort of 360 consecutive thin and intermediate-thickness melanomas and a validation cohort of 146 melanomas. Outcome of interest was SLN biopsy metastasis within 90 days of melanoma diagnosis. Logic and logistic regression analyses were used to develop a model for the likelihood of SLN metastasis from molecular, clinical, and histologic variables. Results ITGB3, LAMB1, PLAT, and TP53 expression were associated with SLN metastasis. The predictive ability of a model that included these molecular variables in combination with clinicopathologic variables (patient age, Breslow depth, and tumor ulceration) was significantly greater than a model that only considered clinicopathologic variables and also performed well in the validation cohort (area under the curve, 0.93; 95% CI, 0.87 to 0.97; false-positive and false-negative rates of 22% and 0%, respectively, using a 10% cutoff for predicted SLN metastasis risk). Conclusion The addition of cell adhesion–linked gene expression variables to clinicopathologic variables improves the identification of patients with SLN metastases within 90 days of melanoma diagnosis. PMID:26150443

  17. Primary cutaneous neuroendocrine carcinoma, Merkel cell carcinoma. Case series 1991-2012.

    PubMed

    Campillo, Ramón; Gil-Carcedo, Elisa; Alonso, David; Vallejo, Luis A; Oñate, Juan M; Gil-Carcedo, Luis M

    2013-01-01

    Merkel cell carcinoma was first described by Toker in 1972. It is an uncommon, primary neuroendocrine skin carcinoma which appears in the dermoepidermic area, grows fast, is very aggressive and has a poor prognosis. The aim of this work is to highlight the importance of this tumour, which develops mainly in the skin of the head and neck area, and whose prevalence has increased in recent years. We gathered data on 16 patients suffering cutaneous neuroendocrine carcinoma treated at our hospital between September 12, 1991 and July 13, 2012. We indicated the age and gender of patients. We described the area where the tumour was located, indicating the size in millimetres, according to the major axis of the lesion. Most of the patients studied were over 70 years old, except for one who was 55. The highest frequency of cases appeared among patients aged over 80 years. In the cases studied, when the tumour appeared in the head and neck region (10/16), its location could be nasal-lateronasal, cheek-malar, upper eyelid, frontal or mandibular. The major axis of the lesion ranged between 7 and 35 mm. Unlike with epidermoid or basocellular carcinomas, recurrence and ganglionar metastases were common. Immunohistochemical (CK20) tests are essential for a correct diagnosis. Treatment is usually surgical and occasionally followed by radiotherapy and chemotherapy. This carcinoma is not a very common skin tumour. It appears in old age, in the head and neck region in 50% of cases and often leads to exitus. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  18. Imaging of cutaneous T cell lymphoma (CTCL) with In-111-T101 monoclonal antibody

    SciTech Connect

    Carrasquillo, J.A.; Bunn, P.A.; Keenan, A.M.; Reynolds, J.C.; Schroff, R.W.; Foon, K.A.; Ming-Hsu, S.; Gazdar, A.F.; Mulshine, J.M.; Perentesis, P.

    1985-05-01

    T101 is a murine monoclonal antibody (MoAb), IgC2a, directed against a cell surface pan T-cell antigen present in high concentration in CTCL cells. In-111 labelling was performed with a modification of the Krejcarek method (Hybritech, Inc.). I mg of DTPA conjugated T101 was labeled with 5 mCi, with a mean incorporation of 95%. Immunoreactivity was preserved, mean 88%. In vivo, less than 3.6% of the injected dose was on circulating transferrin. 11 patients (pts) received 2-6h intravenous infusion of 1 mg (5 pts), 10 mg (3 pts), 50 mg (3 pts) of In-111 T101. By 24h all pts showed avid uptake in pathologically or clinically involved nodes and erythroderma including several previously unsuspected nodal regions. Skin plaques were not visualized. In addition, there was localization in liver, spleen and bone marrow. Concentration of In-111 in biopsied nodes was 0.01, 0.02 and 0.03% of the injected dose per gram. Control studies with In-111Cl/sub 3/ or a nonspecific MoAb, 9.2.27, did not concentrate in nodes or skin disease. No dose dependent differences in tumor localization was seen although blood clearance was prolonged for doses less than or equal to 10 mgs of T101. All pts receiving less than or equal to 10 mgs developed transient itching, urticaria and chills. 1 of 8 pts tested had an antimouse immune response. Modulation of the antigen from circulating T-cells, skin and nodes was seen. This study shows the feasibility of imaging CTCL pts with In-111 T101 and suggest a potential for radioimmunotherapy.

  19. Successful Treatment of Advanced Primary Cutaneous Apocrine Carcinoma on the Scrotum with Systemic Chemotherapy and Radiotherapy Followed by Denosumab

    PubMed Central

    Furudate, Sadanori; Fujimura, Taku; Tsukada, Akira; Sato, Yota; Hidaka, Takanori; Tanita, Kayo; Kambayashi, Yumi; Haga, Takahiro; Hashimoto, Akira; Aiba, Setsuya

    2017-01-01

    Primary cutaneous apocrine carcinoma (PCAC) is a rare and highly aggressive cutaneous adnexal type of tumor that has a high metastasis rate and a poor prognosis. Although there are several case reports describing the successful treatment of PCAC with chemoradiotherapy or molecular targeting therapy, no standard therapy for the treatment of advanced PCAC has been established yet. Since receptor activator of nuclear factor kappa-B ligand (RANKL) is expressed in cancers of apocrine origin, leading to immunosuppression at the tumor site, we hypothesized that targeting RANKL with denosumab might be useful for the treatment of PCAC. In this report, we describe a case with advanced PCAC on the scrotum successfully treated with systemic chemotherapy using carboplatin and paclitaxel, and radiotherapy followed by denosumab. PMID:28203164

  20. Comparative microarray analysis of microRNA expression profiles in primary cutaneous malignant melanoma, cutaneous malignant melanoma metastases, and benign melanocytic nevi.

    PubMed

    Sand, Michael; Skrygan, Marina; Sand, Daniel; Georgas, Dimitrios; Gambichler, Thilo; Hahn, Stephan A; Altmeyer, Peter; Bechara, Falk G

    2013-01-01

    Perturbations in microRNA (miRNA) expression profiles have been reported for cutaneous malignant melanoma (CMM) predominantly when examined in cell lines. Despite the rapidly growing number of newly discovered human miRNA sequences, the availability of up-to-date miRNA expression profiles for clinical samples of primary cutaneous malignant melanoma (PCMM), cutaneous malignant melanoma metastases (CMMM), and benign melanocytic nevi (BMN) is limited. Specimens excised from the center of tumors (lesional) from patients with PCMM (n=9), CMMM (n=4), or BMN (n=8) were obtained during surgery. An exploratory microarray analysis was performed by miRNA expression profiling based on Agilent platform screening for 1205 human miRNAs. The results from the microarray analysis were validated by TaqMan quantitative real-time polymerase chain reaction. In addition to several miRNAs previously known to be associated with CMM, 19 unidentified miRNA candidates were found to be dysregulated in CMM patient samples. Among the 19 novel miRNA candidates, the genes hsa-miR-22, hsa-miR-130b, hsa-miR-146b-5p, hsa-miR-223, hsa-miR-301a, hsa-miR-484, hsa-miR-663, hsa-miR-720, hsa-miR-1260, hsa-miR-1274a, hsa-miR-1274b, hsa-miR-3663-3p, hsa-miR-4281, and hsa-miR-4286 were upregulated, and the genes hsa-miR-24-1*, hsa-miR-26a, hsa-miR-4291, hsa-miR-4317, and hsa-miR-4324 were downregulated. The results of this study partially confirm previous CMM miRNA profiling studies identifying miRNAs that are dysregulated in CMM. However, we report several novel miRNA candidates in CMM tumors; these miRNA sequences require further validation and functional analysis to evaluate whether they play a role in the pathogenesis of CMM.

  1. Cutaneous T-cell lymphoma: 2016 update on diagnosis, risk-stratification, and management

    PubMed Central

    Wilcox, Ryan A.

    2015-01-01

    Disease overview Cutaneous T-cell lymphomas are a heterogenous group of T-cell lymphoproliferative disorders involving the skin, the majority of which may be classified as Mycosis Fungoides (MF) or Sézary Syndrome (SS). Diagnosis The diagnosis of MF or SS requires the integration of clinical and histopathologic data. Risk-adapted therapy TNMB (tumor, node, metastasis, blood) staging remains the most important prognostic factor in MF/SS and forms the basis for a “risk-adapted,” multi-disciplinary approach to treatment. For patients with disease limited to the skin, expectant management or skin-directed therapies is preferred, as both disease-specific and overall survival for these patients is favorable. In contrast, patients with advanced-stage disease with significant nodal, visceral or blood involvement are generally approached with biologic-response modifiers or histone deacetylase inhibitors prior to escalating therapy to include systemic, single-agent chemotherapy. In highly-selected patients, allogeneic stem-cell transplantation may be considered, as this may be curative in some patients. PMID:26607183

  2. Cytogenetic characterization of circulating malignant cells in patients with cutaneous T-cell lymphomas

    SciTech Connect

    Thangavelu, M.; Yelavarthi, K.K.; Finn, W.G.

    1994-09-01

    Peripheral lymphocytes from 20 patients with cutaneous T-cell lymphomas (CTCL) were analyzed for clonal chromosomal abnormalities using phytohemagglutinin or a combination of IL-2 and IL-7 as mitogens. Clonal abnormalities were observed in 10 of 16 patients with circulating Sezary cells but in none of the 4 patients without circulating Sezary cells, suggesting a correlation between the presence of clonal abnormalities and circulating Sezary cells. Complex chromosomal abnormalities appear to correlate with poor prognosis (1 of 6 cases with a single abnormal clone and all 4 cases with complex abnormalities). Clonal abnormalities involving chromosomes 1 and 8 were observed in 6 cases. In 5 cases involving chromosome 1, loss of material involved the region between 1p33 and 1p36. In an additional case, a reciprocal translocation involving the short arm of chromosome 1 and 1p33 was observed. In 2 cases an apparently identical, balanced translocation involving chromosomes 8 and 17, t(8;17)(p21;q21), was observed. Clonal abnormalities involving chromosomes 10 and 17 (5 cases) and chromosomes 2, 4, 5, 9, 13, and 20 (3 cases) were also observed. Future studies of these chromosomes at the molecular level, particularly of the region between 1p33 and 1p36, may help in the identification of the genetic defects associated with malignant transformation in CTCL.

  3. Romidepsin in peripheral and cutaneous T-cell lymphoma: mechanistic implications from clinical and correlative data.

    PubMed

    Bates, Susan E; Eisch, Robin; Ling, Alexander; Rosing, Douglas; Turner, Maria; Pittaluga, Stefania; Prince, H Miles; Kirschbaum, Mark H; Allen, Steven L; Zain, Jasmine; Geskin, Larisa J; Joske, David; Popplewell, Leslie; Cowen, Edward W; Jaffe, Elaine S; Nichols, Jean; Kennedy, Sally; Steinberg, Seth M; Liewehr, David J; Showe, Louise C; Steakley, Caryn; Wright, John; Fojo, Tito; Litman, Thomas; Piekarz, Richard L

    2015-07-01

    Romidepsin is an epigenetic agent approved for the treatment of patients with cutaneous or peripheral T-cell lymphoma (CTCL and PTCL). Here we report data in all patients treated on the National Cancer Institute 1312 trial, demonstrating long-term disease control and the ability to retreat patients relapsing off-therapy. In all, 84 patients with CTCL and 47 with PTCL were enrolled. Responses occurred early, were clinically meaningful and of very long duration in some cases. Notably, patients with PTCL receiving romidepsin as third-line therapy or later had a comparable response rate (32%) of similar duration as the total population (38%). Eight patients had treatment breaks of 3.5 months to 10 years; in four of six patients, re-initiation of treatment led to clear benefit. Safety data show slightly greater haematological and constitutional toxicity in PTCL. cDNA microarray studies show unique individual gene expression profiles, minimal overlap between patients, and both induction and repression of gene expression that reversed within 24 h. These data argue against cell death occurring as a result of an epigenetics-mediated gene induction programme. Together this work supports the safety and activity of romidepsin in T-cell lymphoma, but suggests a complex mechanism of action.

  4. Role for Lyt-2+ T cells in resistance to cutaneous leishmaniasis in immunized mice

    SciTech Connect

    Farrell, J.P.; Muller, I.; Louis, J.A.

    1989-03-15

    The role of Lyt-2+ T cells in immunologic resistance to cutaneous leishmaniasis was analyzed by comparing infection patterns in resistant C57BL/6 mice and susceptible BALB/c mice induced to heal their infections after sub-lethal irradiation or i.v. immunization, with similar mice treated in vivo with anti-Lyt-2 antibodies. Administration of anti-Lyt-2 mAb resulted in a dramatic reduction in the number of lymphoid cells expressing the Lyt-2+ phenotype. Such treatment led to enhanced disease in both resistant C57BL/6 and irradiated BALB/c mice, as assessed by lesion size, but did not affect the capacity of these mice to ultimately resolve their infections. In contrast, anti-Lyt-2 treatment totally blocked the induction of resistance in i.v. immunized mice. These results suggest, that Lyt-2+ T cells may play a role in immunity to a Leishmania major infection and that their relative importance to resistance may depend on how resistance is induced.

  5. Eotaxins and CCR3 interaction regulates the Th2 environment of cutaneous T-cell lymphoma.

    PubMed

    Miyagaki, Tomomitsu; Sugaya, Makoto; Fujita, Hideki; Ohmatsu, Hanako; Kakinuma, Takashi; Kadono, Takafumi; Tamaki, Kunihiko; Sato, Shinichi

    2010-09-01

    CC chemokine receptor 3 (CCR3), the sole receptor for eotaxins, is expressed on eosinophils and T helper type 2 (Th2) cells. In Hodgkin's disease, eotaxin-1 secreted by fibroblasts collects Th2 cells and eosinophils within the tissue. Similarly, many Th2 cells infiltrate the lesional skin of cutaneous T-cell lymphoma (CTCL). In this study, we investigated the role of eotaxins in the development of the Th2 environment of CTCL. We revealed that fibroblasts from lesional skin of CTCL expressed higher amounts of eotaxin-3 messenger RNA (mRNA) compared with those from normal skin. Lesional skin of CTCL at advanced stages contained significantly higher levels of eotaxin-3 and CCR3 mRNA, compared with early stages of CTCL. IL-4 mRNA was expressed in some cases at advanced stages. Immunohistochemistry revealed that keratinocytes, endothelial cells, and dermal fibroblasts in lesional skin of CTCL showed a stronger expression of eotaxin-3 than did normal skin. CCR3(+) lymphocytes and IL-4 expression were observed in some cases of advanced CTCL. Furthermore, both serum eotaxin-3 and eotaxin-1 levels of CTCL patients at advanced stages were significantly higher than those of healthy individuals. The concentrations of these chemokines correlated with serum soluble IL-2 receptor levels. These results suggest that interaction of eotaxins and CCR3 regulates the Th2-dominant tumor environment, which is closely related to the development of CTCL.

  6. Enhanced CCR5+/CCR3+ T helper cell ratio in patients with active cutaneous lupus erythematosus.

    PubMed

    Freutel, S; Gaffal, E; Zahn, S; Bieber, T; Tüting, T; Wenzel, J

    2011-10-01

    Cutaneous lupus erythematosus (CLE) is characterized by enhanced interferon α (IFNα) levels in serum and in tissue. Since IFNα promotes a Th1-biased immune response, we hypothesized that a Th1-associated chemokine receptor profile should be a typical finding in patients with active CLE. Therefore, peripheral blood mononuclear cells were isolated from patients with different CLE subsets (n = 15), healthy controls (n = 13) and patients under immunotherapy with IFNα (n = 7). T helper cells were analysed by flow cytometry for the expression of the chemokines receptor CCR5, indicative for Th1 cells, and of CCR3, indicating Th2. In addition, intracellular levels of the type I IFN-inducible MxA protein were measured. Patients with widespread active CLE skin lesions had a significantly increased expression of CCR5, whereas expression of CCR3 was decreased when compared with healthy controls. MxA expression was significantly enhanced in all investigated CLE subtypes, with the highest levels in patients with widespread skin lesions. The enhanced CCR5/CCR3 ratio closely correlated with the MxA levels in peripheral lymphocytes and with disease activity. Our analyses revealed that active CLE is associated with a systemic type I IFN effect that appears to induce a shift towards a Th1-associated chemokine receptor profile. The CCR5/CCR3 T-helper cell ratio might therefore represent an indirect marker for the disease activity in CLE.

  7. Role of Synchrotron infra red microspectroscopy in studying epidermotropism of cutaneous T-cell lymphoma

    SciTech Connect

    El Bedewi, A.; El Anany, G; El Mofty, M

    2010-01-01

    The molecular mechanisms of epidermotropism in mycosis fungoides (MF) are not well understood to date. The aim of this study was to differentiate between epidermal and dermal lymphocytes within the skin of MF patients. This study was done on 10 MF patients with a mean age of 50 years diagnosed clinically in the Department of Dermatology, Cairo University, Egypt. A 6 mm biopsy was taken from each patient in order to confirm the diagnosis. Skin biopsies were cut, put on low e-slides and then stained with H&E. Further examination with Synchrotron infrared (IR) microspectroscopy was done in National Synchrotron Light Source - Brookhaven National Laboratory, New York, USA. Immunophenotyping using antibodies CD3, CD4, CD8, CD20 and CD30 was also done. Statistical analysis was done by Student's t-test and cluster analysis. Both epidermal and dermal lymphocytes were clustered separately. Also, Amide I and RNA and DNA within the lymphocytes were significantly different between the epidermis and the dermis. The biochemical analysis of protein, RNA and DNA with Synchrotron IR microspectroscopy is a promising tool for studying epidermotropism in cutaneous T-cell lymphoma.

  8. Gallium maltolate inhibits human cutaneous T-cell lymphoma tumor development in mice.

    PubMed

    Wu, Xuesong; Wang, Timothy W; Lessmann, George M; Saleh, Jamal; Liu, Xiping; Chitambar, Christopher R; Hwang, Sam T

    2015-03-01

    Cutaneous T-cell lymphomas (CTCLs) represent a heterogeneous group of non-Hodgkin's lymphoma characterized by an accumulation of malignant CD4 T cells in the skin. The group IIIa metal salt, gallium nitrate, is known to have antineoplastic activity against B-cell lymphoma in humans, but its activity in CTCLs has not been elaborated in detail. Herein, we examined the antineoplastic efficacy of a gallium compound, gallium maltolate (GaM), in vitro and in vivo with murine models of CTCLs. GaM inhibited cell growth and induced apoptosis of cultured CTCL cells. In human CTCL xenograft models, peritumoral injection of GaM limited the growth of CTCL cells, shown by fewer tumor formations, smaller tumor sizes, and decreased neovascularization in tumor microenvironment. To identify key signaling pathways that have a role in GaM-mediated reduction of tumor growth, we analyzed inflammatory cytokines, as well as signal transduction pathways in CTCL cells treated by GaM. IFN-γ-induced chemokines and IL-13 were found to be notably increased in GaM-treated CTCL cells. However, immunosuppressive cytokines, such as IL-10, were decreased with GaM treatment. Interestingly, both oxidative stress and p53 pathways were involved in GaM-induced cytotoxicity. These results warrant further investigation of GaM as a therapeutic agent for CTCLs.

  9. Cutaneous zygomycosis.

    PubMed

    Bonifaz, Alexandro; Vázquez-González, Denisse; Tirado-Sánchez, Andrés; Ponce-Olivera, Rosa María

    2012-01-01

    Cutaneous zygomycosis is a fungal infection caused by zygomycetes that affects the skin. It occurs in uncontrolled diabetic patients and immunosuppressed individuals. It has 2 clinical forms: primary cutaneous zygomycosis and secondary cutaneous zygomycosis. The first is characterized by necrotic lesions and the fungus is usually inoculated by trauma. If diagnosed early, it generally has a good prognosis. Secondary zygomycosis is usually a complication and extension of the rhinocerebral variety that starts as a palpebral fistula and progresses to a necrotic lesion with a poor prognosis. The diagnosis is made by identification of the fungus by direct KOH examination, culture, and biopsy. Treatment for the primary disease is surgical debridement plus amphotericin B. The secondary type is treated with amphotericin B and/or posaconazole.

  10. Cutaneous absorption and decontamination of ( sup 3 H)T-2 toxin in the rat model

    SciTech Connect

    Bunner, B.L.; Wannemacher, R.W. Jr.; Dinterman, R.E.; Broski, F.H. )

    1989-01-01

    Cutaneous absorption and decontamination of ({sup 3}H)T-2 mycotoxin using various treatment modalities incorporating water, detergent, sprays, and scrubbing of application sites were examined in the rat model at 5, 30, 60, and 1440 min (24 h) postexposure. Rats were killed immediately after treatment and radiolabeled T-2 remaining in full-thickness skin samples was determined. Absorption and decontamination were followed over time, and decontaminating treatment modalities were evaluated for efficacy. Less than 1% of the applied dose was absorbed in 5 min, and 50% was absorbed in 24 h. At 5 min, 99.5 {plus minus} 0.05% of nonabsorbed (residual) ({sup 3}H)T-2 was removed, and 58 {plus minus} 5.2% of residual toxin was removed at 24 h with a 2.5% detergent/water spray. When treatment modalities were evaluated at 60 min, a 2.5% detergent/water scrub followed by a detergent/water spray produced optimal decontamination by removing 81 {plus minus} 2.2% of residual toxin. All treatment modalities using detergent and/or water removed significant amounts of toxin, a dry scrub was not efficacious. Treatment should be initiated as soon as possible after exposure for best results. However, the stratum corneum acts as a reservoir for the toxin, and decontamination should be carried out even if delayed several hours or days after exposure. Dermal absorption pharmacokinetics found in these studies are similar to those described for other low-molecular-weight compounds, and the decontamination results from T-2 toxin should be applicable to other, similar toxic substances.

  11. Primary cutaneous CD30+ lymphoproliferative disorders: new insights into biology and therapy.

    PubMed

    Querfeld, Christiane; Kuzel, Timothy M; Guitart, Joan; Rosen, Steven T

    2007-05-01

    The spectrum of CD30+ lymphoproliferative diseases of the skin includes CD30+ cutaneous anaplastic large cell lymphoma, lymphomatoidpapulosis, as well as borderline cases. These entities constitute the second most common group of cutaneous lymphomas according to the newly revised World Health Organization and European Organisation for Research and Treatment of Cancer consensus classification. Recent progress in immune and molecular biology, and identification of therapeutic targets have increased our understanding of these diseases and have led to novel treatment approaches. This review will provide an update on recent findings of immunologic, molecular, cytogenetic features and treatment strategies for patients with CD30+ lymphoproliferative diseases.

  12. Human T-lymphotropic virus type I proviral loads in patients with adult T-cell leukemia-lymphoma: Comparison between cutaneous type and other subtypes.

    PubMed

    Yonekura, Kentaro; Utsunomiya, Atae; Seto, Masao; Takatsuka, Yoshifusa; Takeuchi, Shogo; Tokunaga, Masahito; Kubota, Ayumu; Takeda, Koichiro; Kanzaki, Tamotsu; Uchida, Youhei; Kawai, Kazuhiro; Kanekura, Takuro

    2015-12-01

    Adult T-cell leukemia-lymphoma (ATL), characterized by various clinicopathological features, is divided into four clinical subtypes, namely, acute, lymphoma, chronic and smoldering types, and the treatment strategy differs according to the clinical subtype. The designation cutaneous type ATL has been proposed to describe a peculiar subgroup of smoldering type ATL in which the skin is predominantly affected. However, diagnostic criteria and prognostic factors for cutaneous type ATL remain to be determined. Therefore, we performed a retrospective study to obtain a precise method for subtype classification and to clearly define cutaneous type ATL. A total of 87 ATL patients (acute, n = 31; lymphoma, n = 6; chronic, n = 24; smoldering, n = 26) were enrolled. The human T-lymphotropic virus type I (HTLV-1) proviral load in peripheral blood and the serum soluble interleukin-2 receptor (sIL-2R) level were evaluated with respect to the clinical features of the different types of ATL. The HTLV-1 proviral load was significantly increased in the acute and chronic type and the serum sIL-2R level was increased in the acute and lymphoma type. The HTLV-1 proviral load was significantly lower in cutaneous than other smoldering types of ATL without skin lesions. The clinical findings of cutaneous type ATL were also different from other subtypes. These results indicate that, in combination, determination of the HTLV-1 proviral load and the serum sIL-2R level is useful for distinguishing among the different types of ATL, and strongly suggest that cutaneous type ATL is a distinct clinical entity. © 2015 Japanese Dermatological Association.

  13. Pharmacologic inhibition of RORγt regulates Th17 signature gene expression and suppresses cutaneous inflammation in vivo.

    PubMed

    Skepner, Jill; Ramesh, Radha; Trocha, Mark; Schmidt, Darby; Baloglu, Erkan; Lobera, Mercedes; Carlson, Thaddeus; Hill, Jonathan; Orband-Miller, Lisa A; Barnes, Ashley; Boudjelal, Mohamed; Sundrud, Mark; Ghosh, Shomir; Yang, Jianfei

    2014-03-15

    IL-17-producing CD4(+)Th17 cells, CD8(+)Tc17 cells, and γδ T cells play critical roles in the pathogenesis of autoimmune psoriasis. RORγt is required for the differentiation of Th17 cells and expression of IL-17. In this article, we describe a novel, potent, and selective RORγt inverse agonist (TMP778), and its inactive diastereomer (TMP776). This chemistry, for the first time to our knowledge, provides a unique and powerful set of tools to probe RORγt-dependent functions. TMP778, but not TMP776, blocked human Th17 and Tc17 cell differentiation and also acutely modulated IL-17A production and inflammatory Th17-signature gene expression (Il17a, Il17f, Il22, Il26, Ccr6, and Il23) in mature human Th17 effector/memory T cells. In addition, TMP778, but not TMP776, inhibited IL-17A production in both human and mouse γδ T cells. IL-23-induced IL-17A production was also blocked by TMP778 treatment. In vivo targeting of RORγt in mice via TMP778 administration reduced imiquimod-induced psoriasis-like cutaneous inflammation. Further, TMP778 selectively regulated Th17-signature gene expression in mononuclear cells isolated from both the blood and affected skin of psoriasis patients. In summary, to our knowledge, we are the first to demonstrate that RORγt inverse agonists: 1) inhibit Tc17 cell differentiation, as well as IL-17 production by γδ T cells and CD8(+) Tc17 cells; 2) block imiquimod-induced cutaneous inflammation; 3) inhibit Th17 signature gene expression by cells isolated from psoriatic patient samples; and 4) block IL-23-induced IL-17A expression. Thus, RORγt is a tractable drug target for the treatment of cutaneous inflammatory disorders, which may afford additional therapeutic benefit over existing modalities that target only IL-17A.

  14. Characterization of the tumor microenvironment in primary cutaneous CD30-positive lymphoproliferative disorders: a predominance of CD163-positive M2 macrophages.

    PubMed

    De Souza, Aieska; Tinguely, Marianne; Burghart, Daniel R; Berisha, Arbeneshe; Mertz, Kirsten D; Kempf, Werner

    2016-07-01

    The tumor microenvironment is essential for tumor survival, growth and progression. There are only a few studies on the tumor microenvironment in cutaneous CD30-positive lymphoproliferative disorders. We assessed the composition of the tumor microenvironment using immunohistochemistry studies in skin biopsies from cases diagnosed with lymphomatoid papulosis (LyP: 18 specimens), primary cutaneous anaplastic large-cell lymphoma (PC-ALCL: 8 specimens), and reactive diseases harboring CD30-positive cells (18 specimens). The predominant cells present in LyP and PC-ALCL were CD163+ M2 macrophages (44.7%, 35%), followed by CD8+ tumor infiltrating lymphocytes (11%, 15%), FOXP3+ T-regulatory cells (9%, 4.5%) and programmed cell death 1(PD-1) + lymphocytes (2.2%, 6.8%). In contrast, CD30-positive reactive inflammatory and infectious disorders were characterized by higher numbers of CD123+ plasmacytoid dendritic cells (6.3%) when compared to LyP (1%), and PC-ALCL (1.1%). Key differences exist between the microenvironment of CD30-positive lymphoproliferative disorders and reactive conditions harboring CD30-positive lymphocytes. The high number of tumor associated macrophages, and the close vicinity of these immune cells to the CD30-positive tumor cells might suggest that tumor associated macrophages have direct influence on tumorigenesis in LyP and ALCL. Therefore, modulation of M2 macrophages may represent a new therapeutic strategy in cutaneous CD30-positive lymphoproliferative disorders. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Denileukin diftitox for the treatment of cutaneous T-cell lymphoma

    PubMed Central

    Kaminetzky, David; Hymes, Kenneth B

    2008-01-01

    Cutaneous T-cell lymphoma/mycosis fungoides (CTCL/MF) is a rare lymphoproliferative disorder which can present as an indolent or as an aggressive process involving skin, lymph nodes, and blood. In stages IA, IB and IIA, it is usually managed with topical medications and phototherapy. If there is progression despite application of these treatments, or if the patient presents with a higher stage of disease, systemic chemotherapy or retinoids, rexinoids, biologic response modifiers are often necessary. Consequently, patients are often treated with a sequence of modalities and drugs. Denileukin diftitox (DD, Ontak®) is a targeted immunotoxin which has biological activity against malignancies expressing the IL-2 receptor. In addition to its unique mechanism of action, DD has a toxicity profile which does not overlap with most commonly used chemotherapeutic agents. CTCL/MF has been found be particularly susceptible to treatment with this agent. This review will describe the development DD, its proposed mechanism of action, the clinical trials which identified its utility in the treatment of CTCL/MF, the common toxicities encountered with this agent, and the management of these toxicities. In addition the incorporation of DD in the sequential treatment of CTCL/MF and data suggesting potential combination therapies employing this novel agent will be discussed. PMID:19707452

  16. Denileukin diftitox for the treatment of cutaneous T-cell lymphoma.

    PubMed

    Kaminetzky, David; Hymes, Kenneth B

    2008-12-01

    Cutaneous T-cell lymphoma/mycosis fungoides (CTCL/MF) is a rare lymphoproliferative disorder which can present as an indolent or as an aggressive process involving skin, lymph nodes, and blood. In stages IA, IB and IIA, it is usually managed with topical medications and phototherapy. If there is progression despite application of these treatments, or if the patient presents with a higher stage of disease, systemic chemotherapy or retinoids, rexinoids, biologic response modifiers are often necessary. Consequently, patients are often treated with a sequence of modalities and drugs. Denileukin diftitox (DD, Ontak(R)) is a targeted immunotoxin which has biological activity against malignancies expressing the IL-2 receptor. In addition to its unique mechanism of action, DD has a toxicity profile which does not overlap with most commonly used chemotherapeutic agents. CTCL/MF has been found be particularly susceptible to treatment with this agent. This review will describe the development DD, its proposed mechanism of action, the clinical trials which identified its utility in the treatment of CTCL/MF, the common toxicities encountered with this agent, and the management of these toxicities. In addition the incorporation of DD in the sequential treatment of CTCL/MF and data suggesting potential combination therapies employing this novel agent will be discussed.

  17. [Thyroid and lipidic dysfunction associated with bexarotene in cutaneous T-cell lymphoma].

    PubMed

    Rodriguez Suarez, Santiago; Pamies Andreu, Encarnación; Muñiz Grijalvo, Ovidio; Garcia Morillo, José Salvador

    2016-02-05

    Bexarotene is a synthetic selective X receptor rexinoide approved for the systemic treatment of cutaneous T-cell lymphoma. During treatment is very frequent the occurrence of hypothyroidism and severe mixed hyperlipidemia, both are reversibles and dose-dependent adverse events. Increase of triglycerides and LDL-cholesterol level (up to even higher levels have been associated with pancreatitis in some cases) is widely described (as is the case with other retinoids) but decrease in HDL-cholesterol is poored know. We review our experience with the use of bexarotene. We present a serie of 3 clinical report of patients treated with bexarotene in whose, in addition to these well-known adverse event, a serious lowering of HDL-cholesterol was observed. The 3 patients studied had metabolic complications like central hypothyroidism and severe mixed hyperlipidemia; with special emphasis on the sharp fall (mean decrease>83%) in the HDL-cholesterol level. Cholesterol lowering medication and substitutive hormonal replacement with levotiroxine resulted in an improvement of the biochimical parameters without reaching the correct goals. Bexarotene produce as predictable side effects severe mixed hyperlipidemia with marked decrease in HDL-cholesterol levels and central hypothyroidism, being the both reversible and dose-dependent. A reflection on the possible aetiological mechanisms and implications of this phenomenon are included. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  18. Transcription factor profiling shows new ways towards new treatment options of cutaneous T cell lymphomas.

    PubMed

    Döbbeling, Udo

    2007-06-01

    Most oncogenes encode activators of transcription factors or transcription factors themselves. Transcription factors that are induced by growth stimuli are, in contrast to transcription factors that regulate house keeping genes, tightly regulated and only active, when a stimulus (e.g. cytokines or other growth factors) is given. Examples of such transcription factors are members of the jun, fos, myc, NFkB and STAT gene families. In cancer cells this regulation is interrupted, resulting in constitutive activities of transcription factors that are normally silent. This in turn results in the increased expression of target genes that are necessary for growth and protection from apoptosis. Since inducible transcription factors are activated by specific pathways, the identification of unusual constitutively active transcription factors also identifies the involved signal transduction pathway. Inhibitors of the components of these pathways may be effective anti-cancer agents, as they interrupt the abnormal signalling and in cancer cells. We applied this strategy for two forms of cutaneous T cell lymphomas and identified several groups of agents that may be the prototypes of new drugs to fight these diseases.

  19. Chemotherapeutic treatment is associated with Notch1 induction in cutaneous T-cell lymphoma.

    PubMed

    Kamstrup, Maria R; Biskup, Edyta; Manfè, Valentina; Savorani, Cecilia; Liszewski, Walter; Wirèn, Johan; Specht, Lena; Gniadecki, Robert

    2017-01-01

    The Notch pathway is important for survival of cutaneous T-cell lymphoma (CTCL) cells. We investigated the effect of chemotherapy (doxorubicin, etoposide, and gemcitabine) and radiation modalities on Notch signaling in CTCL cell lines. Chemotherapy induced Notch1 expression at the mRNA and protein level in MyLa2000 and Hut78. Upregulation of well-established Notch targets supported the functional activity of Notch1. Transfection of Notch1 siRNA into MyLa2000 cells was not able to suppress the effects of chemotherapy on Notch1 activation significantly. Notch1 knockdown in combination with doxorubicin, etoposide, or gemcitabine compared to chemotherapy alone decreased cell viability by 12, 20, and 26%, respectively (p < 0.05). Additionally, X-rays (in MyLa2000 but not SeAx) and psoralen plus UVA (PUVA) (in MyLa2000, Hut78, and SeAx) increased the expression of Notch1 family members. Our results indicate that CTCL cells activate the Notch pathway in vitro in response to chemotherapy and radiation modalities as a possible protective mechanism.

  20. Primary cutaneous undifferentiated round cell tumor with concurrent polymyositis in a dog

    PubMed Central

    Gianella, Paola; Avallone, Giancarlo; Bellino, Claudio; Iussich, Selina; Palmieri, Chiara; Roccabianca, Paola; Salvadori, Claudia; Zanatta, Renato; D’Angelo, Antonio

    2012-01-01

    A cutaneous poorly differentiated round cell tumor with concurrent, non-suppurative, polymyositis was diagnosed in a hovawart dog. Histochemical staining, immunohistochemistry, and transmission electron microscopy findings suggested that the tumors cells were of myeloid, or possibly natural killer cell origin. The possibility that the concurrent polymyositis may represent a pre-neoplastic or paraneoplastic process is discussed. PMID:23115370

  1. Failure to detect human T-lymphotropic virus type-I proviral DNA in cell lines and tissues from patients with cutaneous T-cell lymphoma.

    PubMed

    Li, G; Vowels, B R; Benoit, B M; Rook, A H; Lessin, S R

    1996-09-01

    Previous molecular studies investigating the presence of HTLV-I proviral DNA in cell lines and tissue samples of patients with cutaneous T-cell lymphoma (CTCL) have reported a detection rate ranging from 0-92%. Despite the lack of epidemiologic data linking HTLV-I infection with CTCL, the molecular data still invite speculation regarding the precise role of HTLV-I in the pathogenesis of CTCL. To determine the detection rate of HTLV-I proviral DNA among CTCL patients referred to our medical center, we analyzed Epstein-Barr virus-transformed cell lines established from peripheral blood of seven CTCL patients and 43 tissue samples from 22 patients with different stages of disease. Genomic DNA was polymerase chain reaction-amplified with primers within the HTLV-I tax gene region. Amplification products were probed with nested oligonucleotide probes by Southern blot analysis. No HTLV-I proviral sequences were detected in the samples (0/50). Using HTLV-I/II pol primers, no HTLV-I pol gene sequences were detected. In tissues from one patient, HTLV-II pol and tax gene sequences were detected; however, HTLV-II proviral integration was not detected by Southern blot analysis of the genomic DNA. Our data suggest: (i) HTLV-I does not appear to be a primary etiologic agent in CTCL; and (ii) HTLV-II pol and tax gene sequences can be detected in a minority of CTCL patients, but this does not necessarily imply an etiologic role.

  2. [Protocol proposal for the histological report of the primary tumor in patients with cutaneous melanoma from the Task Force for Cutaneous Melanoma of the Valencian Community].

    PubMed

    Nagore, E; Monteagudo, C; Pinazo, M I; Botella-Estrada, R; Oliver, V; Bañuls, J; Moragón, M; Valcuende, F; Calatrava, A; Mayol-Belda, M J; Lázaro, R; Niveiro, M; Guillén, C

    2007-09-01

    This text compiles a histological protocol proposal for cutaneous melanoma agreed by the Task Force for Cutaneous Melanoma of the Valencian Community. It brings together the protocol itself and, in addition, includes a description of each of the proposed variables that has shown to have a greater prognostic impact in previous works.

  3. Gene therapy of primary T cell immunodeficiencies.

    PubMed

    Fischer, Alain; Hacein-Bey-Abina, Salima; Cavazzana-Calvo, Marina

    2013-08-10

    Gene therapy of severe combined immunodeficiencies has been proven to be effective to provide sustained correction of the T cell immunodeficiencies. This has been achieved for 2 forms of SCID, i.e SCID-X1 (γc deficiency) and adenosine deaminase deficiency. Occurrence of gene toxicity generated by integration of first generation retroviral vectors, as observed in the SCID-X1 trials has led to replace these vectors by self inactivated (SIN) retro(or lenti) viruses that may provide equivalent efficacy with a better safety profile. Results of ongoing clinical studies in SCID as well as in other primary immunodeficiencies, such as the Wiskott Aldrich syndrome, will be thus very informative.

  4. Primary cicatricial alopecia: Lymphocytic primary cicatricial alopecias, including chronic cutaneous lupus erythematosus, lichen planopilaris, frontal fibrosing alopecia, and Graham-Little syndrome.

    PubMed

    Bolduc, Chantal; Sperling, Leonard C; Shapiro, Jerry

    2016-12-01

    Both primary and secondary forms of cicatricial alopecia have been described. The hair follicles are the specific target of inflammation in primary cicatricial alopecias. Hair follicles are destroyed randomly with surrounding structures in secondary cicatricial alopecia. This 2-part continuing medical education article will review primary cicatricial alopecias according to the working classification suggested by the North American Hair Research Society. In this classification, the different entities are classified into 3 different groups according to their prominent inflammatory infiltrate (ie, lymphocytic, neutrophilic, and mixed). Part I discusses the following lymphocytic primary cicatricial alopecias: chronic cutaneous lupus erythematosus, lichen planopilaris, frontal fibrosing alopecia, and Graham-Little syndrome. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  5. Comparison of the T cell patterns in leprous and cutaneous sarcoid granulomas. Presence of Valpha24-invariant natural killer T cells in T-cell-reactive leprosy together with a highly biased T cell receptor Valpha repertoire.

    PubMed

    Mempel, M; Flageul, B; Suarez, F; Ronet, C; Dubertret, L; Kourilsky, P; Gachelin, G; Musette, P

    2000-08-01

    The T-cell-reactive (eg, tuberculoid and reversal) forms of leprosy represent a well-defined granulomatous reaction pattern against an invading pathogen. The immune response in cutaneous sarcoidosis is a granulomatous condition that pathologically is very similar to T-cell reactive leprosy. However, it lacks a defined causative agent. In view of the role of NKT cells in murine granulomas induced by mycobacterial cell walls, we have searched for the presence of NKT cells in the cutaneous lesions of both leprosy and sarcoidosis. These cells were present in T-cell-reactive leprosy but were undetectable in cutaneous sarcoidosis. We have also studied the TCR Valpha repertoire in the two diseases. In addition to Valpha24(+) NKT cells, all patients with T-cell-reactive leprosy showed a very restricted T-cell-reactive Valpha repertoire with a strong bias toward the use of the Valpha6 and Valpha14 segments. Valpha6 and Valpha14(+) T cells were polyclonal in terms of CDR3 length and Jalpha usage. In contrast, most sarcoidosis patients showed a diverse usage of Valpha chains associated with clonal or oligoclonal expansions reminiscent of antigen-driven activation of conventional T cells. Thus the origin and perpetuation of the two kinds of granulomatous lesions appear to depend on altogether distinct T-cell recruiting mechanisms.

  6. Regulation of T Cell Immunity in Atopic Dermatitis by Microbes: The Yin and Yang of Cutaneous Inflammation

    PubMed Central

    Biedermann, Tilo; Skabytska, Yuliya; Kaesler, Susanne; Volz, Thomas

    2015-01-01

    Atopic dermatitis (AD) is a chronic inflammatory skin disease predominantly mediated by T helper cells. While numerous adaptive immune mechanisms in AD pathophysiology have been elucidated in detail, deciphering the impact of innate immunity in AD pathogenesis has made substantial progress in recent years and is currently a fast evolving field. As innate and adaptive immunity are intimately linked, cross-talks between these two branches of the immune system are critically influencing the resulting immune response and disease. Innate immune recognition of the cutaneous microbiota was identified to substantially contribute to immune homeostasis and shaping of protective adaptive immunity in the absence of inflammation. Disturbances in the composition of the skin microbiome with reduced microbial diversity and overabundance of Staphylococcus spp. have been shown to be associated with AD inflammation. Distinct Staphylococcus aureus associated microbial associated molecular patterns (MAMPs) binding to TLR2 heterodimers could be identified to initiate long-lasting cutaneous inflammation driven by T helper cells and consecutively local immune suppression by induction of myeloid-derived suppressor cells further favoring secondary skin infections as often seen in AD patients. Moreover dissecting cellular and molecular mechanisms in cutaneous innate immune sensing in AD pathogenesis paved the way for exploiting regulatory and anti-inflammatory pathways to attenuate skin inflammation. Activation of the innate immune system by MAMPs of non-pathogenic bacteria on AD skin alleviated cutaneous inflammation. The induction of tolerogenic dendritic cells, interleukin-10 expression and regulatory Tr1 cells were shown to mediate this beneficial effect. Thus, activation of innate immunity by MAMPs of non-pathogenic bacteria for induction of regulatory T cell phenotypes seems to be a promising strategy for treatment of inflammatory skin disorders such as AD. These new findings

  7. Primary sjögren syndrome manifested as localized cutaneous nodular amyloidosis.

    PubMed

    Wey, Shiow-Jiuan; Chen, Yi-Ming; Lai, Po-Ju; Chen, Der-Yuan

    2011-10-01

    Localized cutaneous nodular amyloidosis (LCNA) is the rarest type of cutaneous amyloidosis. Typically presenting as waxy nodules on the lower extremities, it demonstrates localized deposition of AL-type amyloid in immunohistologic study and is often associated with focal plasma cell proliferation. Sjögren syndrome, an autoimmune lymphoproliferative disorder, is characterized by keratoconjunctivitis sicca and xerostomia with lymphocytic infiltration of exocrine glands. As shown in case reports, the association of LCNA with Sjögren syndrome is considerable. Herein, we report a 78-year-old woman with LCNA, who was further surveyed and diagnosed with Sjögren syndrome. In light of the significant relation between these 2 diseases, further examination for coexistence of Sjögren syndrome in addition to systemic amyloidosis is well warranted. Prompt identification of an underlying Sjögren syndrome in LCNA with polyclonal immunoglobulin amyloid may have important therapeutic consequences.

  8. Effect of biopsy type on outcomes in the treatment of primary cutaneous melanoma.

    PubMed

    Mills, Jane K; White, Ian; Diggs, Brian; Fortino, Jeanine; Vetto, John T

    2013-05-01

    Surgical excision remains the primary and only potentially curative treatment for melanoma. Although current guidelines recommend excisional biopsy as the technique of choice for evaluating lesions suspected of being primary melanomas, other biopsy types are commonly used. We sought to determine the impact of biopsy type (excisional, shave, or punch) on outcomes in melanoma. A prospectively collected, institutional review board-approved database of primary clinically node-negative melanomas (stages cT1-4N0) was reviewed to determine the impact of biopsy type on T-staging accuracy, wide local excision (WLE) area (cm(2)), sentinel lymph node biopsy (SLNB) identification rates and results, tumor recurrence, and patient survival. Seven hundred nine patients were diagnosed by punch biopsy (23%), shave biopsy (34%), and excisional biopsy (43%). Shave biopsy results showed significantly more positive deep margins (P < .001). Both shave and punch biopsy results showed more positive peripheral margins (P < .001) and a higher risk of finding residual tumor (with resulting tumor upstaging) in the WLE (P < .001), compared with excisional biopsy. Punch biopsy resulted in a larger mean WLE area compared with shave and excisional biopsies (P = .030), and this result was sustained on multivariate analysis. SLNB accuracy was 98.5% and was not affected by biopsy type. Similarly, biopsy type did not confer survival advantage or impact tumor recurrence; the finding of residual tumor in the WLE impacted survival on univariate but not multivariate analysis. Both shave and punch biopsies demonstrated a significant risk of finding residual tumor in the WLE, with pathologic upstaging of the WLE. Punch biopsy also led to a larger mean WLE area compared with other biopsy types. However, biopsy type did not impact SLNB accuracy or results, tumor recurrence, or disease-specific survival (DSS). Punch and shave biopsies, when used appropriately, should not be discouraged for the diagnosis of

  9. Primary cutaneous mucormycosis in infants and neonates: case report and review of the literature.

    PubMed

    Oh, Daniel; Notrica, David

    2002-11-01

    A case of angioinvasive cutaneous mucormycosis in a premature infant, eventually requiring extracorporeal membrane oxygenation therapy, is described. The fungal infection began at the site of a brachial artery catheter that had been covered with an adhesive dressing in the left antecubital fossa. The infection progressed rapidly over a 5-day period, and a left arm amputation was required. Fungal hyphae were present at the margins of resection. The patient eventually had disseminated mucormycosis and died. A second case of cutaneous mucormycosis in another premature infant also is presented. This infant had the infection at an intravenous catheter site. Rapid initiation of surgical debridement of the wound and amphotericin B therapy resulted in patient survival. Eighteen reported cases of cutaneous mucormycosis in neonates were found and are reviewed. Prematurity, low birth weight, broad-spectrum antibiotics, corticosteroid therapy, and local trauma to the skin site were common risk factors. Only 7 of the 18 patients survived. Therapy consisted of local debridement and intravenous amphotericin B. High index of suspicion, early diagnosis, and rapid institution of therapy can improve survival rate. The key to prevention appears to be appropriate skin care. Copyright 2002, Elsevier Science (USA). All rights reserved.

  10. Primary cutaneous follicle center lymphoma with Hodgkin and Reed-Sternberg-like cells: a new histopathologic variant.

    PubMed

    Dilly, Marie; Marie, Dilly; Ben-Rejeb, Houda; Houda, Ben-Rejeb; Vergier, Béatrice; Béatrice, Vergier; Feldis, Matthieu; Matthieu, Feldis; Toty, Louis; Louis, Toty; Nohra, Olivier; Olivier, Nohra; Beylot-Barry, Marie; Marie, Beylot-Barry; Gros, Audrey; Audrey, Gros; Merlio, Jean-Philippe; Jean-Philippe, Merlio; Parrens, Marie; Marie, Parrens

    2014-10-01

    Primary cutaneous follicle center lymphoma (PCFCL) is the most frequent cutaneous B-cell lymphoma. A 62-year-old man presented with a solitary indolent subcutaneous nodule for 3 years duration, without other abnormalities. Histological examination showed lymphoproliferation with a nodular growth pattern characterized by fibrous collagen bands surrounding nodules. The nodules were composed of medium-sized centrocytes admixed with many large multilobulated and lacunar cells without eosinophils or granulomatous aspect. Hodgkin-like cells were CD30+, CD15+, PAX5+, OCT2+, BOB1+, MUM1+, Ki67+, Bcl6+ and focally CD20+ and EMA-, CD79a-, Bcl2- and CD10-. The medium-sized cells were CD20+, CD79a+, Bcl2+, Bcl6+ and CD10+, enmeshed in a network of CD21-positive follicular dendritic cells. Epstein-Barr virus detection was negative. Interphase fluorescence in situ hybridization showed the absence of BCL2 or BCL6 rearrangement. In such a case, the presence of Hodgkin-like cells intermixed with the tumor population may result in a pitfall diagnosis of classical Hodgkin lymphoma (CHL). Differential diagnoses to be ruled out are secondary or primary skin localization of rather CHL, or systemic follicular lymphoma. Several clinical, radiological, histological, immunohistochemical and molecular arguments indicated the diagnosis of PCFCL. To our knowledge, this is the first report of PCFCL with Hodgkin-like cells.

  11. Guidelines of the Brazilian Dermatology Society for diagnosis, treatment and follow up of primary cutaneous melanoma - Part I*

    PubMed Central

    Castro, Luiz Guilherme Martins; Messina, Maria Cristina; Loureiro, Walter; Macarenco, Ricardo Silvestre; Duprat Neto, João Pedreira; Giacomo, Thais Helena Bello Di; Bittencourt, Flávia Vasques; Bakos, Renato Marchiori; Serpa, Sérgio Schrader; Stolf, Hamilton Ometto; Gontijo, Gabriel

    2015-01-01

    The last Brazilian guidelines on melanoma were published in 2002. Development in diagnosis and treatment made updating necessary. The coordinators elaborated ten clinical questions, based on PICO system. A Medline search, according to specific MeSH terms for each of the 10 questions was performed and articles selected were classified from A to D according to level of scientific evidence. Based on the results, recommendations were defined and classified according to scientific strength. The present Guidelines were divided in two parts for editorial and publication reasons. In the first part, the following clinical questions were answered: 1) The use of dermoscopy for diagnosis of primary cutaneous melanoma brings benefits for patients when compared with clinical examination? 2) Does dermoscopy favor diagnosis of nail apparatus melanoma? 3) Is there a prognostic difference when incisional or excisional biopsies are used? 4) Does revision by a pathologist trained in melanoma contribute to diagnosis and treatment of primary cutaneous melanoma? What margins should be used to treat lentigo maligna melanoma and melanoma in situ? PMID:26734867

  12. Guidelines of the Brazilian Dermatology Society for diagnosis, treatment and follow up of primary cutaneous melanoma--Part I.

    PubMed

    Castro, Luiz Guilherme Martins; Messina, Maria Cristina; Loureiro, Walter; Macarenco, Ricardo Silvestre; Duprat Neto, João Pedreira; Di Giacomo, Thais Helena Bello; Bittencourt, Flávia Vasques; Bakos, Renato Marchiori; Serpa, Sérgio Schrader; Stolf, Hamilton Ometto; Gontijo, Gabriel

    2015-01-01

    The last Brazilian guidelines on melanoma were published in 2002. Development in diagnosis and treatment made updating necessary. The coordinators elaborated ten clinical questions, based on PICO system. A Medline search, according to specific MeSH terms for each of the 10 questions was performed and articles selected were classified from A to D according to level of scientific evidence. Based on the results, recommendations were defined and classified according to scientific strength. The present Guidelines were divided in two parts for editorial and publication reasons. In the first part, the following clinical questions were answered: 1) The use of dermoscopy for diagnosis of primary cutaneous melanoma brings benefits for patients when compared with clinical examination? 2) Does dermoscopy favor diagnosis of nail apparatus melanoma? 3) Is there a prognostic difference when incisional or excisional biopsies are used? 4) Does revision by a pathologist trained in melanoma contribute to diagnosis and treatment of primary cutaneous melanoma? What margins should be used to treat lentigo maligna melanoma and melanoma in situ?

  13. Ectopic expression of embryonic stem cell and other developmental genes in cutaneous T-cell lymphoma.

    PubMed

    Litvinov, Ivan V; Netchiporouk, Elena; Cordeiro, Brendan; Zargham, Hanieh; Pehr, Kevin; Gilbert, Martin; Zhou, Youwen; Moreau, Linda; Woetmann, Anders; Ødum, Niels; Kupper, Thomas S; Sasseville, Denis

    2014-11-01

    Cutaneous T-cell lymphoma (CTCL) is a potentially devastating malignancy. The pathogenesis of this cancer remains poorly elucidated. Previous studies focused on analysis of expression and function of known oncogenes and tumor suppressor genes. However, emerging reports highlight that it is also important to analyze the expression of genes that are ectopically expressed in CTCL (e.g., embryonic stem cell genes (ESC), cancer testis (CT) genes, etc.). Currently, it is not known whether ESC genes are expressed in CTCL. In the current work, we analyze by RT-PCR the expression of 26 ESC genes, many of which are known to regulate pluripotency and promote cancer stem cell-like phenotype, in a historic cohort of 60 patients from Boston and in a panel of 11 patient-derived CTCL cell lines and compare such expression to benign inflammatory dermatoses that often clinically mimic CTCL. Our findings document that many critical ESC genes including NANOG, SOX2, OCT4 (POU5F1) and their upstream and downstream signaling members are expressed in CTCL. Similarly, polycomb repressive complex 2 (PRC2) genes (i.e., EZH2, EED, and SUZ12) are also expressed in CTCL lesional skin. Furthermore, select ESC genes (OCT4, EED, TCF3, THAP11, CHD7, TIP60, TRIM28) are preferentially expressed in CTCL samples when compared to benign skin biopsies. Our work suggests that ESC genes are ectopically expressed together with CT genes, thymocyte development genes and B cell-specific genes and may be working in concert to promote tumorigenesis. Specifically, while ESC genes may be promoting cancer stem cell-like phenotype, CT genes may be contributing to aneuploidy and genomic instability by producing aberrant chromosomal translocations. Further analysis of ESC expression and function in this cancer will greatly enhance our fundamental understanding of CTCL and will help us identify novel therapeutic targets.

  14. HTLV-associated diseases: human retroviral infection and cutaneous T-cell lymphomas.

    PubMed

    Fujihara, K; Goldman, B; Oseroff, A R; Glenister, N; Jaffe, E S; Bisaccia, E; Pincus, S; Greenberg, S J

    1997-01-01

    An array of neurologic, oncologic, and autoimmune disorders are associated with infection with the human pathogenic retroviruses human T-cell leukemia virus types I and II (HTLV-I, II), as well as the human immunodeficiency viruses (HIV). The cutaneous T-cell lymphomas, mycosis fungoides (MF) and its hematogenous variant Sezary Syndrome (SS), share similar clinical and pathological features to HTLV-I-associated adult T-cell leukemia (ATL) and speculation of a retroviral link to MF and SS, especially in areas non-endemic for ATL, has lead to an intensified search for HTLV- and HIV-like agents in these diseases. To further explore a potential role for human retroviruses in MF and SS, skin biopsy-derived or peripheral blood mononuclear cell-derived DNA from 17 patients (MF, n = 7; erythrodermic MF (EMF), n = 5; SS, n = 5) from the North Eastern United States were screened using gene amplification by PCR and a liquid hybridization detection assay. Previously published primers and probes for HTLV-I (LTR, gag, pol, env, and pX), and our own primers and probes for HTLV-I (gag, pol, and env), HTLV-II (pol and env) and HIV-I (gag and pol) were employed. Serum antibodies to HTLV-I were negative in all but one EMF patient. The single HTLV-I seropositive patient carrying a diagnosis of EMF generated positive amplified signals for all of the eight HTLV-I regions tested. Ultimately, this individual evolved to exhibit clinical manifestations indistinguishable from ATL. The other 16 patients were negative for all 12 HTLV and HIV retroviral regions. Our findings suggest that none of the known prototypic human retroviruses are associated with seronegative MF and SS. The uniformly positive results for HTLV-I in the seropositive patient suggests that this patient initially presented with a smoldering form of ATL and illustrates the difficulty that sometimes may be encountered in the differential diagnosis of MF, SS, and ATL based solely on clinical and histopathological criteria.

  15. Total-skin electron irradiation for cutaneous T-cell lymphoma: the Northern Israel Oncology Center experience.

    PubMed

    Kuten, A; Stein, M; Mandelzweig, Y; Tatcher, M; Yaacov, G; Epelbaum, R; Rosenblatt, E

    1991-07-01

    Total-skin electron irradiation (TSEI) is effective and frequently used in the treatment of cutaneous T-cell lymphoma. A treatment technique has been developed at our center, using the Philips SL 75/10 linear accelerator. In our method, the patient is irradiated in a recumbent position by five pairs of uncollimated electron beams at a source to skin distance of 150 cm. This method provides a practical solution to clinical requirements with respect to uniformity of electron dose and low X-ray contamination. Its implementation does not require special equipment or modification of the linear accelerator, 19 of 23 patients (83%) with mycosis fungoides, treated by this method, achieved complete regression of their cutaneous lesions.

  16. Expression of T-plastin, FoxP3 and other tumor-associated markers by leukemic T-cells of cutaneous T-cell lymphoma.

    PubMed

    Capriotti, Elisabetta; Vonderheid, Eric C; Thoburn, Christopher J; Wasik, Mariusz A; Bahler, David W; Hess, Allan D

    2008-06-01

    Peripheral blood cells from 28 patients with leukemic cutaneous T-cell lymphoma including 25 patients with Sezary syndrome were evaluated for expression of regulatory T-cell-associated markers (FoxP3, CD25, CTLA-4, neurophilin-1), T-cell activation markers (CD28 and its ligands B7.1 and B7.2) and NK cell-associated markers (NKG2D and its ligands Mic-A and Mic-B) using real-time quantitative polymerase chain reaction. T-plastin served as a positive genetic marker, and its expression correlated to blood tumor burden. More than 90% of samples had transcripts for CD28 and Mic-B, but less than 30% of samples expressed FoxP3, CTLA-4 and CD25. Expression of Mic-B by neoplastic cells could provide another mechanism to inhibit anti-tumor immune responses. FoxP3 expression correlated with a poor prognosis. Although the underlying mechanisms accounting for this correlation remain unclear, the expression of the Foxp3 and CTLA-4 regulatory elements indicates that a subset of leukemic cases displays a regulatory T-cell phenotype.

  17. Cryotherapy with liquid nitrogen versus topical salicylic acid application for cutaneous warts in primary care: randomized controlled trial

    PubMed Central

    Bruggink, Sjoerd C.; Gussekloo, Jacobijn; Berger, Marjolein Y.; Zaaijer, Krista; Assendelft, Willem J.J.; de Waal, Margot W.M.; Bavinck, Jan Nico Bouwes; Koes, Bart W.; Eekhof, Just A.H.

    2010-01-01

    Background Cryotherapy is widely used for the treatment of cutaneous warts in primary care. However, evidence favours salicylic acid application. We compared the effectiveness of these treatments as well as a wait-and-see approach. Methods Consecutive patients with new cutaneous warts were recruited in 30 primary care practices in the Netherlands between May 1, 2006, and Jan. 26, 2007. We randomly allocated eligible patients to one of three groups: cryotherapy with liquid nitrogen every two weeks, self-application of salicylic acid daily or a wait-and-see approach. The primary outcome was the proportion of participants whose warts were all cured at 13 weeks. Analysis was on an intention-to-treat basis. Secondary outcomes included treatment adherence, side effects and treatment satisfaction. Research nurses assessed outcomes during home visits at 4, 13 and 26 weeks. Results Of the 250 participants (age 4 to 79 years), 240 were included in the analysis at 13 weeks (loss to follow-up 4%). Cure rates were 39% (95% confidence interval [CI] 29%–51%) in the cryotherapy group, 24% (95% CI 16%–35%) in the salicylic acid group and 16% (95% CI 9.5%–25%) in the wait-and-see group. Differences in effectiveness were most pronounced among participants with common warts (n = 116): cure rates were 49% (95% CI 34%–64%) in the cryotherapy group, 15% (95% CI 7%–30%) in the salicylic acid group and 8% (95% CI 3%–21%) in the wait-and-see group. Cure rates among the participants with plantar warts (n = 124) did not differ significantly between treatment groups. Interpretation For common warts, cryotherapy was the most effective therapy in primary care. For plantar warts, we found no clinically relevant difference in effectiveness between cryotherapy, topical application of salicylic acid or a wait-and-see approach after 13 weeks. (ClinicalTrial.gov registration no. ISRCTN42730629) PMID:20837684

  18. Rearranged T-cell receptor gene and positive Epstein-Barr virus-encoded nuclear RNA in an extranodal NK/T-cell lymphoma with cutaneous manifestation only: case study.

    PubMed

    Wang, J; Geng, S A; Su, Z; Xu, J; Xu, S; Wang, F; Mo, X; Feng, Z

    2007-11-01

    Natural killer (NK)/cytotoxic T-cell lymphoma, a new type of cutaneous neoplasm, has been described recently in the World Health Organization/European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas. We report an 11-year-old boy who had had erythematous plaques and blisters on his face and hands for 4 years and infiltrating plaques and necrosis on his extremities for 4 months. Routine clinical and laboratory examinations found no primary nasal involvement. Biopsies taken from nasal mucosa and skin showed that the tumour only involved dermis and subcutaneous tissue, and the infiltrated lymphohistiocytic tumour cells were CD56+, TIA+, CD45RO+ and CD30+. In situ hybridization for EBV-encoded nuclear RNA was positive. Clonal T-cell receptor-gamma2 gene rearrangement was positive. A diagnosis of extranodal NK/T-cell lymphoma, nasal type, was made. This is a rare case, with slow course and survival for >51 months with the presentation only occurring in the skin.

  19. Recent advances in cutaneous lymphomas.

    PubMed

    Dummer, Reinhard; Asagoe, Kenji; Cozzio, Antonio; Burg, Günter; Doebbeling, Udo; Golling, Philippa; Fujii, Kazuyasu; Urosevic, Mirjana

    2007-12-01

    Cutaneous lymphomas are a heterogeneous group of extranodal lymphomas that are characterized by an initial accumulation of mononuclear, mostly lymphocytic cells in the skin. Recent discoveries of changes in molecular biology and immunology of these tumors have paved the way to a better understanding of the processes that govern lymphomagenesis in the skin and more importantly, they have contributed to the development of the new WHO-EORTC classification system. Only now has the field of cutaneous lymphomas gained a novel, long-awaited basis that may act as a new starting point in the collection of clinical as well molecular and immunological data on comparative basis. This review will try to highlight the newest findings in the pathogenesis of primary cutaneous T- and B-cell lymphomas, hematodermic neoplasm and HTLV-1 positive disorders as well as their translation into efficient therapeutic strategies.

  20. Role of gamma/delta T cell receptor-expressing lymphocytes in cutaneous infection caused by Staphylococcus aureus

    PubMed Central

    MÖLNE, L; CORTHAY, A; HOLMDAHL, R; TARKOWSKI, A

    2003-01-01

    The high number of γ/δ-expressing T cells found in the epithelial lining layer suggests that they form a first line of defence against invading pathogens. To evaluate the role of γ/δ T cell-receptor (TCR)-expressing cells in cutaneous infection caused by Staphylococcus aureus, mice lacking γ/δ-expressing T cells (TCRδ−/−) were inoculated intradermally with S. aureus, and compared with S. aureus-infected congeneic TCRδ+/− control mice. The number of bacteria recovered from the skin of TCRδ−/− mice was significantly higher (P = 0·0071) at early time-points after inoculation compared to the number of bacteria isolated from infected TCRδ+/− congeneic controls. Nevertheless, inflammatory responses measured as serum IL-6 levels, were significantly lower in TCRδ−/− mice than in the control group. A possible explanation for this discrepancy was the observation of significantly decreased overall numbers of infiltrating cutaneous T lymphocytes, which are important producers of IL-6. These results support the notion that the γ/δ-expressing T cells that reside at the epithelial lining layer of the skin is of importance for early containment of the bacteria, thereby limiting their replication and spread. PMID:12699407

  1. Susceptibility of T cell receptor-α chain knock-out mice to ultraviolet B light and fluorouracil: a novel model for drug-induced cutaneous lupus erythematosus

    PubMed Central

    YOSHIMASU, T; NISHIDE, T; SEO, N; HIROI, A; OHTANI, T; UEDE, K; FURUKAWA, F

    2004-01-01

    The anticancer agent 5-fluorouracil (FU) frequently induces cutaneous lupus erythematosus (LE) lesions on sun exposed sites. Based on this observation, we have tried to establish a cutaneous LE model of C57BL/6 J (B6) mice, B6 T cell receptor (TCR)-α–/– mice and B6 TCR-δ–/– mice treated with FU and/or ultraviolet B light (UVBL) in order to clarify the role of T cells and the cytokine profile of cutaneous lupus lesions. Cutaneous LE-like skin lesions could be induced in TCR-α–/– mice with low FU (0·2 mg) plus UVBL, and in B6 mice treated with a high dose of FU (2·0 mg) plus UVBL. In contrast, low FU plus UVBL induced such skin lesions in TCR-δ–/– mice at a very low incidence. Specifically, the skin lesions of TCR-α–/– mice with low FU plus UVBL appeared more rapidly and were more severe than lesions in B6 mice. The former had the common characteristic features of human chronic cutaneous LE such as typical histology, positive IgG at the dermoepidermal junction, low antinuclear antibody and low mortality. Furthermore, a Th1 response was induced in the development of drug-induced cutaneous LE. FU and UVBL-induced cutaneous LE-like eruption is an excellent model for better understanding the pathomechanisms of skin lesion development in LE. PMID:15086387

  2. Human T-cell leukemia-lymphoma virus (HTLV) is in T but not B lymphocytes from a patient with cutaneous T-cell lymphoma.

    PubMed

    Gallo, R C; Mann, D; Broder, S; Ruscetti, F W; Maeda, M; Kalyanaraman, V S; Robert-Guroff, M; Reitz, M S

    1982-09-01

    A human type C retrovirus, designated HTLV, previously was isolated from or identified in some patients with leukemias and lymphomas of mature T lymphocytes. HTLV is genetically and serologically distinct from any known animal retroviruses. The absence of HTLV proviral sequences in DNA from normal humans showed that HTLV is not a ubiquitous endogenous (germ-line transmitted) virus of humans. Antibodies to HTLV core proteins have been identified in some people with T-cell neoplasias and are particularly prevalent in Japanese with adult T-cell leukemia, suggesting that HTLV is acquired horizontally. However, it was possible that HTLV is transmitted through the germ line of some (possibly rare) families and is then expressed in the HTLV- positive malignancies. An opportunity to study this question was provided by the development of several T-cell lines and a B-cell provided by the development of several T-cell lines and a B-cell line from one HTLV-positive patient with a cutaneous T-cell lymphoma. Here we report that HTLV proteins or nucleic acids (or both) are found in three independently derived T-cell lines, all shown by HLA typing to have originated from the patient. In contrast, the B-cell line, the identity of which was also ascertained by HLA typing, contained no detectable HTLV protein, RNA, or proviral DNA. Because the sensitivity of the latter assay is more than sufficient to detect one proviral equivalent per haploid genome, the results indicate that HTLV was not transmitted to this patient through the germ line but rather was acquired by infection.

  3. Cutaneous epitheliotropic T-cell lymphoma in the cat: a review of the literature and five new cases.

    PubMed

    Fontaine, Jacques; Heimann, Marianne; Day, Michael J

    2011-10-01

    Cutaneous epitheliotropic T-cell lymphoma (CETL) is characterized by cutaneous infiltration of neoplastic T lymphocytes with a specific tropism for the epidermis and adnexal epithelium. This disease is reported very rarely in the cat. Clinical data were collected from an informal discussion with veterinary dermatologists through the Vetdermlist (vetderm@lists.ncsu.edu). In parallel, case archives of two European diagnostic histopathology laboratories (Institut de Pathologie et Génétique/Bio.be Gosselies, Belgium and the School of Veterinary Sciences, University of Bristol, UK) were reviewed. Fifteen cases with a good clinical description were selected, and five sets of skin biopsies were available for review. Cutaneous epitheliotropic T-cell lymphoma generally affects older cats with no apparent sex or breed predisposition. Solitary or multiple lesions were reported without predilection for any particular location. The lesions consisted of erythematous plaques or patches, scaly alopecic patches and nonhealing ulcers or nodules, which sometimes mimicked an eosinophilic plaque. Pruritus was rarely reported. No lesions affecting the oral mucosa were observed. Clinical diagnosis of CETL is more challenging in cats than in dogs. Final diagnosis must be based on histopathological examination of skin biopsy samples. The characteristic lesions of feline CETL are similar to those reported in the dog, but involvement of the adnexal glands was not observed in this series (n=5). The neoplastic T cells were generally small to medium in size. The survival time of cats with CETL seems to be more variable than that of affected dogs. Too few cases have been evaluated to permit clear recommendations to be made with respect to treatment.

  4. Cutaneous larva migrans in Hospital Kuala Lumpur, Malaysia: rate of correct diagnosis made by the referring primary care doctors.

    PubMed

    Yap, Felix Boon-Bin

    2011-07-01

    A retrospective study was undertaken to determine the clinical features of cutaneous larva migrans (CLM) seen in the Department of Dermatology, Hospital Kuala Lumpur (Kuala Lumpur, Malaysia) and to assess the rate of correct diagnosis made by the referring primary care doctors. Clinical records of all 31 patients with CLM seen between January 2006 and June 2010 were retrieved. The majority of patients were male. The mean age was 32.2 years. Pruritus was reported in 83.9% of cases and serpiginous tracts in 100%. The mean lesion count was 4.4 and the mean duration of disease before presentation was 3.1 weeks. The majority of skin lesions were on the buttock and lower extremities. Only 45.2% of patients had the correct diagnosis made by the referring primary care doctors. Older age of patients and lower number of lesions were associated with a higher rate of correct diagnosis. The low rate of correct diagnosis made by the referring primary care doctors to the dermatologists in this study warrants the need for education of not only primary care doctors but also future primary care providers, consisting of medical students, house officers and junior medical officers.

  5. Tactile impoverishment and sensorimotor restriction deteriorate the forepaw cutaneous map in the primary somatosensory cortex of adult rats.

    PubMed

    Coq, J O; Xerri, C

    1999-12-01

    We investigated the effects of sensory deprivation on the forepaw representation in the primary somatosensory cortex (SI) in the adult rat. Cortical maps were constructed from high-resolution multiunit recordings of the response of layer IV neurons to somatosensory stimuli. The main features of the forepaw representation were described in terms of areal extent and topography of the cortical map, and sensory submodality, size, and location of the receptive field (RF) of small clusters of the cortical neurons. After being weaned, two groups of Long-Evans rats were housed in a standard (SE) or impoverished (IE) environment for 65-115 days. A third group of SE rats was subjected to severe sensorimotor restriction (SR) of one forepaw for 7 days or 14 days, by using a one-sleeved cast. A concomitant effect of unilateral forelimb immobilization was a forced use of the nonrestricted forelimb in postural balance. The maps of both forepaws were derived 24 h after the cast was removed and the animal was allowed normal limb use. In a fourth group, SE rats experienced a 7-day immobilization followed by symmetrical limb use for 7 days before we mapped the hemisphere contralateral to the casted limb. For the SE and IE rats, the total areal extent of the cutaneous forepaw representation was similar, but IE rats exhibited a significant expansion of cortical islets serving high-threshold, presumably noncutaneous inputs, which were included in the cutaneous maps. In addition, SI neurons of IE rats had greatly enlarged glabrous, but not hairy, skin RFs. For the SR rats, the areal extent of the cutaneous map of the casted forepaw decreased by about 50%, after both 7- and 14-day forelimb immobilization. Large cortical sectors presumed to be formerly activated by cutaneous inputs were driven by high-threshold inputs that disrupted the somatotopic representation of the forepaw skin surfaces. These "emergent" representational sectors were topographically organized. By contrast, the areal

  6. A 92-year-old man with primary cutaneous diffuse large B-cell non-Hodgkin's lymphoma manifesting as a giant scalp mass

    PubMed Central

    Liao, Chenlong; Yang, Min; Liu, Pengfei; Zhang, Wenchuan

    2017-01-01

    Abstract Rationale: Primary cutaneous non-Hodgkin's lymphoma (NHL) is an uncommon entity, representing 10% of all extranodal NHLs. Among all cutaneous sites, the scalp is a rare site of representation. Patient concerns: A 92-year-old Chinese man visited our hospital with a multiple-nodular huge scalp mass on the right parieto-occipital regions. The mass was of 7-month duration and progressively enlarging in size. Diagnoses: On the basis of the result of biopsy, diffuse large B-cell NHL was diagnosed. Interventions: The mass was partially resected by surgery and no further treatment was conducted due to the advanced age and poor physical status. Outcomes: The tumor relapsed in situ after 6 months and the patient died after 2 years. Lessons: This case highlighted the limited access to standard treatment options in patients with advanced age. A thorough examination is necessary to decide upon the treatment for the primary cutaneous lymphoma. PMID:28272240

  7. Epidermal Expression of Intercellular Adhesion Molecule 1 is Not a Primary Inducer of Cutaneous Inflammation in Transgenic Mice

    NASA Astrophysics Data System (ADS)

    Williams, Ifor R.; Kupper, Thomas S.

    1994-10-01

    Keratinocytes at sites of cutaneous inflammation have increased expression of intercellular adhesion molecule 1 (ICAM-1), a cytokine-inducible adhesion molecule which binds the leukocyte integrins LFA-1 and Mac-1. Transgenic mice were prepared in which the expression of mouse ICAM-1 was targeted to basal keratinocytes by using the human K14 keratin promoter. The level of constitutive expression attained in the transgenic mice exceeded the peak level of ICAM-1 expression induced on nontransgenic mouse keratinocytes in vitro by optimal combinations of interferon γ and tumor necrosis factor α or in vivo by proinflammatory stimuli such as phorbol 12-myristate 13-acetate. In vitro adhesion assays demonstrated that cultured transgenic keratinocytes were superior to normal keratinocytes as a substrate for the LFA-1-dependent binding of mouse T cells, confirming that the transgene-encoded ICAM-1 was expressed in a functional form. However, the high level of constitutive ICAM-1 expression achieved on keratinocytes in vivo in these transgenic mice did not result in additional recruitment of CD45^+ leukocytes into transgenic epidermis, nor did it elicit dermal inflammation. Keratinocyte ICAM-1 expression also did not potentiate contact-hypersensitivity reactions to epicutaneous application of haptens. The absence of a spontaneous phenotype in these transgenic mice was not the result of increased levels of soluble ICAM-1, since serum levels of soluble ICAM-1 were equal in transgenic mice and controls. We conclude that elevated ICAM-1 expression on keratinocytes cannot act independently to influence leukocyte trafficking and elicit cutaneous inflammation.

  8. Is bone marrow biopsy always indicated in patients with primary cutaneous marginal zone B-cell lymphoma?

    PubMed

    Muniesa, C; Hernández-Machín, B

    2013-10-01

    Bone marrow involvement at the time of diagnosis is uncommon in patients with primary cutaneous marginal zone B-cell lymphoma (PCMZL). Moreover, in these patients such involvement is rarely found in isolation on diagnosis. Typically the few patients with PCMZL who have early bone marrow involvement also present secondary nodal or visceral involvement, which is detected by other staging studies (usually computed tomography). In recent years, this has given rise to some debate about whether a bone marrow biopsy should be routinely performed in patients diagnosed with PCMZL in view of the good prognosis and low incidence of bone marrow infiltration and/or extracutaneous involvement in this type of lymphoma. Copyright © 2012 Elsevier España, S.L. and AEDV. All rights reserved.

  9. Primary cutaneous mucormycosis in a patient with burn wounds due to Lichtheimia ramosa.

    PubMed

    Kaur, Ravinder; Bala, Kiran; Ahuja, Rajeev B; Srivastav, Prabhat; Bansal, Umesh

    2014-10-01

    Mucormycosis is usually an invasive mycotic disease caused by fungi in the class mucormycetes. Here we report a case of cutaneous mucormycosis due to Lichtheimia ramosa in a 20-year-old female patient with burn injuries. She was admitted to the hospital with accidental flame burns covering 60 % total burn surface area. After 15 days of admission to hospital, the burn wound showed features of fungal infection. Culture showed white cottony growth belonging to the Mucorales order. Morphological identification confirmed it as L. ramosa. She was managed surgically and medically with the help of amphotericin B. Patient survived due to prompt diagnosis and appropriate medical and surgical treatment. Early diagnosis is critical in prevention of morbidity and mortality associated with the disease. Fungal infection in burn wounds can be difficult to diagnose and manage.

  10. [Primary cutane manifestation of a precursor-B-lymphoblastic lymphoma in the external ear].

    PubMed

    Greve, J; Bas, M; Schipper, J; Hoffmann, T K

    2008-10-01

    A Non-Hodgkin Lymphoma (NHL) represents nearly three percent of all malignant tumors. Thirty to fourty percent of the lymphomas are located extra-nodal. Within the head and neck region they might occur in the tonsils, tongue base or the sinuses, the larynx and the pharynx. A cutaneous manifestation is rare. We report on an extranodal B-cell-lymphoma of the ear in a young woman. She reported on a piercing of the pinna months before with a subsequent infection. This infection led to the development of a massive ear tumor. Histologic examination resulted in the final diagnosis. In spite of the considerable extent of the lymphoma there was no systemic manifestation and a total remission was induced by chemotherapy before adjuvant radiation.

  11. Efficient Gene Editing in Primary Human T Cells.

    PubMed

    Chen, Yvonne Y

    2015-11-01

    Recent advances in T-cell therapy for cancer, viral infections, and autoimmune diseases highlight the broad therapeutic potential of T-cell engineering. However, site-specific genetic manipulation in primary human T cells remains challenging. Two recent studies describe efficient genome editing in T cells using CRISPR and TALEN approaches.

  12. Passage of human T-cell leukemia virus type-1 during progression to cutaneous T-cell lymphoma results in myelopathic disease in an HTLV-1 infection model.

    PubMed

    Kindt, T J; Said, W A; Bowers, F S; Mahana, W; Zhao, T M; Simpson, R M

    2000-08-01

    Studies comparing functional differences in human T-cell leukemia virus type 1 (HTLV-1) clones that mediate distinct outcomes in experimentally infected rabbits, resulted in a dermatopathic smoldering adult T-cell leukemia/lymphoma following chronic infection with HTLV-1 strain RH/K34. During the 3.5 years' follow-up, HTLV-1 skin disease progressed to cutaneous T-cell lymphoma. When infection was passed to several naive rabbits, progressive paraparesis due to myelopathic neurodegeneration, analogous to HTLV-associated myelopathy, resulted in one of 4 transfusion recipients. Similar proviral loads were detected in the two diseases, regardless of stage of progression or tissue compartment of infection. Complete proviral sequences obtained from the donor and affected recipient aligned identically with each other and with the inoculated virus clone. Existence of disparate pathogenic outcomes following infectious transmission further extends the analogy of using rabbits to model human infection and disease. Although the experimental outcomes shown are limited by numbers of animals affected, they mimic the infrequency of HTLV-1 disease and authenticate epidemiological evidence of virus sequence stability regardless of disease phenotype. The findings suggest that further investigation of a possible role for HTLV-1 in some forms of cutaneous T-cell lymphoma is warranted.

  13. The role of histone deacetylase inhibitors in the treatment of patients with cutaneous T-cell lymphoma.

    PubMed

    Hymes, Kenneth B

    2010-04-01

    The term epigenetics refers to modifications in gene activity that occur without directly affecting the DNA sequence, and irregularities in cellular epigenetics have been implicated in the development of a number of malignancies. As such, there is considerable interest in the anticancer effects of agents that can modify cellular epigenetics. Histone deacetylase (HDAC) inhibitors represent a class of anticancer agents that have shown promise in the treatment of both solid and hematologic malignancies. Although there are a number of HDAC inhibitors in advanced stages of clinical development, vorinostat, and more recently, romidepsin, are currently the only HDAC inhibitors approved for use. Vorinostat was approved in the United States in 2006 for the treatment of cutaneous manifestations of T-cell lymphoma in patients with progressive, persistent, or recurrent disease on or following 2 systemic therapies. Romidepsin was approved in the United States in 2009 for the treatment of cutaneous T-cell lymphoma (CTCL) in patients who have received >/= 1 prior systemic therapy. This review aims to assess the clinical progress that vorinostat and other HDAC inhibitors have made in symptom relief and treatment of patients with CTCL and to provide practical advice for the management of associated toxicities.

  14. An unusual presentation of a B-cell cutaneous lymphoma mimicking as nasolabial cyst.

    PubMed

    Demir, Uygar Levent; Nazlıoğlu, Hülya Oztürk

    2013-01-01

    Lymphoma is a cancer of the lymphocytes which leads to solid tumors in the lymphoid organs involving lymph nodes, spleen, liver, bone marrow and skin. Primary cutaneous lymphoma, a rare subtype of non-Hodgkin's lymphoma, can be classified as cutaneous T-cell or cutaneous B-cell lymphoma. These tumors are mostly T-cell origin and mainly locate on trunk, extremities and scalp or forehead. In this article, we report a 22-year-old female case without any symptoms of non-Hodgkin's lymphoma except a sign mimicking nasolabial cyst in the nasolabial fold, who was pathologically diagnosed with cutaneous B-cell lymphoma following surgery.

  15. Profound alteration in cutaneous primary afferent activity produced by inflammatory mediators

    PubMed Central

    Smith-Edwards, Kristen M; DeBerry, Jennifer J; Saloman, Jami L; Davis, Brian M; Woodbury, C Jeffery

    2016-01-01

    Inflammatory pain is thought to arise from increased transmission from nociceptors and recruitment of 'silent' afferents. To evaluate inflammation-induced changes, mice expressing GCaMP3 in cutaneous sensory neurons were generated and neuronal responses to mechanical stimulation in vivo before and after subcutaneous infusion of an 'inflammatory soup' (IS) were imaged in an unanesthetized preparation. Infusion of IS rapidly altered mechanical responsiveness in the majority of neurons. Surprisingly, more cells lost, rather than gained, sensitivity and 'silent' afferents that were mechanically insensitive and gained mechanosensitivity after IS exposure were rare. However, the number of formerly 'silent' afferents that became mechanosensitive was increased five fold when the skin was heated briefly prior to infusion of IS. These findings suggest that pain arising from inflamed skin reflects a dramatic shift in the balance of sensory input, where gains and losses in neuronal populations results in novel output that is ultimately interpreted by the CNS as pain. DOI: http://dx.doi.org/10.7554/eLife.20527.001 PMID:27805567

  16. The comparison of expression of cutaneous lymphocyte-associated antigen (CLA), and Th1- and Th2-associated antigens in mycosis fungoides and cutaneous lesions of adult T-cell leukemia/lymphoma.

    PubMed

    Yamaguchi, Takahiro; Ohshima, Koichi; Tsuchiya, Takeshi; Suehuji, Hiroaki; Karube, Kennosuke; Nakayama, Juichiro; Suzumiya, Junji; Yoshino, Tadashi; Kikuchi, Masahiro

    2003-01-01

    Mycosis fungoides (MF) is morphologically similar to cutaneous lesions of adult T cell leukemia/lymphoma (ATLL) of human T-cell lymphotropic virus-type I (HTLV-1). In addition, the Th1 or Th2 characteristic of MF and ATLL is still controversial. In the present study, to discriminate MF and cutaneous lesion of ATLL using immunohistochemical markers, and to elucidate Th1 or Th2 dominancy in both disorders, CLA (cutaneous lymphocyte associated antigen) was expressed on epidermotrophic lymphoma cells in all early stage MF. In contrast, all ATLL were negative for CLA. CXCR3 was especially expressed in epidermotropic small lymphoma cells of MF. CCR5 was expressed in both disorders with variable sized lymphoma cells. ST2 was expressed on large transformed lymphoma cells with ATLL, but not in any MF cases. OX40 was expressed in the large transformed cell population in both disorders. These findings suggest that CLA and ST2 could be potentially useful immunohistochemical markers for discrimination of mycosis fungoides and cutaneous lesions of ATLL. And OX40 could be a useful immunohistochemical marker for the histopathological progression of both disorders.

  17. Lymphoma-type adult T-cell leukaemia-lymphoma with a bulky cutaneous tumour showing multiple human T-lymphotropic virus-1 DNA integration.

    PubMed

    Kato, N; Sugawara, H; Aoyagi, S; Mayuzumi, M

    2001-06-01

    Human T-lymphotropic virus-1 (HTLV-1) is considered to be the cause of adult T-cell leukaemia-lymphoma (ATL). Monoclonal integration of HTLV-1 proviral DNA, as is analysed by Southern blotting, has been demonstrated in ATL patients. Unusual integration patterns of HTLV-1 proviral DNA have occasionally been described, and it is suggested that the patterns have clinical implications for ATL pathophysiology. Multiple, complete and defective types of integration patterns, in that order, are apparently associated with prognoses from good to poor. We report a 73-year-old Japanese woman with lymphoma-type ATL and a bulky cutaneous tumour on the left thigh. Four bands of slightly differing intensity were seen after EcoRI digestion of skin and lymph node samples on Southern blot analysis of HTLV-1 proviral DNA. Analysis for T-cell receptor-beta gene revealed five novel bands after restriction enzyme digestion with HindIII, indicating that the patient has four separate tumour cell clones, each of which carries one copy of the provirus. She was treated with chemotherapy and radiation and remains under reasonable control despite some relapsing cutaneous nodules. The indolent course in this present case could be related to the multiple integration pattern of HTLV-1 proviral DNA detected.

  18. American tegumentary leishmaniasis: T-cell differentiation profile of cutaneous and mucosal forms-co-infection with Trypanosoma cruzi.

    PubMed

    Parodi, Cecilia; García Bustos, María F; Barrio, Alejandra; Ramos, Federico; González Prieto, Ana G; Mora, María C; Baré, Patricia; Basombrío, Miguel A; de Elizalde de Bracco, María M

    2016-08-01

    American tegumentary leishmaniasis displays two main clinical forms: cutaneous (CL) and mucosal (ML). ML is more resistant to treatment and displays a more severe and longer evolution. Since both forms are caused by the same Leishmania species, the immunological response of the host may be an important factor determining the evolution of the disease. Herein, we analyzed the differentiation and memory profile of peripheral CD4(+) and CD8(+) T lymphocytes of patients with CL and ML and their Leishmania-T. cruzi co-infected counterparts. We measured the expression of CD27, CD28, CD45RO, CD127, PD-1 and CD57, together with interferon-γ and perforin. A highly differentiated phenotype was reflected on both T subsets in ML and preferentially on CD8(+) T cells in CL. A positive trend toward a higher T differentiation profile was found in T. cruzi-infected CL and ML patients as compared with Leishmania single infections. Association between CD8(+) T-cell differentiation and illness duration was found within the first year of infection, with progressive increase of highly differentiated markers over time. Follow-up of patients with good response to therapy showed predominance of early differentiated CD8(+) T cells and decrease of highly differentiated cells, while patients with frequent relapses presented the opposite pattern. CD8(+) T cells showed the most striking changes in their phenotype during leishmaniasis. Patients with long-term infections showed the highest differentiated degree implying a relation between T differentiation and parasite persistence. Distinct patterns of CD8(+) T differentiation during follow-up of different clinical outcomes suggest the usefulness of this analysis in the characterization of Leishmania-infected patients.

  19. CUTANEOUS EPITHELIOTROPIC T-CELL LYMPHOMA WITH METASTASES IN A VIRGINIA OPOSSUM (DIDELPHIS VIRGINIANA).

    PubMed

    Higbie, Christine T; Carpenter, James W; Choudhary, Shambhunath; DeBey, Brad; Bagladi-Swanson, Mary; Eshar, David

    2015-06-01

    A 2-yr-old, captive, intact female Virginia opossum ( Didelphis virginiana ) with a 7-mo history of ulcerative dermatitis and weight loss was euthanatized for progressive worsening of clinical signs. Initially the opossum was treated with several courses of antibiotics, both topically and systemically; systemic nonsteroidal anti-inflammatory medication; and, later, systemic glucocorticoids, with no improvement in clinical signs. Histopathologic samples of skin lesions taken 3 mo into the course of disease revealed no evidence of neoplasia; however, cytologic samples of a skin lesion taken 5 mo into the course of disease revealed mature lymphocytes, and were suggestive of cutaneous lymphoma. Postmortem histopathology revealed neoplastic cells consistent with lymphoma; these were found in the haired skin of the forearm, axilla, hind limb, face, and lateral body wall, as well as the liver, kidney, axillary lymph node, heart, and spleen. Multifocal neutrophilic and eosinophilic ulcerative and necrotizing dermatitis and folliculitis of the haired skin were also present. To the authors' knowledge, this is the first documented case of cutaneous lymphoma in a Virginia opossum and the first documented case with visceral metastases in a marsupial.

  20. The use of synchrotron infrared microspectroscopy in the assessment of cutaneous T-cell lymphoma vs. pityriasis lichenoides chronica.

    PubMed

    El Bedewi, Ahmed; El Anany, Galal; El Mofty, Medhat; Kretlow, Ariane; Park, Simone; Miller, Lisa M

    2010-04-01

    The diagnosis of cutaneous lymphomas remains a challenge for both the clinician and dermatopathologist. To differentiate between frank malignant and premalignant lymphocytes within the skin. This study was performed on 20 patients with a mean age of 50 years. They were divided into two groups: mycosis fungoides (MF) (stage IA, IB and IIA) and pityriasis lichenoides chronica (PLC). Immunophenotyping using antibodies CD3, CD4, CD8, CD20 and CD30 was performed. Synchrotron Fourier transform infrared microspectroscopy (S-FTIRM) was performed on cell nuclei to assess chemical differences between MF and PLC cases as a potential complementary screening tool. Dermal spectra of both MF and PLC were compared using principal components analysis (PCA) of the S-FTIRM data. All PLC spectra was clustered together. However, the MF spectra formed two clusters, one that grouped with the PLC and the other grouped separately. Moreover, protein and nucleic acids showed highly significant differences between MF (IIA and IB), MF (IA) and PLC. The malignant transformation within lymphocytes was identifiable through the spectroscopic analysis of protein, RNA and DNA with S-FTIRM, making it a promising tool for classifying the progression of cutaneous T-cell lymphoma.

  1. A rare subset of skin-tropic regulatory T cells expressing Il10/Gzmb inhibits the cutaneous immune response

    PubMed Central

    Ikebuchi, Ryoyo; Teraguchi, Shunsuke; Vandenbon, Alexis; Honda, Tetsuya; Shand, Francis H. W.; Nakanishi, Yasutaka; Watanabe, Takeshi; Tomura, Michio

    2016-01-01

    Foxp3+ regulatory T cells (Tregs) migrating from the skin to the draining lymph node (dLN) have a strong immunosuppressive effect on the cutaneous immune response. However, the subpopulations responsible for their inhibitory function remain unclear. We investigated single-cell gene expression heterogeneity in Tregs from the dLN of inflamed skin in a contact hypersensitivity model. The immunosuppressive genes Ctla4 and Tgfb1 were expressed in the majority of Tregs. Although Il10-expressing Tregs were rare, unexpectedly, the majority of Il10-expressing Tregs co-expressed Gzmb and displayed Th1-skewing. Single-cell profiling revealed that CD43+ CCR5+ Tregs represented the main subset within the Il10/Gzmb-expressing cell population in the dLN. Moreover, CD43+ CCR5+ CXCR3− Tregs expressed skin-tropic chemokine receptors, were preferentially retained in inflamed skin and downregulated the cutaneous immune response. The identification of a rare Treg subset co-expressing multiple immunosuppressive molecules and having tissue-remaining capacity offers a novel strategy for the control of skin inflammatory responses. PMID:27756896

  2. [Sporadic cutaneous lymphosarcoma of T-cell origin with involvement of lymph nodes and internal organs in a Holstein cow].

    PubMed

    Freick, M; Lapko, L; Neubert, M; Hardt, M; Behn, H; Passarge, O; Schöniger, S

    2016-01-01

    Sporadic lymphosarcomas in adult cattle are rare entities with an unknown etiology. This case report describes the course of the disease in a 3.5-year-old cow of the breed German Holstein, which was presented to the veterinarian due to multifocal nodular skin lesions. Several superficial lymph nodes (Lymphonodi mandibulares, parotidei and mammariae) were enlarged, had a tight-elastic consistency and were freely movable. The histopathological and immunohistochemical examination of skin biopsies showed the presence of multifocal cutaneous T-cell lymphosarcomas consistent with a skin leukosis. Bovine leukemia virus infection was excluded by serological investigation of a milk sample and virological examination of a tissue sample, respectively. Seven weeks after the first clinical examination, the cow deteriorated rapidly and was euthanized. A post mortem examination revealed the presence of neoplastic cells within lymph nodes (all superficial lymph nodes of the carcass and Lymphonodi pulmonales), kidney and lungs as well as a liver rupture. Additionally, an overview of the case reports of sporadic bovine cutaneous lymphosarcomas published during the previous 15 years will be provided. The legal background for a further utilization of affected animals for milk and meat production will be discussed. This case report illustrates that sporadic bovine leukosis represents an important differential diagnosis for viral-, bacterial- and parasitic-induced skin lesions and enlargement of lymph nodes in adult cattle.

  3. The Use of Synchrotron Infrared Microspectroscopy in the Assessment of Cutaneous T-cell Lymphoma vs. Pityriasis lichenoides Chronica

    SciTech Connect

    El Bedewi, A.; El Anany, G; El Mofty, M; Kretlow, A; Park, S; Miller, L

    2010-01-01

    The diagnosis of cutaneous lymphomas remains a challenge for both the clinician and dermatopathologist. To differentiate between frank malignant and premalignant lymphocytes within the skin. This study was performed on 20 patients with a mean age of 50 years. They were divided into two groups: mycosis fungoides (MF) (stage IA, IB and IIA) and pityriasis lichenoides chronica (PLC). Immunophenotyping using antibodies CD3, CD4, CD8, CD20 and CD30 was performed. Synchrotron Fourier transform infrared microspectroscopy (S-FTIRM) was performed on cell nuclei to assess chemical differences between MF and PLC cases as a potential complementary screening tool. Dermal spectra of both MF and PLC were compared using principal components analysis (PCA) of the S-FTIRM data. All PLC spectra was clustered together. However, the MF spectra formed two clusters, one that grouped with the PLC and the other grouped separately. Moreover, protein and nucleic acids showed highly significant differences between MF (IIA and IB), MF (IA) and PLC. The malignant transformation within lymphocytes was identifiable through the spectroscopic analysis of protein, RNA and DNA with S-FTIRM, making it a promising tool for classifying the progression of cutaneous T-cell lymphoma.

  4. T-cell primary leptomeningeal lymphoma in cerebellopontine angle

    PubMed Central

    Briongos-Figuero, Laisa Socorro; Gómez-Traveso, Tamara; Pérez-Castrillon, José Luis

    2015-01-01

    Primary meningeal lymphomas are very rare and those derived from T cells are even more infrequent (less than 5% of primary central nervous system lymphomas). Cerebellopontine angle involvement in the primary T-cell lymphoma is exceptional. Clinical presentation depends on the type of lesions, and histological diagnosis is needed. We present a rare case of a 50-year-old woman who presented with clinical cerebellar syndrome with posterior opsoclonus-myoclonus syndrome. Necropsy evaluation revealed primary diffuse leptomeningeal non-Hodgkin's T-cell lymphoma. PMID:25750225

  5. Overexpression of hypoxia-inducible factor 1 alpha impacts FoxP3 levels in mycosis fungoides--cutaneous T-cell lymphoma: clinical implications.

    PubMed

    Alcántara-Hernández, M; Torres-Zárate, C; Pérez-Montesinos, G; Jurado-Santacruz, F; Domínguez-Gómez, M A; Peniche-Castellanos, A; Ferat-Osorio, E; Neri, N; Nambo, M J; Alvarado-Cabrero, I; Moreno-Lafont, M; Huerta-Yepez, S; Bonifaz, L C

    2014-05-01

    Mycosis fungoides (MF) is the most common variant of primary cutaneous T-cell lymphoma, and decreased forkhead box P3 (FoxP3) expression has been reported in MF late stages. Hypoxia-inducible factor 1 alpha (HIF-1α) may regulate FoxP3 expression; however, it is unknown whether HIF-1α is expressed in the CD4(+) T cells of MF patients and how it could affect the expression of FoxP3. Therefore, we evaluated the expression of HIF-1α and FoxP3 in CD4(+) T cells obtained from the skin lesions of MF patients. We found increased cell proliferation and an increase in CD4(+) T cells with an aberrant phenotype among early stage MF patients. HIF-1α was overexpressed in these CD4(+) T cells. In addition, we found a decrease in the percentage of FoxP3(+) cells both in the skin of MF patients, when compared with control skin samples, and with disease progression. In addition, a negative correlation was established between HIF-1α and FoxP3 expression. Skin HIF-1α expression in MF patients correlated with the extent of the affected area and increased with the disease progression. Finally, we showed that ex vivo inhibition of HIF-1α degradation increases the percentage of FoxP3(+) T cells in skin lesions. Our results suggest that overexpression of HIF-1α affects the levels of FoxP3 in MF patients, which could have relevant implications in terms of disease outcome.

  6. Extranodal natural killer cell/t-cell lymphoma, nasal type, presenting as cutaneous nodules and a small-bowel perforation.

    PubMed

    Agarwal, Priyanka; Ruzinova, Marianna B; Harris, Marian H; Qureshi, Abrar A; Stebbins, William G

    2010-02-01

    Extranodal natural killer (NK) cell/T-cell lymphoma, nasal type, is a rare aggressive neoplasm, most commonly presenting as a destructive lesion in the nasal cavity and nasopharynx in middle-aged to older adults. About one third of cases present in an extranasal location, commonly involving skin and gastrointestinal tract, and usually occur in the absence of superficial lymphadenopathy. Diagnosis of this malignancy can be missed given its rarity and heterogeneous presentation. We describe a patient with an extranodal NK cell/T-cell lymphoma, nasal type, who was initially diagnosed and treated for a presumed Mycobacterium marinum infection, after biopsies were unrevealing. However, after more serious complications developed, repeat biopsy was performed. An atypical lymphocytic infiltrate was noted, with cells being positive for NK cell/T-cell markers CD2, CD7, and CD3 (subset), as well as for cytotoxic lymphocyte markers perforin, T-cell intracellular antigen, and CD56. In situ hybridization for Epstein-Barr virus-encoded RNA was also positive. This case demonstrates an important diagnostic pitfall of confusing cutaneous involvement by an aggressive NK cell/T-cell lymphoma with an antibiotic-resistant infection. Repeat biopsies and close clinicopathologic correlation are essential for establishment of correct diagnosis.

  7. Investigating potential exogenous tumor initiating and promoting factors for Cutaneous T-Cell Lymphomas (CTCL), a rare skin malignancy.

    PubMed

    Litvinov, Ivan V; Shtreis, Anna; Kobayashi, Kenneth; Glassman, Steven; Tsang, Matthew; Woetmann, Anders; Sasseville, Denis; Ødum, Niels; Duvic, Madeleine

    2016-07-01

    Most skin malignancies are caused by external and often preventable environmental agents. Multiple reports demonstrated that cutaneous T-cell lymphomas (CTCL) can occur in married couples and cluster in families. Furthermore, recent studies document geographic clustering of this malignancy in Texas as well as in other areas of the United States. Multiple infectious, occupational, and medication causes have been proposed as triggers or promoters of this malignancy including hydrochlorothiazide diuretics, Staphylococcus aureus, dermatophytes, Mycobacterium leprae, Chlamydia pneumoniae, human T-Cell lymphotropic virus type 1 (HTLV1), Epstein-Barr virus (EBV), and herpes simplex virus (HSV). In this report, we review recent evidence evaluating the involvement of these agents in cancer initiation/progression. Most importantly, recent molecular experimental evidence documented for the first time that S. aureus can activate oncogenic STAT3 signaling in malignant T cells. Specifically, S. aureus Enterotoxin type A (SEA) was recently shown to trigger non-malignant infiltrating T cells to release IL-2 and other cytokines. These signals upon binging to their cognate receptors on malignant T cells are then able to activate STAT3 and STAT5 oncogenic signaling and promote cancer progression and IL-17 secretion. In light of these findings, it might be important for patients with exacerbation of their CTCL symptoms to maintain high index of suspicion and treat these individuals for S. aureus colonization and/or sepsis with topical and systemic antibiotics.

  8. Case report of four patients with erythrodermic cutaneous T-cell lymphoma and severe photosensitivity mimicking chronic actinic dermatitis.

    PubMed

    Agar, N; Morris, S; Russell-Jones, R; Hawk, J; Whittaker, S

    2009-03-01

    The marked photosensitivity associated with chronic actinic dermatitis (CAD) is presumed to be due to a T cell-mediated response to ultraviolet (UV)-induced epidermal neoantigens. Photosensitivity is, however, a rare occurrence in cutaneous T-cell lymphoma (CTCL). We discuss a series of four patients with erythrodermic CTCL who exhibited marked photosensitivity mimicking CAD. Significantly, the tumour cells had a CD8 phenotype in half of these patients. All patients had T-cell clones in skin and also demonstrated identical peripheral T-cell clones in blood or lymph node involvement. Sézary cell counts ranged from 6% to 20%, CD4/CD8 ratios from 0.22 to 23.5. Clinical presentation was striking for a marked photosensitive distribution. Monochromator irradiation testing revealed reduced minimal erythema doses throughout UVB and UVA ranges, findings consistent with those seen in CAD. All patients subsequently died from systemic disease. These findings suggest that, rarely, malignant clonal T-cell populations may recognize a unique UV-induced neoantigen, resulting in the clinical features of severe photosensitivity mimicking those seen in CAD.

  9. Multiple primary cutaneous melanomas in patients with FAMMM syndrome and sporadic atypical mole syndrome (AMS): what's worse?

    PubMed

    Tchernev, Georgi; Ananiev, Julian; Cardoso, José-Carlos; Chokoeva, Anastasiya Atanasova; Philipov, Stanislav; Penev, Plamen Kolev; Lotti, Torello; Wollina, Uwe

    2014-08-01

    Atypical Mole Syndrome is the most important phenotypic risk factor for cutaneous melanoma, a malignancy that accounts for about 80% of deaths from skin cancer. Since early diagnosis of melanoma is of great prognostic relevance, the identification of Atypical Mole Syndrome carriers (sporadic and familial) is essential, as well as the recommendation of preventative measures that must be undertaken by these patients.We report two rare cases concerning patients with multiple primary skin melanomas in the setting of a familial and a sporadic syndrome of dysplastic nevi: the first patient is a 67-year-old patient with a history of multiple superficial spreading melanomas localized on his back. The second patient presented with multiple primary melanomas in advanced stage in the context of the so-called sporadic form of the syndrome of dysplastic nevi-AMS (atypical mole syndrome). In the first case, excision of the melanomas was carried out with an uneventful post-operative period. In the second case, disseminated metastases were detected, involving the right fibula, the abdominal cavity as well as multiple lesions in the brain. The patient declined BRAF mutation tests as well as chemotherapy or targeted therapies, and suffered a rapid deterioration in his general condition leading to death. We classified the second case as a sporadic form of the atypical mole syndrome, associated with one nodular and two superficial spreading melanomas.There are no data in the literature to allow us to understand if, in patients with multiple primary melanomas, there is any difference in terms of prognosis between those with and without a family history of a similar phenotype. To answer this and other questions related to these rare cases, further studies with a significant number of patients should be carried out.

  10. Evaluation, Diagnosis, and Staging of Cutaneous Lymphoma.

    PubMed

    Olsen, Elise A

    2015-10-01

    Primary cutaneous lymphomas (PCLs) are an extremely heterogeneous group of non-Hodgkin lymphomas that manifest in the skin. Their diagnosis is complex and based on clinical lesion type and evaluation of findings on light microscopic examination, immunohistochemistry and molecular analysis of representative skin biopsies. The evaluation, classification, and staging system is unique for mycosis fungoides (MF) and Sézary syndrome (SS), the most common subtypes of cutaneous T-cell lymphoma (CTCL) versus the other subtypes of Non-MF/Non-SS CTCL and the subtypes of cutaneous B-cell lymphoma (CBCL). Since current treatment is stage-based, it is particularly important that the correct diagnosis and stage be ascertained initially. The purpose of this article is to review the current evaluation, diagnosis, classification, staging, assessment techniques, and response criteria for the various types of both T-cell and B-cell PCLs. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. A Phase II trial of Belinostat (PXD101) in patients with relapsed or refractory peripheral or cutaneous T-cell lymphoma.

    PubMed

    Foss, Francine; Advani, Ranjana; Duvic, Madeleine; Hymes, Kenneth B; Intragumtornchai, Tanin; Lekhakula, Arnuparp; Shpilberg, Ofer; Lerner, Adam; Belt, Robert J; Jacobsen, Eric D; Laurent, Guy; Ben-Yehuda, Dina; Beylot-Barry, Marie; Hillen, Uwe; Knoblauch, Poul; Bhat, Gajanan; Chawla, Shanta; Allen, Lee F; Pohlman, Brad

    2015-03-01

    Belinostat is a pan-histone deacetylase inhibitor with antitumour and anti-angiogenic properties. An open label, multicentre study was conducted in patients with peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL) who failed ≥1 prior systemic therapy and were treated with belinostat (1000 mg/m(2) intravenously ×5 d of a 21-d cycle). The primary endpoint was objective response rate (ORR). Patients with PTCL (n = 24) had received a median of three prior systemic therapies (range 1-9) and 40% had stage IV disease. Patients with CTCL (n = 29) had received a median of one prior skin-directed therapy (range 0-4) and four prior systemic therapies (range 1-9); 55% had stage IV disease. The ORRs were 25% (PTCL) and 14% (CTCL). Treatment-related adverse events occurred in 77% of patients; nausea (43%), vomiting (21%), infusion site pain (13%) and dizziness (11%) had the highest incidence. Treatment-related serious adverse events were Grade 5 ventricular fibrillation; Grade 4 thrombocytopenia; Grade 3 peripheral oedema, apraxia, paralytic ileus and pneumonitis; and Grade 2 jugular vein thrombosis. Belinostat monotherapy was well tolerated and efficacious in patients with recurrent/refractory PTCL and CTCL. This trial was registered at www.clinicaltrials.gov as NCT00274651. © 2014 John Wiley & Sons Ltd.

  12. Monitoring Pc 4 photodynamic therapy in clinical trials of cutaneous T-cell lymphoma using noninvasive spectroscopy.

    PubMed

    Lee, Tammy K; Baron, Elma D; Foster, Thomas H

    2008-01-01

    Silicon phthalocyanine Pc 4 photodynamic therapy (Pc 4-PDT) has emerged as a potentially effective treatment for cutaneous T-cell lymphoma (CTCL). Noninvasive reflectance and fluorescence spectroscopy before, during, and after PDT may provide useful dose metrics and enable therapy to be tailored to individual lesions. We present the design and implementation of a portable bedside spectroscopy system for initial clinical trials of Pc 4-PDT of CTCL. Reflectance and fluorescence spectra were obtained from an early stage CTCL patient throughout the course of the PDT treatment. Preliminary patient data show a significant effect of Pc 4 on the tissue absorption, modest Pc 4 photobleaching, and heterogeneity of Pc 4 within and between the lesions.

  13. Primary cutaneous cryptococcosis in an eight-year-old immunocompetent child: how to treat?

    PubMed

    Lenz, D; Held, J; Goerke, S; Wagner, D; Tintelnot, K; Henneke, P; Hufnagel, M

    2015-01-01

    Here we report on a case of primary cryptococcal skin infection in an immunocompetent 8-year-old boy. The infection first manifested itself as a subcutaneous abscess around the proximal joint of his right thumb after a minor injury from contact with a thorny shrub. After surgical incision and drainage was performed, Cryptococcus neoformans var. neoformans was the only pathogen cultured from the lesion. An agglutination test for the capsular antigen in serum displayed negative results and the immunological work-up revealed no underlying immunodeficiency. A "watch and wait" strategy - one without systemic antifungal treatment - was adopted and this resulted in uneventful healing. In summary, primary cryptococcal skin infections in immunocompetent hosts may be managed successfully by surgical treatment in combination with careful clinical follow-up. This approach may help avoid unnecessary antimicrobial treatments. © Georg Thieme Verlag KG Stuttgart · New York.

  14. Primary tumor sites in relation to ultraviolet radiation exposure and skin visibility correlate with survival in cutaneous melanoma.

    PubMed

    Gordon, Daniela; Hansson, Johan; Eloranta, Sandra; Gordon, Max; Gillgren, Peter; Smedby, Karin E

    2017-10-01

    The prognostic value of detailed anatomic site and ultraviolet radiation (UVR) exposure patterns has not been fully determined in cutaneous melanoma. Thus, we reviewed medical records for detailed site in a population-based retrospective Swedish patient cohort diagnosed with primary invasive melanoma 1976-2003 (n = 5,973). We followed the patients from date of diagnosis until death, emigration or December 31(st) 2013, and evaluated melanoma-specific survival by subsite in a multivariable regression model adjusting for established prognostic factors. We found that melanoma on chronic UVR exposure sites (face, dorsum of hands; adjusted HR 0.6; CI 0.4-0.7) and moderately intermittent UVR sites (lateral arms, lower legs, dorsum of feet; HR 0.7; CI 0.6-0.8) were associated with a favorable prognosis compared with highly intermittent sites (chest, back, neck, shoulders and thighs). Further, melanoma on poorly visible skin sites upon self-examination (scalp, retroauricular area, back, posterior upper arms and thighs, buttocks, pubic area; HR 1.3; CI 1.1-1.5) had a worse prognosis than those on easily visible sites (face, chest, abdomen, anterior upper arms and thighs, lower arms and legs, dorsum of hands and feet, palms). In conclusion, highly intermittent UVR exposure sites and poor skin visibility presumably correlate with reduced melanoma survival, independent of established tumor characteristics. A limitation of the study was the lack of information on actual individual UVR exposure. © 2017 UICC.

  15. Surveillance and screening of American cutaneous leishmaniasis by Colombian primary health care workers using a clinical prediction rule.

    PubMed

    Rojas, Carlos A; Weigle, Kristen A; Barrera, Lena; Collazos, Constanza

    2002-01-01

    Confirmed cases of American cutaneous leishmaniasis (ACL) and other dermatological diseases were evaluated in Colombia with a clinical prediction rule independently by 3 types of evaluators: community health volunteer (CHV), practical nurse (PN) and programme physician (PP). The adapted prediction rule included 6 variables based upon clinical-historical information. The screening instrument was a rotating tower of coloured squares, one colour for each variable. A score ranging from 0 to 7, and a cutoff point of > or = 4 was selected for ACL classification (sensitivity 94.3%, specificity 53.3% and efficiency 80.3%). Disease classification, total score, and variable-specific score obtained by CHVs and PNs were compared to those obtained by a PP. The impact on case detection in the study area was assessed. Both types of primary health worker had a high agreement with the PP (sensitivity) on the classification of patients with ACL by score, CHV (92.3%) and PN (93.3%). Case detection of ACL increased 3-fold over that observed one year earlier. This screening instrument and prediction rule, when incorporated into a community surveillance programme for ACL, can facilitate greater case detection and appropriate referral for more-specific diagnostic procedures.

  16. Lectin binding as a probe of proliferative and differentiative phases in primary monolayer cultures of cutaneous keratinocytes

    SciTech Connect

    Ku, W.W.; Bernstein, I.A. )

    1988-04-01

    The surface of cells in the cutaneous epidermis of the newborn rat exhibits a discrete change in lectin-binding specificity from Griffonia simplicifolia I-B4 (GS I-B4), specific for {alpha}-D-galactosyl residues, to Ulex europeus agglutinin I (UEA), specific for {alpha}-L-fucose, as the cell leaves the basal layer and differentiates. Primary monolayer cultures of rat keratinocytes maintained in low Ca{sup 2+} medium exhibited a characteristic unimodal pattern in the ratio of bound UEA to bound GS I-B4 (UEA/B4 ratio) over a 7-day culture period as determined by a quantitative fluorometric assay. Estimation of DNA synthesis showed (a) a higher ({sup 3}H)thymidine incorporation when the UEA/B4 ratio was low and (b) a steady but lower incorporation between Days 3 and 4, coincident with the higher UEA/B4 ratio. Autoradiographic results further showed that cells stained intensely with UEA failed to incorporate ({sup 3}H)thymidine into their nuclei. Overall, the results suggest that (a) the increase in the UEA/B4 ratio between Days 2 and 4 reflects the progression of a proportion of the cells in the monolayer to an early spinous cell stage, the ultimate fate of which is desquamation into the medium and (b) the decrease in the UEA/B4 ratio between Days 5 and 7 reflects a consequent proliferative response to this loss of cells.

  17. Reversed cellular polarity in primary cutaneous mucinous carcinoma: A study on tight junction protein expression in sweat gland tumors.

    PubMed

    Nagasawa, Yusuke; Ishida-Yamamoto, Akemi

    2017-04-01

    Primary cutaneous mucinous carcinoma (PCMC) is a rare sweat gland tumor characterized by the presence of abundant mucin around the tumor islands, but the molecular mechanisms for this structure are not well elucidated. Because mucin is epithelial in nature, it is likely to be produced by epithelial tumor cells, not by surrounding stromal cells. We hypothesized that the abundant mucin is a result of reversed cellular polarity of the tumor. To test this hypothesis, we conducted an immunohistological study to investigate expression of tight junction (TJ) proteins occludin and ZO-1 in PCMC, as well as in normal sweat glands and other sweat gland tumors. Dot-like or linear expression of TJ proteins was observed at ductal structures of sweat glands, and ductal or cystic structures of related tumors. In PCMC, however, TJ protein expression was clearly visible at the edges of tumor cell islands. This study provides evidence to show that the characteristic histological structure of PCMC is caused by inverse polarization of the tumor cells, and that TJ proteins are useful markers of ductal differentiation in sweat gland tumors.

  18. Evolving Insights in the Pathogenesis and Therapy of Cutaneous T-cell lymphoma (Mycosis Fungoides and Sezary Syndrome)

    PubMed Central

    Wong, Henry K.; Mishra, Anjali; Hake, Timothy; Porcu, Pierluigi

    2015-01-01

    Cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of malignancies derived from skin-homing T cells. The most common forms of CTCL are Mycosis Fungoides (MF) and Sezary Syndrome (SS). Accurate diagnosis remains a challenge due to the heterogeneity of presentation and the lack of highly characteristic immunophenotypical and genetic markers. Over the past decade molecular studies have improved our understanding of the biology of CTCL. The identification of gene expression differences between normal and malignant T-cells has led to promising new diagnostic and prognostic biomarkers that now need validation to be incorporated into clinical practice. These biomarkers may also provide insight into the mechanism of development of CTCL. Additionally, treatment options have expanded with the approval of new agents, such as histone deacetylase inhibitors. A better understanding of the cell biology, immunology and genetics underlying the development and progression of CTCL will allow the design of more rational treatment strategies for these malignancies. This review summarizes the clinical epidemiology, staging and natural history of MF and SS; discusses the immunopathogenesis of MF and the functional role of the malignant T-cells; and reviews the latest advances in MF and SS treatment. PMID:21883142

  19. Primary cutaneous cryptococcosis in an immunocompetent patient due to Cryptococcus gattii molecular type VGI in Brazil: a case report and review of literature.

    PubMed

    Nascimento, Erika; Bonifácio da Silva, Maria Emília Nadaletto; Martinez, Roberto; von Zeska Kress, Marcia Regina

    2014-07-01

    Primary Cutaneous Cryptococcosis is an uncommon infection caused by the yeast Cryptococcus neoformans and C. gattii. Few case reports are available in the literature describing in detail primary cutaneous cryptococcosis due to C. gattii in immunocompetent patients. Herein, we present a case of a 68-year-old immunocompetent male patient with erythematous nodular lesions on the right forearm due to C. gattii mating-type α and molecular type VGI. The virulence factors test was performed for capsule diameter, melanin production and phospholipase activity. In vitro fluconazole testing showed the sensitivity profile of this clinical isolate. In addition, a review of the literature on this subject was carried out and verified that this is the first reported case of VGI in the south-east region of Brazil.

  20. Primary cellulitis and cutaneous abscess caused by Yersinia enterocolitica in an immunocompetent host: A case report and literature review.

    PubMed

    Kato, Hirofumi; Sasaki, Shugo; Sekiya, Noritaka

    2016-06-01

    Primary extraintestinal complications caused by Yersinia enterocolitica are extremely rare, especially in the form of skin and soft-tissue manifestations, and little is known about their clinical characteristics and treatments. We presented our case and reviewed past cases of primary skin and soft-tissue infections caused by Y enterocolitica. We report a case of primary cellulitis and cutaneous abscess caused by Y enterocolitica in an immunocompetent 70-year-old woman with keratodermia tylodes palmaris progressiva. She presented to an outpatient clinic with redness, swelling, and pain of the left ring finger and left upper arm without fever or gastrointestinal symptoms 3 days before admission. One day later, ulceration of the skin with exposed bone of the proximal interphalangeal joint of the left ring finger developed, and cefditoren pivoxil was described. However, she was admitted to our hospital due to deterioration of symptoms involving the left finger and upper arm. Cefazolin was initiated on admission, then changed to sulbactam/ampicillin and vancomycin with debridement of the left ring finger and drainage of the left upper arm abscess. Wound culture grew Y enterocolitica serotype O:8 and methicillin-sensitive Staphylococcus aureus. Blood cultures were negative and osteomyelitis was ruled out. Vancomycin was switched to ciprofloxacin, then skin and soft-tissue manifestations showed clear improvement within a few days. The patient received 14 days of ciprofloxacin and oral amoxicillin/clavulanate and has since shown no recurrence. We reviewed 12 cases of primary skin and soft-tissue infections caused by Y enterocolitica from the literature. In several past cases, portal entry involved failure of the skin barrier on distal body parts. Thereafter, infection might have spread to the regional lymph nodes from the ruptured skin. Y enterocolitica is typically resistant to aminopenicillins and narrow-spectrum cephalosporins. In most cases, these inefficient

  1. Non-random geographic distribution of patients with cutaneous T-cell lymphoma in the Greater Pittsburgh Area.

    PubMed

    Moreau, Jacqueline F; Buchanich, Jeanine M; Geskin, Jacob Z; Akilov, Oleg E; Geskin, Larisa J

    2014-07-15

    Environmental hazards may play a role in the etiology of cutaneous T-cell lymphoma (CTCL). Some studies have found an increased incidence of CTCL among workers in chemical science, transportation, and manufacturing industries, but other studies have not. This discrepancy may be attributable to population migration, complicating accurate assessment of lifetime exposures. The Pittsburgh population has very low migration rates and most CTCL patients seen at the University of Pittsburgh Medical Center (UPMC) Cutaneous Lymphoma Center are life-long local residents. The Greater Pittsburgh Area used to be an industrial hub. There are residential communities positioned within close proximity to inactive industrial sites that continue to contain pollutants. To determine whether CTCL patients' residences cluster within specific Pittsburgh regions, in particular, those with high levels of environmental pollutants. Our study included patients diagnosed with CTCL at the UPMC Cutaneous Lymphoma Center between 2000 and 2012. We mapped the longitudinal and latitudinal coordinates of patients' residences at diagnosis, superfund sites, toxic release inventory sites, particular matter levels, and dermatologists' offices using ArcMap 10.1. We then performed a SaTScan analysis using zip codes to assess for geographic clustering of patients' residences in the Pittsburgh metropolitan statistical area. We assessed for a correlation between case distribution and both environmental hazards sites and dermatologist density in the area. We identified 274 patients with CTCL in the Greater Pittsburgh area. We identified a statistically significant geographic cluster (p<.001) in zip code 15213, which is the most densely populated neighborhood in Pittsburgh and the site of the region's only CTCL clinic. We observed no relationship between the locations of superfund sites, toxic release inventory sites, or particular matter levels and CTCL case distribution. Our findings do not support an

  2. Variant on Manifestation of Duodenal Metastasis 26 Years after Initial Diagnosis of Primary Cutaneous Melanoma

    PubMed Central

    Kitajima, Kumiko; Bardier-Dupas, Armelle; Breton, Sylvie; Rousseau, Géraldine; Siksik, Jean-Michel; Vaillant, Jean-Christophe; Hannoun, Laurent

    2010-01-01

    Malignant duodenal neoplasms are relatively rare, and the diagnosis is often delayed because of their vague and nonspecific symptoms. We report the case of a 79-year-old female who had a medical history of malignant melanoma of the cheek that had initially been diagnosed at 53 years of age. Work-up revealed severe stenosis of the duodenum caused by a large mass with ulceration at the tip of its mucosal surface. Tumor biopsy led to a histological diagnosis of extremely poorly differentiated carcinoma, but it was impossible to determine whether the lesion was a primary neoplasm or represented secondary involvement. Pancreatoduodenectomy was performed, and the surgical specimen showed a protuberant tumor in the nonampullary region of the second portion of the duodenum. Final diagnosis of metastatic duodenal melanoma was made by immunohistological examination. She is currently alive without recurrence 28 months after the surgical treatment. PMID:21103234

  3. Brentuximab vedotin or physician's choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial.

    PubMed

    Prince, H Miles; Kim, Youn H; Horwitz, Steven M; Dummer, Reinhard; Scarisbrick, Julia; Quaglino, Pietro; Zinzani, Pier Luigi; Wolter, Pascal; Sanches, Jose A; Ortiz-Romero, Pablo L; Akilov, Oleg E; Geskin, Larisa; Trotman, Judith; Taylor, Kerry; Dalle, Stephane; Weichenthal, Michael; Walewski, Jan; Fisher, David; Dréno, Brigitte; Stadler, Rudolf; Feldman, Tatyana; Kuzel, Timothy M; Wang, Yinghui; Palanca-Wessels, Maria Corinna; Zagadailov, Erin; Trepicchio, William L; Zhang, Wenwen; Lin, Hui-Min; Liu, Yi; Huebner, Dirk; Little, Meredith; Whittaker, Sean; Duvic, Madeleine

    2017-08-05

    Cutaneous T-cell lymphomas are rare, generally incurable, and associated with reduced quality of life. Present systemic therapies rarely provide reliable and durable responses. We aimed to assess efficacy and safety of brentuximab vedotin versus conventional therapy for previously treated patients with CD30-positive cutaneous T-cell lymphomas. In this international, open-label, randomised, phase 3, multicentre trial, we enrolled adult patients with CD30-positive mycosis fungoides or primary cutaneous anaplastic large-cell lymphoma who had been previously treated. Patients were enrolled across 52 centres in 13 countries. Patients were randomly assigned (1:1) centrally by an interactive voice and web response system to receive intravenous brentuximab vedotin 1·8 mg/kg once every 3 weeks, for up to 16 3-week cycles, or physician's choice (oral methotrexate 5-50 mg once per week or oral bexarotene 300 mg/m(2) once per day) for up to 48 weeks. The primary endpoint was the proportion of patients in the intention-to-treat population achieving an objective global response lasting at least 4 months per independent review facility. Safety analyses were done in all patients who received at least one dose of study drug. This trial was registered with ClinicalTrials.gov, number NCT01578499. Between Aug 13, 2012, and July 31, 2015, 131 patients were enrolled and randomly assigned to a group (66 to brentuximab vedotin and 65 to physician's choice), with 128 analysed in the intention-to-treat population (64 in each group). At a median follow-up of 22·9 months (95% CI 18·4-26·1), the proportion of patients achieving an objective global response lasting at least 4 months was 56·3% (36 of 64 patients) with brentuximab vedotin versus 12·5% (eight of 64) with physician's choice, resulting in a between-group difference of 43·8% (95% CI 29·1-58·4; p<0·0001). Grade 3-4 adverse events were reported in 27 (41%) of 66 patients in the brentuximab vedotin group and 29 (47%) of 62

  4. CD30-positive cutaneous lymphoma: report of four cases with an emphasis on clinicopathological correlations*

    PubMed Central

    Vargas, Thiago Jeunon de Sousa; Jorge, Samira Barroso; Gonzaga, Yung Bruno de Mello

    2017-01-01

    The classification of cutaneous lymphomas is multidisciplinary and requires the correlation between clinical, histopathological, immunohistochemical, and molecular diagnostic elements. In this article, we present four different cases of CD30-positive T-cell lymphoma with cutaneous manifestations. We compare cases with definitive diagnosis of papulosis lymphomatoid type C, primary cutaneous anaplastic large T-cell lymphoma, systemic anaplastic large T-cell lymphoma with secondary skin involvement, and mycosis fungoides with large cell transformation, highlighting the importance of clinicopathological correlation to classify these cases. PMID:28225962

  5. Identification of Somatic Mutations in Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type by Massive Parallel Sequencing.

    PubMed

    Mareschal, Sylvain; Pham-Ledard, Anne; Viailly, Pierre Julien; Dubois, Sydney; Bertrand, Philippe; Maingonnat, Catherine; Fontanilles, Maxime; Bohers, Elodie; Ruminy, Philippe; Tournier, Isabelle; Courville, Philippe; Lenormand, Bernard; Duval, Anne Bénédicte; Andrieu, Emilie; Verneuil, Laurence; Vergier, Beatrice; Tilly, Hervé; Joly, Pascal; Frebourg, Thierry; Beylot-Barry, Marie; Merlio, Jean-Philippe; Jardin, Fabrice

    2017-09-01

    To determine whether the mutational profile of primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL-LT) is unique by comparison with other diffuse large B-cell lymphoma subtypes, we analyzed a total cohort of 20 PCLBCL-LT patients by using next-generation sequencing with a lymphoma panel designed for diffuse large B-cell lymphoma. We also analyzed 12 pairs of tumor and control DNA samples by whole-exome sequencing, which led us to perform resequencing of three selected genes not included in the lymphoma panel: TBL1XR1, KLHL6, and IKZF3. Our study clearly identifies an original mutational landscape of PCLBCL-LT with a very restricted set of highly recurrent mutations (>40%) involving MYD88 (p.L265P variant), PIM1, and CD79B. Other genes involved in B-cell signaling, NF-κB activation, or DNA modeling were found altered, notably TBL1XR1 (33%), MYC (26%) CREBBP (26%), and IRF4 (21%) or HIST1H1E (41%). MYD88(L265P) variant was associated with copy number variations or copy neutral loss of heterozygosity in 60% of patients. The most frequent genetic losses involved CDKN2A/2B, TNFAIP3/A20, PRDM1, TCF3, and CIITA. Together, these results show that PCLBCL-LT exhibits a unique mutational landscape, combining highly recurrent hotspot mutations in genes involved in NF-kB and B-cell signaling pathways, which provides a rationale for using selective inhibitors of the B-cell receptor. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Cutaneous stimulation of the digits and lips evokes responses with different adaptation patterns in primary somatosensory cortex

    PubMed Central

    Popescu, Mihai; Barlow, Steven; Popescu, Elena-Anda; Estep, Meredith E.; Venkatesan, Lalit; Auer, Edward T.; Brooks, William M.

    2010-01-01

    Neuromagnetic evoked fields were recorded to compare the adaptation of the primary somatosensory cortex (SI) response to tactile stimuli delivered to the glabrous skin at the fingertips of the first three digits (condition 1) and between midline upper and lower lips (condition 2). The stimulation paradigm allowed to characterize the response adaptation in the presence of functional integration of tactile stimuli from adjacent skin areas in each condition. At each stimulation site, cutaneous stimuli (50 ms duration) were delivered in three runs, using trains of 6 pulses with regular stimulus onset asynchrony (SOA). The pulses were separated by SOAs of 500 ms, 250 ms or 125 ms in each run, respectively, while the inter-train interval was fixed (5 s) across runs. The evoked activity in SI (contralateral to the stimulated hand, and bilaterally for lips stimulation) was characterized from the best-fit dipoles of the response component peaking around 70 ms for the hand stimulation, and 8 ms earlier (on average) for the lips stimulation. The SOA-dependent long-term adaptation effects were assessed from the change in the amplitude of the responses to the first stimulus in each train. The short-term adaptation was characterized by the lifetime of an exponentially saturating model function fitted to the set of suppression ratios of the second relative to the first SI response in each train. Our results indicate: 1) the presence of a rate-dependent long-term adaptation effect induced only by the tactile stimulation of the digits; and 2) shorter recovery lifetimes for the digits compared with the lips stimulation. PMID:20561996

  7. Cutaneous leishmaniasis in primary school children in the south-eastern Iranian city of Bam, 1994-95.

    PubMed Central

    Sharifi, I.; Fekri, A. R.; Aflatonian, M. R.; Nadim, A.; Nikian, Y.; Kamesipour, A.

    1998-01-01

    Between August 1994 and July 1995, 11,517 primary school children aged 6-11 years in the south-eastern Iranian city of Bam, comprising 5560 (48.3%) girls and 5957 (51.7%) boys, were examined for the presence of active lesions or scars of cutaneous leishmaniasis (CL). There was a trend towards increasing prevalence with age, the prevalence being 10.7% in 6-year-old and 20% in > or = 11-year-old children. Overall, 1.3% of the children had active lesions and 14.3% had scars. There was no significant difference between the sexes in the prevalence of active lesions and/or scars. Of the children examined, 54 (0.5%) had leishmaniasis recidivans: 19 girls (35.2%) and 35 boys (64.8%). The number of active lesions or scars per child ranged from 1 to 10. The majority (82.3%) had 1 lesion, 12.4% had 2 lesions, and 5.3% had > or = 3. The average number of lesions was 1.08 (1.03 in girls and 1.18 in boys). The face was the part of the body most commonly involved (63.6%), followed by the hands (20.9%), legs (12.8%) and other parts of the body (2.7%). Examination of isolates from 14 children revealed that in 13 (92.9%) the causal organism was Leishmania tropica and in the other (7.1%) L. major. The survey indicates that the geographical distribution of CL is far wider than previously thought. It also shows that Bam is a suitable areas for a vaccine field trial. PMID:9744249

  8. Cutaneous T-cell Lymphoma and Pruritus: The Expression of IL-31 and its Receptors in the Skin.

    PubMed

    Nattkemper, Leigh A; Martinez-Escala, Maria-Estela; Gelman, Ari B; Singer, Elisha M; Rook, Alain H; Guitart, Joan; Yosipovitch, Gil

    2016-11-02

    Approximately 88% of cutaneous T-cell lymphoma (CTCL) patients are affected by pruritus that responds poorly to current antipruritic therapies. Interleukin (IL)-31, a Th2 cytokine, has been found to be increased in the serum of CTCL patients and to correlate with itch severity. This study investigated the role of IL-31 and its receptors (IL-31 receptor-alpha [IL-31RA] and OSMRβ) in the skin of CTCL patients with mild versus moderate/severe pruritus. Expression levels of IL-31, IL-31RA, and OSMRβ in the skin were measured using immunohistochemistry and correlated to pruritus severity and disease stage. In CTCL patients with moderate/severe pruritus, IL-31 was significantly elevated in the epidermis and dermal infiltrate, while IL-31RA and OSMRβ were significantly elevated only in the epidermis. Furthermore, epidermal IL-31 levels correlated to itch severity. These results show that IL-31 may play a role in CTCL pruritus by exerting indirect effects on sensory nerves through epidermal neoplastic T cells and keratinocytes to transmit itch.

  9. CD4(+)CD26(-) lymphocytes are useful to assess blood involvement and define B ratings in cutaneous T cell lymphoma.

    PubMed

    Vonderheid, Eric C; Hou, J Steve

    2018-02-01

    Bernengo et al. reported that >30% CD4(+)CD26(-) lymphocytes detect blood involvement in patients with mycosis fungoides (MF) and Sézary syndrome. In addition, the ISCL/EORTC suggested that this threshold might serve as a criterion for the B2 blood rating for staging. In this manuscript, we report our experience with measurement of CD4(+)CD26(-) and CD4(+)CD7(-) cells, Sézary cell counts, and aberrant T cells with diminished expression of CD2, CD3, or CD5 antigens. CD4(+)CD26(-) ≥30% occurred in 15 of 373 (4.0%) patients with MF, 33 of 47 (70%) patients with erythrodermic cutaneous T cell lymphoma (ECTCL) and 2 of 54 (4%) patients with inflammatory skin diseases. CD4(+)CD26(-) measurements provided a more reliable assessment of neoplastic cell numbers in the blood than Sézary cell or CD4(+)CD7(-) percentages. CD4(+)CD26(-) measurements may be used to define B ratings for staging with B2 defined as CD4(+)CD26(-) ≥ 1000/μL, plus clonality or phenotypically abnormal cells.

  10. Pruritus Reduction with Systemic Anti-lymphoma Treatments in Patients with Cutaneous T Cell Lymphoma: A Narrative Review.

    PubMed

    Field, Halle; Gao, Ling; Motwani, Pooja; Wong, Henry K

    2016-12-01

    Cutaneous T-cell lymphomas (CTCL) are a heterogeneous and relatively rare group of non-Hodgkin lymphomas arising from neoplastic skin-homing memory T cells. There is no known cure for CTCL, and current treatments focus on achieving and maintaining remission, controlling symptoms, limiting toxicities and maintaining or improving quality of life. Patients with CTCL often suffer from pruritus (itching), which can be debilitating and can have a significant impact on physical well-being and quality of life. Although progress has been made towards understanding the mechanisms of pruritus, the pathophysiology of CTCL-related pruritus remains unclear. Currently, there is neither a step-wise treatment algorithm for CTCL nor a standardized approach to treating pruritus in patients with CTCL. Treatments which specifically target pruritus have been reported with varying effectiveness. However, systemic treatments that target CTCL have the potential to alleviate pruritus by treating the underlying disease. Several systemic CTCL treatments have reported anti-pruritic properties, some in both objective responders and nonresponders, but the lack of a standardized method to measure and report pruritus makes it difficult to compare the effectiveness of systemic treatments. In this review, we provide an overview of approved and investigational systemic CTCL treatments that report anti-pruritic properties. For each study, the methods used to measure and report pruritus, as well as the study design are examined so that the clinical benefits of each systemic treatment can be more readily evaluated.

  11. Lesional gene expression profiling in cutaneous T-cell lymphoma reveals natural clusters associated with disease outcome

    PubMed Central

    Shin, Jessica; Monti, Stefano; Aires, Daniel J.; Duvic, Madeleine; Golub, Todd

    2007-01-01

    Cutaneous T-cell lymphoma (CTCL) is defined by infiltration of activated and malignant T cells in the skin. The clinical manifestations and prognosis in CTCL are highly variable. In this study, we hypothesized that gene expression analysis in lesional skin biopsies can improve understanding of the disease and its management. Based on 63 skin samples, we performed consensus clustering, revealing 3 patient clusters. Of these, 2 clusters tended to differentiate limited CTCL (stages IA and IB) from more extensive CTCL (stages IB and III). Stage IB patients appeared in both clusters, but those in the limited CTCL cluster were more responsive to treatment than those in the more extensive CTCL cluster. The third cluster was enriched in lymphocyte activation genes and was associated with a high proportion of tumor (stage IIB) lesions. Survival analysis revealed significant differences in event-free survival between clusters, with poorest survival seen in the activated lymphocyte cluster. Using supervised analysis, we further characterized genes significantly associated with lower-stage/treatment-responsive CTCL versus higher-stage/treatment-resistant CTCL. We conclude that transcriptional profiling of CTCL skin lesions reveals clinically relevant signatures, correlating with differences in survival and response to treatment. Additional prospective long-term studies to validate and refine these findings appear warranted. PMID:17638852

  12. Perforin expression in feline epitheliotropic cutaneous lymphoma.

    PubMed

    Neta, Michal; Naigamwalla, Dinaz; Bienzle, Dorothee

    2008-11-01

    Cutaneous lymphomas are uncommon in people and companion animals. The tumors can be broadly categorized into epitheliotropic and nonepitheliotropic forms, which appear to have different biological behaviors. The present case describes a feline cutaneous epitheliotropic lymphoma. Masses in a 9-year-old cat were first identified on the tail. The cat was treated with chemotherapy, but additional skin masses developed on the flank, face, and ears. Local radiation induced transient tumor regression, but eventual dissemination prompted euthanasia 13 months after initial tumor appearance. Granular lymphocytes were consistently detected on blood smears, and histologically, the tumor involved the skin and superficial subcutis. Tumor lymphocytes expressed cluster of differentiation 3 (CD3) and perforin molecules, suggestive of a cytotoxic phenotype. Location, histopathological features, and perforin expression were similar to a distinct entity in human medicine designated primary cutaneous, CD8-positive, epidermotropic, cytotoxic, T-cell lymphoma.

  13. T cells mediate autoantibody-induced cutaneous inflammation and blistering in epidermolysis bullosa acquisita.

    PubMed

    Bieber, Katja; Witte, Mareike; Sun, Shijie; Hundt, Jennifer E; Kalies, Kathrin; Dräger, Sören; Kasprick, Anika; Twelkmeyer, Trix; Manz, Rudolf A; König, Peter; Köhl, Jörg; Zillikens, Detlef; Ludwig, Ralf J

    2016-12-05

    T cells are key players in autoimmune diseases by supporting the production of autoantibodies. However, their contribution to the effector phase of antibody-mediated autoimmune dermatoses, i.e., tissue injury and inflammation of the skin, has not been investigated. In this paper, we demonstrate that T cells amplify the development of autoantibody-induced tissue injury in a prototypical, organ-specific autoimmune disease, namely epidermolysis bullosa acquisita (EBA) - characterized and caused by autoantibodies targeting type VII collagen. Specifically, we show that immune complex (IC)-induced inflammation depends on the presence of T cells - a process facilitated by T cell receptor (TCR)γδ and NKT cells. Because tissue damage in IC-induced inflammation is neutrophil-dependent, we further analyze the interplay between T cells and neutrophils in an experimental model of EBA. We demonstrate that T cells not only enhance neutrophil recruitment into the site of inflammation but also interact with neutrophils in lymphatic organs. Collectively, this study shows that T cells amplify the effector phase of antibody-induced tissue inflammation.

  14. T cells mediate autoantibody-induced cutaneous inflammation and blistering in epidermolysis bullosa acquisita

    PubMed Central

    Bieber, Katja; Witte, Mareike; Sun, Shijie; Hundt, Jennifer E.; Kalies, Kathrin; Dräger, Sören; Kasprick, Anika; Twelkmeyer, Trix; Manz, Rudolf A.; König, Peter; Köhl, Jörg; Zillikens, Detlef; Ludwig, Ralf J.

    2016-01-01

    T cells are key players in autoimmune diseases by supporting the production of autoantibodies. However, their contribution to the effector phase of antibody-mediated autoimmune dermatoses, i.e., tissue injury and inflammation of the skin, has not been investigated. In this paper, we demonstrate that T cells amplify the development of autoantibody-induced tissue injury in a prototypical, organ-specific autoimmune disease, namely epidermolysis bullosa acquisita (EBA) – characterized and caused by autoantibodies targeting type VII collagen. Specifically, we show that immune complex (IC)-induced inflammation depends on the presence of T cells – a process facilitated by T cell receptor (TCR)γδ and NKT cells. Because tissue damage in IC-induced inflammation is neutrophil-dependent, we further analyze the interplay between T cells and neutrophils in an experimental model of EBA. We demonstrate that T cells not only enhance neutrophil recruitment into the site of inflammation but also interact with neutrophils in lymphatic organs. Collectively, this study shows that T cells amplify the effector phase of antibody-induced tissue inflammation. PMID:27917914

  15. Treatment and Outcomes in Patients With Primary Cutaneous B-Cell Lymphoma: The BC Cancer Agency Experience

    SciTech Connect

    Hamilton, Sarah N.; Wai, Elaine S.; Tan, King; Alexander, Cheryl; Gascoyne, Randy D.; Connors, Joseph M.

    2013-11-15

    Purpose: To review the treatment and outcomes of patients with primary cutaneous B-cell lymphoma (CBCL). Methods and Materials: Clinical characteristics, treatment, and outcomes were analyzed for all patients referred to our institution from 1981 through 2011 with primary CBCL without extracutaneous or distant nodal spread at diagnosis (n=136). Hematopathologists classified 99% of cases using the World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) guidelines. Results: Median age at diagnosis was 62 years. Classification was 18% diffuse large B-cell leg-type (DLBCL-leg), 32% follicle center (FCCL), 45% marginal zone (MZL), and 6% nonclassifiable (OTHER). Of the 111 subjects with indolent lymphoma (FCCL, MZL, OTHER), 79% received radiation alone (RT), 11% surgery alone, 3% chemotherapy alone, 4% chemotherapy followed by RT, and 3% observation. Following treatment, 29% of subjects relapsed. In-field recurrence occurred in 2% treated with RT and in 33% treated with surgery alone. Of the 25 subjects with DLBCL-leg, 52% received chemotherapy followed by RT, 24% chemotherapy, 20% RT, and 4% surgery alone. Seventy-nine percent received CHOP-type chemotherapy (cyclophosphamide, doxorubicin or epirubicin, vincristine, prednisone), 47% with rituximab added. Overall and disease-specific survival and time to progression at 5 years were 81%, 92%, and 69% for indolent and 26%, 61%, and 54% for DLBCL-leg, respectively. On Cox regression analysis of indolent subjects, RT was associated with better time to progression (P=.05). RT dose, chemo, age >60 y, and >1 lesion were not significantly associated with time to progression. For DLBCL-leg, disease-specific survival at 5 years was 100% for those receiving rituximab versus 67% for no rituximab (P=.13). Conclusions: This review demonstrates better outcomes for indolent histology compared with DLBCL-leg, validating the prognostic utility of the WHO-EORTC classification. In the indolent group

  16. Lethal cutaneous disease in transgenic mice conditionally expressing type I human T cell leukemia virus Tax.

    PubMed

    Kwon, Hakju; Ogle, Louise; Benitez, Bobby; Bohuslav, Jan; Montano, Mauricio; Felsher, Dean W; Greene, Warner C

    2005-10-21

    Type I human T cell leukemia virus (HTLV-I) is etiologically linked with adult T cell leukemia, an aggressive and usually fatal expansion of activated CD4+ T lymphocytes that frequently traffic to skin. T cell transformation induced by HTLV-I involves the action of the 40-kDa viral Tax transactivator protein. Tax both stimulates the HTLV-I long terminal repeat and deregulates the expression of select cellular genes by altering the activity of specific host transcription factors, including cyclic AMP-responsive element-binding protein (CREB)/activating transcription factor, NF-kappaB/Rel, and serum response factor. To study initiating events involved in HTLV-I Tax-induced T cell transformation, we generated "Tet-off" transgenic mice conditionally expressing in a lymphocyte-restricted manner (EmuSR alpha promoter-enhancer) either wild-type Tax or mutant forms of Tax that selectively compromise the NF-kappaB (M22) or CREB/activating transcription factor (M47) activation pathways. Wild-type Tax and M47 Tax-expressing mice, but not M22-Tax expressing mice, developed progressive alopecia, hyperkeratosis, and skin lesions containing profuse activated CD4 T cell infiltrates with evidence of deregulated inflammatory cytokine production. In addition, these animals displayed systemic lymphadenopathy and splenomegaly. These findings suggest that Tax-mediated activation of NF-kappaB plays a key role in the development of this aggressive skin disease that shares several features in common with the skin disease occurring during the preleukemic stage in HTLV-I-infected patients. Of note, this skin disease completely resolved when Tax transgene expression was suppressed by administration of doxycycline, emphasizing the key role played by this viral oncoprotein in the observed pathology.

  17. Recruitment of CD8+ T cells expressing granzymeA is associated with lesion progression in human cutaneous leishmaniasis

    PubMed Central

    Faria, D.R.; Souza, P.E.A.; Durães, F.V; Carvalho, E.M.; Gollob, K.J.; Machado, P.R.; Dutra, W.O.

    2009-01-01

    Human infection with Leishmania braziliensis leads to the establishment of cutaneous leishmaniasis (CL), characterized by the appearance of skin lesions that progress from non-ulcerated to ulcerated forms. Our goal was to characterize the immunological kinetics associated with this progression, comparing the cellular composition, cytokines and granzyme expression between lesions of patients with early (E-CL) and late stages (L-CL) of CL. Histopathological analysis showed that lesions from L-CL had more exuberant inflammatory infiltrate as compared to E-CL. Although E-CL and L-CL lesions were predominantly mononuclear, lesions from E-CL patients presented higher neutrophil and eosinophil counts than L-CL. While percentages of CD4+ and of CD68+ cells were slightly higher in L-CL, a five-fold increase of CD8+ cells was observed in L-CL, as compared to E-CL. Moreover, CD8+ T-cells from L-CL expressed significantly higher levels of granzymeA than E-CL. Interestingly, granzymeA expression was positively correlated with intensity of the inflammatory infiltrate in L-CL but not E-CL. Lastly, percentages of IFN-γ+ and IL-10+ cells were higher in L-CL as compared to E-CL, with CD4+ T-cells and CD68+ monocytes as the main sources of these cytokines, respectively. These results suggest that recruitment of CD8+granzymeA+ T-cells is involved in lesion progression in human CL. PMID:19646207

  18. p16 expression in cutaneous squamous carcinomas with neck metastases: a potential pitfall in identifying unknown primaries of the head and neck.

    PubMed

    Beadle, Beth M; William, William N; McLemore, Michael S; Sturgis, Erich M; Williams, Michelle D

    2013-11-01

    Human papillomavirus (HPV) positivity (+) has been used to identify oropharyngeal squamous carcinomas (SCCs) presenting as unknown primaries in the neck. p16 overexpression correlates with HPV+ in the oropharynx; however, the use of p16 alone as a surrogate marker of oropharyngeal HPV+ tumors has not been validated. We immunohistochemically analyzed p16 expression in surgically resected aggressive cutaneous head and neck SCC primaries and their nodal metastases from 24 patients to determine the potential overlap of p16 expression outside of the oropharynx. Five of 24 primary tumors (20.8%) and 3 lymph node metastases (12.5%) in levels II, III, and V, and the periparotid region diffusely expressed p16. HPV (high-risk types by in situ hybridization) was negative. p16 expression is relatively common in lymph node-positive cutaneous head and neck SCCs; thus, p16 expression as an independent biomarker and mechanism to determine the oropharyngeal source of an unknown primary is not advised. Copyright © 2012 Wiley Periodicals, Inc.

  19. Cutaneous T cell lymphomas: mycosis fungoides, Sezary syndrome and HTLV-I-associated adult T cell leukemia (ATL) in Mali, West Africa: a clinical, pathological and immunovirological study of 14 cases and a review of the African ATL cases.

    PubMed

    Fouchard, N; Mahe, A; Huerre, M; Fraitag, S; Valensi, F; Macintyre, E; Sanou, F; de The, G; Gessain, A

    1998-04-01

    Cutaneous T cell lymphomas (CTCL) are rare lymphoproliferative diseases, which are frequently suspected to be of viral origin. As very few data were available concerning cutaneous T cell lymphomas in tropical Africa, we undertook a clinical, histopathological, immunological and viro-molecular study of patients with a clinical diagnosis of cutaneous lymphoma, in Bamako, Mali. While prior to this study, no case of CTCL had been reported in this country, 14 patients (five women, nine men; mean age 58 years) with a diagnosis of cutaneous lymphoma were seen over a period of 30 months (1992-1994) in the only dermatological department in Mali. Clinically, the most frequent pattern was an infiltrated erythrodermia similar to Sezary syndrome. Nodular lesions and/or plaques were rarely observed. All these cutaneous tumors were T cell lymphoproliferations, only one expressing the CD8+ antigen. A comprehensive analysis of all the available data permitted characterization of three cases of adult T cell leukemia/lymphoma (ATL) associated with HTLV-I (one definitive case, of leukemic type, with demonstration of clonal integration of HTLV-I proviral genome and two probable ATL cases), three cases of Sezary syndrome (SS), two cases of mycosis fungoides (MF) and five cases of pleomorphic cutaneous lymphoma. In one case, the differentiation between MF and pleomorphic cutaneous lymphoma could not be established. HTLV-I serological and/or molecular markers were restricted to the three ATL cases. From the unique definitive ATL case, a T cell line was established from culture of peripheral blood mononuclear cells and sequence analysis of the env gene and the U3-LTR region demonstrated that the virus present in this patient belonged to the cosmopolitan subtype A. Thus, we report here the first evidence of HTLV-I infection and associated ATL in Mali. This is the second ATL case described for the whole Sahelian region (one ATL of the lymphoma type was reported previously in a Mauritanian

  20. T cell-B cell interactions in primary immunodeficiencies.

    PubMed

    Tangye, Stuart G; Deenick, Elissa K; Palendira, Umaimainthan; Ma, Cindy S

    2012-02-01

    Regulated interactions between cells of the immune system facilitate the generation of successful immune responses, thereby enabling efficient neutralization and clearance of pathogens and the establishment of both cell- and humoral-mediated immunological memory. The corollary of this is that impediments to efficient cell-cell interactions, normally necessary for differentiation and effector functions of immune cells, underly the clinical features and disease pathogenesis of primary immunodeficiencies. In affected individuals, these defects manifest as impaired long-term humoral immunity and susceptibility to infection by specific pathogens. In this review, we discuss the importance of, and requirements for, effective interactions between B cells and T cells during the formation of CD4(+) T follicular helper cells and the elicitation of cytotoxic function of virus-specific CD8(+) T cells, as well as how these processes are abrogated in primary immunodeficiencies due to loss-of-function mutations in defined genes. © 2012 New York Academy of Sciences.

  1. Demographic patterns of cutaneous T-cell lymphoma incidence in Texas based on two different cancer registries.

    PubMed

    Litvinov, Ivan V; Tetzlaff, Michael T; Rahme, Elham; Jennings, Michelle A; Risser, David R; Gangar, Pamela; Netchiporouk, Elena; Moreau, Linda; Prieto, Victor G; Sasseville, Denis; Duvic, Madeleine

    2015-09-01

    Cutaneous T-cell lymohomas (CTCLs) are rare, but potentially devastating malignancies, with Mycosis fungoides and Sézary Syndrome being the most common. In our previous study, we identified and described regions of geographic clustering of CTCL cases in Texas by analyzing ~1990 patients using two distinct cancer registries. In the current work, we describe in detail demographic patterns for this malignancy in our study population and apply logistic regression models to analyze the incidence of CTCL by sex, race, age, and clinical stage at the time of diagnosis. Furthermore, using Fisher's exact test, we analyze changes in incidence over time in the identified Houston communities with unusually high CTCL incidence. While CTCL primarily affects Caucasian individuals >55 years old, we confirm that it presents at a younger age and with more advanced disease stages in African-American and Hispanic individuals. Also, we demonstrate a significant increase in CTCL incidence over time in the identified communities. Spring, Katy, and Houston Memorial areas had high baseline rates. Furthermore, a statistically significant disease surge was observed in these areas after ~2005. This report supplements our initial study documenting the existence of geographic clustering of CTCL cases in Texas and in greater detail describes demographic trends for our patient population. The observed surge in CTCL incidence in the three identified communities further argues that this malignancy may be triggered by one or more external etiologic agents.

  2. Comparative analysis of rosacea and cutaneous lupus erythematosus: histopathologic features, T-cell subsets, and plasmacytoid dendritic cells.

    PubMed

    Brown, Theodore T; Choi, Eun-Young K; Thomas, Dafydd G; Hristov, Alexandra C; Chan, May P

    2014-07-01

    Distinction of rosacea and cutaneous lupus erythematosus (LE) can be challenging because of significant clinical and histologic overlap. A controlled study comparing these conditions is lacking. We compared the histologic features, T-cell subsets, and plasmacytoid dendritic cells in rosacea and LE. Biopsy specimens of rosacea (n = 27) and facial LE (n = 30) were retrospectively reviewed and reacted with Alcian blue and periodic acid-Schiff stains, and CD4, CD8, CD25, and CD123 immunostains. LE demonstrates a lower CD4:CD8 ratio (1.74 vs 2.80, P = .0064), fewer CD4(+)CD25(+) regulatory T cells (13% vs 31%, P < .0001), and more CD123(+) plasmacytoid dendritic cells (18% vs 6%, P = .0137) than rosacea. The plasmacytoid dendritic cells in LE are more likely to form clusters (P = .0137) and comprise at least 20% of the infiltrate (P = .0340). Also associated with LE are follicular plugging (P = .0039), perineural lymphocytic infiltrate (P = .0211), abundant mucin deposition (P = .0031), and conspicuous basement membrane thickening (P = .0073), whereas Demodex infestation (P = .0064) and sebaceous hyperplasia (P = .0029) are significantly associated with rosacea. Although statistically significant, the immunophenotypic differences are rather small and limited for routine use. The infiltrates in rosacea and LE differ immunophenotypically, and may aid in their distinction in addition to conventional histologic examination. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  3. Cutaneous type of adult T cell leukemia/lymphoma in a French West Indian woman. Clonal rearrangement of T-cell receptor beta and gamma genes and monoclonal integration of HTLV-I proviral DNA in the skin infiltrate.

    PubMed

    Gessain, A; Moulonguet, I; Flageul, B; Perrin, P; Capesius, C; D'Agay, M F; Gisselbrecht, C; Sigaux, F; Civatte, J

    1990-11-01

    A 45-year-old woman, a native of the French West Indies who had lived in France since 1973, developed multiple cutaneous plaques and nodules in 1987. Histopathologic studies revealed dermal infiltration with mature activated T cells (CD4+, CD25+, DR+) with nuclear convolutions and epidermatotropisim. High titers of specific human T lymphotropic virus (HTLV)-I antibodies were detected in the serum. Molecular analysis of DNA extracted from the skin tumor biopsy specimen showed a clonal integration of an HTLV-I provirus and a T-cell clonal population as demonstrated by T-cell receptor beta and gamma gene rearrangement studies. Neither HTLV-I provirus nor T-cell receptor rearrangements were detected in peripheral blood mononuclear cells DNA despite the presence of rare adult T cell leukemia cells (less than 1%) and a small excess of DR-expressing cells, and detection of HTLV-I Pol and Px sequences by in vitro gene amplification. In this case only gene analysis of the skin lesions made possible an early diagnosis of a cutaneous adult T cell leukemia. This illustrates the need for such molecular studies to differentiate, in HTLV-I seropositive patients from endemic areas, a HTLV-I-induced T cell lymphoma from HTLV-I-nonrelated cutaneous T cell lymphomas.

  4. Skin inflammation arising from cutaneous regulatory T cell deficiency leads to impaired viral immune responses.

    PubMed

    Freyschmidt, Eva-Jasmin; Mathias, Clinton B; Diaz, Natalia; MacArthur, Daniel H; Laouar, Amale; Manjunath, Narasimhaswamy; Hofer, Matthias D; Wurbel, Marc-Andre; Campbell, James J; Chatila, Talal A; Oettgen, Hans C

    2010-07-15

    Individuals with atopic dermatitis immunized with the small pox vaccine, vaccinia virus (VV), are susceptible to eczema vaccinatum (EV), a potentially fatal disseminated infection. Dysfunction of Forkhead box P3 (FoxP3)-positive regulatory T cells (Treg) has been implicated in the pathogenesis of atopic dermatitis. To test whether Treg deficiency predisposes to EV, we percutaneously VV infected FoxP3-deficient (FoxP3(KO)) mice, which completely lack FoxP3(+) Treg. These animals generated both fewer VV-specific CD8(+) effector T cells and IFN-gamma-producing CD8(+) T cells than controls, had higher viral loads, and exhibited abnormal Th2-polarized responses to the virus. To focus on the consequences of Treg deficiency confined to the skin, we generated mixed CCR4(KO) FoxP3(KO) bone marrow (CCR4/FoxP3) chimeras in which skin, but not other tissues or central lymphoid organs, lack Treg. Like FoxP3(KO) mice, the chimeras had impaired VV-specific effector T cell responses and higher viral loads. Skin cytokine expression was significantly altered in infected chimeras compared with controls. Levels of the antiviral cytokines, type I and II IFNs and IL-12, were reduced, whereas expression of the proinflammatory cytokines, IL-6, IL-10, TGF-beta, and IL-23, was increased. Importantly, infection of CCR4/FoxP3 chimeras by a noncutaneous route (i.p.) induced immune responses comparable to controls. Our findings implicate allergic skin inflammation resulting from local Treg deficiency in the pathogenesis of EV.

  5. Cutaneous T-cell lymphoma, tropical spastic paraparesis, cerebral vasculitis, and protein S deficiency in a patient with HTLV-I.

    PubMed

    Schwartz, J; Gonzalez, J; Rosenberg, R; Fujihara, K; Cottrill, C M; Klainer, A S; Bisaccia, E

    1996-10-01

    The clinical spectrum of retroviruses is expanding rapidly. Human T-cell lymphotropic virus type I (HTLV-I) was the first retrovirus to be described, and its role had been established in adult T-cell leukemia/lymphoma and tropical spastic paraparesis. We report the case of a 35-year-old woman with HTLV-I and the unusual combination of cutaneous T-cell lymphoma, tropical spastic paraparesis, cerebral vasculitis, and protein S deficiency. We discuss the relationship of all her diseases to HTLV-I.

  6. The cutaneous T cell lymphoma, mycosis fungoides, is a human T cell lymphotropic virus-associated disease. A study of 50 patients.

    PubMed Central

    Pancake, B A; Zucker-Franklin, D; Coutavas, E E

    1995-01-01

    For nearly two decades it has been suspected that the cutaneous T cell lymphoma, mycosis fungoides (MF), and its leukemic variant, the Sézary syndrome, are caused by the human T lymphotropic virus (HTLV-I/II). Arguments against this concept included the finding that only a small number of MF patients have antibodies to HTLV-I/II and that attempts to detect proviral sequences by mere Southern hybridization of extracted DNA usually met with failure. However, we have reported repeatedly that HTLV-like particles emerge in blood mononuclear cell (PBMC) cultures of practically all patients with this disease. In several instances, the particles were identified as HTLV by immunoelectron microscopy as well as biomolecular analysis. With the assumptions that the virus in MF patients may have become detection by Southern hybridization alone, the extracts of freshly isolated PBMC of 50 consecutive patients were subjected to combined PCR/Southern analysis. Here we report the presence of HTLV pol and/or tax proviral sequences in 46 out of 50 (92%) of the patients tested. In addition, five of the patients, who lacked antibodies to HTLV-I/II structural proteins, were found to be seropositive for tax. It thus seems reasonable to conclude that MF/Sézary syndrome is an HTLV-associated disease and that lack of an immune response does not preclude infection with this type of virus. Images PMID:7860737

  7. An Aggressive Primary Cutaneous Follicle Center Lymphoma With c-MYC Translocation and CDKN2A (9p21) Deletion: A Case Report and Review of the Literature.

    PubMed

    Tsang, Hamilton C; Mathew, Susan; Magro, Cynthia M

    2017-03-01

    Diffuse large cell B-cell lymphoma of the skin is most commonly represented by diffuse large cell variants of primary cutaneous follicle center lymphoma and the leg-type lymphoma. In a minority of cases, the infiltrates are an expression of stage 4 disease of established extracutaneous B-cell lymphoma. We describe 1 female patient 85 years of age with an aggressive form of primary cutaneous B-cell lymphoma manifesting in multiple firm erythematous indurated solid nodules 1-2 cm each symmetrically on the face periorbitally and on the upper extremities bilaterally. The tumor was a de novo presentation of this aggressive form of lymphoma. The disease demonstrated an aggressive course with only transient improvement of skin lesions after chemotherapy. Punch biopsy taken from a left arm skin lesion showed a diffuse and nodular large cell lymphocytic infiltrate in the 15-20 μm range exhibiting round to oval nuclei and prominent eosinophilic nucleoli. Phenotypically, the tumor cells were CD10, Bcl-2, Bcl-6, and CD43 positive with a residuum of a follicular dendritic cell network revealed by CD21 staining. There was c-MYC rearrangement and CDKN2A deletion in this sample. The importance in reporting this case is to emphasize that in the context of primary cutaneous B-cell lymphoma, the 9p21 deletion while characteristic of the leg-type lymphoma is not a unique signature of the leg-type lymphoma and is not exclusionary to lymphomas falling under the designation of follicle center lymphoma. As with the leg-type lymphoma, however, this cytogenetic abnormality is a critical determinant to a more aggressive clinical course.

  8. Cancer-testis antigen expression in primary cutaneous melanoma has independent prognostic value comparable to that of Breslow thickness, ulceration and mitotic rate.

    PubMed

    Svobodová, Suzanne; Browning, Judy; MacGregor, Duncan; Pollara, Gabriele; Scolyer, Richard A; Murali, Rajmohan; Thompson, John F; Deb, Siddhartha; Azad, Arun; Davis, Ian D; Cebon, Jonathan S

    2011-02-01

    To determine the effect of Cancer-Testis Antigen (CTAg) expression on the natural history of primary cutaneous melanoma we compared its impact on prognosis with that of known prognostic factors and its relationship with other clinicopathologic characteristics. The immunohistochemical expression of three CTAgs (MAGE-A1, MAGE-A4 and NY-ESO-1) in 348 cases of stage I and stage II primary cutaneous melanoma was analysed and correlated with clinicopathologic characteristics, relapse free survival (RFS) and overall survival (OS). A Cox proportional hazards regression model was used to analyse factors which independently predicted RFS. All three CTAgs were significantly co-expressed with each other (p < 0.001). The median RFS for patients with CTAg-negative tumours and CTAg-positive tumours was 72 months and 45 months, respectively, (P = 0.008). Univariate analysis demonstrated that the impact of CTAg expression on RFS was comparable in magnitude to that of Breslow thickness, ulceration and tumour mitotic rate. Multivariate Cox regression analysis indicated that CTAg expression was a powerful independent predictor of RFS (risk ratio (RR) = 1.715, 95% confidence interval (CI) = 0.430-0.902, P = 0.010). In contrast, CTAg expression was demonstrated to have no prognostic impact on overall survival. This study demonstrates that CTAg expression in primary cutaneous melanoma is a strong independent predictor of RFS and it is comparable to other known important prognostic factors. CTAg expression has no relationship with overall survival, suggesting anti-melanoma immunity directed towards CTAg expression may contribute to the natural history of the disease. In view of these results, further investigation of the function of CTAgs and their potential use in therapeutic targeting is warranted. Copyright © 2010 Elsevier Ltd. All rights reserved.

  9. Association between BRAFV600E and NRASQ61R Mutations and Clinicopathologic Characteristics, Risk Factors and Clinical Outcome of Primary Invasive Cutaneous Melanoma

    PubMed Central

    Wu, Shaowei; Kuo, Helen; Li, Wen-Qing; Canales, Alvaro Laga; Han, Jiali; Qureshi, Abrar A.

    2014-01-01

    Purpose Previous studies suggest that solar UV exposure in early life is predictive of cutaneous melanoma risk in adulthood, whereas the relation of BRAF mutation with sun exposure and disease prognosis has been less certain. We investigated the associations between BRAFV600E and NRASQ61R mutations and known risk factors, clinicopathologic characteristics and clinical outcomes of melanoma in a case series of primary invasive cutaneous melanoma from the Nurses' Health Study (NHS). Methods Somatic BRAFV600E and NRASQ61R mutations of 127 primary invasive melanomas from the NHS cohort were determined by pyrosequencing using formalin-fixed, paraffin-embedded block tissues. Logistic regression analyses were performed to detect the associations of mutations with melanoma risk factors, and Kaplan-Meier method was used to examine associations between mutations and survival. Results The odds ratios for harboring BRAFV600E mutations was 5.54 (95% CI, 1.19-25.8, Ptrend=0.02) for women residing in states with UV index ≥7 versus those residing in states with UV index ≤5 at 30 years of age. Patients with BRAFV600E mutations tended to have shorter melanoma-specific survival when compared to patients wild-type at both loci (median survival time 110 months vs. 159 months) (P=0.03). Conclusions BRAF V600E mutations in primary cutaneous melanomas were associated with residence in locations with medium and high UV indices in mid life. BRAFV600E mutation may be associated with an unfavorable prognosis among melanoma patients. PMID:25048604

  10. Identification of geographic clustering and regions spared by cutaneous T-cell lymphoma in Texas using 2 distinct cancer registries.

    PubMed

    Litvinov, Ivan V; Tetzlaff, Michael T; Rahme, Elham; Habel, Youssef; Risser, David R; Gangar, Pamela; Jennings, Michelle A; Pehr, Kevin; Prieto, Victor G; Sasseville, Denis; Duvic, Madeleine

    2015-06-15

    Cutaneous T-cell lymphomas (CTCLs) (mycosis fungoides and its leukemic variant, Sezary syndrome) are rare malignancies. Reports of the occurrence of mycosis fungoides in married couples and families raise the possibility of an environmental trigger for this cancer. Although it has been suggested that CTCL arises from inappropriate T-cell stimulation, to the authors' knowledge no preventable trigger has been identified to date. Using region, zip code, age, sex, and ethnicity, the authors analyzed the demographic data of 1047 patients from Texas who were seen in a CTCL clinic at The University of Texas MD Anderson Cancer Center during 2000 through 2012 (the MDACC database) and 1990 patients who were recorded in the population-based Texas Cancer Registry between 1996 and 2010. Subsequently, data from both databases were cross-analyzed and compared. The current study findings, based on the MDACC database, documented geographic clustering of patients in 3 communities within the Houston metropolitan area, in which CTCL incidence rates were 5 to 20 times higher than the expected population rate. Analysis of the Texas Cancer Registry database defined the CTCL population rate for the state to be 5.8 cases per million individuals per year (95% confidence interval, 5.5-6.0 per million individuals per year), thus confirming the observations from the MDACC database and further highlighting additional areas of geographic clustering and regions spared from CTCL in Texas. The current study documented geographic clustering of CTCL cases in Texas and argued for the existence of yet unknown external causes/triggers for this rare malignancy. © 2015 American Cancer Society.

  11. Th17 cytokine differentiation and loss of plasticity after SOCS1 inactivation in a cutaneous T-cell lymphoma

    PubMed Central

    Ehrentraut, Stefan; Schneider, Björn; Nagel, Stefan; Pommerenke, Claudia; Quentmeier, Hilmar; Geffers, Robert; Feist, Maren; Kaufmann, Maren; Meyer, Corinna; Kadin, Marshall E.; Drexler, Hans G.; MacLeod, Roderick A. F.

    2016-01-01

    We propose that deregulated T-helper-cell (Th) signaling underlies evolving Th17 cytokine expression seen during progression of cutaneous T-cell lymphoma (CTCL). Accordingly, we developed a lymphoma progression model comprising cell lines established at indolent (MAC-1) and aggressive (MAC-2A) CTCL stages. We discovered activating JAK3 (V722I) mutations present at indolent disease, reinforced in aggressive disease by novel compound heterozygous SOCS1 (G78R/D105N) JAK-binding domain inactivating mutations. Though isogenic, indolent and aggressive-stage cell lines had diverged phenotypically, the latter expressing multiple Th17 related cytokines, the former a narrower profile. Importantly, indolent stage cells remained poised for Th17 cytokine expression, readily inducible by treatment with IL-2 - a cytokine which mitigates Th17 differentiation in mice. In indolent stage cells JAK3 expression was boosted by IL-2 treatment. Th17 conversion of MAC-1 cells by IL-2 was blocked by pharmacological inhibition of JAK3 or STAT5, implicating IL2RG - JAK3 – STAT5 signaling in plasticity responses. Like IL-2 treatment, SOCS1 knockdown drove indolent stage cells to mimic key aggressive stage properties, notably IL17F upregulation. Co-immunoprecipitation experiments showed that SOCS1 mutations abolished JAK3 binding, revealing a key role for SOCS1 in regulating JAK3/STAT5 signaling. Collectively, our results show how JAK/STAT pathway mutations contribute to disease progression in CTCL cells by potentiating inflammatory cytokine signaling, widening the potential therapeutic target range for this intractable entity. MAC-1/2A cells also provide a candidate human Th17 laboratory model for identifying potentally actionable CTCL markers or targets and testing their druggability in vitro. PMID:27144517

  12. Expression of apoptosis markers on peripheral blood lymphocytes from patients with cutaneous T-cell lymphoma during extracorporeal photochemotherapy.

    PubMed

    Osella-Abate, S; Zaccagna, A; Savoia, P; Quaglino, P; Salomone, B; Bernengo, M G

    2001-01-01

    The mechanisms of extracorporeal photochemotherapy (ExP) therapeutic activity in cutaneous T-cell lymphomas (CTCLs) are not yet well understood, even though it has been suggested that a major mechanism may be induction of apoptosis. In vitro studies demonstrate that UVA-induced apoptosis is mediated by CD95-Fas expression and inhibited by Bcl-2 up-regulation and that UVA irradiation is able to down-regulate Bcl-2 expression. High-resolution multiparameter flow-cytometric analyses were used to evaluate Bcl-2/CD95-Fas expression on phenotypically identifiable circulating clonal T cells from 7 patients with CTCL (4 with Sézary syndrome and 3 with mycosis fungoides with peripheral involvement) before and during ExP, in an attempt to ascertain whether Bcl-2/CD95-Fas status can be related to the hematologic response. A Bcl-2 normal phenotype before ExP or a normalization in Bcl-2 expression during ExP were related to a better clinical response, whereas a persistent Bcl-2 high expression was a negative prognostic factor. On the other hand, no response was found in patients with a CD95-Fas-negative phenotype, whereas the expression of CD95-Fas was associated with hematologic remission. Although further studies are needed to confirm these preliminary results, this study suggests that Bcl-2 and CD95-Fas expression could be evaluated, together with the other known clinical and immunologic factors, as additional parameters related to clinical response in patients with CTCL undergoing ExP.

  13. An association between newly diagnosed cutaneous T cell lymphoma and prior impetigo: a nested case-control study.

    PubMed

    Boursi, Ben; Haynes, Kevin; Mamtani, Ronac; Yang, Yu-Xiao

    2016-11-01

    Colonization with staphylococcus aureus (SA) is associated with disease activity and progression in patients with cutaneous T-cell lymphoma (CTCL) secondary to T-cell activation by bacterial superantigens. The aim of the current study was to evaluate the possible role of SA as an etiologic factor affecting CTCL initiation. We conducted a nested case-control study in a large population-representative database from the UK. Cases were defined as all patients with an incident diagnosis of mycosis fungoides (MF) or Sezary syndrome (SS) between 1995 and 2013. For every case, four eligible controls matched on age, sex, practice-site, and duration of follow-up were selected. Exposure of interest was clinical diagnosis of impetigo prior to CTCL diagnosis. Conditional logistic regression was used to calculate odds-ratio (ORs) and 95 % confidence-interval (CI) for CTCL risk. The results were further stratified according to age, sex and time interval between impetigo and CTCL diagnosis. The study population included 310 cases with MF or SS and 1223 matched controls. Among cases with CTCL 4.8 % (n = 15) had impetigo prior to cancer diagnosis compared to 2 % (n = 24) of controls. The adjusted OR for CTCL diagnosis among patients with prior impetigo was 2.33 (95 % CI 1.12-4.83). The risk was elevated among individuals with impetigo 1-5 years before cancer diagnosis (OR 3.33, 95 % CI 1.00-11.10). There was no change in risk among patients with impetigo more than 5 years before cancer diagnosis (OR 1.09, 95 % CI 0.35-3.37). Our results suggest a possible association between SA colonization and CTCL initiation that might serve as an important etiological factor for the disease.

  14. Blocking of PDL-1 Interaction Enhances Primary and Secondary CD8 T Cell Response to Herpes Simplex Virus-1 Infection

    PubMed Central

    Channappanavar, Rudragouda; Twardy, Brandon S.; Suvas, Susmit

    2012-01-01

    The blocking of programmed death ligand-1 (PDL-1) has been shown to enhance virus-specific CD8 T cell function during chronic viral infections. Though, how PDL-1 blocking at the time of priming affects the quality of CD8 T cell response to acute infections is not well understood and remains controversial. This report demonstrates that the magnitude of the primary and secondary CD8 T cell responses to herpes simplex virus-1 (HSV-1) infection is subject to control by PDL-1. Our results showed that after footpad HSV-1 infection, PD-1 expression increases on immunodominant SSIEFARL peptide specific CD8 T cells. Additionally, post-infection, the level of PDL-1 expression also increases on CD11c+ dendritic cells. Intraperitoneal administration of anti-PDL-1 monoclonal antibody given one day prior to and three days after cutaneous HSV-1 infection, resulted in a marked increase in effector and memory CD8 T cell response to SSIEFARL peptide. This was shown by measuring the quantity and quality of SSIEFARL-specific CD8 T cells by making use of ex-vivo assays that determine antigen specific CD8 T cell function, such as intracellular cytokine assay, degranulation assay to measure cytotoxicity and viral clearance. Our results are discussed in terms of the beneficial effects of blocking PDL-1 interactions, while giving prophylactic vaccines, to generate a more effective CD8 T cell response to viral infection. PMID:22808056

  15. Effects of cigarette smoke extract on primary activated T cells.

    PubMed

    Hernandez, Claudia P; Morrow, Kevin; Velasco, Cruz; Wyczechowska, Dorota D; Naura, Amarjit S; Rodriguez, Paulo C

    2013-03-01

    Tobacco smoking predisposes the development of diseases characterized by chronic inflammation and T cell dysfunction. In this study, we aimed to determine the direct effects of cigarette smoke on primary T cells and to identify the corresponding molecular mediators. Activated T cells cultured in the presence of cigarette smoke extract (CSE) displayed a dose-dependent decrease in cell proliferation, which associated with the induction of cellular apoptosis. T cell apoptosis by CSE was independent of caspases and mediated through reactive oxygen and nitrogen species endogenously contained within CSE. Additional results showed that exposure of T cells to CSE induced phosphorylation of the stress mediator eukaryotic-translation-initiation-factor 2 alpha (eIF2α). Inhibition of the phosphorylation of eIF2α in T cells prevented the cellular apoptosis induced by CSE. Altogether, the results show the direct effects of CSE on T cells, which advance in the understanding of how cigarette smoking promotes chronic inflammation and immune dysfunction. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Cutaneous amebiasis.

    PubMed

    Rimsza, M E; Berg, R A

    1983-04-01

    An infant with cutaneous amebiasis of the vulva and amebic liver abscess is described. Epidemiologic investigations and serologic studies were crucial in establishing the diagnosis. The vulvar amebic ulcers responded dramatically to metronidazole therapy. Cutaneous amebiasis is a rare complication of Entamoeba histolytica infection which should be considered in the differential diagnosis of perineovulvar or penile ulcers. Cutaneous amebiasis may also occur on the abdominal wall surrounding a draining hepatic abscess, colostomy site, or laparotomy incision.

  17. T regulatory cells distinguish two types of primary hypophysitis.

    PubMed

    Mirocha, S; Elagin, R B; Salamat, S; Jaume, J C

    2009-03-01

    Numerous cases of primary hypophysitis have been described over the past 25 years with, however, little insight into the cause(s) of this disease. In order to guide treatment, a better understanding of the pathogenesis is needed. We studied the pathogenesis of primary hypophysitis by analysing systematically the immune response at the pituitary tissue level of consecutive cases of 'lymphocytic' hypophysitis who underwent pituitary biopsy. In order to investigate further the pathogenesis of their diseases we characterized two cases at clinical, cellular and molecular levels. We show here, for the first time, that lymphocytic hypophysitis probably encompasses at least two separate entities. One entity, in agreement with the classical description of lymphocytic hypophysitis, demonstrates an autoimmune process with T helper 17 cell dominance and lack of T regulatory cells. The other entity represents a process in which T regulatory cells seem to control the immune response, which may not be self- but foreign-targeted. Our data suggest that it may be necessary to biopsy suspected primary hypophysitis and to analyse pituitary tissue with immune markers to guide treatment. Based on our results, hypophysitis driven by an immune homeostatic process should not be treated with immunosuppression, while autoimmune-defined hypophysitis may benefit from it. We show here for the first time two different pathogenic processes classified under one disease type and how to distinguish them. Because of our findings, changes in current diagnostic and therapeutic approaches may need to be considered.

  18. Dysregulation of the TOX-RUNX3 pathway in cutaneous T-cell lymphoma.

    PubMed

    Dulmage, Brittany O; Akilov, Oleg; Vu, John R; Falo, Louis D; Geskin, Larisa J

    2015-11-06

    Studies have examined gene expression changes in Sézary syndrome (SS), but disease pathogenesis remains largely unknown, and diagnosis and treatment are difficult. TOX is a transcription factor involved in CD4+ T-cell development with downstream effects on RUNX3, a known tumor suppressor gene. We sought to identify genes involved in SS disease pathogenesis with the potential to enable diagnosis and treatment. We utilized previously reported transcriptome sequencing data to construct a list of candidate genes, which was narrowed using pathway analysis. qRT-PCR confirmed TOX upregulation (>7 fold increase) in SS (n = 5), as well as two established markers, PLS3 and KIRD3DL2. We also evaluated expression of members of the TOX-RUNX3 pathway and confirmed downregulation of RUNX3 (0.59 fold decrease) and upregulation of GATA3 (2 fold increase). Moreover, TOX and RUNX3 expression were significantly inversely proportional. Using siRNA to suppress TOX, we demonstrated that TOX knockdown rescues RUNX3 expression and reduces cell viability. We evaluated TOX protein expression in paraffin-embedded skin biopsies with immunohistochemistry, showing nuclear staining of CTCL infiltrates, suggesting it is a candidate diagnostic biomarker. Further studies validating our findings and evaluating the TOX-RUNX3 pathway and the role of TOX as a disease marker and therapeutic target are warranted.

  19. Structural Alterations of the FAS Gene in Cutaneous T-Cell Lymphoma (CTCL)

    PubMed Central

    Wu, Jianqiang; Siddiqui, Jawed; Nihal, Minakshi; Vonderheid, Eric C.; Wood, Gary S.

    2010-01-01

    FAS (TNF receptor superfamily member 6, also known as CD95) plays a major role in T-cell apoptosis and is often dysregulated in CTCL. We searched for structural alterations of the FAS gene with the potential to affect its function. Although several heterozygous FAS promoter single nucleotide polymorphisms (SNPs) were detected, the only homozygous one was the -671 GG SNP present in 24/80 CTCL cases (30%). This SNP maps to an interferon response element activated by STAT-1. EMSA and supershift EMSA showed decreased CTCL nuclear protein/STAT-1 binding to oligonucleotides bearing this SNP. Luciferase reporters showed significantly less interferon-alfa responsive expression by FAS promoter constructs containing this SNP in multiple CTCL lines. Finally, FAS was upregulated by interferon-alfa in wildtype CTCL cells but not those bearing the -671 GG SNP. These findings indicate that many CTCL patients harbor the homozygous FAS promoter -671 GG SNP capable of blunting its response to interferon. This may have implications for CTCL pathogenesis, racial incidence and the response of patients to interferon-alfa therapy. In contrast, functionally significant mutations in FAS coding sequences were detected uncommonly. Among CTCL lines with the potential to serve as models of FAS regulation, FAS-high MyLa had both FAS alleles, FAS-low HH was FAS-hemizygous and FAS-negative SeAx was FAS-null. PMID:21036138

  20. Humanization of an anti-CCR4 antibody that kills cutaneous T-cell lymphoma cells and abrogates suppression by T-regulatory cells.

    PubMed

    Chang, De-Kuan; Sui, Jianhua; Geng, Shusheng; Muvaffak, Asli; Bai, Mei; Fuhlbrigge, Robert C; Lo, Agnes; Yammanuru, Anuradha; Hubbard, Luke; Sheehan, Jared; Campbell, James J; Zhu, Quan; Kupper, Thomas S; Marasco, Wayne A

    2012-11-01

    Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of neoplastic disorders characterized by clonally derived and skin-homing malignant T cells that express high level of chemokine receptor CCR4, which is associated with their skin-homing capacity. CCR4 is also highly expressed on T-regulatory cells (Tregs) that can migrate to several different types of chemotactic ligand CCL17- and CCL22-secreting tumors to facilitate tumor cell evasion from immune surveillance. Thus, its high-level expression on CTCL cells and Tregs makes CCR4 a potential ideal target for antibody-based immunotherapy for CTCL and other types of solid tumors. Here, we conducted humanization and affinity optimization of a murine anti-CCR4 monoclonal antibody (mAb), mAb1567, that recognizes both the N-terminal and extracellular domains of CCR4 with high affinity and inhibits chemotaxis of CCR4(+) CTCL cells. In a mouse CTCL tumor model, mAb1567 exhibited a potent antitumor effect and in vitro mechanistic studies showed that both complement-dependent cytotoxicity (CDC) and neutrophil-mediated antibody-dependent cellular cytotoxicity (ADCC) likely mediated this effect. mAb1567 also exerts human NK cell-mediated ADCC activity in vitro. Moreover, mAb1567 also effectively inhibits chemotaxis of CD4(+)CD25(high) Tregs via CCL22 and abrogates Treg suppression activity in vitro. An affinity-optimized variant of humanized mAb1567, mAb2-3, was selected for further preclinical development based on its higher binding affinity and more potent ADCC and CDC activities. Taken together, this high-affinity humanized mAb2-3 with potent antitumor effect and a broad range of mechanisms of action may provide a novel immunotherapy for CTCL and other solid tumors.

  1. Examination of HTLV-I integration in the skin lesions of various types of adult T-cell leukemia (ATL): independence of cutaneous-type ATL confirmed by Southern blot analysis.

    PubMed

    Dosaka, N; Tanaka, T; Miyachi, Y; Imamura, S; Kakizuka, A

    1991-02-01

    The various clinical features of adult T-cell leukemia/lymphoma (ATL) are frequently accompanied by skin eruptions. Recently, a cutaneous type of ATL has been proposed by clinical studies. We analyzed the viral integration of human T-cell leukemia virus-I (HTLV-I) and monoclonal rearrangement of T-cell receptor (TCR) gene in blood lymphocytes and the cutaneous infiltrated cells of nine ATL patients with various clinical features and skin eruptions. We classified them by the results of Southern blot analysis and propose a cutaneous-type ATL accordingly. In two of them, we could detect the monoclonal integration of HTLV-I and T-cell monoclonality only in the skin but not in the peripheral lymphocytes. We also demonstrated the time course study in one patient. Clinicians should be aware of the HTLV-I positive cutaneous T cell lymphoma that can be named cutaneous-type ATL. Examination of viral integration and T-cell monoclonality in skin lesions is required to make an exact diagnosis of cutaneous ATL.

  2. Cutaneous sarcoidosis.

    PubMed

    Noe, Megan H; Rosenbach, Misha

    2017-09-01

    Cutaneous sarcoidosis occurs in up to 30% of patients with sarcoidosis and skin findings are often the initial presenting symptom. Cutaneous sarcoidosis is a rare skin disease and many aspects of the disease presentation and treatment are not well understood. This review will highlight developments in the epidemiology, clinical presentation, diagnosis and treatment of cutaneous sarcoidosis over the past several years. Epidemiological studies from several different populations reaffirm that cutaneous sarcoidosis is more common in women and is often the presenting symptom of systemic sarcoidosis. Recently, more cases are being reported in association with oncologic immune modulators, which will be of great interest as use of those agents increases. Also, ultrasound has shown promise for the imaging of cutaneous granulomas for disease assessment and measuring response to treatment. Finally, the treatment of cutaneous sarcoidosis remains difficult and is based largely on retrospective data with a paucity of large, prospective trials. There have been recently introduced and validated cutaneous scoring tools which show promise and may lead to more high-quality studies going forward. The recent developments in cutaneous sarcoidosis have identified many new pharmacologic and physical triggers of disease, but the evidence for effective treatment is still lacking. Further research is necessary to improve the care of patients with cutaneous sarcoidosis.

  3. Ectopic expression of cancer testis antigens in Cutaneous T-Cell Lymphoma (CTCL) patients

    PubMed Central

    Litvinov, Ivan V.; Cordeiro, Brendan; Huang, Yuanshen; Zargham, Hanieh; Pehr, Kevin; Doré, Marc-André; Gilbert, Martin; Zhou, Youwen; Kupper, Thomas S.; Sasseville, Denis

    2015-01-01

    Purpose The pathogenesis of CTCL remains only partially understood. A number of recent studies attempted to identify novel diagnostic markers and future therapeutic targets. One group of antigens, cancer-testis (CT) antigens, normally present solely in testicular germ cells, can be ectopically expressed in a variety of cancers. Currently only a few studies attempted to investigate the expression of CT antigens in CTCL. Experimental Design In the present work we test the expression of CT genes in a cohort of CTCL patients, normal skin samples, skin from benign inflammatory dermatoses and in patient-derived CTCL cells. We correlate such expression with the p53 status and explore molecular mechanisms behind their ectopic expression in these cells. Results Our findings demonstrate that SYCP1, SYCP3, REC8, SPO11 and GTSF1 genes are heterogeneously expressed in CTCL patients and patient-derived cell lines, while cTAGE1 was found to be robustly expressed in both. Mutated p53 status did not appear to be a requirement for the ectopic expression of CT antigens. While T cell stimulation resulted in a significant upregulation of STAT3 and JUNB expression, it did not significantly alter the expression of CT antigens. Treatment of CTCL cells in-vitro with Vorinostat or Romidepsin Histone Deacetylase inhibitors resulted in a significant dose-dependent upregulation of mRNA, but not protein. Further expression analysis demonstrated that SYCP1, cTAGE1 and GTSF1 were expressed in CTCL, but not in normal skin or benign inflammatory dermatoses. Conclusions A number of CT genes are ectopically expressed in CTCL patients and can be used as biomarkers or novel targets for immunotherapy. PMID:24850846

  4. No evidence of HTLV-I proviral integration in lymphoproliferative disorders associated with cutaneous T-cell lymphoma.

    PubMed

    Wood, G S; Schaffer, J M; Boni, R; Dummer, R; Burg, G; Takeshita, M; Kikuchi, M

    1997-02-01

    Several recent studies have reported detection of HTLV-I genetic sequences in patients with cutaneous T-cell lymphoma (CTCL) including mycosis fungoides and Sezary syndrome. The purpose of this study was to determine whether HTLV-I was detectable in lesional tissues of patients suffering from diseases known to be associated with CTCL. Thirty-five cases were obtained from diverse geographical locations including Ohio, California, Switzerland, and Japan. Six of them had concurrent CTCL. Cases were analyzed using a combination of genomic polymerase chain reaction (PCR)/ Southern blot, dot blot, and Southern blot analyses. All assays were specific for HTLV-I provirus. Sensitivity ranged from approximately 10(-6) for PCR-based studies to 10(-2) for unamplified genomic blotting. Lesional DNA from patients with lymphomatoid papulosis (fourteen cases), Hodgkin's disease (twelve cases), and CD30+ large-cell lymphoma (nine cases) was tested for the HTLV-I proviral pX region using a genomic PCR assay followed by confirmatory Southern blot analysis with a nested oligonucleotide pX probe. All cases were uniformly negative. All of the Hodgkin's disease cases, eight of the large-cell lymphoma cases, and six of the lymphomatoid papulosis cases were then subjected to dot blot analysis of genomic DNA using a full-length HTLV-I proviral DNA probe that spans all regions of the HTLV-I genome. Again, all cases were negative. Finally, eleven of the Hodgkin's disease cases were also subjected to Southern blot analysis of EcoRI-digested genomic DNA using the same full-length HTLV-I probe. Once again, all cases were negative. These findings indicated that, despite utilization of a variety of sensitive and specific molecular biological methods, HTLV-I genetic sequences were not detectable in patients with CTCL-associated lymphoproliferative disorders. These results strongly suggest that the HTLV-I retrovirus is not involved in the pathogenesis of these diseases.

  5. Outcome of Patients Treated With a Single-Fraction Dose of Palliative Radiation for Cutaneous T-Cell Lymphoma

    SciTech Connect

    Thomas, Tarita O.; Agrawal, Priya; Guitart, Joan; Rosen, Steven T.; Querfeld, Christiane; Kuzel, Timothy M.

    2013-03-01

    Purpose: Cutaneous T-cell lymphoma (CTCL) is a radiosensitive tumor. Presently, treatment with radiation is given in multiple fractions. The current literature lacks data that support single-fraction treatment for CTCL. This retrospective review assesses the clinical response in patients treated with a single fraction of radiation. Methods and Materials: This study reviewed the records of 58 patients with CTCL, primarily mycosis fungoides, treated with a single fraction of palliative radiation therapy (RT) between October 1991 and January 2011. Patient and tumor characteristics were reviewed. Response rates were compared using Fisher's exact test and multiple logistic regressions. Survival rates were determined using the Kaplan-Meier method. Cost-effectiveness analysis was performed to assess the cost of a single vs a multifractionated treatment regimen. Results: Two hundred seventy individual lesions were treated, with the majority (97%) treated with ≥700 cGy; mean follow-up was 41.3 months (range, 3-180 months). Response rate by lesion was assessed, with a complete response (CR) in 255 (94.4%) lesions, a partial response in 10 (3.7%) lesions, a partial response converted to a CR after a second treatment in 4 (1.5%) lesions, and no response in 1 (0.4%) lesion. The CR in lower extremity lesions was lower than in other sites (P=.0016). Lesions treated with photons had lower CR than those treated with electrons (P=.017). Patients with lesions exhibiting large cell transformation and tumor morphology had lower CR (P=.04 and P=.035, respectively). Immunophenotype did not impact response rate (P=.23). Overall survival was significantly lower for patients with Sézary syndrome (P=.0003) and erythroderma (P<.0001). The cost of multifractionated radiation was >200% higher than that for single-fraction radiation. Conclusions: A single fraction of 700 cGy-800 cGy provides excellent palliation for CTCL lesions and is cost effective and convenient for the patient.

  6. Histone deacetylase inhibitor panobinostat induces clinical responses with associated alterations in gene expression profiles in cutaneous T-cell lymphoma.

    PubMed

    Ellis, Leigh; Pan, Yan; Smyth, Gordon K; George, Daniel J; McCormack, Chris; Williams-Truax, Roxanne; Mita, Monica; Beck, Joachim; Burris, Howard; Ryan, Gail; Atadja, Peter; Butterfoss, Dale; Dugan, Margaret; Culver, Kenneth; Johnstone, Ricky W; Prince, H Miles

    2008-07-15

    Histone deacetylase inhibitors can alter gene expression and mediate diverse antitumor activities. Herein, we report the safety and activity of the histone deacetylase inhibitor panobinostat (LBH589) in cutaneous T-cell lymphoma (CTCL) and identify genes commonly regulated by panobinostat. Panobinostat was administered orally to patients with CTCL on Monday, Wednesday, and Friday of each week on a 28-day cycle. A dose of 30 mg was considered excessively toxic, and subsequent patients were treated at the expanded maximum tolerated dose of 20 mg. Biopsies from six patients taken 0, 4, 8, and 24 h after administration were subjected to microarray gene expression profiling and real-time quantitative PCR of selected genes. Patients attained a complete response (n = 2), attained a partial response (n = 4), achieved stable disease with ongoing improvement (n = 1), and progressed on treatment (n = 2). Microarray data showed distinct gene expression response profiles over time following panobinostat treatment, with the majority of genes being repressed. Twenty-three genes were commonly regulated by panobinostat in all patients tested. Panobinostat is well tolerated and induces clinical responses in CTCL patients. Microarray analyses of tumor samples indicate that panobinostat induces rapid changes in gene expression, and surprisingly more genes are repressed than are activated. A unique set of genes that can mediate biological responses such as apoptosis, immune regulation, and angiogenesis were commonly regulated in response to panobinostat. These genes are potential molecular biomarkers for panobinostat activity and are strong candidates for the future assessment of their functional role(s) in mediating the antitumor responses of panobinostat.

  7. How big is your hand and should you use it to score skin in cutaneous T-cell lymphoma?

    PubMed

    Scarisbrick, J J; Morris, S

    2013-08-01

    Assessing burn surface area is essential to triage patients and determine fluid resuscitation. The three commonly used methods are: (i) the palmar method, where palmar surface area is assumed to equal 1% of body surface area (BSA); (ii) the rule of nines; and (iii) the Lund and Browder method, where body parts are assigned a percentage surface area. Calculation of BSA involvement in dermatological disease is used to measure disease severity and treatment responses. The grid-point counting method may also be used. Mycosis fungoides (MF), a form of cutaneous T-cell lymphoma, typically presents with patches and plaques with progression to tumours and erythroderma in advanced disease. Quantifying skin involvement in MF requires assessment of both BSA involvement and lesion type. The severity-weighted assessment tool (SWAT) was designed for this purpose, using grid-point counting, and weighting patch as × 1, plaque as × 2 and tumour as × 3. The SWAT was modified in an international consensus paper to use Lund and Browder charts, and the weighting of tumours was increased to × 4. The patients' palm or hand is frequently the method of choice for skin scoring. However, both the definition of the palm and whether this includes the fingers or even the thumb, and the percentage BSA assigned to the palm, vary in the literature. A review of published planimetry studies found that the most consistent measure across age and race was the palm without fingers reflecting 0·5% total BSA. We recommend the use of the patient's palm to represent 0·5% BSA as the most convenient and reliable tool to measure surface area, and we introduce an iPhone application to record BSA electronically and calculate modified SWAT. © 2013 British Association of Dermatologists.

  8. Oligoclonal expansion of HIV-specific cytotoxic CD8 T lymphocytes in the skin of HIV-1-infected patients with cutaneous pseudolymphoma.

    PubMed Central

    Bachelez, H; Hadida, F; Parizot, C; Flageul, B; Kemula, M; Dubertret, L; Debree, P; Gorochov, G

    1998-01-01

    A massive infiltration of the skin by activated CD8+ T lymphocytes involving both the dermis and the epidermis has been found in HIV-1-infected patients presenting with a chronic skin rash. We characterized the T cell receptor (TCR) BV-BJ junctional diversity of the skin-infiltrating lymphocytes (SILs) in four patients. The SILs expressed a limited set of TCRBV gene segments. Complementarity determining region 3 length analysis further emphasized their oligoclonality, suggesting that antigen stimulation might be responsible for the cutaneous T cell expansion. Furthermore, independent skin biopsies obtained from the same individual were shown to harbor distinct T cell repertoires, possibly reflecting the spatial heterogeneity of the antigenic stimuli. The CD8+ cytotoxic T lymphocyte (CTL) lines isolated from the skin rash in one patient exhibited a specific, class I MHC-restricted cytotoxic activity against HIV-1 Gag- and Pol-expressing target cells, whereas CTL lines derived from the skin lesions of a second patient were shown to be predominantly Env-specific. Taken together, these data demonstrate the infiltration of HIV-specific CTLs in the skin of HIV-infected patients, and suggest that in addition to their known role in controlling the retroviral infection, these CTLs may also be involved in the pathogenesis of cutaneous inflammatory disorders occurring during the course of HIV infection. PMID:9616222

  9. MHC class II restricted innate-like double negative T cells contribute to optimal primary and secondary immunity to Leishmania major.

    PubMed

    Mou, Zhirong; Liu, Dong; Okwor, Ifeoma; Jia, Ping; Orihara, Kanami; Uzonna, Jude Ezeh

    2014-09-01

    Although it is generally believed that CD4(+) T cells play important roles in anti-Leishmania immunity, some studies suggest that they may be dispensable, and that MHC II-restricted CD3(+)CD4(-)CD8(-) (double negative, DN) T cells may be more important in regulating primary anti-Leishmania immunity. In addition, while there are reports of increased numbers of DN T cells in Leishmania-infected patients, dogs and mice, concrete evidence implicating these cells in secondary anti-Leishmania immunity has not yet been documented. Here, we report that DN T cells extensively proliferate and produce effector cytokines (IFN-γ, TNF and IL-17) and granzyme B (GrzB) in the draining lymph nodes and spleens of mice following primary and secondary L. major infections. DN T cells from healed mice display functional characteristics of protective anti-Leishmania memory-like cells: rapid and extensive proliferation and effector cytokines production following L. major challenge in vitro and in vivo. DN T cells express predominantly (> 95%) alpha-beta T cell receptor (αβ TCR), are Leishmania-specific, restricted mostly by MHC class II molecules and display transcriptional profile of innate-like genes. Using in vivo depletion and adoptive transfer studies, we show that DN T cells contribute to optimal primary and secondary anti-Leishmania immunity in mice. These results directly identify DN T cells as important players in effective and protective primary and secondary anti-L. major immunity in experimental cutaneous leishmaniasis.

  10. Primary antitumor immune response mediated by CD4+ T cells.

    PubMed

    Corthay, Alexandre; Skovseth, Dag K; Lundin, Katrin U; Røsjø, Egil; Omholt, Hilde; Hofgaard, Peter O; Haraldsen, Guttorm; Bogen, Bjarne

    2005-03-01

    Gene-targeted mice have recently revealed a role for lymphocytes and interferon-gamma (IFNgamma) in conferring protection against cancer, but the mechanisms remain unclear. Here, we have characterized a successful primary antitumor immune response initiated by naive CD4+ T cells. Major histocompatibility complex class II (MHC-II)-negative myeloma cells injected subcutaneously into syngeneic mice were surrounded within 3 days by macrophages that captured tumor antigens. Within 6 days, naive myeloma-specific CD4+ T cells became activated in draining lymph nodes and subsequently migrated to the incipient tumor site. Upon recognition of tumor-derived antigenic peptides presented on MHC-II by macrophages, the myeloma-specific CD4+ T cells were reactivated and started to secrete cytokines. T cell-derived IFNgamma activated macrophages in close proximity to the tumor cells. Tumor cell growth was completely inhibited by such locally activated macrophages. These data indicate a mechanism for immunosurveillance of MHC-II-negative cancer cells by tumor-specific CD4+ T cells through collaboration with macrophages.

  11. The Nrf2 activator tBHQ inhibits T cell activation of primary human CD4 T cells

    PubMed Central

    Turley, Alexandra E.; Zagorski, Joseph W.; Rockwell, Cheryl E.

    2014-01-01

    The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) regulates a battery of antioxidant, detoxification, and cell stress genes. It is activated by oxidative stress and a number of exogenous compounds, one of which is tert-butylhydroquinone (tBHQ), a widely used food preservative. Nrf2 modulates immune responses in numerous rodent models of inflammation, but its effects on human immune cells are not well characterized. The purpose of these studies was to evaluate the effects of the Nrf2 activator tBHQ on early events of T cell activation in primary human cells. Treatment with tBHQ induced mRNA expression of the Nrf2 target genes HMOX-1, GCLC, and NQO1, and also increased NRF2 mRNA expression, albeit to a lesser extent than the other target genes. tBHQ decreased production of the cytokines IL-2 and IFN-γ at both the protein and mRNA levels after stimulation with anti-CD3/anti-CD28 in human peripheral blood mononuclear cells and to an even greater extent in isolated CD4 T cells. Likewise, tBHQ decreased induction of CD25 and CD69 in peripheral blood mononuclear cells and this decrease was even more marked in isolated CD4 T cells. In addition, tBHQ inhibited induction of NFκB DNA binding in anti-CD3/anti-CD28-activated PBMCs. Collectively, these data suggest that tBHQ inhibits activation of primary human CD4 T cells, which correlates with activation of Nrf2 and inhibition of NFκB DNA binding. Although these studies suggest the food additive tBHQ negatively impacts T cell activation, further studies will be needed to fully elucidate the effect of tBHQ on human immune response. PMID:25484350

  12. The Nrf2 activator tBHQ inhibits T cell activation of primary human CD4 T cells.

    PubMed

    Turley, Alexandra E; Zagorski, Joseph W; Rockwell, Cheryl E

    2015-02-01

    The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) regulates a battery of antioxidant, detoxification, and cell stress genes. It is activated by oxidative stress and a number of exogenous compounds, one of which is tert-butylhydroquinone (tBHQ), a widely used food preservative. Nrf2 modulates immune responses in numerous rodent models of inflammation, but its effects on human immune cells are not well characterized. The purpose of these studies was to evaluate the effects of the Nrf2 activator tBHQ on early events of T cell activation in primary human cells. Treatment with tBHQ induced mRNA expression of the Nrf2 target genes HMOX-1, GCLC, and NQO1, and also increased NRF2 mRNA expression, albeit to a lesser extent than the other target genes. tBHQ decreased production of the cytokines IL-2 and IFN-γ at both the protein and mRNA levels after stimulation with anti-CD3/anti-CD28 in human peripheral blood mononuclear cells and to an even greater extent in isolated CD4 T cells. Likewise, tBHQ decreased induction of CD25 and CD69 in peripheral blood mononuclear cells (PBMCs) and this decrease was even more marked in isolated CD4 T cells. In addition, tBHQ inhibited induction of NFκB DNA binding in anti-CD3/anti-CD28-activated PBMCs. Collectively, these data suggest that tBHQ inhibits activation of primary human CD4 T cells, which correlates with activation of Nrf2 and inhibition of NFκB DNA binding. Although these studies suggest the food additive tBHQ negatively impacts T cell activation, further studies will be needed to fully elucidate the effect of tBHQ on human immune responses. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Cutaneous Manifestations of DOCK8 Deficiency Syndrome

    PubMed Central

    Chu, Emily Y.; Freeman, Alexandra F.; Jing, Huie; Cowen, Edward W.; Davis, Joie; Su, Helen C.; Holland, Steven M.; Chanco Turner, Maria L.

    2014-01-01

    Background Mutations in the dedicator of cytokinesis 8 gene (DOCK8) cause a combined primary immunodeficiency syndrome that is characterized by elevated serum IgE levels, depressed IgM levels, eosinophilia, sinopulmonary infections, cutaneous viral infections, and lymphopenia. Many patients with DOCK8 deficiency were previously thought to have a variant of Job’s syndrome. Distinguishing between DOCK8 deficiency and Job’s syndrome, also referred to as autosomal dominant hyper-IgE syndrome, on the basis of clinical findings alone is challenging. The discovery of the DOCK8 mutation has made it possible to differentiate the cutaneous manifestations of these hyper-IgE syndromes. Observations Twenty-one patients from 14 families with confirmed homozygous or compound heterozygous mutations in DOCK8 were evaluated. Clinical findings included dermatitis, asthma, food and environmental allergies, recurrent sinopulmonary infections, staphylococcal skin abscesses, and severe cutaneous viral infections. Malignant neoplasms, including aggressive cutaneous T-cell lymphoma, anal and vulvar squamous cell carcinomas, and diffuse large B-cell lymphoma, developed in 5 patients during adolescence and young adulthood. Conclusions DOCK8 deficiency and Job’s syndrome share several clinical features, including elevated serum IgE levels, dermatitis, recurrent sinopulmonary infections, and cutaneous staphylococcal abscesses. However, the presence of recalcitrant, widespread cutaneous viral infections, asthma, and food and environmental allergies, as well as the absence of newborn rash and coarse facies, favors the clinical diagnosis of DOCK8 deficiency. Rates of malignancy and overall mortality in patients with DOCK8 deficiency were higher than in those with Job’s syndrome, highlighting the value of distinguishing between these conditions and the importance of close monitoring for neoplasia. PMID:21931011

  14. Primary Central Nervous System Anaplastic Large T-cell Lymphoma

    PubMed Central

    Splavski, Bruno; Muzevic, Dario; Ladenhauser-Palijan, Tatjana; Jr, Brano Splavski

    2016-01-01

    Introduction: Primary central nervous system lymphoma (PCNSL) of T-cell origin is an exceptionally rare, highly malignant intracranial neoplasm. Although such a tumor typically presents with a focal mass lesion. Case report: Past medical history of a 26-year-old male patient with a PCNS lymphoma of T-cell origin was not suggestive of intracranial pathology or any disorder of other organs and organic systems. To achieve a gross total tumor resection, surgery was performed via osteoplastic craniotomy using the left frontal transcortical transventricular approach. Histological and immunohistochemical analyses of the tissue removed described tumor as anaplastic large cell lymphoma of T-cells (T-ALCL). Postoperative and neurological recovery was complete, while control imaging of the brain showed no signs of residual tumor at a six-month follow-up. The patient, who did not appear immunocompromized, was referred to a hematologist and an oncologist where corticosteroids, the particular chemotherapeutic protocol and irradiation therapy were applied. Conclusion: Since PCNS lymphoma is a potentially curable brain tumor, we believe that proper selection of the management options, including early radical tumor resection for solitary PCNS lymphoma, may be proposed as a major treatment of such a tumor in selected patients, resulting in a satisfactory outcome. PMID:27703297

  15. Excellent Outcome of Immunomodulation or Bruton's Tyrosine Kinase Inhibition in Highly Refractory Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type.

    PubMed

    Gupta, Eva; Accurso, Joseph; Sluzevich, Jason; Menke, David M; Tun, Han W

    2015-12-29

    Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) is a rare diffuse large B-cell lymphoma confined to the skin of the legs. The typical presentation is characterized by solitary or multiple growing plaques, usually confined to one leg. We report a case of PCDLBCL-LT of activated B-cell subtype characterized by multiple local relapses in the legs, initially, and systemic relapses about seven years after the diagnosis. Local relapses were sensitive to radiation therapy. Cutaneous and systemic relapses responded well to immunomodulatory therapy with lenalidomide followed by Bruton's tyrosine kinase inhibition with ibrutinib. Ibrutinib is the only treatment that resulted in long-lasting complete remission. Lenalidomide and especially ibrutinib appear to have a significant activity against this lymphoma and should be incorporated in the treatment of this resistant and aggressive lymphoma. To our knowledge, this is the first case of PCDLBCL-LT reported in the literature exhibiting a complete response to ibrutinib.

  16. Cutaneous Tuberculosis

    PubMed Central

    Frankel, Amylynne; Penrose, Carolin

    2009-01-01

    Cutaneous tuberculosis occurs rarely, despite a high and increasing prevalence of tuberculosis worldwide. Mycobacterium tuberculosis, Mycobacterrium bovis, and the Bacille Calmette-Guérin vaccine can cause tuberculosis involving the skin. Cutaneous tuberculosis can be acquired exogenously or endogenously and present as a multitude of differing clinical morphologies. Diagnosis of these lesions can be difficult, as they resemble many other dermatological conditions that are often primarily considered. Further, microbiological confirmation is poor, despite scientific advances, such as the more frequent use of polymerase chain reaction. The authors report a case that illustrates the challenges faced by dermatologists when considering a diagnosis of cutaneous tuberculosis. PMID:20725570

  17. Increased percentage of CD8+CD28- T cells correlates with clinical activity in primary Sjögren's syndrome.

    PubMed

    Smoleńska, Zaneta; Pawłowska, Justyna; Zdrojewski, Zbigniew; Daca, Agnieszka; Bryl, Ewa

    2012-01-01

    The role of CD28- T cell subpopulations in primary Sjögren's syndrome (pSS) has become controversial. Changes in the number of CD28- T cells have been demonstrated in autoimmune diseases in co-existence with Sjögren's syndrome. The study aimed to indicate differences in the number of CD4+CD28- and CD8+CD28- T cells in patients with sicca syndrome and suspected pSS. Thirty patients with sicca syndrome at baseline were studied and followed up for 5 months. After final diagnosis, comparison was made of the previously recorded lymphocyte subpopulations in patients with pSS and those in other defined subgroups. Notably high percentages of CD8+CD28- T cells were indicated in pSS patients, which correlated with the severity of the sicca symptoms and cutaneous and muscular systemic disease activity. Changes in CD8+CD28- T cell percentages may thus assist in the early differential diagnosis of pSS patients from those with similar clinical symptoms. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Anti-ICOS Monoclonal Antibody MEDI-570 in Treating Patients With Relapsed or Refractory Peripheral T-cell Lymphoma Follicular Variant or Angioimmunoblastic T-cell Lymphoma

    ClinicalTrials.gov

    2017-09-28

    Follicular Variant Peripheral T-Cell Lymphoma; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3a Follicular Lymphoma; Recurrent Angioimmunoblastic T-cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides; Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Angioimmunoblastic T-cell Lymphoma; Refractory Follicular Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Stage IB Mycosis Fungoides; Stage II Mycosis Fungoides; Stage III Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage III Mycosis Fungoides; Stage IV Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage IV Mycosis Fungoides

  19. Evidence against a role for human T-cell lymphotrophic virus type I (HTLV-I) in the pathogenesis of American cutaneous T-cell lymphoma.

    PubMed

    Wood, G S; Salvekar, A; Schaffer, J; Crooks, C F; Henghold, W; Fivenson, D P; Kim, Y H; Smoller, B R

    1996-09-01

    We used a standard polymerase chain reaction (PCR)/Southern blot assay (sensitivity > 10(-5)) to detect human T-cell lymphotrophic virus type I (HTLV-I) proviral pX, pol, and env genes in the lesional skin of 42 American patients with cutaneous T-cell lymphoma (CTCL). As in some prior reports using similar methods, a variable proportion of PCR tests were positive (seven of 42 for pX, three of 42 for pol, and two of 37 for env), resulting in an overall positive test rate of 12 of 121 (10%). To determine the significance of these positive test results, we performed several additional studies. D1S80 polymorphism analysis of CTCL cases and HTLV-I PCR analysis of non-CTCL dermatosis controls showed no evidence that positive PCR tests resulted from sample mislabeling, gross HTLV-I contamination, or human endogenous retroviruses. We then modified the standard PCR assay to incorporate ultraviolet (UV) light to destroy low-level PCR contamination. With this modified assay (sensitivity > 10(-5)), only three of 12 previously positive cases were still positive, suggesting that the earlier positives were due to trace contamination of PCR reagents or trace contamination of sample DNA. This interpretation was also supported by: (i) a match between pX and pol sequences cloned from one PCR-positive specimen and the MT4-positive control, (ii) our inability to confirm HTLV-I in any PCR-positive case using genomic dot blotting (sensitivity > 10(-2)), and (iii) negative PCR results when new samples from two of the remaining positive cases were analyzed. Finally, we used our modified UV/ PCR/Southern blot assay to test an additional 28 cases of American CTCL for pX. All of them were negative. Although these studies of 70 cases of American CTCL do not exclude the possibility that another virus is involved in the pathogenesis of this disease, they provide strong evidence against a role for HTLV-I. Furthermore, they emphasize the need for special strategies to control for false

  20. Characterization of systemic disease in primary Sjögren's syndrome: EULAR-SS Task Force recommendations for articular, cutaneous, pulmonary and renal involvements.

    PubMed

    Ramos-Casals, Manuel; Brito-Zerón, Pilar; Seror, Raphaèle; Bootsma, Hendrika; Bowman, Simon J; Dörner, Thomas; Gottenberg, Jacques-Eric; Mariette, Xavier; Theander, Elke; Bombardieri, Stefano; De Vita, Salvatore; Mandl, Thomas; Ng, Wan-Fai; Kruize, Aike; Tzioufas, Athanasios; Vitali, Claudio

    2015-12-01

    To reach a European consensus on the definition and characterization of the main organ-specific extraglandular manifestations in primary SS. The EULAR-SS Task Force Group steering committee agreed to approach SS-related systemic involvement according to the EULAR SS Disease Activity Index (ESSDAI) classification and proposed the preparation of four separate manuscripts: articular, cutaneous, pulmonary and renal ESSDAI involvement; muscular, peripheral nervous system, CNS and haematological ESSDAI involvement; organs not included in the ESSDAI classification; and lymphoproliferative disease. Currently available evidence was obtained by a systematic literature review focused on SS-related systemic features. The following information was summarized for articular, cutaneous, pulmonary and renal involvement: a clear, consensual definition of the clinical feature, a brief epidemiological description including an estimate of the prevalence reported in the main clinical series and a brief list of the key clinical and diagnostic features that could help physicians clearly identify these features. Unfortunately we found that the body of evidence relied predominantly on information retrieved from individual cases, and the scientific information provided was heterogeneous. The analysis of types of involvement was biased due to the unbalanced reporting of severe cases over non-severe cases, although the main sources of bias were the heterogeneous definitions of organ involvement (or even the lack of definition in some studies) and the heterogeneous diagnostic approach used in studies to investigate involvment of each organ. The proposals included in this article are a first step to developing an optimal diagnostic approach to systemic involvement in primary SS and may pave the way for further development of evidence-based diagnostic and therapeutic guidelines. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights

  1. Treatment Selection for T3/T4a Laryngeal Cancer: Chemoradiation Versus Primary Surgery.

    PubMed

    Timme, David W; Jonnalagadda, Sashikanth; Patel, Raunak; Rao, Krishna; Robbins, K Thomas

    2015-11-01

    We report the treatment outcomes, including organ preservation, for patients with locally advanced (T3/T4a) laryngeal cancer receiving both surgical and nonsurgical approaches. We hypothesize that selection of treatment protocols aimed to optimize organ preservation does not compromise survival provided careful selection is done through the process of multidisciplinary treatment planning. Patients with T3-4a laryngeal squamous cell cancer were evaluated and recommended for primary treatment with total or partial laryngectomy (37 patients) or chemoradiotherapy (34 patients). Treatment outcomes were compared between the 2 cohorts. In addition, the laryngeal preservation rate and laryngoesophageal dysfunction-free survival (LEDFS) were determined for the chemoradiation group. The 5-year overall survival rate for patients with T3 lesions was 41% and 40% for the surgical and nonsurgical groups, respectively, and for T4 lesions it was 54% and 53%, respectively. For the chemoradiation group, the rate of overall laryngeal preservation was 79%. LEDFS at 2 years was 40% for T3 lesions and 33% for T4 lesions. Through careful selection, some patients with locally advanced laryngeal cancer can be offered chemoradiation (organ preservation) without compromising survival. However, the patients selected to receive chemoradiation have a high rate of laryngeal and esophageal dysfunction. © The Author(s) 2015.

  2. In vitro differentiation from naive to mature E-selectin binding CD4 T cells: acquisition of skin-homing properties occurs independently of cutaneous lymphocyte antigen expression.

    PubMed

    Takahashi, Ryo; Mizukawa, Yoshiko; Yamazaki, Yoshimi; Hayakawa, Kazuhito; Hayakawa, Jun; Kudo, Akihiko; Shiohara, Tetsuo

    2003-12-01

    We previously showed that skin-homing CD4 T cells in peripheral blood can be subdivided into three populations on the basis of the expression pattern of the cutaneous lymphocyte Ag (CLA) and fucosyltransferase VII (FucT-VII): FucT-VII(+)CLA(-), FucT-VII(+)CLA(+), and FucT-VII(-)CLA(+). In view of the known late appearance of CLA during T cell differentiation, T cells programmed to attain skin-homing properties may start to generate E-selectin-binding epitopes at early stages of differentiation before induction of CLA expression. To this end, the in vitro differentiation from naive to CLA(+) memory T cells was followed after activation with anti-CD3 mAb. Here we demonstrate that naive skin-homing CD4 T cell precursors undergo a linear differentiation process from the FucT-VII(+)CLA(-) phenotype to the FucT-VII(+)CLA(+) phenotype and eventually to the FucT-VII(-)CLA(+) phenotype. The appearance of the FucT-VII(+)CLA(-) subset coincided with or could be immediately followed by the generation of E-selectin binding epitopes, and even after E-selectin-binding epitopes were no longer detectable, CLA remained expressed for prolonged periods of time, suggesting that induction of functional E-selectin ligands depends primarily on the expression of FucT-VII, but not CLA. Immunofluorescence and confocal microscopy studies of these T cells confirm that most E-selectin ligands were found independently of CLA expression.

  3. PCR-based identification of Treponema maltophilum, T amylovorum, T medium, and T lecithinolyticum in primary root canal infections.

    PubMed

    Siqueira, José F; Rôças, Isabela N

    2003-07-01

    Molecular genetic methods have significantly contributed to the knowledge about the microbiota associated with infected root canals. Albeit spirochetes have been commonly observed in primary root canal infections, only recently they have been identified. The purpose of the present study was to investigate the occurrence of four treponemes-Treponema maltophilum, Treponema lecithinolyticum, Treponema amylovorum, and Treponema medium-in cases of primary endodontic infections associated with different forms of periradicular diseases through a 16S rDNA-based nested PCR assay. Samples were taken from thirty-one infected root canals associated with either asymptomatic or symptomatic apical periodontitis. DNA extracted from the samples was initially amplified using universal 16S rDNA primers, followed by a second round of amplification using the first PCR products to detect a specific fragment of the 16S rDNA of each target Treponema species. All cases were positive for the universal bacterial primers, indicating that samples contained bacterial DNA. Of the four target species, T. maltophilum was the most prevalent, being detected in 39% of the cases (33% of the asymptomatic cases and 50% of the symptomatic cases). T. lecithinolyticum was the next more prevalent among the species tested, being found in 26% of the samples (33% of asymptomatic cases and 10% of the symptomatic cases). T. amylovorum was found in 7% of the cases (5% of the asymptomatic cases and 10% of the symptomatic cases), while T. medium was in 13% of the cases (14% of the asymptomatic cases and 10% of the symptomatic cases). None of the species tested was significantly associated with clinical symptoms. This was possibly the hitherto first study to report the occurrence of T. lecithinolyticum, T. amylovorum, and T. medium in infections of endodontic origin. Overall, findings suggested that these oral treponemes, particularly T. maltophilum and T. lecithinolyticum, can be involved in the pathogenesis of

  4. The antihistamines clemastine and desloratadine inhibit STAT3 and c-Myc activities and induce apoptosis in cutaneous T-cell lymphoma cell lines.

    PubMed

    Döbbeling, Udo; Waeckerle-Men, Ying; Zabel, Franziska; Graf, Nicole; Kündig, Thomas M; Johansen, Pål

    2013-02-01

    Mycosis fungoides and its leukaemic counterpart Sézary syndrome are the most frequent cutaneous T-cell lymphomas (CTCL), and there is no cure for these diseases. We evaluated the effect of clinically approved antihistamines on the growth of CTCL cell lines. CTCL cell lines as well as blood lymphocytes from patients with Sézary syndrome were cultured with antihistamines, and the cell were analysed for proliferation, apoptosis and expression of programmed death molecules and transcription factors. The two antihistamines clemastine and desloratadine, currently used for symptom alleviation in allergy, induced potent reduction of the activities of the constitutively active transcription factors c-Myc, STAT3, STAT5a and STAT5b in mycosis fungoides and Sézary syndrome cell lines. This inhibition was followed by apoptosis and cell death, especially in the Sézary syndrome-derived cell line Hut78 that also showed increased expression of the programmed death-1 (PD-1) after clemastine treatment. In lymphocytes isolated from Sézary syndrome patients, the CD4-positive fraction underwent apoptosis after clemastine treatment, while CD4-negative lymphocytes were little affected. Because both c-Myc and STAT transcription factors are highly expressed in proliferating tumours, their inhibition by clemastine, desloratadine and other inhibitors could complement established chemotherapies not only for cutaneous T-cell lymphomas but perhaps also other cancers.

  5. Transgenic expression of CXCR3 on T cells enhances susceptibility to cutaneous Leishmania major infection by inhibiting monocyte maturation and promoting a Th2 response.

    PubMed

    Oghumu, Steve; Stock, James C; Varikuti, Sanjay; Dong, Ran; Terrazas, Cesar; Edwards, Jessica A; Rappleye, Chad A; Holovatyk, Ariel; Sharpe, Arlene; Satoskar, Abhay R

    2015-01-01

    Cutaneous leishmaniasis, caused mainly by Leishmania major, an obligate intracellular parasite, is a disfiguring disease characterized by large skin lesions and is transmitted by a sand fly vector. We previously showed that the chemokine receptor CXCR3 plays a critical role in mediating resistance to cutaneous leishmaniasis caused by Leishmania major. Furthermore, T cells from L. major-susceptible BALB/c but not L. major-resistant C57BL/6 mice fail to efficiently upregulate CXCR3 upon activation. We therefore examined whether transgenic expression of CXCR3 on T cells would enhance resistance to L. major infection in susceptible BALB/c mice. We generated BALB/c and C57BL/6 transgenic mice, which constitutively overexpressed CXCR3 under a CD2 promoter, and then examined the outcomes with L. major infection. Contrary to our hypothesis, transgenic expression of CXCR3 (CXCR3(Tg)) on T cells of BALB/c mice resulted in increased lesion sizes and parasite burdens compared to wild-type (WT) littermates after L. major infection. Restimulated lymph node cells from L. major-infected BALB/c-CXCR3(Tg) mice produced more interleukin-4 (IL-4) and IL-10 and less gamma interferon (IFN-γ). Cells in draining lymph nodes from BALB/c-CXCR3(Tg) mice showed enhanced Th2 and reduced Th1 cell accumulation associated with increased neutrophils and inflammatory monocytes. However, monocytes displayed an immature phenotype which correlated with increased parasite burdens. Interestingly, transgenic expression of CXCR3 on T cells did not impact the outcome of L. major infection in C57BL/6 mice, which mounted a predominantly Th1 response and spontaneously resolved their infection similar to WT littermates. Our findings demonstrate that transgenic expression of CXCR3 on T cells increases susceptibility of BALB/c mice to L. major.

  6. TRPV1, but not TRPA1, in primary sensory neurons contributes to cutaneous incision-mediated hypersensitivity.

    PubMed

    Barabas, Marie E; Stucky, Cheryl L

    2013-03-04

    Mechanisms underlying postoperative pain remain poorly understood. In rodents, skin-only incisions induce mechanical and heat hypersensitivity similar to levels observed with skin plus deep incisions. Therefore, cutaneous injury might drive the majority of postoperative pain. TRPA1 and TRPV1 channels are known to mediate inflammatory and nerve injury pain, making them key targets for pain therapeutics. These channels are also expressed extensively in cutaneous nerve fibers. Therefore, we investigated whether TRPA1 and TRPV1 contribute to mechanical and heat hypersensitivity following skin-only surgical incision. Behavioral responses to mechanical and heat stimulation were compared between skin-incised and uninjured, sham control groups. Elevated mechanical responsiveness occurred 1 day post skin-incision regardless of genetic ablation or pharmacological inhibition of TRPA1. To determine whether functional changes in TRPA1 occur at the level of sensory neuron somata, we evaluated cytoplasmic calcium changes in sensory neurons isolated from ipsilateral lumbar 3-5 DRGs of skin-only incised and sham wild type (WT) mice during stimulation with the TRPA1 agonist cinnamaldehyde. There were no changes in the percentage of neurons responding to cinnamaldehyde or in their response amplitudes. Likewise, the subpopulation of DRG somata retrogradely labeled specifically from the incised region of the plantar hind paw showed no functional up-regulation of TRPA1 after skin-only incision. Next, we conducted behavior tests for heat sensitivity and found that heat hypersensitivity peaked at day 1 post skin-only incision. Skin incision-induced heat hypersensitivity was significantly decreased in TRPV1-deficient mice. In addition, we conducted calcium imaging with the TRPV1 agonist capsaicin. DRG neurons from WT mice exhibited sensitization to TRPV1 activation, as more neurons (66%) from skin-incised mice responded to capsaicin compared to controls (46%), and the sensitization

  7. TRPV1, but not TRPA1, in primary sensory neurons contributes to cutaneous incision-mediated hypersensitivity

    PubMed Central

    2013-01-01

    Background Mechanisms underlying postoperative pain remain poorly understood. In rodents, skin-only incisions induce mechanical and heat hypersensitivity similar to levels observed with skin plus deep incisions. Therefore, cutaneous injury might drive the majority of postoperative pain. TRPA1 and TRPV1 channels are known to mediate inflammatory and nerve injury pain, making them key targets for pain therapeutics. These channels are also expressed extensively in cutaneous nerve fibers. Therefore, we investigated whether TRPA1 and TRPV1 contribute to mechanical and heat hypersensitivity following skin-only surgical incision. Results Behavioral responses to mechanical and heat stimulation were compared between skin-incised and uninjured, sham control groups. Elevated mechanical responsiveness occurred 1 day post skin-incision regardless of genetic ablation or pharmacological inhibition of TRPA1. To determine whether functional changes in TRPA1 occur at the level of sensory neuron somata, we evaluated cytoplasmic calcium changes in sensory neurons isolated from ipsilateral lumbar 3–5 DRGs of skin-only incised and sham wild type (WT) mice during stimulation with the TRPA1 agonist cinnamaldehyde. There were no changes in the percentage of neurons responding to cinnamaldehyde or in their response amplitudes. Likewise, the subpopulation of DRG somata retrogradely labeled specifically from the incised region of the plantar hind paw showed no functional up-regulation of TRPA1 after skin-only incision. Next, we conducted behavior tests for heat sensitivity and found that heat hypersensitivity peaked at day 1 post skin-only incision. Skin incision-induced heat hypersensitivity was significantly decreased in TRPV1-deficient mice. In addition, we conducted calcium imaging with the TRPV1 agonist capsaicin. DRG neurons from WT mice exhibited sensitization to TRPV1 activation, as more neurons (66%) from skin-incised mice responded to capsaicin compared to controls (46%), and the

  8. Primary cutaneous large B-cell lymphoma: the relation between morphology, clinical presentation, immunohistochemical markers, and survival.

    PubMed

    Fernández-Vázquez, A; Rodríguez-Peralto, J L; Martínez, M A; Platón, E M; Algara, P; Camacho, F I; López-Ríos, F; Zarco, C; Sánchez-Yus, E; Fresno, M F; Barthe, L; Aliaga, A; Fraga, M; Forteza, J; Oliva, H; Piris, M A

    2001-03-01

    The histogenesis, morphology, immunophenotype, and clinical behavior of cutaneous large B-cell lymphomas (CLBCL) are largely a matter of controversy. We performed an investigation to determine whether CLBCL have features that differentiate them from other large B-cell lymphomas and whether CLBCL is itself a heterogeneous group. To this end, we reviewed the main characteristics of a series of 32 cases of LBCL found in the skin. We reviewed the clinical findings and paraffin sections of the tumors from these 32 patients. The immunohistochemical study performed included p53, MIB1, Bcl2, Bcl6, and CD10 markers. We carried out statistical analysis of these data (univariate and multivariate), seeking an association between the features of the tumors and clinical outcome, as defined by failure-free survival time. Only one patient died as a consequence of the lymphoma. Nevertheless, the accumulated probability of survival without failure at 48 months was 0.46. The number, type, and localization of the lesions were not associated with variations in either survival or failure-free survival. The expression of p53 was negative in this group of CLBCL, whereas Bcl-2 expression or localization in the lower leg did not relate to any other significant feature. Histologic examination of the cases disclosed three different groups: Grade III follicular lymphomas (FLs), monomorphous large B-cell lymphomas (LBCL type I), and LBCL with an admixed component of small B-lymphocytes (LBCL type II). Grade III FL (11 cases) tended to be found in the head and neck and showed CD10 expression in a majority of cases. A higher probability of lymph node relapses was associated with cases located in the head and neck and with CD10+ tumors. Cutaneous large B-cell lymphomas are indolent tumors, but follow an insidious course. Our data support the interpretation that CLBCL is a heterogeneous condition; comprises some LBCL derived from CD10+ germinal center cells which manifests more frequently as tumors

  9. Low-Dose (10-Gy) Total Skin Electron Beam Therapy for Cutaneous T-Cell Lymphoma: An Open Clinical Study and Pooled Data Analysis

    SciTech Connect

    Kamstrup, Maria R.; Gniadecki, Robert; Iversen, Lars; Skov, Lone; Petersen, Peter Meidahl; Loft, Annika; Specht, Lena

    2015-05-01

    Purpose: Cutaneous T-cell lymphomas (CTCLs) are dominated by mycosis fungoides (MF) and Sézary syndrome (SS), and durable disease control is a therapeutic challenge. Standard total skin electron beam therapy (TSEBT) is an effective skin-directed therapy, but the possibility of retreatments is limited to 2 to 3 courses in a lifetime due to skin toxicity. This study aimed to determine the clinical effect of low-dose TSEBT in patients with MF and SS. Methods and Materials: In an open clinical study, 21 patients with MF/SS stages IB to IV were treated with low-dose TSEBT over <2.5 weeks, receiving a total dose of 10 Gy in 10 fractions. Data from 10 of these patients were published previously but were included in the current pooled data analysis. Outcome measures were response rate, duration of response, and toxicity. Results: The overall response rate was 95% with a complete cutaneous response or a very good partial response rate (<1% skin involvement with patches or plaques) documented in 57% of the patients. Median duration of overall cutaneous response was 174 days (5.8 months; range: 60-675 days). TSEBT-related acute adverse events (grade 1 or 2) were observed in 60% of patients. Conclusions: Low-dose (10-Gy) TSEBT offers a high overall response rate and is relatively safe. With this approach, reirradiation at times of relapse or progression is likely to be less toxic than standard dose TSEBT. It remains to be established whether adjuvant and combination treatments can prolong the beneficial effects of low-dose TSEBT.

  10. No detection of HTLV-I proviral DNA in lesional skin biopsies from Swiss and German patients with cutaneous T-cell lymphoma.

    PubMed

    Böni, R; Davis-Daneshfar, A; Burg, G; Fuchs, D; Wood, G S

    1996-02-01

    The search for an infective agent linked to cutaneous T-cell lymphoma (CTCL) has also included the human T-cell lymphotropic virus type I (HTLV-I). Using sensitive techniques such as Southern blotting under low stringency conditions of hybridization and polymerase chain reaction (PCR) with primer sets designed to match pol, env and pX sequences of HTLV-I, we have screened lesional skin biopsies of 50 Swiss and German patients suffering from CTCL. No evidence of proviral integration of HTLV-I could be demonstrated in any of our patients. Our results, as well as a review of the literature, indicate that at least for European patients, HTLV-I does not seem to play a role in the aetiology of CTCL.

  11. Involvement of substance P present in primary afferent neurones in modulation of cutaneous blood flow in the instep of rat hind paw.

    PubMed Central

    Yonehara, N.; Chen, J. Q.; Imai, Y.; Inoki, R.

    1992-01-01

    1. The participation of small-diameter afferent fibres in the microcirculatory haemodynamics of cutaneous tissue was examined by studies on the effects of antidromic stimulation of primary afferent neurones on cutaneous blood flow (CBF) and tachykinin release into the subcutaneous space in the instep of the hind paw of rats. 2. Antidromic stimulation of the sectioned sciatic nerve induced a biphasic flow response, an initial transient decrease followed by an increase, with no alteration in the blood pressure. 3. Neither phase was affected by pretreatment with phentolamine (0.1 mg kg-1, i.a.), propranolol (0.5 mg kg-1, i.a.), atropine (0.5 mg kg-1, i.a.), methysergide (0.5 mg kg-1, i.a.) or mepyramine (10 mg kg-1, i.a.) plus cimetidine (10 mg kg-1, i.a.), but both were significantly inhibited by pretreatment with capsaicin (50 mg kg-1, s.c.). 4. Spantide (1-2 mumol kg-1, i.a.), a substance P (SP) antagonist, reduced the basal CBF, and also inhibited both phases of the biphasic flow response evoked by antidromic stimulation of the sectioned sciatic nerve. 5. Intra-arterial infusion of SP (0.5 mumol kg-1, i.a.) induced a biphasic flow response similar to that elicited by antidromic stimulation of the sectioned sciatic nerve. 6. Antidromic stimulation of the sectioned sciatic nerve caused a marked increase in SP release into the subcutaneous perfusate of the instep of the rat hind paw, but no detectable increase in neurokinin A release.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1382777

  12. Clinical practice guidelines for identification, screening and follow-up of individuals at high risk of primary cutaneous melanoma: a systematic review.

    PubMed

    Watts, C G; Dieng, M; Morton, R L; Mann, G J; Menzies, S W; Cust, A E

    2015-01-01

    Understanding how individuals at high-risk of primary cutaneous melanoma are best identified, screened and followed up will help optimize melanoma prevention strategies and clinical management. We conducted a systematic review of international clinical practice guidelines and documented the quality of supporting evidence for recommendations for clinical management of individuals at high risk of melanoma. Guidelines published between January 2000 and July 2014 were identified from a systematic search of Medline, Embase and four guideline databases; 34 guidelines from 20 countries were included. High-risk characteristics that were consistently reported included many melanocytic naevi, dysplastic naevi, family history, large congenital naevi, and Fitzpatrick Type I and II skin types. Most guidelines identify risk factors and recommend that individuals at high risk of cutaneous melanoma be monitored, but only half of the guidelines provide recommendations for screening based on level of risk. There is disagreement in screening and follow-up recommendations for those with an increased risk of future melanoma. High-level evidence supports long-term screening of individuals at high risk and monitoring using dermoscopy. Evidence is low for defining screening intervals and duration of follow-up, and for skin self-examination, although education about skin self-examination is widely encouraged. Clinical practice guidelines would benefit from a dedicated section for identification, screening and follow-up of individuals at high risk of melanoma. Guidelines could be improved with clear definitions of multiple naevi, family history and frequency of follow-up. Research examining the benefits and costs of alternative management strategies for groups at high risk will enhance the quality of recommendations.

  13. Cutaneous lymphocyte antigen and α4β7 T-lymphocyte responses are associated with peanut allergy and tolerance in children.

    PubMed

    Chan, S M H; Turcanu, V; Stephens, A C; Fox, A T; Grieve, A P; Lack, G

    2012-03-01

    It is unclear whether the initial route of allergen exposure in early life could influence the subsequent development of allergy, with cutaneous sensitization leading to peanut allergy (PA), and tolerance induced by oral exposure. The skin- and gastrointestinal (GI)-homing markers, cutaneous lymphocyte antigen (CLA) and α4β7 integrin, are used to determine whether the state of PA correlates with peanut-specific CLA responses, with tolerance associated with predominant α4β7 responses. CLA+ and α4β7+ memory T cells were isolated and cultured with peanut extract to assess their proliferation. Stimulation indices were compared in peanut allergic and non-allergic (NA) groups, and peanut-specific cytokine production was measured. In peanut allergic patients, peanut-specific proliferation predominates in the skin-homing CLA+ subset, whilst peanut-tolerant groups have a mixed CLA/α4β7 response (P = 0.008). Comparison with a control food antigen (ovalbumin) showed that these differences are allergen specific. Cytokine responses showed trends towards Th1 skewing in the GI-homing α4β7+ cells of peanut-tolerant groups and Th2 skewing in the skin-homing CLA+ cells of peanut allergic patients. The predominance of the CLA+ response to peanut in peanut allergic patients is consistent with the hypothesis that allergic sensitization occurs through the skin. The predominant α4β7+ response in peanut-tolerant groups suggests that allergen exposure through the GI tract induces tolerance.

  14. Cutaneous Infections in Wrestlers

    PubMed Central

    Wilson, Eugene K.; deWeber, Kevin; Berry, James W.; Wilckens, John H.

    2013-01-01

    Context: Cutaneous infections are common in wrestlers. Although many are simply a nuisance in the everyday population, they can be problematic to wrestlers because such infections may result in disqualification from practice or competition. Prompt diagnosis and treatment are therefore important. Evidence Acquisition: Medline and PubMed databases, the Cochrane Database of Systematic Reviews, and UpToDate were searched through 2012 with the following keywords in various combinations: skin infections, cutaneous infections, wrestlers, athletes, methicillin-resistant Staphylococcus aureus, skin and soft tissue infections, tinea corporis, tinea capitis, herpes simplex, varicella zoster, molluscum contagiosum, verruca vulgaris, warts, scabies, and pediculosis. Relevant articles found in the primary search, and selected references from those articles were reviewed for pertinent clinical information. Results: The most commonly reported cutaneous infections in wrestlers are herpes simplex virus infections (herpes gladiatorum), bacterial skin and soft tissue infections, and dermatophyte infections (tinea gladiatorum). The clinical appearance of these infections can be different in wrestlers than in the community at large. Conclusion: For most cutaneous infections, diagnosis and management options in wrestlers are similar to those in the community at large. With atypical presentations, testing methods are recommended to confirm the diagnosis of herpes gladiatorum and tinea gladiatorum. There is evidence to support the use of prophylactic medications to prevent recurrence of herpes simplex virus and reduce the incidence of dermatophyte infections in wrestlers. PMID:24427413

  15. Distinct CD4 T-cell effects on primary versus recall CD8 T-cell responses during viral encephalomyelitis.

    PubMed

    Hwang, Mihyun; Phares, Timothy W; Hinton, David R; Stohlman, Stephen A; Bergmann, Cornelia C; Min, Booki

    2015-03-01

    CD4 T-cell help is not a universal requirement for effective primary CD8 T cells but is essential to generate memory CD8 T cells capable of recall responses. This study examined how CD4 T cells affect primary and secondary anti-viral CD8 T-cell responses within the central nervous system (CNS) during encephalomyelitis induced by sublethal gliatropic coronavirus. CD4 T-cell depletion before infection did not impair peripheral expansion, interferon-γ production, CNS recruitment or initial CNS effector capacity of virus-specific CD8 T cells ex vivo. Nevertheless, impaired virus control in the absence of CD4 T cells was associated with gradually diminished CNS CD8 T-cell interferon-γ production. Furthermore, within the CD8 T-cell population short-lived effector cells were increased and memory precursor effector cells were significantly decreased, consistent with higher T-cell turnover. Transfer of memory CD8 T cells to reduce viral load in CD4-depleted mice reverted the recipient CNS CD8 T-cell phenotype to that in wild-type control mice. However, memory CD8 T cells primed without CD4 T cells and transferred into infected CD4-sufficient recipients expanded less efficiently and were not sustained in the CNS, contrasting with their helped counterparts. These data suggest that CD4 T cells are dispensable for initial expansion, CNS recruitment and differentiation of primary resident memory CD8 T cells as long as the duration of antigen exposure is limited. By contrast, CD4 T cells are essential to prolong primary CD8 T-cell function in the CNS and imprint memory CD8 T cells for recall responses. © 2014 John Wiley & Sons Ltd.

  16. Distinct CD4 T-cell effects on primary versus recall CD8 T-cell responses during viral encephalomyelitis

    PubMed Central

    Hwang, Mihyun; Phares, Timothy W; Hinton, David R; Stohlman, Stephen A; Bergmann, Cornelia C; Min, Booki

    2015-01-01

    CD4 T-cell help is not a universal requirement for effective primary CD8 T cells but is essential to generate memory CD8 T cells capable of recall responses. This study examined how CD4 T cells affect primary and secondary anti-viral CD8 T-cell responses within the central nervous system (CNS) during encephalomyelitis induced by sublethal gliatropic coronavirus. CD4 T-cell depletion before infection did not impair peripheral expansion, interferon-γ production, CNS recruitment or initial CNS effector capacity of virus-specific CD8 T cells ex vivo. Nevertheless, impaired virus control in the absence of CD4 T cells was associated with gradually diminished CNS CD8 T-cell interferon-γ production. Furthermore, within the CD8 T-cell population short-lived effector cells were increased and memory precursor effector cells were significantly decreased, consistent with higher T-cell turnover. Transfer of memory CD8 T cells to reduce viral load in CD4-depleted mice reverted the recipient CNS CD8 T-cell phenotype to that in wild-type control mice. However, memory CD8 T cells primed without CD4 T cells and transferred into infected CD4-sufficient recipients expanded less efficiently and were not sustained in the CNS, contrasting with their helped counterparts. These data suggest that CD4 T cells are dispensable for initial expansion, CNS recruitment and differentiation of primary resident memory CD8 T cells as long as the duration of antigen exposure is limited. By contrast, CD4 T cells are essential to prolong primary CD8 T-cell function in the CNS and imprint memory CD8 T cells for recall responses. PMID:25187405

  17. Immunocytochemical characterisation of cutaneous lymphomas other than mycosis fungoides.

    PubMed Central

    Ralfkiaer, E; Saati, T A; Bosq, J; Delsol, G; Gatter, K C; Mason, D Y

    1986-01-01

    The immunophenotypic properties of 25 cutaneous non-Hodgkin lymphomas other than mycosis fungoides or Sezary syndrome were investigated and correlated with clinical and histopathological data. The 11 low grade lymphomas were all of B cell origin, whereas the 14 high grade lymphomas comprised B and T cell tumours, true histiocytic proliferations, and one "nul" cell lymphoid neoplasm. For the high grade lymphomas correct prediction of the immunological phenotype based on morphological criteria was only possible in three cases. In contrast, all of the low grade lymphomas showed the non-epidermotropic infiltration pattern considered to be characteristic of cutaneous B cell tumours. For these conditions, however, immunophenotypic investigations provided a convenient means of improving discrimination between benign (polyclonal) and malignant (monoclonal) lesions, and also showed similarities with nodal lymphomas in terms of expression of lymphoid subset markers and composition of the non-neoplastic white cell infiltrate. No differences were identified between primary and secondary or concurrent cutaneous and extracutaneous lymphomas. Cutaneous non-Hodgkin lymphomas other than mycosis fungoides or Sezary syndrome constitute a heterogeneous group of neoplasms and most of these disorders are likely to represent cutaneous equivalents of nodal malignancies. Immunophenotypic investigations form a useful supplement to their histogenetic characterisation and may provide a common conceptual basis for their classification. Images PMID:3522633

  18. Epithelial to mesenchymal transition markers are associated with an increased metastatic risk in primary cutaneous squamous cell carcinomas but are attenuated in lymph node metastases.

    PubMed

    Toll, Agustí; Masferrer, Emili; Hernández-Ruiz, M E; Ferrandiz-Pulido, Carla; Yébenes, Mireia; Jaka, Ane; Tuneu, Anna; Jucglà, Anna; Gimeno, Javier; Baró, Teresa; Casado, Beatriz; Gandarillas, Alberto; Costa, Irmgard; Mojal, Sergi; Peña, Raul; de Herreros, Antonio García; García-Patos, Vicenç; Pujol, Ramon M; Hernández-Muñoz, Inmaculada

    2013-11-01

    Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy in humans and approximately 5% metastasize, usually to regional lymph nodes. Epithelial to mesenchymal transition (EMT) is a process involving loss of intercellular adhesion, acquisition of a mesenchymal phenotype and enhanced migratory potential; epithelial markers, such as E-cadherin, are down-regulated and mesenchymal proteins (Vimentin), increased. To investigate the expression of EMT markers in metastatic SCC (MSCC) and their corresponding metastases, and to correlate them with clinico-pathological factors associated with an increased risk of metastasis. We performed a retrospective study that included 146 cSCC samples (51 primary non-metastatic, 56 primary metastatic, 39 lymphatic metastases). Immunohistochemistry for E-cadherin, Vimentin, Snail, beta-catenin, Twist, Zeb1 and Podoplanin was performed. Loss of membranous E-cadherin was observed in 77% cSCCs, with no differences between MSCC and non-MSCC. Among the transcriptional factors controlling EMT, no significant Snail1 expression was detected. Twist, Zeb1, Vimentin, beta-catenin and Podoplanin were significantly overexpressed in MSCCs. Twist ectopic expression in SCC13 cells induced Zeb1, Vimentin and Podoplanin expression and E-cadherin delocalization. These changes resulted in a scattered migration pattern in vitro. Expression of EMT markers was decreased in the metastases when compared with the corresponding primary tumors. These results suggest that a partial EMT, characterized by the expression of Twist but without a total E-cadherin depletion, is involved in the acquisition of invasive traits by cSCC, but the process is downregulated in lymph node metastases. Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  19. MHC Class II Restricted Innate-Like Double Negative T Cells Contribute to Optimal Primary and Secondary Immunity to Leishmania major

    PubMed Central

    Mou, Zhirong; Liu, Dong; Okwor, Ifeoma; Jia, Ping; Orihara, Kanami; Uzonna, Jude Ezeh

    2014-01-01

    Although it is generally believed that CD4+ T cells play important roles in anti-Leishmania immunity, some studies suggest that they may be dispensable, and that MHC II-restricted CD3+CD4−CD8− (double negative, DN) T cells may be more important in regulating primary anti-Leishmania immunity. In addition, while there are reports of increased numbers of DN T cells in Leishmania-infected patients, dogs and mice, concrete evidence implicating these cells in secondary anti-Leishmania immunity has not yet been documented. Here, we report that DN T cells extensively proliferate and produce effector cytokines (IFN-γ, TNF and IL-17) and granzyme B (GrzB) in the draining lymph nodes and spleens of mice following primary and secondary L. major infections. DN T cells from healed mice display functional characteristics of protective anti-Leishmania memory-like cells: rapid and extensive proliferation and effector cytokines production following L. major challenge in vitro and in vivo. DN T cells express predominantly (> 95%) alpha-beta T cell receptor (αβ TCR), are Leishmania-specific, restricted mostly by MHC class II molecules and display transcriptional profile of innate-like genes. Using in vivo depletion and adoptive transfer studies, we show that DN T cells contribute to optimal primary and secondary anti-Leishmania immunity in mice. These results directly identify DN T cells as important players in effective and protective primary and secondary anti-L. major immunity in experimental cutaneous leishmaniasis. PMID:25233487

  20. [Initial evaluation, diagnosis, staging, treatment, and follow-up of patients with primary cutaneous malignant melanoma. Consensus statement of the Network of Catalan and Balearic Melanoma Centers].

    PubMed

    Mangas, C; Paradelo, C; Puig, S; Gallardo, F; Marcoval, J; Azon, A; Bartralot, R; Bel, S; Bigatà, X; Curcó, N; Dalmau, J; del Pozo, L J; Ferrándiz, C; Formigón, M; González, A; Just, M; Llambrich, A; Llistosella, E; Malvehy, J; Martí, R M; Nogués, M E; Pedragosa, R; Rocamora, V; Sàbat, M; Salleras, M

    2010-03-01

    The consensus statement on the management of primary cutaneous melanoma that we present here was based on selection, discussion, review, and comparison of recent literature (including national and international guidelines). The protocols for the diagnosis, treatment, and follow-up used in the hospital centers throughout Catalonia and the Balearic Isles belonging to the Network of Catalan and Balearic Melanoma Centers were also considered. The main objective of this statement was to present the overall management of melanoma patients typically used in our region at the present time. As such, the statement was not designed to be an obligatory protocol for health professionals caring for this group of patients, and neither can it nor should it be used for this purpose. Professionals reading the statement should not therefore consider it binding on their practice, and in no case can this text be used to guarantee or seek responsibility for a given medical opinion. The group of dermatologists who have signed this statement was created 3 years ago with the aim of making our authorities aware of the importance of this complex tumor, which, in comparison with other types of cancer, we believe does not receive sufficient attention in Spain. In addition, the regular meetings of the group have produced interesting proposals for collaboration in various epidemiological, clinical, and basic applied research projects on the subject of malignant melanoma in our society.

  1. Cutaneous leiomyosarcoma.

    PubMed

    Porter, Christopher J W; Januszkiewicz, Janek S

    2002-03-01

    Cutaneous leiomyosarcoma is a rare soft-tissue sarcoma with negligible metastatic potential, but local recurrence rates after surgical excision have ranged from 14 percent to 42 percent. Unlike other sarcomas, guidelines for the optimal surgical excision margin of cutaneous leiomyosarcoma are not clearly defined in the existing literature. A review of local experience with this condition revealed eight patients over 12 years, none of whom developed local recurrence or distant metastases. This is despite poor prognostic factors in seven patients and excision margins ranging from 1 to 27 mm. These findings are compared with previously published data, and conclusions are drawn based on analysis of the collective results. Complete surgical excision with a narrow margin is recommended, and patients should be observed for a minimum of 5 years after surgery.

  2. Cutaneous Leishmaniasis

    DTIC Science & Technology

    2011-06-01

    is common. No oral agents can be generally recommended for the treatment of any of the cutaneous syndromes. Antifungal agents such as ketoconazole ...the New World and the Old World. Itraconazole and fluconazole are only slightly more effective than placebo. Ketoconazole is modestly effective...against L. major, L. panamensis, and L. mexicana, but ineffective against L. tropica and L. brazil- iensis. In Guatemala, ketoconazole has proven

  3. Cutaneous ectoparasites.

    PubMed

    Nordlund, James J

    2009-01-01

    Parasites inhabit many places in the world. Some of these can inhabit the human skin or body. Many of these have been eradicated in the developed countries but persist in some tropical environments that are fun places to visit. Visitors can bring such parasites home with them such as scabies, cutaneous larva migrans, tungiasis and myiasis. Their clinical manifestations and treatment are presented for physicians evaluating and treating travelers from exotic places.

  4. c-CBL E3 Ubiquitin Ligase is Over-Expressed in Cutaneous T-Cell Lymphoma: Its Inhibition Promotes Activation Induced Cell Death

    PubMed Central

    Wu, Jianqiang; Salva, Katrin A.; Wood, Gary S.

    2014-01-01

    Mycosis fungoides (MF) and Sezary syndrome (SS) are two major forms of cutaneous T-cell lymphoma (CTCL) characterized by resistance to apoptosis. A central pathway for T-cell apoptosis is activation-induced cell death (AICD) which is triggered through the T-cell receptor (TCR). This results in upregulation of FAS-ligand (FASL) and subsequent apoptosis through the FAS death receptor pathway. It has been known for more than a decade that TCR signaling is defective in CTCL; however, the underlying mechanism has not been apparent. In this report, we show that the E3 ubiquitin ligase, c-CBL, is over-expressed in CTCL and that its knockdown overcomes defective TCR signaling resulting in phosphorylation of PLCg1, calcium influx, ROS generation, up-regulation of FASL and extrinsic pathway apoptosis in CTCL cells expressing adequate FAS. In CTCL cells with suboptimal FAS expression, FAS can be upregulated epigenetically by derepression of the FAS promoter using methotrexate (MTX) which we showed previously has activity as a DNA methylation inhibitor. Using these combined strategies, FAS-low as well as FAS-high CTCL cells can be killed effectively. PMID:25140833

  5. LINE-1 hypomethylation and mutational status in cutaneous melanomas.

    PubMed

    Pramio, Dimitrius T; Pennacchi, Paula C; Maria-Engler, Silvya S; Campos, Antônio H J F M; Duprat, João P; Carraro, Dirce M; Krepischi, Ana C V

    2016-04-01

    Epigenetic dysregulation is an important emerging hallmark of cutaneous melanoma development. The global loss of DNA methylation in gene-poor regions and transposable DNA elements of cancer cells contributes to increased genomic instability. Long interspersed element-1 (LINE-1) sequences are the most abundant repetitive sequence of the genome and can be evaluated as a surrogate marker of the global level of DNA methylation. In this work, LINE-1 methylation levels were evaluated in cutaneous melanomas and normal melanocyte primary cell cultures to investigate their possible association with both distinct clinicopathological characteristics and tumor mutational profile. A set of driver mutations frequently identified in cutaneous melanoma was assessed by sequencing (actionable mutations in BRAF, NRAS, and KIT genes, and mutations affecting the TER T promoter) or multiplex ligation-dependent probe amplification (MLPA) (CDKN2A deletions). Pyrosequencing was performed to investigate the methylation level of LINE-1 and CDKN2A promoter sequences. The qualitative analysis showed a trend toward an association between LINE-1 hypomethylation and CDKN2A inactivation (p=0.05). In a quantitative approach, primary tumors, mainly the thicker ones (>4 mm), exhibited a trend toward LINE-1 hypomethylation when compared with control melanocytes. To date, this is the first study reporting in cutaneous melanomas a possible link between the dysregulation of LINE-1 methylation and the presence of driver mutations. Copyright © 2016 American Federation for Medical Research.

  6. Problems in Cutaneous Communication from Psychophysics to Information Processing.

    ERIC Educational Resources Information Center

    Gilmer, B. VonHaller; Clark, Leslie L., Ed.

    After reviewing the history of communication through the skin, this paper considers recent research into the problem of cutaneous stimulation induced both mechanically and electrically. The general demands of a cutaneous communication system are discussed, and four primary dimensions of cutaneous stimulation are summarized (locus, intensity,…

  7. Modern management of primary T-cell immunodeficiencies.

    PubMed

    Pachlopnik Schmid, Jana; Güngör, Tayfun; Seger, Reinhard

    2014-06-01

    The study of human T-cell PIDs with Mendelian inheritance has enabled the molecular characterization of important key functions and pathways in T-cell biology. In most cases, T-cell PIDs become apparent as combined T- and B-cell deficiencies. Severe combined immunodeficiencies (SCIDs) are characterized by a complete lack of T-cell development and, in some cases, a developmental block in other lymphoid lineages and manifest within the first year of life. Combined immunodeficiency syndromes (CIDs) result from hypomorphic mutations in typical SCID associated genes or from partial defects of T-cell development and manifest later in childhood by increased susceptibility to infection often combined with disturbances in immune homeostasis, e.g., autoimmunity and increased incidence in lymphoproliferation. The discovery of mutations and characterization of the cellular changes that underlie lymphocyte defects and immune dysregulation have led to novel, specific, successful therapies for severe diseases which are often fatal if left untreated. Over the last few years, impressive progress has been made in understanding the disease mechanisms of T-cell immunodeficiencies and in improving the long-term outcomes of potentially curative treatments, including gene therapy.

  8. Vorinostat combined with bexarotene for treatment of cutaneous T-cell lymphoma: in vitro and phase I clinical evidence supporting augmentation of retinoic acid receptor/retinoid X receptor activation by histone deacetylase inhibition.

    PubMed

    Dummer, Reinhard; Beyer, Marc; Hymes, Kenneth; Epping, Mirjam T; Bernards, Rene; Steinhoff, Matthias; Sterry, Wolfram; Kerl, Helmut; Heath, Karl; Ahern, Janet D; Hardwick, James S; Garcia-Vargas, Jose; Baumann, Katrin; Rizvi, Syed; Frankel, Stanley R; Whittaker, Sean J; Assaf, Chalid

    2012-08-01

    The retinoid X receptor (RXR)-agonist bexarotene and the histone deacetylase inhibitor (HDACI) vorinostat are each established monotherapies for cutaneous T-cell lymphomas (CTCLs). We investigated the combination of HDACI and retinoic acid receptor (RAR)/RXR agonists in vitro and in a phase I, multicenter, open-label, two-part dose-escalation study. The combination of bexarotene with a HDACI in vitro leads to cooperative activation of gene transcription and reduction of cell viability in human tumor cell lines. The primary clinical objective was to determine the maximum tolerated dose (MTD) of bexarotene plus vorinostat in 23 patients with CTCLs. The MTD for part I was established at vorinostat 200 mg/day plus bexarotene 300 mg/m(2)/day. The MTD for part II was not reached. Four patients had an objective response and seven patients experienced pruritus relief. We conclude that concomitant administration of vorinostat and bexarotene is feasible only if lower doses of each drug are administered relative to the product label monotherapy doses.

  9. Leishmania OligoC-TesT as a Simple, Rapid, and Standardized Tool for Molecular Diagnosis of Cutaneous Leishmaniasis in Peru▿

    PubMed Central

    Espinosa, Diego; Boggild, Andrea K.; Deborggraeve, Stijn; Laurent, Thierry; Valencia, Cristian; Pacheco, Rosa; Miranda-Verástegui, César; Llanos-Cuentas, Alejandro; Leclipteux, Thierry; Dujardin, Jean-Claude; Büscher, Philippe; Arévalo, Jorge

    2009-01-01

    Molecular methods such as PCR have become attractive tools for diagnosis of cutaneous leishmaniasis (CL), both for their high sensitivity and for their specificity. However, their practical use in routine diagnosis is limited due to the infrastructural requirements and the lack of any standardization. Recently, a simplified and standardized PCR format for molecular detection of Leishmania was developed. The Leishmania OligoC-TesT is based on simple and rapid detection using a dipstick with PCR-amplified Leishmania DNA. In this study, we estimated the diagnostic accuracy of the Leishmania OligoC-TesT for 61 specimens from 44 CL-suspected patients presenting at the leishmaniasis clinic of the Instituto de Medicina Tropical Alexander von Humboldt, Peru. On the basis of parasitological detection and the leishmanin skin test (LST), patients were classified as (i) confirmed CL cases, (ii) LST-positive cases, and (iii) LST-negative cases. The sensitivities of the Leishmania OligoC-TesT was 74% (95% confidence interval (CI), 60.5% to 84.1%) for lesion aspirates and 92% (95% CI, 81.2% to 96.9%) for scrapings. A significantly higher sensitivity was observed with a conventional PCR targeting the kinetoplast DNA on the aspirates (94%) (P = 0.001), while there was no significant difference in sensitivity for the lesion scrapings (88%) (P = 0.317). In addition, the Leishmania OligoC-TesT was evaluated for 13 CL-suspected patients in two different peripheral health centers in the central jungle of Peru. Our findings clearly indicate the high accuracy of the Leishmania OligoC-TesT for lesion scrapings for simple and rapid molecular diagnosis of CL in Peru. PMID:19553579

  10. Leishmania OligoC-TesT as a simple, rapid, and standardized tool for molecular diagnosis of cutaneous leishmaniasis in Peru.

    PubMed

    Espinosa, Diego; Boggild, Andrea K; Deborggraeve, Stijn; Laurent, Thierry; Valencia, Cristian; Pacheco, Rosa; Miranda-Verástegui, César; Llanos-Cuentas, Alejandro; Leclipteux, Thierry; Dujardin, Jean-Claude; Büscher, Philippe; Arévalo, Jorge

    2009-08-01

    Molecular methods such as PCR have become attractive tools for diagnosis of cutaneous leishmaniasis (CL), both for their high sensitivity and for their specificity. However, their practical use in routine diagnosis is limited due to the infrastructural requirements and the lack of any standardization. Recently, a simplified and standardized PCR format for molecular detection of Leishmania was developed. The Leishmania OligoC-TesT is based on simple and rapid detection using a dipstick with PCR-amplified Leishmania DNA. In this study, we estimated the diagnostic accuracy of the Leishmania OligoC-TesT for 61 specimens from 44 CL-suspected patients presenting at the leishmaniasis clinic of the Instituto de Medicina Tropical Alexander von Humboldt, Peru. On the basis of parasitological detection and the leishmanin skin test (LST), patients were classified as (i) confirmed CL cases, (ii) LST-positive cases, and (iii) LST-negative cases. The sensitivities of the Leishmania OligoC-TesT was 74% (95% confidence interval (CI), 60.5% to 84.1%) for lesion aspirates and 92% (95% CI, 81.2% to 96.9%) for scrapings. A significantly higher sensitivity was observed with a conventional PCR targeting the kinetoplast DNA on the aspirates (94%) (P = 0.001), while there was no significant difference in sensitivity for the lesion scrapings (88%) (P = 0.317). In addition, the Leishmania OligoC-TesT was evaluated for 13 CL-suspected patients in two different peripheral health centers in the central jungle of Peru. Our findings clearly indicate the high accuracy of the Leishmania OligoC-TesT for lesion scrapings for simple and rapid molecular diagnosis of CL in Peru.

  11. Management of Gustilo Anderson III B open tibial fractures by primary fascio-septo-cutaneous local flap and primary fixation: The ‘fix and shift’ technique

    PubMed Central

    Ramasamy, P R

    2017-01-01

    Background: Open fractures of tibia have posed great difficulty in managing both the soft tissue and the skeletal components of the injured limb. Gustilo Anderson III B open tibial fractures are more difficult to manage than I, II, and III A fractures. Stable skeletal fixation with immediate soft tissue cover has been the key to the successful outcome in treating open tibial fractures, in particular, Gustilo Anderson III B types. If the length of the open wound is larger and if the exposed surface of tibial fracture and tibial shaft is greater, then the management becomes still more difficult. Materials and Methods: Thirty six Gustilo Anderson III B open tibial fractures managed between June 2002 and December 2013 with “fix and shift” technique were retrospectively reviewed. All the 36 patients managed by this technique had open wounds measuring >5 cm (post debridement). Under fix and shift technique, stable fixation involved primary external fixator application or primary intramedullary nailing of the tibial fracture and immediate soft tissue cover involved septocutaneous shift, i.e., shifting of fasciocutaneous segments based on septocutaneous perforators. Results: Primary fracture union rate was 50% and reoperation rate (bone stimulating procedures) was 50%. Overall fracture union rate was 100%. The rate of malunion was 14% and deep infection was 16%. Failure of septocutaneous shift was 2.7%. There was no incidence of amputation. Conclusion: Management of Gustilo Anderson III B open tibial fractures with “fix and shift” technique has resulted in better outcome in terms of skeletal factors (primary fracture union, overall union, and time for union and malunion) and soft tissue factors (wound healing, flap failure, access to secondary procedures, and esthetic appearance) when compared to standard methods adopted earlier. Hence, “fix and shift” could be recommended as one of the treatment modalities for open III B tibial fractures. PMID:28216752

  12. γδ T-cell-rich variants of pityriasis lichenoides and lymphomatoid papulosis: benign cutaneous disorders to be distinguished from aggressive cutaneous γδ T-cell lymphomas.

    PubMed

    Martinez-Escala, M E; Sidiropoulos, M; Deonizio, J; Gerami, P; Kadin, M E; Guitart, J

    2015-02-01

    T cells with a γδ phenotype have been associated with aggressive lymphomas. Yet, inflammatory skin disorders and low-grade lymphoproliferative disorders have rarely been described with a predominant γδ T-cell infiltrate. To review our experience and determine the clinical relevance of the γδ T-cell phenotype in lymphomatoid papulosis (LyP) and pityriasis lichenoides (PL). A retrospective dermatopathology file review looking for LyP and PL characterized by a γδ T-cell phenotype was performed. Clinical manifestations and course, histological features and molecular data were analyzed. Six of 16 cases of LyP and four of 23 cases diagnosed as PL during a 5-year period (2009-14) were identified. The median follow-up for the whole group was 16 months (range 3-64), showing an indolent clinical course in all cases. The detection of a predominantly γδ T-cell phenotype in papular lymphoid-rich infiltrates in the absence of other lesions is not associated with a clinically aggressive course. γδ T-cell-rich variants of LyP and PL may reflect a spectrum of related conditions. This is a single academic centre retrospective chart review of a relatively small sample. © 2014 British Association of Dermatologists.

  13. Identification of geographic clustering and regions spared by the Cutaneous T-Cell Lymphoma (CTCL) in Texas using two distinct cancer registries

    PubMed Central

    Litvinov, Ivan V.; Tetzlaff, Michael T.; Rahme, Elham; Habel, Youssef; Risser, David R.; Gangar, Pamela; Jennings, Michelle A.; Pehr, Kevin; Prieto, Victor G.; Sasseville, Denis; Duvic, Madeleine

    2015-01-01

    Background Cutaneous T-Cell Lymphomas (Mycosis Fungoides and its leukemic variant, Sézary Syndrome) are rare malignancies. Reports of occurrence of Mycosis Fungoides in married couples and families raise the possibility of an environmental trigger for this cancer. While it was suggested that CTLC arises from inappropriate T cell stimulation, currently no preventable trigger has been identified. Methods We analyzed by region, zip code, age, sex and ethnicity the demographic data of 1047 patients from Texas, who were seen in a CTCL clinic at the MD Anderson Cancer Center during 2000-2012 (the MDACC database) and 1990 patients that were recorded in the population-based Texas Cancer Registry (TCR) between 1996-2010. Subsequently data from both databases was cross analyzed and compared. Results Our findings, based on the MDACC database, document geographic clustering of patients in three communities within the Houston metropolitan area, where CTCL incidence rates were 5-20 times higher than the expected population rate. Analysis of the TCR database defined the CTCL population rate for the state to be 5.8 [95% CI 5.5, 6.0] cases per million individuals per year, confirmed the observations from the MDACC database and further highlighted additional areas of geographic clustering and regions spared by CTCL in Texas. Conclusions Our study documents geographic clustering of CTCL cases in Texas and argues for the existence of yet unknown external causes/triggers for this rare malignancy. PMID:25728286

  14. Alemtuzumab for relapsed and refractory erythrodermic cutaneous T-cell lymphoma: a single institution experience from the Robert H. Lurie Comprehensive Cancer Center.

    PubMed

    Querfeld, Christiane; Mehta, Neha; Rosen, Steven T; Guitart, Joan; Rademaker, Alfred; Gerami, Pedram; Kuzel, Timothy M

    2009-12-01

    We present the results of an open-label clinical trial and the clinical use of alemtuzumab in 19 heavily pretreated patients with advanced erythrodermic cutaneous T-cell lymphomas (CTCL) (erythrodermic mycosis fungoides and Sézary syndrome). Ten patients received alemtuzumab intravenously using an escalating dose regimen with a final dose of 30 mg three times weekly for 4 weeks followed by subcutaneous administration for 8 weeks. Nine patients were treated with only the SQ or IV dosing. The overall response rate was 84%, with 9 (47%) complete and 7 (37%) partial remissions. The median follow-up was 24 months (range, 6 to 62+ months). Median overall survival was 41 months whereas median progression free survival was 6 months. Minimal residual disease by T-cell gene rearrangement studies was detected in 11 patients who achieved complete response and partial response. Toxicities included myelosuppression and infections; however, the majority of side effects were of Grade 2 in severity and transient. One patient was diagnosed with a concurrent lymphoma (mantle cell lymphoma) 6 months after completing alemtuzumab therapy. Alemtuzumab is particularly effective in patients with erythrodermic CTCL with acceptable toxicities. Combined strategies with alemtuzumab may achieve molecular remissions with longer response durations.

  15. cMyc/miR-125b-5p Signalling Determines Sensitivity to Bortezomib in Preclinical Model of Cutaneous T-Cell Lymphomas

    PubMed Central

    Willumsgaard, Ayalah; Skov, Anne Guldhammer; Palmieri, Dario; Gasparini, Pierluigi; Laganá, Alessandro; Woetmann, Anders; Ødum, Niels; Croce, Carlo Maria; Gniadecki, Robert

    2013-01-01

    Successful/effective cancer therapy in low grade lymphoma is often hampered by cell resistance to anti-neoplastic agents. The crucial mechanisms responsible for this phenomenon are poorly understood. Overcoming resistance of tumor cells to anticancer agents, such as proteasome inhibitors, could improve their clinical efficacy. Using cutaneous T-cell lymphoma (CTCL) as a model of the chemotherapy-resistant peripheral lymphoid malignancy, we demonstrated that resistance to proteasome inhibition involved a signaling between the oncogene cMyc and miR-125b-5p. Bortezomib repressed cMyc and simultaneously induced miR-125b-5p that exerted a cytoprotective effect through the downmodulation of MAD4. Overexpression of cMyc repressed miR-125b-5p transcription and sensitized lymphoma cells to bortezomib. The central role of miR-125b-5p was further confirmed in a mouse model of T-cell lymphoma, where xenotransplantation of human CTCL cells overexpressing miR-125b-5p resulted in enhanced tumor growth and a shorter median survival. Our findings describe a novel mechanism through which miR-125b-5p not only regulates tumor growth in vivo, but also increases cellular resistance to proteasome inhibitors via modulation of MAD4. PMID:23527180

  16. Durable Regression of Primary Cutaneous B-Cell Lymphoma Following Fever-inducing Mistletoe Treatment: Two Case Reports.

    PubMed

    Orange, Maurice; Lace, Aija; Fonseca, Maria P; von Laue, Broder H; Geider, Stefan; Kienle, Gunver S

    2012-03-01

    背景:槲寄生疗法是一种广泛使 用的补充性癌症治疗方法,通常 作为常规癌症治疗的补充疗法, 或伴随常规疗法共同使用。然 而, 在皮肤淋巴瘤的治疗过程 中,人们对该疗法的使用、有效 性和安全性知之甚少。病例报告:两名原发性皮肤B-细 胞淋巴瘤患者(pT2bcNxM0滤泡 中心和pT2acNxM0边缘区域)取 消或推迟推荐的常规治疗,并接 受高剂量、可引起发热的槲寄生 疗法;通过瘤内、皮下和静脉注 射方式进行组合给药,其中一名 患者还接受了全身过热疗法。这 两名患者在分别接受12.98 g 和 4.63g累积剂量的槲寄生提取物 治疗后,分别在12个月和8个月后 淋巴瘤出现退化。迄今为止,即 在开始治疗的3年半之后,患者病 情正处于缓解期。在整个观察期 期间,两名患者都未接受常规癌 症治疗。

  17. Optimal level of sympathectomy for primary palmar hyperhidrosis: T3 versus T4 in a retrospective cohort study.

    PubMed

    Abd Ellatif, Mohamed E; Hadidi, Amro El; Musa, Adil M; Askar, Walid; Abbas, Ashraf; Negm, Ahmed; Moatamed, Ahmed; Dawoud, Ibrahim

    2014-01-01

    To compare the results obtained with T3 versus T4 sympathectomy in treatment of primary palmar hyperhidrosis (PH). By retrospective review of medical records of patients with PH who underwent thoracoscopic sympathectomy from February, 2009 to September, 2012. The patients were categorized into two groups: T3 group underwent T3 sympathectomy and T4 group underwent T4 sympathectomy. Patients were evaluated according to the results of sweating, compensatory hyperhidrosis (CH), degree of satisfaction, complications and recurrence. Mean follow up was 19 ± 7 months. A total of 274 consecutive patients with PH were included in this study. There were 169 females and 105 males, with mean age of 29 ± 11 years. 129 patients underwent T3 sympathectomy (T3 group). The T4 group included 145 patients who underwent T4 sympathectomy. 71.7% patients of T4 group did not complain of CH in comparison to 25.6% patients in group T3 (P = 0.001) and the incidence of mild to moderate CH was higher in the T3 group than T4 (64.4% vs. 26.9%; p = 0.001). T4 group showed a great significance in the (very satisfied category) in comparison to T3 group (P = 0.001). The incidence of over-dry hands was significantly lower in group T4 (0.7%, 1 out of 145) than in group T3 (8.5%, 11 out of 129). The recurrence rate was similar in the two groups (0.8% vs. 1.4%; P = 0.19). Video-assisted T3 or T4 sympathectomy is a safe and effective procedure for treatment of palmar hyperhidrosis. T4 sympathectomy appears associated with less severe dryness and CH than T3 sympathectomy at long-term follow-up. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

  18. Clinical significance of BRAF V600E mutational status in capsular nevi of sentinel lymph nodes in patients with primary cutaneous melanoma.

    PubMed

    Siroy, Alan E; Aung, Phyu P; Torres-Cabala, Carlos A; Tetzlaff, Michael T; Nagarajan, Priyadharsini; Milton, Denái R; Curry, Jonathan L; Ivan, Doina; Prieto, Victor G

    2017-01-01

    Capsular nevi (CN) are clusters of benign melanocytes situated in the capsule of lymph nodes and occur in up to 20% of lympadenectomy specimens. The molecular profile of CN in relation to prognostic parameters in patients with primary cutaneous melanoma (PCM) has not been previously investigated. We assessed BRAF V600E mutation by immunohistochemistry (IHC) in the CN of sentinel lymph nodes (SLN) in PCM patients and correlated the findings with demographic characteristics, PCM histopathologic and molecular features, and clinical outcome parameters. Seventy-eight cases of CN involving SLN of PCM patients were evaluated for BRAF V600E mutation by IHC. The results were correlated with patient demographics, PCM histopathologic and molecular features, and outcome measures. Thirty-six (46%) of 78 CN cases expressed BRAF V600E mutation by IHC. Nineteen (53%) of those BRAF-positive CN cases were from patients with at least American Joint Committee on Cancer stage II melanoma, whereas 62% of BRAF-negative CN cases (26/42) were from patients with stage I melanoma (P = .013). Twelve (33%) of the 36 BRAF-positive CN cases had metastatic melanoma involving lymph nodes, compared with 14% (6/42) of BRAF-negative CN cases (P = .061). CN mutation status was not associated with patient demographics, histopathologic or molecular features of the PCM, or survival outcomes. A high percentage of CN identified in the SLN of patients with PCM harbor BRAF V600E mutation. Positive mutation was associated with adverse clinicopathological parameters, specifically increased tumor stage and lymph node metastasis. These findings suggest that BRAF V600E mutation in CN of SLN may be useful as an adverse predictive biomarker in patients with melanoma. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Prognostic Implication of Lymphovascular Invasion Detected by Double Immunostaining for D2-40 and MITF1 in Primary Cutaneous Melanoma.

    PubMed

    Feldmeyer, Laurence; Tetzlaff, Michael; Fox, Patricia; Nagarajan, Priyadharsini; Curry, Jonathan; Ivan, Doina; Torres Cabala, Carlos A; Prieto, Victor G; Aung, Phyu P

    2016-07-01

    Lymphovascular invasion (LVI) is associated with adverse outcomes in primary cutaneous melanoma (PCM). Detection of LVI by hematoxylin and eosin staining alone is 0%-6%, but targeting lymphovascular structures increases the detection rate. To examine the prognostic significance of LVI detected by immunostaining for D2-40 and microphthalmia-associated transcription factor 1 (MITF1) in PCM. The authors retrospectively analyzed 120 PCM samples. We compared the LVI detection rates of immunostaining for D2-40 only (22%), double staining for D2-40 and MITF1 (38%), and hematoxylin and eosin, and examined the association of LVI with clinicopathologic variables and clinical outcomes. Immunolabeling with both methods significantly increased the LVI detection rate. Double staining for D2-40 and MITF1 as well as D2-40-detected LVI was significantly associated with increased Breslow thickness, number of mitoses, and sentinel lymph node (SLN) metastasis. D2-40-detected LVI was also associated with ulceration. Although the difference was not significant, double staining for D2-40 and MITF1 allowed for easier detection of LVI than D2-40 alone. This study was conducted in a tertiary referral institution; therefore, a referral bias cannot be excluded. Immunolabeling increased detection of LVI in PCM. Because LVI is a positive predictive marker for SLN metastasis, the authors propose using anti-D2-40 and anti-MITF1 in the evaluation of LVI in patients with PCM with a certain risk of SLN metastasis.

  20. Jak3, STAT3, and STAT5 inhibit expression of miR-22, a novel tumor suppressor microRNA, in cutaneous T-Cell lymphoma.

    PubMed

    Sibbesen, Nina A; Kopp, Katharina L; Litvinov, Ivan V; Jønson, Lars; Willerslev-Olsen, Andreas; Fredholm, Simon; Petersen, David L; Nastasi, Claudia; Krejsgaard, Thorbjørn; Lindahl, Lise M; Gniadecki, Robert; Mongan, Nigel P; Sasseville, Denis; Wasik, Mariusz A; Iversen, Lars; Bonefeld, Charlotte M; Geisler, Carsten; Woetmann, Anders; Odum, Niels

    2015-08-21

    Aberrant activation of Janus kinase-3 (Jak3) and its key down-stream effectors, Signal Transducer and Activator of Transcription-3 (STAT3) and STAT5, is a key feature of malignant transformation in cutaneous T-cell lymphoma (CTCL). However, it remains only partially understood how Jak3/STAT activation promotes lymphomagenesis. Recently, non-coding microRNAs (miRNAs) have been implicated in the pathogenesis of this malignancy. Here, we show that (i) malignant T cells display a decreased expression of a tumor suppressor miRNA, miR-22, when compared to non-malignant T cells, (ii) STAT5 binds the promoter of the miR-22 host gene, and (iii) inhibition of Jak3, STAT3, and STAT5 triggers increased expression of pri-miR-22 and miR-22. Curcumin, a nutrient with anti-Jak3 activity and histone deacetylase inhibitors (HDACi) also trigger increased expression of pri-miR-22 and miR-22. Transfection of malignant T cells with recombinant miR-22 inhibits the expression of validated miR-22 targets including NCoA1, a transcriptional co-activator in others cancers, as well as HDAC6, MAX, MYCBP, PTEN, and CDK2, which have all been implicated in CTCL pathogenesis. In conclusion, we provide the first evidence that de-regulated Jak3/STAT3/STAT5 signalling in CTCL cells represses the expression of the gene encoding miR-22, a novel tumor suppressor miRNA.

  1. Jak3, STAT3, and STAT5 inhibit expression of miR-22, a novel tumor suppressor microRNA, in cutaneous T-Cell lymphoma

    PubMed Central

    Sibbesen, Nina A.; Kopp, Katharina L.; Litvinov, Ivan V.; Jønson, Lars; Willerslev-Olsen, Andreas; Fredholm, Simon; Petersen, David L.; Nastasi, Claudia; Krejsgaard, Thorbjørn; Lindahl, Lise M.; Gniadecki, Robert; Mongan, Nigel P.; Sasseville, Denis; Wasik, Mariusz A.; Iversen, Lars; Bonefeld, Charlotte M.; Geisler, Carsten; Woetmann, Anders; Odum, Niels

    2015-01-01

    Aberrant activation of Janus kinase-3 (Jak3) and its key down-stream effectors, Signal Transducer and Activator of Transcription-3 (STAT3) and STAT5, is a key feature of malignant transformation in cutaneous T-cell lymphoma (CTCL). However, it remains only partially understood how Jak3/STAT activation promotes lymphomagenesis. Recently, non-coding microRNAs (miRNAs) have been implicated in the pathogenesis of this malignancy. Here, we show that (i) malignant T cells display a decreased expression of a tumor suppressor miRNA, miR-22, when compared to non-malignant T cells, (ii) STAT5 binds the promoter of the miR-22 host gene, and (iii) inhibition of Jak3, STAT3, and STAT5 triggers increased expression of pri-miR-22 and miR-22. Curcumin, a nutrient with anti-Jak3 activity and histone deacetylase inhibitors (HDACi) also trigger increased expression of pri-miR-22 and miR-22. Transfection of malignant T cells with recombinant miR-22 inhibits the expression of validated miR-22 targets including NCoA1, a transcriptional co-activator in others cancers, as well as HDAC6, MAX, MYCBP, PTEN, and CDK2, which have all been implicated in CTCL pathogenesis. In conclusion, we provide the first evidence that de-regulated Jak3/STAT3/STAT5 signalling in CTCL cells represses the expression of the gene encoding miR-22, a novel tumor suppressor miRNA. PMID:26244872

  2. Increased Levels of Plasma Epstein Barr Virus DNA Identify a Poor-Risk Subset of Patients With Advanced Stage Cutaneous T-Cell Lymphoma

    PubMed Central

    Haverkos, Bradley M.; Gru, Alejandro A.; Geyer, Susan M.; Bingman, Anissa K.; Hemminger, Jessica A.; Mishra, Anjali; Wong, Henry K.; Pancholi, Preeti; Freud, Aharon G.; Caligiuri, Michael A.; Baiocchi, Robert A.; Porcu, Pierluigi

    2016-01-01

    Discovering prognostic factors that simultaneously describe tumor characteristics and improve risk stratification is a priority in cutaneous T-cell lymphoma (CTCL). More than a third of advanced stage CTCL patients in this cohort had detectable cell free plasma Epstein–Barr virus (EBV)-DNA (pEBVd) using quantitative real-time polymerase chain reaction. An increased level of pEBVd was highly concordant with EBV (ie, Epstein–Barr virus RNAs) in tumor tissue and was associated with inferior survival. Introduction Outcomes in advanced stage (AS) cutaneous T-cell lymphomas (CTCL) are poor but with great variability. Epstein–Barr virus (EBV) is associated with a subset of non-Hodgkin lymphomas. Frequency of plasma EBV-DNA (pEBVd) detection, concordance with EBV RNA (EBER) in tumor tissue, codetection of plasma cytomegalovirus DNA (pCMVd), and prognostic effect in AS CTCL are unknown. Patients and Methods Patients (n = 46; 2006–2013) with AS CTCL (≥IIB) were retrospectively studied. pEBVd and pCMVd were longitudinally measured using quantitative real-time polymerase chain reaction. EBER in situ hybridization (ISH) was performed on tumor samples. Survival from time of diagnosis (ToD) and time of progression to AS was assessed. Results Plasma EBV-DNA and pCMVd were detected in 37% (17 of 46) and 17% (8 of 46) of AS CTCL patients, respectively. pCMVd detection was significantly more frequent in pEBVd-positive (pEBVd+) than pEBVd− patients (35% vs. 7%; P = .038). Tumor tissue for EBER-ISH was available in 14 of 17 pEBVd+ and 22 of 29 pEBVd− patients; 12 of 14 (85.7%) pEBVd+ patients were EBER+ versus 0 of 22 pEBVd− patients. Frequency of large cell transformation (LCT) tended to be greater in pEBVd+ patients, but was not significant (10 of 14 pEBVd+ vs. 10 of 23 pEBVd−; P = .17). No notable differences in rates of increased levels of serum lactate dehydrogenase (LDH) were observed (17 of 17 pEBVd+ vs. 27 of 29 pEBVd−). pEBVd detection was associated with

  3. Phase I Clinical Trial of O6-Benzylguanine and Topical Carmustine in the Treatment of Cutaneous T-Cell Lymphoma, Mycosis Fungoides Type

    PubMed Central

    Apisarnthanarax, Narin; Wood, Gary S.; Stevens, Seth R.; Carlson, Sean; Chan, Derek V.; Liu, Lili; Szabo, Sarolta K.; Fu, Pingfu; Gilliam, Anita C.; Gerson, Stanton L.; Remick, Scot C.; Cooper, Kevin D.

    2012-01-01

    Objectives To evaluate the toxic effects and maximum tolerated dose of topical carmustine [1,3-bis (2-chloroethyl)-1-nitrosourea] following intravenous O6-benzylguanine in the treatment of cutaneous T-cell lymphoma (CTCL), and to determine pharmacodynamics of O6-alkylguanine DNA alkyltransferase activity in treated CTCL lesions. Design Open-label, dose-escalation, phase I trial. Setting Dermatology outpatient clinic and clinical research unit at a university teaching hospital. Patients A total of 21 adult patients (11 male, 10 female) with early-stage (IA-IIA) refractory CTCL, mycosis fungoides type, treated with topical carmustine following intravenous O6-benzylguanine. Intervention Treatment once every 2 weeks with 120 mg/m2 intravenous O6-benzylguanine followed 1 hour later by whole-body, low-dose topical carmustine starting at 10 mg, with 10-mg incremental dose-escalation in 3 patient cohorts. Cutaneous T-cell lymphoma lesional skin biopsy specimens were taken at baseline and 6 hours, 24 hours, and 1 week after the first O6-benzylguanine infusion for analysis of O6-alkylguanine-DNA alkyltransferase activity. Main Outcome Measures Clinical response measured by physical examination and severity-weighted assessment tool measurements, safety data acquired by review of adverse events at study visits, and O6-alkylguanine-DNA alkyltransferase activity in treated lesion skin biopsy specimens. Results A minimal toxic effect was observed through the 40-mg carmustine dose level with 76% of adverse events being grade 1 based on the National Cancer Institute Common Terminology Criteria for Adverse Events. Mean baseline O6-alkylguanine-DNA alkyl-transferase activity in CTCL lesions was 3 times greater than in normal controls and was diminished by a median of 100% at 6 and 24 hours following O6-benzyl-guanine with recovery at 1 week. Clinical disease reduction correlated positively with O6-alkylguanine-DNA alkyltransferase activity at 168 hours (P= .02) and inversely with

  4. Cutaneous pseudovasculitis.

    PubMed

    Carlson, J Andrew; Chen, Ko-Ron

    2007-02-01

    Cutaneous pseudovasculitis represents a heterogeneous collection of disorders that are capable of simulating cutaneous vasculitis and can be broadly classified into diseases that produce hemorrhage (petechiae, purpura, and ecchymoses) or vessel occlusion with resultant livedo, cyanosis, ulcers, digital necrosis, and/or gangrene. Overlap is not uncommon, but if present, one mechanism dominates. Hemorrhagic pseudovasculitis is due to vessel wall dysfunction (incompetence), which can be related to diverse factors that include vessel wall deposition of metabolic substances (amyloid, calcium), nutritional deficiencies (scurvy), nonvasculitic inflammatory purpura (pigmented purpuric dermatitis, arthropod, viral and drug reactions), degeneration of the vessel wall and supporting stroma (senile/solar purpura), direct vessel wall invasion of infective organisms, coagulation-fibrinolytic disorders (eg, thrombocytopenia), and vessel wall trauma. Cyanotic-infarctive pseudovasculitis is due vaso-occlusion by emboli, thrombi, or fibrointimal hyperplasia (endarteritis obliterans) and includes varied conditions such as purpura fulminans, Coumadin necrosis, antiphospholipid antibody syndrome, cardiac myxoma, cholesterol embolization, calciphylaxis, and radiation arteritis. Delayed and inappropriate diagnosis of pseudovasculitis leads to incorrect management and exposure to potentially deleterious treatment modalities such as corticosteroids and cytotoxic agents. The diagnosis of a pseudovasculitic disorder requires a high index of suspicion and should always be part of the differential diagnosis of vasculitis. Skin biopsy is a crucial step in differentiating pseudovasculitis from authentic vasculitis; absence of histologic evidence of vasculitis, particularly after multiple biopsies, should direct evaluation and diagnosis towards pseudovasculitis.

  5. Cutaneous sarcoidosis.

    PubMed

    Marchell, Richard M; Judson, Marc A

    2010-08-01

    Sarcoidosis is a systemic disease with skin manifestations. Skin manifestations are classified as nonspecific if they are not characterized by granulomatous inflammation and specific if the lesions have granulomas histologically. Erythema nodosum is the most common nonspecific skin manifestation, and it portends a good prognosis. Specific skin lesions have a varied clinical appearance, although often they can be distinguished by their yellow translucent character. Despite the potential variable appearance, there are common clinical presentations. Lupus pernio lesions are nodular violaceous specific skin lesions found predominantly on the face associated with scarring and a poor prognosis. Treatment of cutaneous sarcoidosis is primarily done to avoid scarring and cosmetic disfigurement. Local and systemic corticosteroids are the mainstay of treatment for the disease. Corticosteroid-sparing agents used to manage the disease include antimalarials, methotrexate, and tetracycline antibiotics. Tumor necrosis factor-alpha (TNF-alpha) antagonists such as infliximab may have a role in cutaneous sarcoidosis, especially in refractory cases that are resistant to the standard regimens.

  6. T cell reactions of Eimeria bovis primary and challenge-infected calves.

    PubMed

    Sühwold, Anke; Hermosilla, Carlos; Seeger, Torsten; Zahner, Horst; Taubert, Anja

    2010-02-01

    Eimeria bovis infections commonly have clinical impact only on young animals, as homologous reinfections generally are under immunological control. So far, the nature of the immune responses delivering protection to calves has not been investigated. In this study we therefore analysed local and peripheral proliferative T cell activities of primary and challenge-infected calves and investigated the occurrence of T cell phenotypes in the peripheral blood and in mucosal gut segments isolated either by bioptic means or by necropsies.We show that lymphocytes of E. bovis-infected calves exhibit effective, transient antigen-specific proliferative responses in the course of prepatency of primary infection but fail to react after homologous reinfection suggesting early abrogation of parasite development. Whilst in primary infection an expansion of peripheral CD4+ T cells was observed, reinfection had no effect on the proportions of CD4+, CD8+ subsets or gammadeltaTCR+ T cells. In contrast, both E. bovis primary and challenge infections had an impact on local tissue T cell distribution. Primary infection was characterised by a CD4+ T cell infiltration early in prepatency in ileum and later in colon mucosa, whereas CD8+ T cells were only found accumulating in the latter gut segment. Challenge infection led to infiltration of both CD4+ and CD8+ T cells in small intestine and large intestine segments indicating protective functions of both cell types. In contrast, infiltration of ileum and colon mucosa with gammadeltaTCR+ T cells was restricted to primary infection.

  7. High expression of the taurine transporter TauT in primary cilia of NIH3T3 fibroblasts.

    PubMed

    Christensen, Søren T; Voss, Jesper W; Teilmann, Stefan C; Lambert, Ian H

    2005-05-01

    Taurine, present in high concentrations in various mammalian cells, is essential for regulation of cell volume, cellular oxidative status as well as the cellular Ca2+ homeostasis. Cellular taurine content is a balance between active uptake through the saturable, Na(+)-dependent taurine transporter TauT, and passive release via a volume-sensitive leak pathway. Here we demonstrate that: (i) TauT localizes to the primary cilium of growth-arrested NIH3T3 fibroblasts, (ii) long-term exposure to TNF(alpha) or hypertonic sucrose medium, i.e., growth medium supplemented with 100 mM sucrose, increases ciliary TauT expression and (iii) long-term exposure to hypertonic taurine medium, i.e., growth medium supplemented with 100 mM taurine, reduces ciliary TauT expression. These results point to an important role of taurine in the regulation of physiological processes located to the primary cilium.

  8. The role of polymorphism of interleukin-2, -10, -13 and TNF-α genes in cutaneous T-cell lymphoma pathogenesis

    PubMed Central

    Olszewska, Berenika; Roszkiewicz, Jadwiga; Glen, Jolanta; Zabłotna, Monika; Ługowska-Umer, Hanna; Nowicki, Roman; Sokołowska-Wojdyło, Małgorzata

    2016-01-01

    Introduction As the pathogenesis of cutaneous T-cell lymphomas (CTCL) is not fully understood, inherited gene polymorphisms are considered to play a role in the development of lymphomas. Aim To investigate whether certain gene polymorphisms might be involved in the development of CTCL. Material and methods In the case-control study we compared the frequency of nine selected single nucleotide polymorphisms (SNP) of seven genes (rs1800587/–889 C/T of interleukin (IL)-1α, rs2069762/–330G/T) and rs2069763/+166G/T of IL-2, rs1800925/–1112 C/T of IL-13, rs1800896/–1082 A/G of IL-10, rs4073/–251 A/T of IL-8, rs5370/K198N, rs180054/–1370T/G of endothelin-1 and rs1800629/–308 G/A of TNF-α) in 43 CTCL and Polish cases using the amplification refractory mutation system polymerase chain reaction method. Results We have found that two genotypes, –330GG of IL-2 and –1112TT of IL-13 both promoter variants associated with “hypertranscription phenotype”, were over-represented in CTCL patients compared to healthy controls, and they increase the risk of malignancy development (OR = 5.82, p = 0.001 for IL-2 –330 GG, and OR = 5.67, p = 0.0024 for IL-13 –1112 TT). On the other hand, high transcription –308A allele of the TNF-α gene and –1082GG of IL-10 genotype is less frequent in lymphoma patients and has protective effects on the development of CTCL (OR = 0.45, p = 0.0466 for –308A of TNF-α, and OR = 0.35, p = 0.0329 for –1082GG of IL-10 genes). Conclusions Our results indicate that hypertranscription promoter variants of IL-2 and IL-13 genes could be estimated as the risk factor for development of CTCL, while TNF-α and IL-10 variants have a protective effect. PMID:28035219

  9. Combination of retinoid and histone deacetylase inhibitor produced an anti-tumor effect in cutaneous T-cell lymphoma by restoring tumor suppressor gene, retinoic acid receptorβ2, via histone acetylation.

    PubMed

    Kato, Yukihiko; Egusa, Chizu; Maeda, Tatsuo; Tsuboi, Ryoji

    2016-01-01

    Retinoids exert anti-proliferative, differentiative, and apoptosis-inducing effects through their receptors. Retinoic acid receptor (RAR) β2 behaves as a tumor suppressor gene, and its expression is suppressible by DNA methylation in many malignancies. We aimed to determine whether combining a retinoid, Am 80, with a histone deacetylase inhibitor, MS-275, could suppress tumor growth in a RARβ2-negative human cutaneous T cell lymphoma (CTCL) cell lines and freshly isolated primary CTCL cells, and to elucidate the epigenetic mechanism behind the phenomena. SeAx cells were implanted subcutaneously in NOD-SCID mice which were randomly divided into four groups and treated with either Am80, MS-275 by oral gavage (five days/week), or a combination of the two agents. Cell proliferation assay, methylation-specific PCR, flow cytometric analysis of cell cycle and apoptosis and chromatin immunoprecipitation assay were employed. Quantitative PCR analysis revealed that RARβ2 gene expression was restored only by this combination rather than by either of the agents singly. Restored retinoid sensitivity was observed in combining retinoid with a histone deacetylase inhibitor significantly inhibited cell growth in vitro, suppressed subcutaneously transplanted tumor growth, and prolonged survival of tumor-bearing mice in vivo by more strongly inducing apoptosis and p21 expression in CTCL cells than either agent alone. In the combination treatment, the histone H4 acetylation level at lysine 12 and 16 in the promoter region increased after restoration of RARβ2 expression although the DNA methylation of RARβ2 remained unchanged. This is the first report of histone acetylation as the primary event in the restoration of RARβ2. Inducible RARβ2 expression may serve as a reliable predictor for tumor response in patients undergoing 'epigenetic & differentiation' therapy. Copyright © 2015. Published by Elsevier Ireland Ltd.

  10. miR-122 Regulates p53/Akt Signalling and the Chemotherapy-Induced Apoptosis in Cutaneous T-Cell Lymphoma

    PubMed Central

    Manfè, Valentina; Biskup, Edyta; Rosbjerg, Anne; Kamstrup, Maria; Skov, Anne Guldhammer; Lerche, Catharina Margrethe; Lauenborg, Britt Thyssing; Ødum, Niels; Gniadecki, Robert

    2012-01-01

    Advanced cutaneous T-cell lymphoma (CTCL) is resistant to chemotherapy and presents a major area of medical need. In view of the known role of microRNAs (miRNAs) in the regulation of cellular signalling, we aimed to identify the functionally important miRNA species, which regulate apoptosis in CTCL. Using a recently established model in which apoptosis of CTCL cell lines is induced by Notch-1 inhibition by γ-secretase inhibitors (GSIs), we found that miR-122 was significantly increased in the apoptotic cells. miR-122 up-regulation was not specific for GSI-1 but was also seen during apoptosis induced by chemotherapies including doxorubicin and proteasome blockers (bortezomib, MG132). miR-122 was not expressed in quiescent T-cells, but was detectable in CTCL: in lesional skin in mycosis fungoides and in Sézary cells purified from peripheral blood. In situ hybridization results showed that miR-122 was expressed in the malignant T-cell infiltrate and increased in the advanced stage mycosis fungoides. Surprisingly, miR-122 overexpression decreased the sensitivity to the chemotherapy-induced apoptosis via a signaling circuit involving the activation of Akt and inhibition of p53. We have also shown that induction of miR-122 occurred via p53 and that p53 post-transcriptionally up-regulated miR-122. miR-122 is thus an amplifier of the antiapoptotic Akt/p53 circuit and it is conceivable that a pharmacological intervention in this pathway may provide basis for novel therapies for CTCL. PMID:22235305

  11. Graft-versus-lymphoma effect in refractory cutaneous T-cell lymphoma after reduced-intensity HLA-matched sibling allogeneic stem cell transplantation.

    PubMed

    Herbert, K E; Spencer, A; Grigg, A; Ryan, G; McCormack, C; Prince, H M

    2004-09-01

    Cutaneous T-cell lymphomas (CTCL) are rare diseases that, in their advanced stages or in transformation, have a poor prognosis. Autologous stem cell transplantation (Au-SCT) after high-dose therapy has yielded disappointing results. Allogeneic transplantation (allo-SCT) provides the potential advantage of an immune-mediated graft-versus-lymphoma (GVL) effect. Reduced-intensity allo-SCT potentially offers a GVL effect, but with diminished toxicity related to the induction regimen; however, published experience with this approach in CTCL is limited. We report a series of three patients (age 35-49) with advanced, refractory (n=2) or transformed (n=1) CTCL who underwent reduced-intensity allo-SCT in the context of active disease. All three survived the peri-transplant period and, despite later having disease relapse, all exhibited evidence of a GVL effect. Relapses of the disease were in the context of immune suppression for graft-versus-host disease (GVHD), and when immune suppression was reduced, responses were regained. A comparison is made of these results to those in a review of the published literature to date. We conclude that while a GVL can be achieved for CTCL with reduced-intensity allogeneic transplantation, the clinical benefits are short lived and novel approaches are required to obtain sustained remissions.

  12. Cutaneous (non-HIV) infections.

    PubMed

    Callahan, E F; Adal, K A; Tomecki, K J

    2000-07-01

    Cutaneous infections continue to represent a large proportion of inpatient dermatology. Though most infectious skin diseases do not warrant hospitalization, some do and can rapidly become fatal if not treated promptly. A selected group of infections are reviewed--primary cutaneous infections, exotoxin-mediated syndromes, and systemic infections--that warrant hospitalization. Dermatologists play a critical role in the synthesis of patient history and appreciation of morphologic skin disease, which, when coupled with appropriate lab tests, may help to establish a diagnosis allowing for the timely implementation of effective and targeted therapy.

  13. [Cutaneous leishmaniasis].

    PubMed

    Enk, C D; Gardlo, K; Hochberg, M; Ingber, A; Ruzicka, T

    2003-06-01

    Leishmaniasis is a vector-borne disease caused by an obligate intracellular protozoa, Leishmania, which resides in macrophages. The parasite is transmitted by an infected female sandfly. The incidence of cutaneous leishmaniasis approaches 2 million new cases per year with 90% of the cases occurring in the "Old World", while the "New World" accounts for the rest. Infection may be restricted to the skin with development of characteristic ulcers, or may affect the mucous membranes in its mucocutaneous form. The clinical diagnosis is verified by the presence of amastigotes in slit-skin smears. Therapeutic modalities include systemic treatments such as the pentavalent antimony compound sodium stibogluconate, liposomal formulations of amphotericin B, oral ketoconazole or itraconazole, as well as topical paromomycin sulphate, local heat, freezing with liquid nitrogen, or photodynamic therapy. An effective vaccine is not available.

  14. Cutaneous mucormycosis*

    PubMed Central

    Castrejón-Pérez, Ana Daniela; Welsh, Esperanza C.; Miranda, Ivett; Ocampo-Candiani, Jorge; Welsh, Oliverio

    2017-01-01

    Cutaneous mucormycosis is an emerging fungal infection caused by opportunistic fungi of the phylum Glomeromycota. It is frequent in poorly controlled diabetic patients and individuals with immunosuppression. It is usually acquired by direct inoculation through trauma. The clinical presentation is nonspecific, but an indurated plaque that rapidly evolves to necrosis is a common finding. Diagnosis should be confirmed by demonstration of the etiological agent and new molecular diagnostic tools have recently been described. It is an invasive life-threatening disease and in order to improve survival, a prompt diagnosis and multidisciplinary management should be provided. The treatment of choice is amphotericin B, but new azoles, such as posaconazole and isavuconazole, must be considered.

  15. Primary structure of tRNA-Lys of E. coli B.

    PubMed Central

    Chakraburtty, K; Steinschneider, A; Case, R V; Mehler, A H

    1975-01-01

    The primary structure of tRNALys of E. coli was determined by use of [32P]-tRNA. The sequence is pGGGUCGUUAGCUCAGDDGGDAGAGCAGUUGACUmam5-s2-UUU-t6AApsiCAAUUGm7GXCGCAGGTpsiCGAAUCCUGCACGACCCACCA. No s4-U was detected in position 8. No other lysine tRNA was detected but the existence of another species has not been ruled out. Images PMID:802509

  16. Primary cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome): part II. Prognosis, management, and future directions.

    PubMed

    Jawed, Sarah I; Myskowski, Patricia L; Horwitz, Steven; Moskowitz, Alison; Querfeld, Christiane

    2014-02-01

    Both mycosis fungoides (MF) and Sézary syndrome (SS) have a chronic, relapsing course, with patients frequently undergoing multiple, consecutive therapies. Treatment is aimed at the clearance of skin disease, the minimization of recurrence, the prevention of disease progression, and the preservation of quality of life. Other important considerations are symptom severity, including pruritus and patient age/comorbidities. In general, for limited patch and plaque disease, patients have excellent prognosis on ≥1 topical formulations, including topical corticosteroids and nitrogen mustard, with widespread patch/plaque disease often requiring phototherapy. In refractory early stage MF, transformed MF, and folliculotropic MF, a combination of skin-directed therapy plus low-dose immunomodulators (eg, interferon or bexarotene) may be effective. Patients with advanced and erythrodermic MF/SS can have profound immunosuppression, with treatments targeting tumor cells aimed for immune reconstitution. Biologic agents or targeted therapies either alone or in combination--including immunomodulators and histone-deacetylase inhibitors--are tried first, with more immunosuppressive therapies, such as alemtuzumab or chemotherapy, being generally reserved for refractory or rapidly progressive disease or extensive lymph node and metastatic involvement. Recently, an increased understanding of the pathogenesis of MF and SS with identification of important molecular markers has led to the development of new targeted therapies that are currently being explored in clinical trials in advanced MF and SS.

  17. Low-affinity CD4+ T cells are major responders in the primary immune response.

    PubMed

    Martinez, Ryan J; Andargachew, Rakieb; Martinez, Hunter A; Evavold, Brian D

    2016-12-15

    A robust primary immune response has been correlated with the precursor number of antigen-specific T cells, as identified using peptide MHCII tetramers. However, these tetramers identify only the highest-affinity T cells. Here we show the entire CD4+ T-cell repertoire, inclusive of low-affinity T cells missed by tetramers, using a T-cell receptor (TCR) signalling reporter and micropipette assay to quantify naive precursors and expanded populations. In vivo limiting dilution assays reveal hundreds more precursor T cells than previously thought, with higher-affinity tetramer-positive T cells, comprising only 5-30% of the total antigen-specific naive repertoire. Lower-affinity T cells maintain their predominance as the primary immune response progresses, with no enhancement of survival of T cells with high-affinity TCRs. These findings demonstrate that affinity for antigen does not control CD4+ T-cell entry into the primary immune response, as a diverse range in affinity is maintained from precursor through peak of T-cell expansion.

  18. Low-affinity CD4+ T cells are major responders in the primary immune response

    PubMed Central

    Martinez, Ryan J.; Andargachew, Rakieb; Martinez, Hunter A.; Evavold, Brian D.

    2016-01-01

    A robust primary immune response has been correlated with the precursor number of antigen-specific T cells, as identified using peptide MHCII tetramers. However, these tetramers identify only the highest-affinity T cells. Here we show the entire CD4+ T-cell repertoire, inclusive of low-affinity T cells missed by tetramers, using a T-cell receptor (TCR) signalling reporter and micropipette assay to quantify naive precursors and expanded populations. In vivo limiting dilution assays reveal hundreds more precursor T cells than previously thought, with higher-affinity tetramer-positive T cells, comprising only 5–30% of the total antigen-specific naive repertoire. Lower-affinity T cells maintain their predominance as the primary immune response progresses, with no enhancement of survival of T cells with high-affinity TCRs. These findings demonstrate that affinity for antigen does not control CD4+ T-cell entry into the primary immune response, as a diverse range in affinity is maintained from precursor through peak of T-cell expansion. PMID:27976744

  19. Temporal Dynamics of CD8+ T Cell Effector Responses during Primary HIV Infection

    PubMed Central

    Demers, Korey R.; Makedonas, George; Buggert, Marcus; Eller, Michael A.; Ratcliffe, Sarah J.; Goonetilleke, Nilu; Li, Chris K.; Eller, Leigh Anne; Rono, Kathleen; Maganga, Lucas; Nitayaphan, Sorachai; Kibuuka, Hannah; Routy, Jean-Pierre; Slifka, Mark K.; Haynes, Barton F.; Bernard, Nicole F.; Robb, Merlin L.; Betts, Michael R.

    2016-01-01

    The loss of HIV-specific CD8+ T cell cytolytic function is a primary factor underlying progressive HIV infection, but whether HIV-specific CD8+ T cells initially possess cytolytic effector capacity, and when and why this may be lost during infection, is unclear. Here, we assessed CD8+ T cell functional evolution from primary to chronic HIV infection. We observed a profound expansion of perforin+ CD8+ T cells immediately following HIV infection that quickly waned after acute viremia resolution. Selective expression of the effector-associated transcription factors T-bet and eomesodermin in cytokine-producing HIV-specific CD8+ T cells differentiated HIV-specific from bulk memory CD8+ T cell effector expansion. As infection progressed expression of perforin was maintained in HIV-specific CD8+ T cells with high levels of T-bet, but not necessarily in the population of T-betLo HIV-specific CD8+ T cells that expand as infection progresses. Together, these data demonstrate that while HIV-specific CD8+ T cells in acute HIV infection initially possess cytolytic potential, progressive transcriptional dysregulation leads to the reduced CD8+ T cell perforin expression characteristic of chronic HIV infection. PMID:27486665

  20. Commensal bacteria and cutaneous immunity.

    PubMed

    Nakamizo, Satoshi; Egawa, Gyohei; Honda, Tetsuya; Nakajima, Saeko; Belkaid, Yasmine; Kabashima, Kenji

    2015-01-01

    The skin is the human body's largest organ and is home to a diverse and complex variety of innate and adaptive immune functions that protect against pathogenic invasion. Recent studies have demonstrated that cutaneous commensal bacteria modulated the host immune system. For example, Staphylococcus epidermidis, a skin commensal bacterium, has been demonstrated to induce cutaneous interferon (IFN)-γ- and interleukin (IL)-17A-producing T cells. In addition, cutaneous microbiota changes occur in the chronic inflammatory skin disorders, such as atopic dermatitis, and may influence the activity of skin diseases. In this article, we will review the recent findings related to the interactions of the commensal bacteria with skin homeostasis and discuss the role of the dysbiosis of these bacteria in the pathogenesis of skin diseases.

  1. Cutaneous melanoma of the breast.

    PubMed

    Papachristou, D N; Kinne, D W; Rosen, P P; Ashikari, R; Fortner, J G

    1979-03-01

    A study of 115 cutaneous melanomas of the breast demonstrated that these neoplasms follow different metastatic patterns than do primary carcinomas of the breast and require a different therapuetic approach. Lesions located below a 3 cm from the clavicle metastasized exclusively to the axillary nodes regardless of location. None of 19 internal mammary node chains examined histologically contained tumor deposits. Microstaging of the primary lesion correlated closely with prognosis and lymph node metastasis. Treatment by mastectomy (radical, modified, extended radical) offered no advantage over local excision of the primary plus axillary dissection. The latter procedure is recommended for all cutaneous melanomas of the breast which require node dissection. Mastectomy is not indicated unless the breast is in the field of wide local excision. Internal mammary node dissections are not indicated.

  2. Cutaneous mucormycosis.

    PubMed

    Skiada, Anna; Petrikkos, George

    2013-01-01

    Mucormycosis is an invasive fungal infection caused by fungi of the order Mucorales, mainly affecting immunocompromised patients. Cutaneous mucormycosis is the third most common clinical form of the disease, after pulmonary and rhino-cerebral. The usual factors predisposing to this infection are hematological malignancies and diabetes mellitus, but a significant proportion of patients are immunocompetent. The agents of mucormycosis are ubiquitous in nature and are transmitted to the skin by direct inoculation, as a result of various types of trauma. These include needle sticks, stings and bites by animals, motor vehicle accidents, natural disasters, and burn injuries. The typical presentation of mucormycosis is the necrotic eschar, but it can present with various other signs. The infection can be locally invasive and penetrate into the adjacent fat, muscle, fascia, and bone, or become disseminated. Diagnosis is difficult because of the nonspecific findings of mucormycosis. Biopsy and culture should be performed. The treatment of mucormycosis is multimodal and consists of surgical debridement, use of antifungal drugs (amphotericin B and posaconazole), and reversal of underlying risk factors, when possible. Mortality rates, although lower than in other forms of the disease, are significant, ranging from 4% to 10% when the infection is localized.

  3. Extracorporeal photopheresis for the treatment of erythrodermic cutaneous T-cell lymphoma: a single center clinical experience with long-term follow-up data and a brief overview of the literature.

    PubMed

    Quaglino, Pietro; Knobler, Robert; Fierro, Maria T; Savoia, Paola; Marra, Elena; Fava, Paolo; Bernengo, Maria G

    2013-11-01

    Extracorporeal photopheresis (ECP) is a therapeutic procedure in which leukapheresed peripheral blood mononuclear cells are exposed to ultraviolet A in the presence of the photosensitizer 8-methoxypsoralen and then reinfused. Several guidelines recommend ECP as a treatment of choice in erythrodermic primary cutaneous T-cell lymphomas (E-CTCL). However, the level of evidence is low due to the rarity of this disease and the lack of randomized controlled trials. We performed a review of the English literature, restricting our analysis to studies including erythrodermic patients and more than 10 cases. Based on these criteria, we identified 28 studies, with a total of 407 patients. The median response rate in erythrodermic patients was 63% (range 31-86%), with a complete response rate ranging between 0 and 62% (median 20%). In our experience, we treated 51 patients with E-CTCL since 1992. A clinical response was obtained in 32 of 51 patients (63%), with a 16% complete response rate. The median time for response induction was eight months (range: 1-23). The median response duration was 22.4 months (range six months to 11 years). The treatment was generally well tolerated without systemic toxicities grade III-IV. The pretreatment parameters significantly associated with a higher likelihood to obtain a clinical response were the B-score in the peripheral blood, CD4/CD8 ratio, and amount of circulating CD3+CD8+ cells. Literature data together with our personal experience clearly support the clinical activity and tolerability of ECP in patients with E-CTCL. Prospective controlled clinical trials are strongly recommended to better document the evidence.

  4. A dominant inhibitory mutant of the type II transforming growth factor beta receptor in the malignant progression of a cutaneous T-cell lymphoma.

    PubMed Central

    Knaus, P I; Lindemann, D; DeCoteau, J F; Perlman, R; Yankelev, H; Hille, M; Kadin, M E; Lodish, H F

    1996-01-01

    In many cancers, inactivating mutations in both alleles of the transforming growth factor beta (TGF-beta) type 11 receptor (TbetaRII) gene occur and correlate with loss of sensitivity to TGF-beta. Here we describe a novel mechanism for loss of sensitivity to growth inhibition by TGF-beta in tumor development. Mac-1 cells, isolated from the blood of a patient with an indolent form of cutaneous T-cell lymphoma, express wild-type TbetaRII and are sensitive to TGF-beta. Mac-2A cells, clonally related to Mac-1 and isolated from a skin nodule of the same patient at a later, clinically aggressive stage of lymphoma, are resistant to TGF-beta. They express both the wild-type TbetaRII and a receptor with a single point mutation (Asp-404-Gly [D404G]) in the kinase domain (D404G-->TbetaRII); no TbetaRI or TbetaRII is found on the plasma membrane, suggesting that D404G-TbetaRII dominantly inhibits the function of the wild-type receptor by inhibiting its appearance on the plasma membrane. Indeed, inducible expression, under control of a tetracycline-regulated promoter, of D404G-TbetaRII in TGF-beta- sensitive Mac-1 cells as well as in Hep3B hepatoma cells results in resistance to TGF-beta and disappearance of cell surface TbetaRI and TbetaRII. Overexpression of wild-type TbetaRII in Mac-2A cells restores cell surface TbetaRI and TbetaRH and sensitivity to TGF-beta. The ability of the D404G-TbetaRH to dominantly inhibit function of wild-type TGF-beta receptors represents a new mechanism for loss of sensitivity to the growth-inhibitory functions of TGF-beta in tumor development. PMID:8668164

  5. 'We're all carrying a burden that we're not sharing': a qualitative study of the impact of cutaneous T-cell lymphoma on the family.

    PubMed

    Selman, L E; Beynon, T; Radcliffe, E; Whittaker, S; Orlowska, D; Child, F; Harding, R

    2015-06-01

    Cutaneous T-cell lymphoma (CTCL) is a rare, progressive cancer that can be life limiting and highly disfiguring. Patients with CTCL experience poor quality of life; however, there is little published about the experiences of their families. To describe the impact of CTCL on family members and how they cope and adjust, to inform support services. Semistructured qualitative interviews were conducted with adult informal caregivers of patients with CTCL recruited via a supraregional CTCL clinic. Interviews explored the history of each patient's illness, the impact of CTCL on the patient and the family, and views about family support. Data were analysed thematically using the Family Adjustment and Adaptation Response model as an interpretative framework. Fourteen caregivers were interviewed (11 spouses, one friend, two daughters; 10 women, four men; all white British; aged 39-85 years). Three key themes emerged: (i) demands of CTCL (the disease, caregiving, financial impact, physical and emotional intimacy); (ii) family capabilities (family support, information, healthcare provider support, other coping strategies); and (iii) adjustment and adaptation (acceptance, changes in patient-caregiver relationship and family dynamics). CTCL was central in many aspects of caregivers' lives, particularly relationships, communication and intimacy. Our findings demonstrate the multiple demands that CTCL places on caregivers, the capabilities and resources they draw upon to cope, and the significant impact of CTCL on the family. To support families and patients, easily accessible services are needed that include the family in the unit of care, provide support and information, and understand the process of family adjustment and adaptation. © 2014 British Association of Dermatologists.

  6. T-cell subpopulations, expression of interleukin-2 receptor, and production of interleukin-2 and gamma interferon in human American cutaneous leishmaniasis.

    PubMed Central

    Castes, M; Cabrera, M; Trujillo, D; Convit, J

    1988-01-01

    Leukocyte subpopulations, the expression of the interleukin-2 (IL-2) receptor, and the production of IL-2 and gamma interferon (IFN-gamma) were studied in the peripheral blood mononuclear cells of American cutaneous leishmaniasis patients that had been stimulated in vitro with either leishmanial antigen or mitogen (phytohemagglutinin M). The 75 patients examined were classified as having either the localized (LCL; 66 patients), mucocutaneous (MCL; 5 patients), or the rare diffuse (DCL; 4 patients) form of the disease. Patients with DCL, who are characterized by their defective cell-mediated immune response to leishmanial antigen, failed to express the IL-2 receptor and did not produce IFN-gamma when exposed to the antigen but did so when stimulated by phytohemagglutinin M. Both LCL and MCL patients showed strong proliferative responses to leishmanial antigen; these were by far the greatest in MCL patients. Both groups had significantly increased IL-2 receptor expression and IFN-gamma production after exposure to either antigen or mitogen, and these were highest in the MCL patients. Concerning the leukocyte subpopulations evaluated (CD2, CD4, CD8, CD20, MO2), the most significant findings were a decrease of both CD4+ cells and the CD4/CD8 ratio in MCL patients compared with the other groups. Considering IL-2 production, in response to phytohemagglutinin M both MCL and LCL patients showed amounts of IL-2 comparable to those of the controls. Our results help explain the anergy of T cells from DCL patients to leishmanial antigen, which could lead to a defective production of IFN-gamma and possibly contribute to their incapacity to kill the Leishmania parasite. Concerning MCL patients, the significantly increased expression of IL-2 receptor, decreased expression of the CD4 (helper-inducer of suppression) phenotype, and elevated IFV-gamma production might partially explains the state of hypersensitivity and mucosal damage exhibited by these patients. PMID:3133391

  7. Atopy, IgE and eosinophilic cationic protein concentration, specific IgE positivity, eosinophil count in cutaneous T Cell lymphoma.

    PubMed

    Kural, Yasemin Balsever; Su, Ozlem; Onsun, Nahide; Uras, Ahmet Riza

    2010-04-01

    Even though several case studies have reported a relationship between Cutaneous T Cell Lymphoma (CTCL) and atopic diathesis, this association is still controversial. The aim of this study was to investigate the actual presence of atopic status in CTCL patients. A total of 78 patients with both clinical and histological features typical of CTCL and 77 control cases from our outpatient dermatology clinic were included in this study. After initial evaluation and staging, all patients were investigated for history of atopic disease, serum total IgE and eosinophil cationic protein concentration (ECP), eosinophil count, serum specific IgE, and skin prick test positivity. Personal atopy in CTCL group was 23,1% (n = 18) and familial atopy was 9.0% (n = 7) whereas in the control group, these values were 11.7% (n = 9) and 7.8% (n = 6), respectively. There was no statistically significant difference, however, the number of atopic patients were higher in CTCL group than the control group (p = 0.151). Serum total IgE levels were significantly increased in patients with CTCL when compared to control group (p = 0.04). Serum specific IgE panel and prick test positivity between patients and controls were significantly different, respectively (p = 0. 03) (p = 0. 00). Eosinophil counts and ECP levels were not significantly different, respectively (p = 0.10) (p = 0.885). In high stages of CTCL, patients were found to have elevated IgE, ECP levels and eosinophil count. These results were statistically significant (p = 0.011) (p = 0.009) (p = 0.007). Eventhough the number of patients with atopy in the CTCL group was higher than the control cases, there was no significant different. On the other hand high levels of serum IgE, elevated eosinophil count and specific IgE positivity may be found in CTCL patients with or without atopic disease, especially with high stages.

  8. Comprehensive analysis of cutaneous T-cell lymphoma (CTCL) incidence and mortality in Canada reveals changing trends and geographic clustering for this malignancy.

    PubMed

    Ghazawi, Feras M; Netchiporouk, Elena; Rahme, Elham; Tsang, Matthew; Moreau, Linda; Glassman, Steven; Provost, Nathalie; Gilbert, Martin; Jean, Sara-Elizabeth; Pehr, Kevin; Sasseville, Denis; Litvinov, Ivan V

    2017-09-15

    Previous reports of geographic clustering of cutaneous T-cell lymphoma (CTCL) in Texas, Pittsburgh, and Sweden as well as the occurrence of CTCL in married couples and family members raise a possibility of the existence of an external and potentially preventable trigger(s) for this rare skin cancer. The authors studied CTCL incidence and mortality in Canada using 3 distinct population-based cancer databases. Data on patients' sex, age at the time of diagnosis, subtype of CTCL malignancy, reporting province, city, and postal code were analyzed. CTCL cases were mapped across Canada using geographic information systems software. In total, 6685 patients with CTCL were identified in Canada during 1992 through 2010 (CTCL incidence rate, 11.32 cases per million individuals per year), of which 58% were males. The mean age at diagnosis was 59.4 ± 21.5 years. Geographic analysis of patients revealed increased CTCL incidence on the provincial and city levels in several eastern provinces and in Manitoba. An analysis according to postal codes (Forward Sortation Area [FSA]) identified select communities in which several high-incidence FSAs were contiguous or adjacent. Several of these FSAs were located in industrial regions of Canadian cities. Conversely, 3 of 8 low-incidence FSAs were clustered in Ottawa, Ontario, which has very little industrial presence. An analysis of CTCL mortality in Canada corroborated the current incidence findings. The current results provide a comprehensive analysis of CTCL burden in Canada and highlight several important areas of geographic case clustering. These findings argue that industrial exposures may play an important role in promoting CTCL pathogenesis. Cancer 2017;123:3550-67. © 2017 American Cancer Society. © 2017 American Cancer Society.

  9. Cutaneous vasculitis: diagnosis and management.

    PubMed

    Carlson, J Andrew; Cavaliere, L Frank; Grant-Kels, Jane M

    2006-01-01

    Vasculitis is histologically defined as inflammatory cell infiltration and destruction of blood vessels. Vasculitis is classified as primary (idiopathic, eg, cutaneous leukocytoclastic angiitis, Wegener's granulomatosis) or secondary, a manifestation of connective tissue diseases, infections, adverse drug eruptions, or a paraneoplastic phenomenon. Cutaneous vasculitis, manifested as urticaria, purpura, hemorrhagic vesicles, ulcers, nodules, livedo, infarcts, or digital gangrene, is a frequent and often significant component of many systemic vasculitic syndromes such as lupus or rheumatoid vasculitis and antineutrophil cytoplasmic antibody-associated primary vasculitic syndromes such as Churg-Strauss syndrome. In most instances, cutaneous vasculitis represents a self-limited, single-episode phenomenon, the treatment of which consists of general measures such as leg elevation, warming, avoidance of standing, cold temperatures and tight fitting clothing, and therapy with antihistamines, aspirin, or nonsteroidal anti-inflammatory drugs. More extensive therapy is indicated for symptomatic, recurrent, extensive, and persistent skin disease or coexistence of systemic disease. For mild recurrent or persistent disease, colchicine and dapsone are first-choice agents. Severe cutaneous and systemic disease requires more potent immunosuppression (prednisone plus azathioprine, methotrexate, cyclophosphamide, cyclosporine, or mycophenolate mofetil). In cases of refractory vasculitis, plasmapheresis and intravenous immunoglobulin are viable considerations. The new biologic therapies that work via cytokine blockade or lymphocyte depletion such as tumor alpha inhibitor infliximab and the anti-B-cell antibody rituximab, respectively, are showing benefit in certain settings such as Wegener's granulomatosis, antineutrophil cytoplasmic antibody-associated vasculitis, Behçet's disease, and cryoglobulinemic vasculitis.

  10. Persistent parasites and immunologic memory in cutaneous leishmaniasis: implications for vaccine designs and vaccination strategies.

    PubMed

    Okwor, Ifeoma; Uzonna, Jude

    2008-01-01

    Despite a plethora of publications on the murine model of cutaneous leishmaniasis and their contribution to our understanding of the factors that regulate the development of CD4+ T cell immunity in vivo, there is still no effective vaccine against the human disease. While recovery from natural or experimental infection with Leishmania major, the causative agent of human cutaneous leishmaniasis, results in persistence of parasites at the primary infection site and the development of long-lasting immunity to reinfection, vaccination with killed parasites or recombinant proteins induces only short-term protection. The reasons for the difference in protective immunity following recovery from live infection and vaccination with heat-killed parasites are not known. This may in part be related to persistence of live parasites following healing of primary cutaneous lesions, because complete clearance of parasites leads to rapid loss of infection-induced immunity. Recent reports indicate that in addition to persistent parasites, IL-10-producing natural regulatory T cells may also play critical roles in the maintenance and loss of infection-induced immunity. This review focuses on current understanding of the factors that regulate the development, maintenance and loss of anti-Leishmania memory responses and highlights the role of persistent parasites and regulatory T cells in this process. Understanding these factors is crucial for designing effective vaccines and vaccination strategies against cutaneous leishmaniasis.

  11. Foxp3-dependent transformation of human primary CD4+ T lymphocytes by the retroviral protein tax.

    PubMed

    Chen, Li; Liu, Dan; Zhang, Yang; Zhang, Huan; Cheng, Hua

    2015-10-23

    The retroviral Tax proteins of human T cell leukemia virus type 1 and 2 (HTLV-1 and -2) are highly homologous viral transactivators. Both viral proteins can immortalize human primary CD4+ memory T cells, but when expressed alone they rarely transform T cells. In the present study, we found that the Tax proteins displayed a differential ability to immortalize human CD4+Foxp3+ T cells with characteristic expression of CTLA-4 and GITR. Because epidermal growth factor receptor (EGFR) was reportedly expressed and activated in a subset of CD4+Foxp3+ T cells, we introduced an activated EGFR into Tax-immortalized CD4+Foxp3+ T cells. We observed that these modified cells were grown independently of exogenous IL-2, correlating with a T cell transformation phenotype. In Tax-immortalized CD4+Foxp3- T cells, ectopic expression of Foxp3 was a prerequisite for Tax transformation of T cells. Accordingly, treatment of the transformed T cells with erlotinib, a selective inhibitor of EGFR, induced degradation of EGFR in lysosome, consequently causing T cell growth inhibition. Further, we identified autophagy as a crucial cellular survival pathway for the transformed T cells. Silencing key autophagy molecules including Beclin1, Atg5 and PI3 kinase class III (PI3KC3) resulted in drastic impairment of T cell growth. Our data, therefore, unveiled a previously unidentified role of Foxp3 in T cell transformation, providing a molecular basis for HTLV-1 transformation of CD4+Foxp3+ T cells.

  12. Demonstration of antibodies to human T-cell lymphotropic virus-I tax in patients with the cutaneous T-cell lymphoma, mycosis fungoides, who are seronegative for antibodies to the structural proteins of the virus.

    PubMed

    Pancake, B A; Wassef, E H; Zucker-Franklin, D

    1996-10-15

    Although most patients with the cutaneous T-cell lymphoma, mycosis fungoides (MF), are seronegative for human T-cell lymphotropic virus-I or -II (HTLV-I/II) when tested by assays that measure only antibodies to the viral structural proteins, the majority of such patients harbor HTLV-I-related pol and tax proviral sequences that encode proteins not included in routinely used serologic tests. Tax mRNA has also been detected in their peripheral blood mononuclear cells (PBMC). Therefore, it seemed possible that these patients have antibodies to the tax protein. To investigate this, enzyme-linked immunosorbent assays (ELI-SAs) and Western blot assays were set up, using as antigens the full-length HTLV-I tax cloned from the prototypic HTLV-I-infected cell line, C91PL, and from PBMC of a MF patient, as well as a synthetic peptide made to the carboxy-terminal 20 amino acids of tax-I. Of 60 MF patients whose PBMC were shown to be positive for tax proviral DNA and mRNA, 50 (83%) were shown to have tax antibodies. The antigen derived from the MF patient was most useful in detecting such antibodies. These results demonstrate the need for including other HTLV-related antigens in addition to gag and env in serologic tests used to identify HTLV-infected individuals. The findings underscore the fact that individuals considered seronegative on the basis of currently used tests can be infected with HTLV.

  13. Reduction of CD147 surface expression on primary T cells leads to enhanced cell proliferation.

    PubMed

    Biegler, Brian; Kasinrerk, Watchara

    2012-12-01

    CD147 is a ubiquitously expressed membrane glycoprotein that has numerous functional associations in health and disease. However, the molecular mechanisms by which CD147 participates in these processes are unclear. Establishing physiologically relevant silencing of CD147 in primary T cells could provide clues essential for elucidating some aspects of CD147 biology. To date, achieving the knockdown of CD147 in primary T cells has remained elusive. Utilizing RNA interference and the Nucleofector transfection system, we were able to reduce the expression of CD147 in primary T cells. Comparison of basic functions, such as proliferation and CD25 expression, were then made between control populations and populations with reduced expression. Up-regulation of CD147 was found upon T-cell activation, indicating a role in T-cell responses. To better understand the possible importance of this up-regulation, we knocked down the expression of CD147 using RNA interference. When compared to control populations the CD147 knockdown populations exhibited increased proliferation. This alteration of cell proliferation, however, was not linked to a change in CD25 expression. We achieved reduction of CD147 surface expression in primary T cells by siRNA-mediated gene silencing. Our results point to CD147 having a possible negative regulatory role in T cell-mediated immune responses.

  14. Gibbon ape leukemia virus poorly replicates in primary human T lymphocytes: implications for safety testing of primary human T lymphocytes transduced with GALV-pseudotyped vectors.

    PubMed

    Lamers, Cor H J; Willemsen, Ralph A; van Elzakker, Pascal M M L; Gratama, Jan Willem; Debets, Reno

    2009-04-01

    The Food and Drug Administration/Center for Biologics Evaluation and Research has defined that for retroviral gene therapy, the vector-producing cell, the vector preparation, and the ex vivo gene-transduced cells have to be tested for absence of replication-competent retrovirus (RCR) if the transduced cells are cultured for >4 days. We assessed the sensitivity of the "extended PG4(S+L-) assay" to detect gibbon ape leukemia virus (GALV) RCR, and applied this assay to measure GALV RCR spread in retrovirally transduced T cells. To this end, T cells were expanded for 12 days after transduction with a GALV-envelope pseudotyped retroviral vector expressing single chain variable fragment (anticarbonic anhydrase IX) in presence or absence of GALV RCR. Results showed that: (1) the "extended PG4(S+L-) assay" detects 1 focus-forming unit (ffu) GALV RCR and thus is applicable and sufficiently sensitive to screen human T-cell cultures for absence of infectious GALV RCR; (2) although GALV RCR infect human T cells, it very poorly replicate in T cells; (3) GALV RCR, when present at low levels immediately upon gene transduction (ie, 100 ffu/20x10 T cells in 100 mL), did not spread during a 12-day T-cell culture at clinical scale. Our observation that GALV RCR poorly spreads in primary human T-cell cultures questions the relevance of testing T-cell transductants for RCR on top of testing the vector-producing cells and the clinical vector batch for RCR and warrants evaluation of the current policy for safety testing of ex vivo retrovirally transduced T lymphocytes for GALV RCR.

  15. Cutaneous aspergillosis in patients with haematological malignancies.

    PubMed

    D'Antonio, D; Pagano, L; Girmenia, C; Parruti, G; Mele, L; Candoni, A; Ricci, P; Martino, P

    2000-05-01

    The aim of the present study was to evaluate skin infections caused by Aspergillus in patients with haematological malignancies. Fifteen cases of cutaneous aspergillosis are reported, 12 of which occurred among 4448 consecutive patients with acute leukaemia. Cutaneous involvement occurred in 4% of patients with documented Aspergillus infection. Primary cutaneous aspergillosis was diagnosed in five cases. Infection was fatal in 11 of 15 cases; the absence of additional sites of infection other than cutis at presentation appeared to be the only factor related to a favourable outcome.

  16. Serial High-Sensitivity Troponin T in Post-Primary Angioplasty Exercise Test

    PubMed Central

    Vaz, Humberto Andres; Vanz, Ana Paula; Castro, Iran

    2016-01-01

    Background The kinetics of high-sensitivity troponin T (hscTnT) release should be studied in different situations, including functional tests with transient ischemic abnormalities. Objective To evaluate the release of hscTnT by serial measurements after exercise testing (ET), and to correlate hscTnT elevations with abnormalities suggestive of ischemia. Methods Patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary angioplasty were referred for ET 3 months after infarction. Blood samples were collected to measure basal hscTnT immediately before (TnT0h), 2 (TnT2h), 5 (TnT5h), and 8 hours (TnT8h) after ET. The outcomes were peak hscTnT, TnT5h/TnT0h ratio, and the area under the blood concentration-time curve (AUC) for hscTnT levels. Log-transformation was performed on hscTnT values, and comparisons were assessed with the geometric mean ratio, along with their 95% confidence intervals. Statistical significance was assessed by analysis of covariance with no adjustment, and then, adjusted for TnT0h, age and sex, followed by additional variables (metabolic equivalents, maximum heart rate achieved, anterior wall STEMI, and creatinine clearance). Results This study included 95 patients. The highest geometric means were observed at 5 hours (TnT5h). After adjustments, peak hscTnT, TnT5h/TnT0h and AUC were 59% (p = 0.002), 59% (p = 0.003) and 45% (p = 0.003) higher, respectively, in patients with an abnormal ET as compared to those with normal tests. Conclusion Higher elevations of hscTnT may occur after an abnormal ET as compared to a normal ET in patients with STEMI. PMID:26959404

  17. Primary Cytomegalovirus Infection Significantly Impacts Circulating T Cells in Kidney Transplant Recipients.

    PubMed

    Meijers, R W J; Litjens, N H R; Hesselink, D A; Langerak, A W; Baan, C C; Betjes, M G H

    2015-12-01

    Cytomegalovirus (CMV) infection profoundly affects the T cell compartment and is associated with alterations in T cell aging parameters and generation of cytotoxic CD4(+) CD28null T cells. Hence, the effect of a primary CMV infection post-kidney transplantation (KT) on the peripheral T cell compartment was examined. As aging parameters, we determined the T cell differentiation status, T cell receptor excision circle (TREC) content, CD31(+) naïve T cell numbers and relative telomere length (RTL) pre-KT and 12 months post-KT. CMV-seronegative KT recipients, receiving a kidney from a CMV-seropositive donor (D+/R-) were compared to D+/R+ KT recipients. Eleven out of the 22 D+/R- KT recipients had CMV viremia post-KT. They developed CMV-specific CD4(+) and CD8(+) T cells and their T cell compartment shifted towards a more differentiated memory phenotype with expansion of CD4(+) CD28null and CD8(+) CD28null cells. One year post-KT, the CD8(+) T cell count was almost doubled compared to nonviremic D+/R- and D+/R+ KT recipients. In addition, the RTL of the CD8(+) T cell was significantly lower and both the TREC content and CD31(+) naïve T cell numbers significantly decreased. Moreover, primary CMV infection was associated with a negative impact on glomerular filtration rate. In conclusion, primary CMV infection has a substantial impact on the number and phenotype of peripheral T cells and may negatively affect renal allograft function. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  18. Peripheral stellate telangiectasias: a clinical-dermoscopic clue for diganosing cutaneous melanoma metastases.

    PubMed

    Julian, Yamina; Argenziano, Giuseppe; Moscarella, Elvira; de Paula Ramos Castro, Raquel; Longo, Caterina; Abeldaño, Alejandra; Zalaudek, Iris

    2012-12-31

    The clinical and dermoscopic diagnosis of cutaneous melanoma metastases may be challenging especially in patients with unknown primary melanoma. We observed repetitive dermoscopic patterns of peripheral stellate telangiectasias in cutaneous melanoma metastases from 3 patients, of whom 2 had an unknown primary melanoma. Stellate telangiectasias surrounding bluish to purple or red nodules with recent onset may represent a clue for cutaneous melanoma metastases.

  19. Unusual presentation of primary T-cell lymphoblastic lymphoma: description of two cases.

    PubMed

    Ambrosio, Maria R; Onorati, Monica; Rocca, Bruno J; Ginori, Alessandro; Lobello, Giuseppe; Petracco, Guido; Videtta, Alessandro Davide; Di Nuovo, Franca; Santopietro, Rosa; Lazzi, Stefano

    2014-06-20

    T-cell lymphoblastic lymphoma comprises approximately 85-90% of all lymphoblastic lymphomas. It often arises as a mediastinal mass, and with bone marrow involvement. Presentation at other sites without nodal or mediastinal localization is uncommon. We describe clinical, histologic, immunohistochemical, and molecular features of two cases of primary T-cell lymphoblastic lymphoma arising respectively in uterine corpus and testis. The tumors were composed by medium to large cells, exhibiting a diffuse pattern of growth but sometimes forming indian files or pseudo-rosettes. The neoplastic cells strongly expressed TdT and T-cell markers in both uterine corpus and testis. However, the testis case also showed aberrant expression of B-cell markers, thus molecular biology was necessary to achieve a final diagnosis. T-cell receptor gene rearrangement analysis identified a T-cell origin. To the best of our knowledge, only one doubtful previous case of primary uterine T-cell lymphoblastic lymphoma and no previous cases of primary testicular T-cell lymphoblastic lymphoma have been reported. Due to the morphology of neoplastic cells, a challenging differential diagnosis with all the tumors belonging to the so-called small round blue cell tumor category is mandatory. In ambiguous lineage cases, molecular biology may represent an adequate tool to confirm diagnosis. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1559880973128230.

  20. Cutaneous necrotizing vasculitis. Relation to systemic disease.

    PubMed

    Lotti, T M; Comacchi, C; Ghersetich, I

    1999-01-01

    Cutaneous necrotizing vasculitis (CNV) is a complex multisystem disease generally involving the skin and mucous membranes, often accompanied by renal, gastrointestinal, pericardial, neurological, and articular signs and symptoms. CNV may be idiopatical or occur in association with a drug, infection, or underlying disease. CNV has been shown in patients with chronic infections (viral, bacterial, protozoa, helminthic), serum sickness, a variety of collagen vascular diseases (systemic lupus erythematous, Sjögren's syndrome, rheumatoid arthritis, Behçet's disease) hyperglobulinemic states, cryoglobulinemia, bowel bypass syndrome, ulcerative colitis, cystic fibrosis, primary biliary cirrhosis and HIV infection. Association with malignancies is not frequent. Lymphoproliferative disorders (Hodgkin's disease, mycosis fungoides, lymphosarcoma, adult T-cell leukemia, multiple mieloma) and solid tumors (lung cancer, colon carcinoma, renal, prostate, head and neck cancer and breast cancer) may be associated with CNV. Whenever possible, treatment is directed at the elimination of the cause. In other cases after adequate laboratory screening local and systemic therapy are recommended.

  1. T Regulatory and T Helper 17 Cells in Primary Sjögren's Syndrome: Facts and Perspectives

    PubMed Central

    Alunno, Alessia; Carubbi, Francesco; Bistoni, Onelia; Caterbi, Sara; Bartoloni, Elena; Mirabelli, Giulia; Cannarile, Francesca; Cipriani, Paola; Giacomelli, Roberto; Gerli, Roberto

    2015-01-01

    Historically, primary Sjögren's syndrome (pSS) was thought to be a T helper (h) 1 driven disease due to the predominance of CD4+T lymphocytes and their products in target organs and peripheral blood of patients. In the last decades, the identification of a number of T cell subsets, including Th17, T regulatory (Treg), and follicular helper T cells, challenged this long-standing paradigm and prompted to identify their role in pSS pathogenesis. In addition the impact of abnormal proinflammatory cytokine production, such as IL-6, IL-17, IL-22, and IL-23, has also attracted considerable attention. However, although several studies have been carried out in experimental models and patients with pSS, many aspects concerning the role of Treg cells and IL-17/Th17 cell system in pSS pathogenesis are not fully elucidated. In particular, the role played by different IL-17-producing T cell subsets as well as the effects of pharmacological therapies on Treg/Th17 cell balance represents an intriguing issue. The aim of this review article is to provide an overview of current knowledge on Treg cells and IL-17-producing T cells in pSS pathogenesis. We believe that these insights into pSS pathogenesis may provide the basis for successful therapeutic intervention in this disease. PMID:26060357

  2. Cutaneous innate immune sensing of Toll-like receptor 2-6 ligands suppresses T cell immunity by inducing myeloid-derived suppressor cells.

    PubMed

    Skabytska, Yuliya; Wölbing, Florian; Günther, Claudia; Köberle, Martin; Kaesler, Susanne; Chen, Ko-Ming; Guenova, Emmanuella; Demircioglu, Doruk; Kempf, Wolfgang E; Volz, Thomas; Rammensee, Hans-Georg; Schaller, Martin; Röcken, Martin; Götz, Friedrich; Biedermann, Tilo

    2014-11-20

    Skin is constantly exposed to bacteria and antigens, and cutaneous innate immune sensing orchestrates adaptive immune responses. In its absence, skin pathogens can expand, entering deeper tissues and leading to life-threatening infectious diseases. To characterize skin-driven immunity better, we applied living bacteria, defined lipopeptides, and antigens cutaneously. We found suppression of immune responses due to cutaneous infection with Gram-positive S. aureus, which was based on bacterial lipopeptides. Skin exposure to Toll-like receptor (TLR)2-6-binding lipopeptides, but not TLR2-1-binding lipopeptides, potently suppressed immune responses through induction of Gr1(+)CD11b(+) myeloid-derived suppressor cells (MDSCs). Investigating human atopic dermatitis, in which Gram-positive bacteria accumulate, we detected high MDSC amounts in blood and skin. TLR2 activation in skin resident cells triggered interleukin-6 (IL-6), which induced suppressive MDSCs, which are then recruited to the skin suppressing T cell-mediated recall responses such as dermatitis. Thus, cutaneous bacteria can negatively regulate skin-driven immune responses by inducing MDSCs via TLR2-6 activation.

  3. Exposure to zidovudine adversely affects mitochondrial turnover in primary T cells.

    PubMed

    Wallace, Zoë R; Sanderson, Sharon; Simon, Anna Katarina; Dorrell, Lucy

    2016-09-01

    Zidovudine (ZDV) is a widely used component of antiretroviral therapy (ART) in resource-limited settings, despite its known adverse effects, which include mitochondrial toxicity in muscle, liver and adipose tissue. It has also been associated with impaired immunological recovery. We hypothesised that ZDV might impair mitochondrial health and survival of primary T cells. We performed a cross-sectional analysis of mitochondrial function, mitophagy and susceptibility to apoptosis in healthy donor primary T cells after exposure to ZDV in vitro, together with T cells from patients who were virologically suppressed on ZDV-containing ART regimens for ≥1 year and age-matched subjects receiving non-ZDV ART regimens. The proportion of T cells expressing mitochondrial reactive oxygen species (mtROS) was significantly higher after in vitro (CD4(+) T cells and CD8(+) T cells) and in vivo (CD4(+) T cells) exposure to ZDV than other antiretroviral agents. We did not detect any effect of ZDV on mitophagy, as indicated by change in autophagic flux. However, spontaneous apoptosis, indicated by upregulation of caspase-3 was greater in ZDV-exposed T cells. In conclusion, ZDV exposure was associated with impaired mitochondrial turnover and increased susceptibility to apoptosis in T cells. These mechanisms could contribute to sub-optimal immune reconstitution.

  4. Biology of Human Cutaneous Melanoma

    PubMed Central

    Elias, Elias G.; Hasskamp, Joanne H.; Sharma, Bhuvnesh K.

    2010-01-01

    A review of the natural behavior of cutaneous melanoma, clinical and pathological factors, prognostic indicators, some basic research and the present and possible futuristic strategies in the management of this disease are presented. While surgery remains to be the most effective therapeutic approach in the management of early primary lesions, there is no standard adjuvant therapy after surgical resection, or for metastatic disease. PMID:24281039

  5. [Cutaneous lupus erythematosus].

    PubMed

    Sandreva, Tatjana; Voss, Anne; Bygum, Anette

    2015-07-27

    Cutaneous lupus erythematosus (LE) is an autoimmune disease. The most common clinical forms are acute cutaneous LE (ACLE), subacute cutaneous LE (SCLE) and discoid LE (DLE). Cutaneous LE, mainly ACLE, can be the first sign of systemic LE (SLE). DLE and SCLE are less associated with development of SLE, however, up to 85% of patients with SLE have cutaneous manifestations. The aetiology is multifactorial. Drugs such as proton pump inhibitors can induce SCLE, while UV-light and smoking can worsen the lesions. Treatment includes preventive strategies in addition to topical steroids and systemic hydroxychloroquine.

  6. A20 Curtails Primary but Augments Secondary CD8+ T Cell Responses in Intracellular Bacterial Infection

    PubMed Central

    Just, Sissy; Nishanth, Gopala; Buchbinder, Jörn H.; Wang, Xu; Naumann, Michael; Lavrik, Inna; Schlüter, Dirk

    2016-01-01

    The ubiquitin-modifying enzyme A20, an important negative feedback regulator of NF-κB, impairs the expansion of tumor-specific CD8+ T cells but augments the proliferation of autoimmune CD4+ T cells. To study the T cell-specific function of A20 in bacterial infection, we infected T cell-specific A20 knockout (CD4-Cre A20fl/fl) and control mice with Listeria monocytogenes. A20-deficient pathogen-specific CD8+ T cells expanded stronger resulting in improved pathogen control at day 7 p.i. Imaging flow cytometry revealed that A20-deficient Listeria-specific CD8+ T cells underwent increased apoptosis and necroptosis resulting in reduced numbers of memory CD8+ T cells. In contrast, the primary CD4+ T cell response was A20-independent. Upon secondary infection, the increase and function of pathogen-specific CD8+ T cells, as well as pathogen control were significantly impaired in CD4-Cre A20fl/fl mice. In vitro, apoptosis and necroptosis of Listeria-specific A20-deficient CD8+ T cells were strongly induced as demonstrated by increased caspase-3/7 activity, RIPK1/RIPK3 complex formation and more morphologically apoptotic and necroptotic CD8+ T cells. In vitro, A20 limited CD95L and TNF-induced caspase3/7 activation. In conclusion, T cell-specific A20 limited the expansion but reduced apoptosis and necroptosis of Listeria-specific CD8+ T cells, resulting in an impaired pathogen control in primary but improved clearance in secondary infection. PMID:28004776

  7. Arctigenin from Arctium lappa inhibits interleukin-2 and interferon gene expression in primary human T lymphocytes

    PubMed Central

    2011-01-01

    Background Arctium lappa (Niubang), a Chinese herbal medicine, is used to treat tissue inflammation. This study investigates the effects of arctigenin (AC), isolated from A. lappa, on anti-CD3/CD28 Ab-stimulated cell proliferation and cytokine gene expression in primary human T lymphocytes. Methods Cell proliferation was determined with enzyme immunoassays and the tritiated thymidine uptake method. Cytokine production and gene expression were analyzed with reverse transcription-polymerase chain reaction. Results AC inhibited primary human T lymphocytes proliferation activated by anti-CD3/CD28 Ab. Cell viability test indicated that the inhibitory effects of AC on primary human T lymphocyte proliferation were not due to direct cytotoxicity. AC suppressed interleukin-2 (IL-2) and interferon-γ (IFN-γ) production in a concentration-dependent manner. Furthermore, AC decreased the IL-2 and IFN-γ gene expression in primary human T lymphocytes induced by anti-CD3/CD28 Ab. Reporter gene analyses revealed that AC decreased NF-AT-mediated reporter gene expression. Conclusion AC inhibited T lymphocyte proliferation and decreased the gene expression of IL-2, IFN-γ and NF-AT. PMID:21435270

  8. Arctigenin from Arctium lappa inhibits interleukin-2 and interferon gene expression in primary human T lymphocytes.

    PubMed

    Tsai, Wei-Jern; Chang, Chu-Ting; Wang, Guei-Jane; Lee, Tzong-Huei; Chang, Shwu-Fen; Lu, Shao-Chun; Kuo, Yuh-Chi

    2011-03-25

    Arctium lappa (Niubang), a Chinese herbal medicine, is used to treat tissue inflammation. This study investigates the effects of arctigenin (AC), isolated from A. lappa, on anti-CD3/CD28 Ab-stimulated cell proliferation and cytokine gene expression in primary human T lymphocytes. Cell proliferation was determined with enzyme immunoassays and the tritiated thymidine uptake method. Cytokine production and gene expression were analyzed with reverse transcription-polymerase chain reaction. AC inhibited primary human T lymphocytes proliferation activated by anti-CD3/CD28 Ab. Cell viability test indicated that the inhibitory effects of AC on primary human T lymphocyte proliferation were not due to direct cytotoxicity. AC suppressed interleukin-2 (IL-2) and interferon-γ (IFN-γ) production in a concentration-dependent manner. Furthermore, AC decreased the IL-2 and IFN-γ gene expression in primary human T lymphocytes induced by anti-CD3/CD28 Ab. Reporter gene analyses revealed that AC decreased NF-AT-mediated reporter gene expression. AC inhibited T lymphocyte proliferation and decreased the gene expression of IL-2, IFN-γ and NF-AT.

  9. The investigation of CD4+T-cell functions in primary HIV infection with antiretroviral therapy

    PubMed Central

    Sun, Yu; Fu, Yajing; Zhang, Zining; Tang, Tian; Liu, Jing; Ding, Haibo; Han, Xiaoxu; Xu, Junjie; Chu, Zhenxing; Shang, Hong; Jiang, Yongjun

    2017-01-01

    Abstract Human immunodeficiency virus (HIV) infection leads to reduced CD4+T-cell counts and immune dysfunction. Initiation of antiretroviral therapy (ART) in HIV primary infection has been recommended to achieve an optimal clinical outcome, but a comprehensive study on restoration of CD4+T-cell function in primary HIV-infected individuals with ART still needs to be eluciated. We investigated longitudinal changes in the CD4+T-cell counts, phenotypes, and functions in HIV-infected individuals with early ART (initiated within 6 months after HIV infection) or later ART (initiated more than 12 months after HIV infection). Patients from early ART and later ART groups had received ART for at least 1 year. Individuals with early ART had more CD4+T cells, a faster rate of CD4+T-cell recovery than those receiving later ART; the levels of CD4+T-cell activation and senescence were lower in early ART compared to those with later ART (P = .031; P = .016), but the activation was higher than normal controls (NC) (P = .001); thymic emigrant function was more upregulated in early ART than in later ART (P = .015), but still lower than NC (P = .027); proliferative capacity and interferon-γ secretion of CD4+T cells were significantly decreased in primary infection (P < .001; P = .029), and early ART restored these CD4+T-cell functions, there is no difference with NC, later ART could partially restore the functions of CD4+T cells, but it remained lower than that of NC (P = .005; P = .019). Early ART could better improve CD4+T-cell function. PMID:28700479

  10. Mitochondrial tRNAMet mutation is associated with clinical and biochemical characteristics in primary hypertension.

    PubMed

    Lu, Chang-Qing; Zhang, Jin-Ying; Xu, Ai-Guo; Zhang, Juang-Juang; Li, Dan-Dan; Fu, Xin; Guo, Jing; Xu, Qin-Fu

    2013-06-01

    Mitochondrial DNA mutations have been increasingly associated with various diseases. An association between the mitochondrial tRNA gene mutation, tRNAMet, and primary hypertension has been suggested. In the present study, the association between the tRNAMet mutation and the development of primary hypertension was investigated by assessing clinical and biological indicators in 800 patients with primary hypertension. General [gender, age, age of onset, body mass index (BMI) and family history] and clinical data (routine blood counts, blood biochemistry profiles and color Doppler echocardiography) were obtained. Venous blood samples were drawn from all the subjects for the separation of white blood cells (WBCs) and DNA extraction. Mitochondrial tRNAMet was amplified using PCR, purified and sequenced; samples identified to have a mutation were sequenced in triplicate for validation. Comparisons were made between 7 hypertensive patients with mutations (0.875%) and 10 age-, gender- and medication‑matched hypertensive patients without mutations (controls). A maternal history of hypertension was present in 57.1% of patients with tRNAMet mutations and only 20.0% of patients without mutations. Notably, tRNAMet mutations were associated with a significantly earlier age of hypertension onset, decreased red blood cell (RBC) counts and hemoglobin (Hb) levels and increased total cholesterol (TC), triacylglycerol (TG), high‑density lipoprotein cholesterol (HDL-C) and glucose levels (all P<0.05). Heart structure and function differences were also assessed between the two groups. In conclusion, mitochondrial tRNAMet mutations may induce changes in tRNA structure and function, which contributes to the pathogenesis of primary hypertension by disturbing blood lipid metabolism, the steady state of blood cells and cardiac structure and function.

  11. Primary T-Cell Non-Hodgkin Lymphoma of the Vagina

    PubMed Central

    Herraiz, J. L.; Llueca, A.; Maazouzi, Y.; Piquer, D.; Palmeiro, A.; Calpe, E.

    2015-01-01

    The primary vaginal T-cell non-Hodgkin lymphoma is a rare form of lymphoma. Most of the previously published cases were about B-cell non-Hodgkin lymphomas. We present the case of a vaginal mass in an 82-year-old patient presenting vaginal bleeding. The results of the immunohistological studies of the mass revealed the presence of a cytotoxic T-cell non-Hodgkin lymphoma, which is the least common subtype. PMID:26101677

  12. Imbalances of T cell subpopulations in primary immunodeficiencies and systemic lupus erythematosus.

    PubMed

    Pandolfi, F; Quinti, I; Sirianni, M C; Fiorilli, M; Zolla, S; Aiuti, F

    1981-01-01

    In the present report we describe a recently proposed technique for the enumeration of T lymphocyte subpopulations. The study was performed on peripheral blood lymphocytes (PBL) of 21 patients with primary immunodeficiencies and 10 with systemic lupus erythematosus (SLE). With this methodology, sheep rosettes are evaluated before and after preincubation with theophylline. Previous reports have shown that cells rosetting after the preincubation (T-res) contain most of the percentages of the helper activity, whereas sensitive cells (T-sens) exert suppression. T-res and T-sens cells were compared to several clinical and immunological parameters, including the detection of lymphocytes with Fc IgM and IgG receptors. We demonstrated a significant positive correlation between T-res and and EAox IgM cells and between T-sens and EAox IgG cells. In addition, patients with Ig defects demonstrated heterogeneity regarding alterations in the proportions of T-res and T-sens cells. On the contrary, in 8 patients with SLE, there was a markedly reduced proportion of T-sens cells. Variations in the balance of subpopulations were observed after treatment with thymic hormones and levamisole. We may conclude that theophylline rosettes represent an easy technique that can be profitably used in the evaluation of T cell subpopulations in immunological diseases.

  13. Nosocomial post-traumatic cutaneous mucormycosis: a systematic review.

    PubMed

    Simbli, Mohammad; Hakim, Fayaz; Koudieh, Mohammad; Tleyjeh, Imad M

    2008-01-01

    Mucormycosis is a rare, rapidly fatal opportunistic invasive fungal infection occurring in immunocompromised patients. Primary cutaneous mucormycosis usually follows direct inoculation of fungal spores at the site of damaged or traumatized skin. We report a case of fatal nosocomial post-traumatic cutaneous mucormycosis in a diabetic patient and we performed a systematic review of reported cases of nosocomial post-traumatic cutaneous mucormycosis to describe their demographic profile, predisposing factors, treatment and outcome.

  14. Cutaneous manifestations of human toxocariasis.

    PubMed

    Gavignet, Béatrice; Piarroux, Renaud; Aubin, François; Millon, Laurence; Humbert, Philippe

    2008-12-01

    Human toxocariasis is a parasitic disease characterized by the presence of larvae of the genus Toxocara in human tissues. T canis and T cati, the adult roundworms of which are found in dog and cat intestines, respectively, are the most common causative agents of the disease. Toxocaral larvae usually cause two severe syndromes: visceral larva migrans and ocular larva migrans, depending on the location of the larvae. Two other syndromes, covert toxocariasis and common toxocariasis, which are less typical and not as severe, have also been described. During the last two decades, cutaneous manifestations such as chronic urticaria, chronic pruritus, and miscellaneous eczema, in patients with Toxocara antibodies, have been studied by different authors. In some cases, these cutaneous manifestations are the only signs indicating the presence of the disease, and they are cured after antihelmintic treatment when there is good patient compliance. In this review, we focus on these particular skin manifestations regarding their clinical description, diagnosis, and treatment.

  15. Pseudolymphoma and cutaneous lymphoma: facts and controversies.

    PubMed

    Bergman, Reuven

    2010-01-01

    Cutaneous pseudolymphoma refers to a heterogenous group of benign reactive T-cell or B-cell lymphoproliferative processes of diverse causes that simulate cutaneous lymphomas clinically and histologically. Pseudolymphomas may arise in response to a wide variety of foreign antigens, but most are idiopathic. Major advances have been made in the histologic classification, immunohistochemistry, and molecular studies of cutaneous pseudolymphoma. Although this enables a more precise differentiation from cutaneous lymphoma, a substantial number of patients still present in whom the differential diagnosis is difficult or impossible. Some evidence suggests that pseudolymphomas may progress to cutaneous lymphoma due to persistent antigenic stimulation. More compelling evidence is needed, especially when most cutaneous pseudolymphoma are not associated with known antigens and the differentiation from cutaneous lymphoma may be difficult; therefore, a careful approach should be used, and the antigenic stimulus should be removed whenever possible. A watchful follow-up is warranted in idiopathic cases, and consideration should always be given to surgical or medical therapy.

  16. Zosteriform cutaneous leiomyoma: a rare cutaneous neoplasm.

    PubMed

    Arfan-ul-Bari

    2013-08-01

    Cutaneous leiomyomas are firm, round to oval, skin-coloured to brownish papules and nodules that may present as a solitary, few discrete or multiple clustered lesions. Different uncommon patterns of multiple leiomyoma distribution have been noted as bilateral, symmetrical, linear, zosteriform, or dermatomal-like arrangement. One such rare presentation was seen in a 23-year-old patient who presented with zosteriform skin coloured, occasionally painful cutaneous lesions over left shoulder region. Histopathology confirmed the diagnosis of cutaneous leiomyoma. He was symptomatically managed with non-steroidal anti-inflammatory agents and topical capcicum cream. Case is reported here due to rare occurrence of this benign cutaneous neoplasm in an atypical pattern and on uncommon site.

  17. Rabbit liver tRNA1Val:I. Primary structure and unusual codon recognition.

    PubMed

    Jank, P; Shindo-Okada, N; Nishimura, S; Gross, H J

    1977-06-01

    The major valine acceptor tRNA1Val from rabbit liver was purified and its nucleotide sequence determined by in vitro [32P] - labeling with T4 phage induced polynucleotide kinase and finger-printing techniques. Its primary structure was found to be identical with the major valine tRNA from mouse myeloma cells. According to the wobble hypothesis this tRNA, which exclusively has an IAC anticodon, should decode the valine codons GUU, GUC and GUA only. However, this tRNA recognizes all four valine codons with a surprising preference for GUG. It is unknown whether this is due to the lack of A37 modification next to the 3' end of the anticodon IAC. The nature of the inosine-guanosine interaction remains to be clarified.

  18. Generation of knock-in primary human T cells using Cas9 ribonucleoproteins

    SciTech Connect

    Schumann, Kathrin; Lin, Steven; Boyer, Eric; Simeonov, Dimitre R.; Subramaniam, Meena; Gate, Rachel E.; Haliburton, Genevieve E.; Ye, Chun J.; Bluestone, Jeffrey A.; Doudna, Jennifer A.; Marson, Alexander

    2015-07-27

    T-cell genome engineering holds great promise for cell-based therapies for cancer, HIV, primary immune deficiencies, and autoimmune diseases, but genetic manipulation of human T cells has been challenging. Improved tools are needed to efficiently “knock out” genes and “knock in” targeted genome modifications to modulate T-cell function and correct disease-associated mutations. CRISPR/Cas9 technology is facilitating genome engineering in many cell types, but in human T cells its efficiency has been limited and it has not yet proven useful for targeted nucleotide replacements. Here we report efficient genome engineering in human CD4+ T cells using Cas9:single-guide RNA ribonucleoproteins (Cas9 RNPs). Cas9 RNPs allowed ablation of CXCR4, a coreceptor for HIV entry. Cas9 RNP electroporation caused up to ~40% of cells to lose high-level cell-surface expression of CXCR4, and edited cells could be enriched by sorting based on low CXCR4 expression. Importantly, Cas9 RNPs paired with homology-directed repair template oligonucleotides generated a high frequency of targeted genome modifications in primary T cells. Targeted nucleotide replacement was achieved in CXCR4 and PD-1 (PDCD1), a regulator of T-cell exhaustion that is a validated target for tumor immunotherapy. Deep sequencing of a target site confirmed that Cas9 RNPs generated knock-in genome modifications with up to ~20% efficiency, which accounted for up to approximately one-third of total editing events. These results establish Cas9 RNP technology for diverse experimental and therapeutic genome engineering applications in primary human T cells.

  19. Generation of knock-in primary human T cells using Cas9 ribonucleoproteins