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Sample records for primary cutaneous t

  1. Multifocal primary cutaneous extranodal NK/T lymphoma nasal type*

    PubMed Central

    de Vasconcelos, Pedro; Ferreira, Cristina; Soares-Almeida, Luís; Filipe, Paulo

    2016-01-01

    Nasal type extranodal NK/T-cell lymphoma is a distinct entity according to the World Health Organization classification. Although 60% to 90% of patients with this disease present with a destructive mass in the midline facial tissues, it may also primarily or secondarily involve extranasal sites, like the skin. We report the case of a 77-year-old patient that came to our department with erythematous plaques of the right leg and eczematous lesions of the trunk. These lesions were biopsied and the patient was diagnosed with extranodal NK/T-cell lymphoma, nasal type. He was treated with multi-agent systemic chemotherapy but died 5 months after diagnosis. This case highlights the rarity and variability of cutaneous features of this disease and its aggressive course and poor prognosis. PMID:27192524

  2. Expression of programmed death-1 in primary cutaneous CD4-positive small/medium-sized pleomorphic T-cell lymphoma, cutaneous pseudo-T-cell lymphoma, and other types of cutaneous T-cell lymphoma.

    PubMed

    Cetinözman, Fatma; Jansen, Patty M; Willemze, Rein

    2012-01-01

    In this study we investigated whether programmed death-1 (PD-1) could serve as a useful diagnostic marker to differentiate between primary cutaneous CD4 small/medium-sized pleomorphic T-cell lymphoma (PCSM-TCL) and cutaneous pseudo-T-cell lymphomas on the one hand and other types of cutaneous T-cell lymphomas (CTCLs) on the other. Formalin-fixed, paraffin-embedded skin biopsies from 26 patients with PCSM-TCL or pseudo-T-cell lymphoma, including 1 patient with a lymphomatoid drug eruption, and 52 skin biopsies from other types of CTCLs were stained for PD-1. In addition, PD-1-positive cases were stained with antibodies against BCL6, CXCL13, and CD10 to determine a possible relationship with follicular helper T (TFH) cells. In all 26 cases of PCSM-TCL or pseudo-T-cell lymphoma, the medium-sized to large-sized atypical T cells consistently expressed PD-1, BCL6, and CXCL13 but not CD10. PD-1 expression was found in only 2 of 21 cases of mycosis fungoides and in only 2 of 16 cases of cutaneous peripheral T-cell lymphoma, unspecified. All 4 patients with an aggressive epidermotropic cytotoxic CD8 CTCL and all 11 cases with a primary cutaneous CD30 lymphoproliferative disorder were negative for PD-1. In conclusion, PD-1 is typically expressed by atypical cells in PCSM-TCL and pseudo-T-cell lymphoma but is not expressed or is rarely expressed in other types of CTCLs. Therefore, it may serve as a suitable adjunct in differential diagnosis. Our results demonstrate that the atypical cells in PCSM-TCL and pseudo-T-cell lymphomas share a common TFH phenotype and support the view that most cases classified nowadays as PCSM-TCL are identical to cutaneous pseudo-T-cell lymphomas described previously. PMID:21989349

  3. Methotrexate and etanercept-induced primary cutaneous CD4 positive small/medium-sized pleomorphic T-cell lymphoma*

    PubMed Central

    MA, Han; Qiu, Shu; Lu, Rongbiao; Feng, Peiying; Lu, Chun

    2016-01-01

    Immunosuppressive drugs and biological agents may represent a potential risk of lymphoma development in patients with rheumatoid arthritis. But most cases are diffuse, large B-cell lymphomas. Primary cutaneous CD4+ small/medium-sized pleomorphic T-cell lymphoma, a provisional entity in the 2005 WHO-EORTC classification of cutaneous lymphomas, is only described in a limited number of reports. To our knowledge, our case is a rare instance of primary cutaneous CD4+ small/medium-sized pleomorphic T-cell lymphoma, after associated treatment with methotrexate and etanercept, in a patient with moderate rheumatoid arthritis who had undergone an orchidectomy incorrectly.

  4. [Primary cutaneous plasmacytoma].

    PubMed

    Dhouib Sellami, Rym; Sassi, Samia; Mrad, Karima; Abess, Imen; Driss, Maha; Ben Romdhane, Khaled

    2007-04-01

    Primary cutaneous plasmacytoma (PCP) is a rare cutaneous B cell lymphoma. We report a case of PCP in a 64 year old woman presenting with a nodular lesion of the left cheek. Histologically, the lesion was composed predominately of variably maturated plasma cells with monotypic expression of lambda chain. Extracutaneous localizations of the disease had been excluded. The prognosis of PCP is better than that of the metastatic cutaneous lesion of myeloma. The main prognosis factors are the size tumor and clinical presentation (solitary, versus multiple lesions). Solitary lesions of the PCP are treated by surgical excision and sometimes local radiotherapy. PMID:17909472

  5. ESHAP for primary cutaneous T-cell lymphomas: efficacy and tolerance in 11 patients.

    PubMed

    Mebazaa, Amel; Dupuy, Alain; Rybojad, Michel; Mouly, Frédéric; Moulonguet, Isabelle; Vignon-Pennamen, Marie-Dominique; Rivet, Jacqueline; Janin, Anne; Lebbé, Celeste; Dubertret, Louis; Morel, Patrice; Bachelez, Hervé; Brice, Pauline

    2005-01-01

    Systemic multiagent hemotherapy has been used to treat aggressive forms of primary cutaneous T-cell lymphomas (CTCL) with controversial results. Our objective was to retrospectively assess efficacy and toxicity of ESHAP (etoposide, cisplatin, high-dose aracytine, methylprednisolone) in patients with advanced CTCL. A total of 11 patients with aggressive primary CTCL, treated with the ESHAP protocol between 1995 and 2002, were studied. Two patients achieved complete remissions lasting 30+ and 6+ months, seven had partial remissions of short duration, one had stable disease and one experienced disease progression. ESHAP was poorly tolerated because of prolonged myelosuppression (91%) and infectious complications (82%). Our results suggest that ESHAP has a poor risk/benefit ratio in advanced CTCL because of the low number of complete remissions, the short duration of partial remissions and its high-grade toxicity. PMID:15692599

  6. 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. PMID:26392387

  7. Primary cutaneous nocardiosis.

    PubMed

    Jiang, Shan; Jiang, Guan; Lei, Tie-Chi

    2014-11-01

    Nocardiosis is a rare human infection due to ubiquitous soil born gram-positive, filametous aerobic bacteria. First signs are frequently cutaneous either as part of systemic infection disseminated to the skin, or as primary cutaneous inoculation. An 88 years old man presented with a 3-day history of red papules and pustules with pain on his forehead. The combination of the unusual clinical presentation, laboratory examinations, and a favorable response to co-trimoxazole therapy were consistent with a diagnosis of primary cuteneous nocardiosis. Early recognition and treatment of the disease will improve the cure rate. PMID:25518763

  8. Pegylated liposomal doxorubicin in the treatment of primary cutaneous T-cell lymphomas.

    PubMed

    Pulini, Stefano; Rupoli, Serena; Goteri, Gaia; Pimpinelli, Nicola; Alterini, Renato; Tassetti, Angela; Scortechini, Anna Rita; Offidani, Massimo; Mulattieri, Simonetta; Stronati, Andrea; Brandozzi, Giuliano; Giacchetti, Alfredo; Mozzicafreddo, Giorgio; Ricotti, Giuseppe; Filosa, Giorgio; Bettacchi, Alberta; Simonacci, Marco; Novelli, Nicolino; Leoni, Pietro

    2007-05-01

    Pegylated liposomal doxorubicin (Peg-Doxo) is a promising drug for advanced/recalcitrant primary cutaneous T-cell lymphomas (CTCLs). This prospective phase II trial enrolled 19 patients. We observed overall and complete response rates of 84.2% and 42.1% (with no significant differences between stage I-IIA and IIB-IV patients), and 11% grade III/IV toxicity. After a maximum 46 month-follow-up, median overall (OS), event-free (EFS) and progression-free (PFS) survival were 34, 18 and 19 months. OS, EFS and PFS rates at 46 months were 44%, 30% and 37% respectively. Peg-Doxo seems to be an active and safe principle that should be used in plurirelapsed, early stage-MF and in combination with other chemotherapeutic agents in advanced and aggressive CTCLs. PMID:17488695

  9. Characteristics of Primary Cutaneous T-Cell Lymphoma in Iran: A 10-Year Retrospective Study

    PubMed Central

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

    2014-01-01

    Background. Primary cutaneous T-cell lymphomas (CTCLs) are a group of extranodal non-Hodgkin lymphomas that may be present in the skin without any evidence of extracutaneous disease. The aim of this study was to evaluate the epidemiological characteristics of primary CTCL in Isfahan, Iran. Method. A total of 95 patients who were diagnosed as having primary CTCL were recruited during a 10-year period (2003–2013) and were classified according to the new WHO-EORTC criteria. Results. The patient group consisted of 43 (44.8%) males and 53 (55.2%) females, which indicated a female predominance (M : F ratio 1 : 1.2). The mean age at the time of diagnosis was 41.78 ± 16.88 years (range: 7–84 years). Prior to diagnosis, the lesions had persisted for a mean of 8.34 ± 4.38 years (range: 0–55 years). The age at peak diagnosis was 20–40 years (43%). The most frequent subtypes were mycosis fungoides (MF) (88.5%). Four patients died from CTCL-related complications. Conclusions. The distinguishing epidemiologic characteristics of primary CTCL, particularly those MF, in Iran, are the absence of a male predominance and lower age at diagnosis. This is likely because of the characteristic ethnic group diversity and increased susceptibility among younger population.

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

    PubMed

    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

  12. 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

  13. Rapid progression of primary cutaneous gamma-delta T-cell lymphoma with an initial indolent clinical presentation.

    PubMed

    Alexander, Riley E; Webb, Alden R; Abuel-Haija, Mohammad; Czader, Magdalena

    2014-10-01

    Primary cutaneous gamma-delta T-cell lymphoma (CGD-TCL) is a rare cutaneous T-cell lymphoma characterized by a rapidly progressive clinical course and a poor prognosis. We report a case of a 52-year-old man with a 10-year history of erythematous nodules and a rapid terminal progression diagnosed as CGD-TCL. Biopsies taken at the time of progression showed a dense lymphocytic infiltrate involving the subcutaneous adipose tissue and deep dermis. One of the biopsies displayed much more limited involvement by CGD-TCL that was nearly identical to the biopsies of the erythematous lesions 10 years before. In conclusion, this case demonstrates a case of CGD-TCL presenting as a longstanding indolent disease with a rapid terminal progression. The indolent clinical course and histological heterogeneity make diagnosing this entity during the initial stage extremely challenging. This case underscores a diverse clinical presentations and a need to consider CGD-TCL in patients showing subcutaneous lesions with an indolent clinical course. PMID:25247673

  14. A Primary Cutaneous CD30-Positive T-Cell Lymphoproliferative Disorder Arising in a Patient With Multiple Myeloma and Cutaneous Amyloidosis.

    PubMed

    Romano, Ryan C; Cohen, Daniel N; Howard, Matthew T; Wieland, Carilyn N

    2016-05-01

    CD30-positive cutaneous lymphoproliferative disorders, a group of T-cell neoplasms, including lymphomatoid papulosis (LyP) and cutaneous anaplastic large cell lymphoma, require careful clinicopathologic correlation for diagnosis. An association between LyP and the development of a second hematolymphoid malignancy has been established in the literature. LyP has also been reported with systemic amyloidosis, but no such reports have documented coexisting cutaneous amyloid deposition with LyP to our knowledge. A 66-year-old woman with cutaneous amyloidosis, secondary to multiple myeloma, in remission, presented with erythematous and dark-brown papules involving the right arm, scalp, and torso. Punch biopsy of the arm showed a dermal infiltrate of intermediate-sized lymphocytes, some of which displayed a plasmacytoid morphology and prominent nodular subepidermal amyloid deposition. Punch biopsy of the scalp similarly showed a nonepidermotropic dense dermal infiltrate of intermediate-sized plasmacytoid lymphocytes and multifocal amyloid deposition. Both infiltrates were immunophenotypically CD30-positive, anaplastic lymphoma kinase-negative T-cell lymphoproliferative processes. Subsequent studies showed no systemic involvement, and clinical correlation suggested a final diagnosis of LyP. We present this case of LyP, which histologically mimics a B-cell proliferation with a plasmacytoid morphology arising in association with cutaneous amyloidosis to highlight the importance of clinicopathologic correlation, a thorough battery of immunohistochemical studies, and consideration for a second hematologic malignancy arising in the setting of LyP. PMID:26981738

  15. Resident Rounds: Primary Cutaneous Mucormycosis.

    PubMed

    Johnson, Mariah; Fathi, Ramin; Alkousakis, Theodore

    2015-08-01

    We present the case of a 36-year-old neutropenic man with acute myelogenous leukemia who presented for evaluation of a rapidly expanding necrotic eschar after adhesive placement. Histopathology revealed infection with primary cutaneous mucormycosis. Our case reviews the presentation and management of this condition as well highlights an uncommon cause in the hospital that can lead to this dangerous infection. PMID:27120566

  16. 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

  17. Primary cutaneous cryptococcosis of the penis.

    PubMed

    Narváez-Moreno, Basilio; Bernabeu-Wittel, José; Zulueta-Dorado, Teresa; Conejo-Mir, Julián; Lissen, Eduardo

    2012-10-01

    Primary cutaneous cryptococcosis is characterized by skin lesions confined to one body region, without evidence of simultaneous dissemination. Skin lesions frequently occur in immunocompromised patients. We report a case of primary cutaneous cryptococcosis in an immunocompetent patient affecting genital area successfully treated with oral itraconazole. PMID:23007707

  18. Primary Cutaneous Aspergillosis in a Preterm Infant.

    PubMed

    Frick, Marie Antoinette; Boix, Hector; Camba Longueira, Fátima; Martin-Gomez, M Teresa; Rodrigo-Pendás, José Ángel; Soler-Palacin, Pere

    2016-06-01

    Primary cutaneous aspergillosis is rare in premature infants. It requires combined medical and surgical strategies. Liposomal amphotericin B is recommended as first-line therapy, but salvage regimens with others antifungal agents, such as voriconazole, have been reported. Voriconazole's pharmacodynamics is unknown in this population. We report a case of severe toxicity to voriconazole in a preterm patient with primary cutaneous aspergillosis. PMID:26974892

  19. 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. PMID:23756295

  20. Cutaneous T-Cell Lymphoma in Asians

    PubMed Central

    Jang, Min Soo; Kang, Dong Young; Park, Jong Bin; Kim, Sang Tae; Suh, Kee Suck

    2012-01-01

    Cutaneous T-cell lymphoma describes a heterogeneous group of neoplasms of skin homing T cells that vary considerably in clinical presentation, histologic appearance, immunophenotype, and prognosis. This paper addresses the cutaneous T-cell lymphoma in Asians with respect to clinical-epidemiologic and histopathological features. Compared with Western countries, Asia usually has higher rates of cutaneous T-cell lymphomas such as extranodal NK/T-cell lymphoma, hydroa vacciniforme-like lymphoma, subcutaneous panniculitis T-cell lymphoma, and adult T-cell leukemia/lymphoma and lower rates of cutaneous B-cell lymphomas. Among many variants of mycosis fungoides, hypopigmented lesions, pityriasis lichenoides-like lesions, and ichthyosiform lesions are more prevalent in Asia than in the West. Adult T-cell leukemia/lymphoma is endemic in southwestern Japan especially in the Kyushu island. The clinicopathologic characteristics of cutaneous lymphoma vary according to geography, and this may be ascribed to genetic and environmental etiologic factors. PMID:22844610

  1. Cutaneous T-cell lymphoma in asians.

    PubMed

    Jang, Min Soo; Kang, Dong Young; Park, Jong Bin; Kim, Sang Tae; Suh, Kee Suck

    2012-01-01

    Cutaneous T-cell lymphoma describes a heterogeneous group of neoplasms of skin homing T cells that vary considerably in clinical presentation, histologic appearance, immunophenotype, and prognosis. This paper addresses the cutaneous T-cell lymphoma in Asians with respect to clinical-epidemiologic and histopathological features. Compared with Western countries, Asia usually has higher rates of cutaneous T-cell lymphomas such as extranodal NK/T-cell lymphoma, hydroa vacciniforme-like lymphoma, subcutaneous panniculitis T-cell lymphoma, and adult T-cell leukemia/lymphoma and lower rates of cutaneous B-cell lymphomas. Among many variants of mycosis fungoides, hypopigmented lesions, pityriasis lichenoides-like lesions, and ichthyosiform lesions are more prevalent in Asia than in the West. Adult T-cell leukemia/lymphoma is endemic in southwestern Japan especially in the Kyushu island. The clinicopathologic characteristics of cutaneous lymphoma vary according to geography, and this may be ascribed to genetic and environmental etiologic factors. PMID:22844610

  2. Primary Cutaneous Actinomycosis:A Case Report

    PubMed Central

    Ghosh, Ranadeep; Mukherjee, Kheya; Ghoshal, Loknath

    2014-01-01

    Actinomycosis is a subacute or chronic suppurative bacterial infection caused by filamentous gram positive, anaerobic to microaerophilic non acid fast bacilli primarily of the genus Actinomyces that normally colonize the mouth, colon and vagina. Primary cutaneous actinomycosis is a rare entity and is generally associated with trauma. We report a case of primary cutaneous actinomycosis of the back and left axilla in a 32-year-old female patient with no suggestive history of trauma.The diagnosis was suggested by the characteristic lesions with multiple discharging sinuses draining sero-sanguinous fluid scattered all over the lesions. Gram positive bacilli with plenty of pus cells were demonstrated in the direct examination of the discharging pus. Diagnosis was confirmed by isolation of the organisms by anaerobic culture giving typical molar tooth colonies. Final confirmation was done by histopathological examination. PMID:25177623

  3. Primary cutaneous mucormycosis caused by Mucor irregularis.

    PubMed

    Xia, X J; Shen, H; Liu, Z H

    2015-12-01

    We describe a case of primary cutaneous mucormycosis in a 44-year-old man with an 18-month history of infiltrative erythematous plaques and haemorrhagic crusting on the dorsum of his left hand. The isolate was identified as Mucor irregularis (formerly Rhizomucor variabilis) based on the fungus morphology and DNA sequencing results. Improvement was observed after a 6-month treatment course of itraconazole. No recrudescence was seen during a follow-up of 23 months after treatment. PMID:25810249

  4. Primary cutaneous γδ-T-cell lymphoma (CGD-TCL) with unilateral lower extremity swelling as first-onset symptom: a rare case report.

    PubMed

    Li, Duo; Huang, Lijun; Guo, Bin; Wen, Qiuyuan; Wang, Weiyuan; Luo, Jiadi; Fan, Songqing

    2014-01-01

    Primary cutaneous γδ-T-cell lymphoma (CGD-TCL) is a distinct disease entity which is an extremely rare neoplasm with poor prognosis, characterized by the γ/δ T-cell receptor expression on atypical lymphocytes. We report the case of a 42-year-old man who first presented with a swelling in the extremities and subsequent appeared subcutaneous nodule over the body. In order to clarify the diagnosis, a biopsy of subcutaneous nodule for pathology had been done. CGD-TCL was diagnosed by histopathology, immunophenotype, in situ hybridization and analysis of TCRγ genes rearrangement. The patient was treated with chemotherapeutic regimens-CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone). After one period of chemotherapy, subcutaneous nodules became small, even disappeared, swelling and ulcer in the left pedal gone away gradually. One month later after first chemotherapy, tumor relapsed with lesions growing back rapidly, also showed disease in double lungs. The patient was just 10-month survival time from the onset. To our knowledge, this case is the first report of CGD-TCL with unilateral lower extremity swelling as the first-onset symptom. If patient is presented the first symptoms such as swelling of extremities, especially when ulceration appears, it is of great significance to be considerate about the possibility of CGD-TCL. PMID:25197420

  5. Primary cutaneous aspergillosis in a preterm neonate.

    PubMed

    Rogdo, Bjarte; Kahlert, Christian; Diener, Pierre André; Micallef, John

    2014-01-01

    Primary cutaneous aspergillosis (PCA) is a rare fungal infection in premature infants. Extreme prematurity, immature immune system, therapy with broad-spectrum antibiotics and systemic steroids, as well as hyperglycaemia and a vulnerable and very thin epidermal layer are considered risk factors in this patient population. We present a premature male infant born at 24(+3) weeks of gestation with PCA, successfully treated with amphotericin and surgical curettage of the ulcerating skin lesions. Complete resolution of the lesions was achieved and scarring was barely visible at later follow-up. PMID:25178889

  6. Primary cutaneous mucormycosis in an immunocompetent patient.

    PubMed

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

    2016-01-01

    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. PMID:27530872

  7. Two cases of primary cutaneous lymphoma with a γ/δ+ phenotype and an indolent course: further evidence of heterogeneity of cutaneous γ/δ+ T-cell lymphomas.

    PubMed

    Kempf, Werner; Kazakov, Dmitry V; Scheidegger, Paul E; Schlaak, Max; Tantcheva-Poor, Iliana

    2014-07-01

    Cutaneous γ/δ+ T-cell lymphoma (CGD-TCL) is a rare but aggressive lymphoma associated with a poor prognosis in most patients. The clinicopathological spectrum is variable including predominantly epidermotropic infiltrates manifesting with patches and plaques or tumors with dermal and/or subcutaneous infiltrates. The diagnosis of CGD-TCL requires the demonstration of a γ/δ+ phenotype by immunohistochemistry. We report 2 patients with epidermotropic cutaneous T-cell lymphomas displaying a γ/δ+ phenotype, but exhibiting an indolent course. In one patient, the clinical presentation was similar to mycosis fungoides in patch and plaque stage, but recurrent blister formation within the lesions was observed accompanied by fever and arthralgias, whereas the second patient presented with 2 localized erosive plaques on the left temple and dense epidermotropic and dermal diffuse and folliculotropic infiltrates of atypical small-to-medium-sized lymphocytes. These cases corroborate the view that expression of a γ/δ+ phenotype in cutaneous T-cell lymphomas per se does not portend a worse prognosis and that CGD-TCL may represent a clinically and prognostically heterogeneous group. PMID:24950419

  8. A case of primary cutaneous mucormycosis caused by minor trauma.

    PubMed

    Gelman, Ari; Valdes-Rodriguez, Rodrigo; Bhattacharyya, Siddharth; Yosipovitch, Gil

    2015-01-01

    We present the case of a 66-year-old neutropenic man with mantle-cell lymphoma who presented for evaluation of a rapidly expanding necrotic eschar after a minor cutaneous injury. Histopathology revealed infection with Rhizopus indicating primary cutaneous mucormycosis. Our case reviews the presentation and management of this condition as well highlights the potential for minor cutaneous injuries in the hospital to lead to this dangerous infection. PMID:25612128

  9. Genomic landscape of cutaneous T cell lymphoma

    PubMed Central

    Choi, Jaehyuk; Goh, Gerald; Walradt, Trent; Hong, Bok S.; Bunick, Christopher G.; Chen, Kan; Bjornson, Robert D.; Maman, Yaakov; Wang, Tiffany; Tordoff, Jesse; Carlson, Kacie; Overton, John D.; Liu, Kristina J.; Lewis, Julia M.; Devine, Lesley; Barbarotta, Lisa; Foss, Francine M.; Subtil, Antonio; Vonderheid, Eric C.; Edelson, Richard L.; Schatz, David G.; Boggon, Titus J.; Girardi, Michael; Lifton, Richard P.

    2015-01-01

    Cutaneous T cell lymphoma (CTCL) is a non-Hodgkin lymphoma of skin-homing T lymphocytes. We performed exome and whole genome DNA sequence and RNA sequencing on purified CTCL and matched normal cells. The results implicate mutations in 17 genes in CTCL pathogenesis, including genes involved in T cell activation and apoptosis, NFκB signaling, chromatin remodeling, and DNA damage response. CTCL is distinctive in that somatic copy number variants (SCNVs) comprise 92% of all driver mutations (mean of 11.8 pathogenic SCNVs vs. 1.0 somatic single nucleotide variants per CTCL). These findings have implications for novel therapeutics. PMID:26192916

  10. [Typing of infiltration cells in primary, localized, nodular, cutaneous amyloidosis].

    PubMed

    Sepp, N; Grünewald, K; Soyer, H P; Kerl, H; Breathnach, S M; Fritsch, P; Hintner, H

    1992-04-01

    Amyloid tumours in two patients with primary localized nodular cutaneous amyloidosis contained very dense infiltrates consisting mainly of plasma cells and lymphocytes. In one case IgM was detected on many cells of the infiltrate, while in the other IgA was found in morphologically apparently normal plasma cells. Immunohistochemical investigations did not reveal any immunoglobulin light chain restriction in either of the tumours. Numerous cells expressed B cell markers, such as CD20 or CD38. Rearrangement studies on material from the amyloid tumour of one of the patients confirmed the monoclonality of plasma cells. This observation indicates that the nodules of primary localized nodular cutaneous amyloidosis indeed represent an extramedullary plasmocytoma, which consists of amyloid-producing plasma cells. Of special interest was the unexpectedly high proportion of cells expressing T cell markers (CD3, CD5, CD4 greater than CD8) in the amyloid nodules of both patients. After excluding co-expression of B and T cell markers on identical cells by immunohistochemical studies on serial sections and also after molecular biological studies, we assume that this is a separate T cell population that may have a regulatory effect on the production of amyloid. PMID:1597370

  11. A Case of Aggressive NK/T-cell Lymphoma/Leukemia with Cutaneous Involvement in Adolescence

    PubMed Central

    Kim, Soo Ho; Ko, Woo Tae; Ha, Gyoung Yim; Kim, Jung Ran

    2008-01-01

    NK/T-cell lymphoma (NKTCL) is characterized by the expression of the NK-cell antigen CD56. Non-nasal NK/T-cell lymphomas are subdivided into primary cutaneous and 4 subtypes of secondary cutaneous lymphomas; nasal type, aggressive, blastic (blastoid), and other specific NK-like cell lymphoma. Aggressive NK/T-cell lymphoma/leukemia is a rare leukemic variant of nasal type NKTCL. We herein report a rare case of aggressive NK/T-cell lymphoma/leukemia with cutaneous involvement in adolescence. PMID:27303165

  12. Isolated benign primary cutaneous plasmacytosis in a child.

    PubMed

    On, Hye Rang; Lee, Sang Eun; Kim, You Chan; Kim, Soo-Chan

    2014-01-01

    Isolated benign primary cutaneous plasmacytosis in a child is a very rare and benign disease. Herein we present a case of this condition occurring in a child who showed good response to topical corticosteroid. PMID:25424220

  13. Primary Axillary Porocarcinoma: A Rare Cutaneous Tumour.

    PubMed

    Devi, Nalli R Sumitra; Valarmathi, K; Lilly, Mary; Satish, Selvi; Mishra, Nidhi

    2016-02-01

    Eccrine porocarcinoma, a rare cutaneous malignant tumour accounts for a fraction of sweat gland tumours. This tumour is found to originate from the intraepithelial parts of the sweat glands. It commonly involves the lower extremities in elderly patients and carries an aggressive behaviour. Cutaneous and visceral metastasis can occur and hence prompt treatment is mandatory. Surgical excision is the mainstay of treatment modality. We hereby present a case of eccrine porocarcinoma in a 50-year-old male in the right axillary region presenting as a verrucous lesion. PMID:27042472

  14. Primary Axillary Porocarcinoma: A Rare Cutaneous Tumour

    PubMed Central

    Valarmathi, K.; Lilly, Mary; Satish, Selvi; Mishra, Nidhi

    2016-01-01

    Eccrine porocarcinoma, a rare cutaneous malignant tumour accounts for a fraction of sweat gland tumours. This tumour is found to originate from the intraepithelial parts of the sweat glands. It commonly involves the lower extremities in elderly patients and carries an aggressive behaviour. Cutaneous and visceral metastasis can occur and hence prompt treatment is mandatory. Surgical excision is the mainstay of treatment modality. We hereby present a case of eccrine porocarcinoma in a 50-year-old male in the right axillary region presenting as a verrucous lesion. PMID:27042472

  15. Poikiloderma-like cutaneous amyloidosis - a rare presentation of primary localized cutaneous amyloidosis.

    PubMed

    Heng, Jun Khee; Ho, Sue Ann; Tan, Kong Bing

    2016-01-01

    Poikiloderma-like cutaneous amyloidosis (PCA) is a rare variant of primary cutaneous amyloidosis. It was first described in 1929 and there are two clinical forms of PCA, the ordinary type and PCA syndrome. The characteristics of PCA include poikiloderma-like skin changes, lichenoid papules, blister formation, and cutaneous amyloid deposits on histological examination. These skin lesions usually occur at the extremities, consistent with the few cases that have been reported. We present a case of a 62-year-old man who presented with the features of poikiloderma-like cutaneous amyloidosis. Diagnosis of this unique condition is a challenge and a skin biopsy is necessary in such instances. A discussion of the differential diagnosis of this condition is also included. PMID:26990468

  16. Retinoids in cutaneous T cell lymphomas.

    PubMed

    Mahrle, G; Thiele, B

    1987-01-01

    Sixteen patients - 12 with cutaneous T cell lymphoma (CTCL), 1 with Sézary syndrome, 1 with actinic reticuloid, and 2 with parapsoriasis variegata - were treated with either a new, potent arotinoid alone or with combined etretinate (Tigason) and PUVA therapy (Re-PUVA). 92% of all patients showed a minor up to a distinct response of their skin lesions within 12.6 +/- 7.4 weeks. More than 50% of the skin lesions cleared in 67% of the patients. After discontinuation of the retinoid therapy, relapses occurred in all cases within 3-10 weeks. There was no difference between the therapeutic efficacy of arotinoid alone and the Re-PUVA regimen, but the latter was less toxic. PMID:3500880

  17. Extracorporeal Photochemotherapy Of Cutaneous T Cell Lymphoma.

    NASA Astrophysics Data System (ADS)

    Gasparro, Francis P.

    1988-02-01

    A photochemotherapy based on the synergistic action of 8-methoxypsoralen (8-MOP) and long wavelength ultraviolet light (UVA, 320-400 nm) has been used extensively since 1974 for the treatment of psoriasis, a hyperprolifierative disease of the skin. More recently, this photochemotherapy has been used for the extracorporeal irradiation ot the blood of cutaneous T cell lymphoma (CTCL) patients in the leukemic stage of the disease. 8-MOP is ingested; two hours later when peak blood levels have been achieved the affected tissue is irradiated (skin in psoriasis and blood in CTCL). Using 8-MCP-DNA photoadduct formation as a cheillical actinometer, the effective dose of UVA radiation delivered to lymphocytes during photochemotherapy in the presence of erythrocytes was found to be ~1 J/cm2. In addition, a monoclonal antibody prepared in our laboratory was used in competitive ELISA assays to quantify the formation of 8-MOP photoadducts during the photochemotherapy.

  18. 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

  19. Primary cutaneous mucoepidermoid carcinoma infiltrating the parotid gland.

    PubMed

    Minni, A; Roukos, R; De Carlo, A; Di Tillo, G; Illuminati, G; Gallo, P

    2012-10-01

    Mucoepidermoid carcinoma (MEC) of the skin is an extremely rare neoplasm but is common in the major and minor salivary glands accounting of approximately 30% of all malignant tumors arising from these glands. Cutaneous involvement should be carefully assessed to exclude the possibility of metastases from distant sites. We report an 81 year-old man presenting a primary cutaneous mucoepidermoid carcinoma infiltrating his left parotid gland. Excision of the affected skin and a total parotidectomy with supraomohyoid neck dissection (level I-III) was performed followed by radiotherapy. No relapse after 2 years follow up has been observed. Since the primary cutaneous mucoepidermoid carcinoma is an aggressive neoplasm that frequently develops metastases it is important to distinguish it from primary MEC originating from the salivary glands for better management and suitable therapeutic decisions. PMID:23090800

  20. 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

  1. Primary Cutaneous Plasmacytosis: Masquerading as Hidradenitis Suppurativa.

    PubMed

    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

  2. [Cutaneous lymphoma].

    PubMed

    Beyeler, M; Burg, G; Dummer, R

    2004-10-01

    Cutaneous lymphomas are uncommon. They must be distinguished from secondary skin manifestations of primary nodal lymphomas. Primary cutaneous lymphomas are divided into B-cell- and T-cell cutaneous lymphoma and commonly have good prognosis. Therapy is based on the stage of the disease. Since cure is not possible, the aim of treatment is to control the disease and reduce symptoms. A variety of new and promising therapeutic modalities have been introduced in recent years. PMID:15349694

  3. Primary cutaneous plasmablastic lymphoma revealing clinically unsuspected HIV infection.

    PubMed

    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

  4. Primary Cutaneous B-Cell Lymphoma: Management and Patterns of Recurrence at the Multimodality Cutaneous Lymphoma Clinic of The Ohio State University

    PubMed Central

    Tyler, Kelly; Gru, Alejandro A.; Winardi, Francisca Kartono; Frederickson, Julie; Hastings, Justin; Elkins, Camille; Zhang, Xiaoli; Xu-Welliver, Meng; Wong, Henry K.

    2015-01-01

    Background. The increasing incidence of primary cutaneous B-cell lymphomas (PCBCLs) presents new challenges for clinicians. Despite advances in the clinical and pathologic characterization of PCBCL, the significance of the current staging approach as a risk profiling tool and the effect of various treatments on outcome remain unclear. Materials and Methods. We retrospectively reviewed patients who presented with a diagnosis of PCBCL seen at The Ohio State University between 1998 and 2012. We reviewed the initial presentation and treatment modality. We then assessed whether the treatment modality (conservative skin-directed vs. definitive radiation with or without systemic therapy), stage (T1 or ≥T2), or histologic subtype (primary cutaneous follicle center lymphoma [PCFCL] vs. primary cutaneous marginal zone B-cell lymphoma [PCMZL]) affected the risk of recurrence. Results. We identified 67 patients referred with an initial diagnosis of PCBCL. After imaging, 12 did not meet the criteria for PCBCL and were classified as having systemic B-cell lymphoma with cutaneous involvement. The remaining 55 patients included 25 with PCMZL, 24 with PCFCL, 2 with primary cutaneous large B-cell lymphoma leg type, and 4 with unclassifiable disease. According to the International Society of Cutaneous Lymphoma-European Organization for Research and Treatment of Cancer staging, 30 cases were T1 (55%), 14 T2 (25%), and 11 T3 (20%). Comparing the time to first recurrence (TFR) by indolent PCBCL subtypes, we found no difference in the recurrence risk for either stage (T1, p = .51 vs. T2/T3, p = .30). Comparing TFR by treatment modality, we found no difference in TFR within T1 patients (p = .34) or T2/T3 patients (p = .44). Conclusion. Our limited analysis highlights the importance of complete staging at diagnosis and suggests that the treatment modality does not affect the risk of recurrence in T1 indolent PCBCL. Implications for Practice: Primary cutaneous B-cell lymphoma (PCBCL) is a

  5. A rare pediatric case of cutaneous gamma/delta T-cell lymphoma.

    PubMed

    Kerbout, Malika; Mekouar, Fedoua; Bahadi, Nisrine; El Omri, Nawal; Assoufi, Nawfal; El Qatni, Mohamed; Mikdame, Mohamed; Ghafir, Driss

    2014-01-01

    Cutaneous γ/δ T-cell lymphoma (CGD-TCL) is a recent entity described in the newly revised World health organization-European organization for research and treatment of cancer classification of cutaneous lymphomas. Only a few cases have been reported, of which two pediatric cases. A 15 years old child with a 6 months history of polyadenopathy, cutaneous lesions, general edema and deterioration of general condition was hospitalized. Results from laboratory testing, cutaneous histopathology and immunohistochemistry showed a primary CGD-TCL. Staging was completed by a total body computed tomography. Therapy was planified with SMILE protocol. It is a highly aggressive tumor resistant to chemotherapy, immunotherapy, and radiation therapy. The GDTCL is characterized by a worse prognosis with a median survival of 15 months. Early diagnosis is essential and aggressive therapy is necessary. PMID:25119808

  6. Primary cutaneous anaplastic large-cell lymphoma: a case report.

    PubMed

    Cao, Can; Zeng, Kang; Wang, Menglei; Han, Kai; Peng, Yusheng; Xiong, Hao; Wang, Qi; Li, Qian; Wang, Qian; Li, Li

    2016-07-01

    Primary cutaneous anaplastic large-cell lymphoma (PCALCL) is a part of the spectrum of CD30+ lymphoproliferative cutaneous processes. The characteristics include single or multifocal nodules that ulcerate as skin lesion, slow disease progression, autoregressive, and recurrent in few years. The present study report the case of a 16-year-old boy presenting PCALCL with single nodules, ulcer, keloid, and scab in his right-side face. He showed a good response to the treatment with systemic chemotherapy and dermatoplasty, and regained confidence after the appearance of recovery. There is no relapse of the primary lesion and organs involved till now. The chemotherapy combining with surgical excision and dermatoplasty is a good method for PCALCL, per the lesion biopsy and positron emission tomography-computed tomography before and after treatment. PMID:26970422

  7. Primary cutaneous aspergillosis and idiopathic bone marrow aplasia.

    PubMed

    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

  8. 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

  9. 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.

  10. 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

  11. [Standard and experimental therapy of cutaneous T-cell lymphoma].

    PubMed

    Beyeler, M; Dummer, R

    2003-12-01

    Cutaneous T-cell lymphoma represent a heterogeneous group of diseases characterized by skin invasion of monoclonal T-lymphocytes. These cutaneous T-cell lymphomas are divided into 3 groups based on clinical, histological and immunohistological characteristics: Indolent with a survival time of over 10 years, aggressive with a survival time less than 10 years and provisional (EORTC classification). Standard treatments such as PUVA, total skin electron beam, methotrexate, polychemotherapy regimens, retinoids and photopheresis have been used for years. Bexarotene is a newly registered drug. To achieve better response rates, several new drugs are being evaluated in clinical trails, including imiquimod, denileukon-diftitox, liposomal doxorubicin, adeno-interferon-gamma and various combination approaches. PMID:14634747

  12. Primary cutaneous precursor B cell lymphoblastic lymphoma in a child, complicated by fatal disseminated varicella zoster virus.

    PubMed

    Rashidghamat, E; Robson, A

    2015-12-01

    Precursor B-cell lymphoblastic lymphoma (PBLL) is a rare subtype of childhood non-Hodgkin lymphoma (NHL). Most lymphoblastic lymphomas have a T-cell immunophenotype, but a small distinct proportion is of precursor B-cell origin. Skin and bone involvement is seen more commonly in this clinical variant. Primary cutaneous PBLL is rare. We describe an 8-year-old girl who presented with an asymptomatic nodule on the left upper arm. Histopathological features were consistent with pre-B-cell lymphoblastic lymphoma, and staging investigations excluded extracutaneous disease, resulting in a diagnosis of primary cutaneous PBLL. The child was started on induction chemotherapy, UKALL 2003 regimen B. She developed disseminated varicella zoster virus and died despite treatment. We discuss previously reported cases of primary cutaneous PBLL and their outcomes. PMID:25959984

  13. 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

  14. Pruritus in Cutaneous T-cell Lymphoma: A Review

    PubMed Central

    Ahern, Kristen; Gilmore, Elaine S.; Poligone, Brian

    2012-01-01

    Background Pruritus can be a distressing and even debilitating symptom for patients with cutaneous T-cell lymphoma (CTCL). To date, few studies have evaluated the pathophysiology of this symptom. Due to this, therapy for pruritus in CTCL has mainly relied on those therapies that target and treat the lymphoma. For patients living with CTCL that relapses or becomes refractory to treatment, and who continue to experience severe itch, this lymphoma-targeted treatment may not be enough to combat their pruritus. Therefore, other itch-targeted therapies are needed for use in this disease Objective Evaluate the current evidence regarding the mechanism of action and treatments for pruritus associated with cutaneous T-cell lymphoma. Methods An explicit and thorough search was restricted to all peer-reviewed literature available through MEDLINE (1950 to September 2011) and pubmed.org. Search terms used were pruritus, cutaneous T-cell lymphoma (CTCL), mycosis fungoides (MF), and Sézary Syndrome (SS). All studies that involved pruritus in either CTCL, MF, or SS were evaluated by all three authors. Results The current literature helps to identify therapies and possible mechanisms for treating patients with CTCL associated pruritus. . Limitation Most studies were pre-clinical. Only studies involving mechanisms of action or treatment were included Conclusion A guideline is necessary to assist in the treatment of pruritus in CTCL and additional studies are necessary to uncover the exact mechanism(s) of action. PMID:22285672

  15. 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

  16. 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

  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. PMID:24213148

  18. Immunopathogenesis and therapy of cutaneous T cell lymphoma

    PubMed Central

    Kim, Ellen J.; Hess, Stephen; Richardson, Stephen K.; Newton, Sara; Showe, Louise C.; Benoit, Bernice M.; Ubriani, Ravi; Vittorio, Carmela C.; Junkins-Hopkins, Jacqueline M.; Wysocka, Maria; Rook, Alain H.

    2005-01-01

    Cutaneous T cell lymphomas (CTCLs) are a heterogenous group of lymphoproliferative disorders caused by clonally derived, skin-invasive T cells. Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common types of CTCLs and are characterized by malignant CD4+/CLA+/CCR4+ T cells that also lack the usual T cell surface markers CD7 and/or CD26. As MF/SS advances, the clonal dominance of the malignant cells results in the expression of predominantly Th2 cytokines, progressive immune dysregulation in patients, and further tumor cell growth. This review summarizes recent insights into the pathogenesis and immunobiology of MF/SS and how these have shaped current therapeutic approaches, in particular the growing emphasis on enhancement of host antitumor immune responses as the key to successful therapy. PMID:15841167

  19. Standard and experimental therapy in cutaneous T-cell lymphomas.

    PubMed

    Dummer, Reinhard; Cozzio, Antonio; Meier, Sibylle; Beyeler, Mirjam; Laetsch, Barbara; Doebbeling, Udo; Urosevic, Mirjana

    2006-02-01

    Cutaneous T-cell lymphomas are a heterogeneous group of lymphoproliferative disorders, characterized by the accumulation of clonal lymphocytes in the skin. Skin-directed therapies are the preferred first-line modalities. There are interesting new developments in topical therapy using retinoids and gene-therapy products such as adenovirus- interferon (IFN)-gamma. Systemic treatment uses biologicals such as fusion molecules, monoclonal antibodies and immune response modifiers (IFNs and retinoids), and well-tolerated antiproliferative drugs such as methotrexate. Evidence-based treatment recommendation exists but is hampered by the lack of large multicenter randomized trials. PMID:16412213

  20. 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

    2015-01-01

    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. PMID:26449225

  1. 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. PMID:27319963

  2. Primary cutaneous dermal mucinosis on herpes zoster scars.

    PubMed

    Camacho, Diana; Feltes, Federico; Machán, Salma; Pielasinski, Úrsula; Fariña, María C; Gavin, Eduardo; Requena, Luis

    2016-07-01

    The term isotopic response refers to the appearance of a new skin disease at the site of another unrelated and already healed skin disorder. Often, the first disease is herpes zoster (HZ). Several cutaneous reactions have been described in a dermatome recently affected by HZ. We present the case of a 33-year-old man who developed whitish papules with a zosteriform distribution on HZ scars. Histopathologic study with hematoxylin and eosin and Alcian blue (pH 2.5) staining demonstrated abundant deposits of mucin interstitially arranged between collagen bundles of the papillary dermis. Cutaneous dermal mucinosis as a postherpetic isotopic response is rare, but it should be added to the list of cutaneous reactions arising in HZ scars. PMID:27529717

  3. Tumor-associated B cells in cutaneous primary melanoma and improved clinical outcome.

    PubMed

    Garg, Kanika; Maurer, Margarita; Griss, Johannes; Brüggen, Marie-Charlotte; Wolf, Ingrid H; Wagner, Christine; Willi, Niels; Mertz, Kirsten D; Wagner, Stephan N

    2016-08-01

    B cells often infiltrate the microenvironment of human tumors. B cells can both positively and negatively regulate antitumor immune responses. In several human cancers, higher numbers of CD20(+) TAB are associated with a favorable prognosis, whereas in human primary melanomas, this association is contentious. In this study, we determined the association of TAB numbers in cutaneous primary melanoma tissue samples and patients' overall survival. The CD20 immunohistochemistry on archival nonmetastasized and metastasized cutaneous primary melanoma tissues from 2 independent patient cohorts was performed. One cohort was used in class comparison for metastasis, the most important prognostic factor for overall survival, and the other cohort for a subsequent survival analysis. Survival association was further validated with RNA data from a third independent cohort. Whole tissue sections were read automatically via quantitative digital imaging and analysis. Survival data were analyzed by Cox proportional hazard modeling. We discovered that cutaneous primary melanomas without metastasis contain significantly more TAB than primary melanomas that had metastasized. At time of first diagnosis, a higher number of TAB is associated with a significantly better overall survival in patients with cutaneous primary melanomas of >1 mm Breslow depth. Also, higher CD20/CD19 tumor mRNA levels are correlated with a significantly better overall survival. Thus, our data support TAB numbers as a prognostic biomarker in cutaneous primary melanoma patients with a tumor of >1 mm Breslow depth. For a survey in larger studies, whole tissue section analysis seems to be key to accurate assessment of TAB numbers. PMID:27107457

  4. Prognostic factors in primary cutaneous lymphomas other than mycosis fungoides and the Sézary syndrome. The French Study Group on Cutaneous Lymphomas.

    PubMed

    Grange, F; Hedelin, G; Joly, P; Beylot-Barry, M; D'Incan, M; Delaunay, M; Vaillant, L; Avril, M F; Bosq, J; Wechsler, J; Dalac, S; Grosieux, C; Franck, N; Esteve, E; Michel, C; Bodemer, C; Vergier, B; Laroche, L; Bagot, M

    1999-06-01

    Prognostic studies of primary cutaneous lymphomas (PCL) other than mycosis fungoides (MF) and the Sézary syndrome (SS; non-MF/SS PCL) have been mainly performed on subgroups or on small numbers of patients by using univariate analyses. Our aim was to identify independent prognostic factors in a large series of patients with non-MF/SS PCL. We evaluated 158 patients who were registered in the French Study Group on Cutaneous Lymphomas database from January 1, 1986 to March 1, 1997. Variables analyzed for prognostic value were: age; sex; type of clinical lesions; maximum diameter, location, and number of skin lesions; cutaneous distribution (ie, local, regional, or generalized); prognostic group according to the European Organization for Research and Treatment of Cancer (EORTC) classification for PCL; B- or T-cell phenotype; serum lactate dehydrogenase (LDH) level; and B symptoms. Univariate and multivariate analyses were performed using a model of relative survival. Forty-nine patients (31%) died. The median relative survival time was 81 months. In univariate analysis, EORTC prognostic group, serum LDH level, B symptoms, and variables related to tumor extension (ie, distribution, maximum diameter, and number of skin lesions) were significantly associated with survival. When these variables were considered together in a multivariate analysis, EORTC prognostic group and distribution of skin lesions remained statistically significant, independent prognostic factors. This study confirms the good predictive value of the EORTC classification for PCL and shows that the distribution of skin lesions at initial evaluation is an important prognostic indicator. PMID:10339469

  5. Leucoderma associated with flares of erythrodermic cutaneous T-cell lymphomas: four cases. The French Study Group of Cutaneous Lymphomas.

    PubMed

    Bouloc, A; Grange, F; Delfau-Larue, M H; Dieng, M T; Tortel, M C; Avril, M F; Revuz, J; Bagot, M; Wechsler, J

    2000-10-01

    We describe four patients with erythrodermic cutaneous T-cell lymphomas (two with erythrodermic mycosis fungoides, and two with Sézary syndrome) who presented with extensive hypopigmented lesions that occurred during flares of their cutaneous disease. These cases must be distinguished from previously described hypopigmented mycosis fungoides where hypopigmented lesions were the sole manifestation of the lymphoma. In two cases a biopsy was performed on hypopigmented skin, showing an infiltrate of atypical lymphocytes with epidermotropism and absence of melanocytes, as in vitiligo. It is suggested that the hypopigmentation could be due to the cytotoxicity of tumour or reactional lymphocytes directed against melanocytes. PMID:11069466

  6. 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

  7. Cutaneous vasculitis in primary Sjögren syndrome: classification and clinical significance of 52 patients.

    PubMed

    Ramos-Casals, Manuel; Anaya, Juan-Manuel; García-Carrasco, Mario; Rosas, José; Bové, Albert; Claver, Gisela; Diaz, Luis-Aurelio; Herrero, Carmen; Font, Josep

    2004-03-01

    To analyze the different clinical and histologic types of cutaneous vasculitis in patients with primary Sjögren syndrome (SS), we investigated the clinical and immunologic characteristics of 558 consecutive patients with primary SS from our units and selected those with clinical evidence of cutaneous lesions, excluding drug reactions and xeroderma. All patients fulfilled 4 or more of the diagnostic criteria for SS proposed by the European Community Study Group in 1993. A total of 89 (16%) patients presented with cutaneous involvement (88 female patients and 1 male; mean age, 51.8 yr). The main cutaneous involvement was cutaneous vasculitis, present in 52 (58%) patients. There were 51 (98%) female patients and 1 (2%) male, with a mean age at diagnosis of cutaneous vasculitis of 51 years (range, 20-80 yr). Fourteen presented with cryoglobulinemic vasculitis, 11 with urticarial vasculitis, and the remaining 26, with cutaneous purpura not associated with cryoglobulins. A skin biopsy specimen was obtained in 38 patients (73%). Involvement of small-sized vessels was observed in 36 (95%) patients (leukocytoclastic vasculitis), while the remaining 2 (5%) presented with medium-sized vessel vasculitis (necrotizing vasculitis). Patients with cutaneous vasculitis had a higher prevalence of articular involvement (50% vs 29%, p = 0.044), peripheral neuropathy (31% vs 4%, p < 0.001), Raynaud phenomenon (40% vs 15%, p = 0.008), renal involvement (10% vs 0%, p = 0.028), antinuclear antibodies (88% vs 60%, p = 0.002), rheumatoid factor (78% vs 48%, p = 0.004), anti-Ro/SS-A antibodies (70% vs 43%, p = 0.011), and hospitalization (25% vs 4%, p = 0.005) compared with SS patients without vasculitis. Six (12%) patients died, all of whom had multisystemic cryoglobulinemia.In conclusion, cutaneous involvement was detected in 16% of patients with primary SS, with cutaneous vasculitis being the most frequent process. The main characteristics of SS-associated cutaneous vasculitis were the

  8. Robotic Intracorporeal Continent Cutaneous Urinary Diversion: Primary Description.

    PubMed

    Goh, Alvin C; Aghazadeh, Monty A; Krasnow, Ross E; Pastuszak, Alexander W; Stewart, Julie N; Miles, Brian J

    2015-11-01

    The purpose is to present the first report and describe our novel technique for intracorporeal continent cutaneous diversion after robotic cystectomy. After completion of robot-assisted cystectomy using a standard six-port transperitoneal technique, three additional ports are placed, and the robot is redocked laterally over the patient's right side in the modified lateral position. Our technique replicates step-by-step the principles of the open approach. Ileocolonic anastomosis, ureteroenteral anastomoses, and construction of a hand-sewn right colonic pouch are all performed intracorporeally. Tapering of efferent ileal limb and reinforcement of the ileocecal valve are performed via the extraction site, while the stoma is matured through a prospective port site. Successful robotic intracorporeal creation of a modified Indiana pouch was achieved. Operative time for diversion was 3 hours, with negligible blood loss, and without any intraoperative complications. No major (Clavien III-V) 90-day complications were observed. At a follow-up of 1 year, the patient continues to catheterize without difficulty. We demonstrate the first description of robotic intracorporeal continent cutaneous urinary diversion after robot-assisted cystectomy. We present a systematic minimally invasive approach, replicating the principles of open surgery, which is technically feasible and safe with a good functional result. PMID:25556514

  9. 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. PMID:26433845

  10. Primary effusion lymphoma presenting as a cutaneous intravascular lymphoma

    PubMed Central

    Crane, Genevieve M.; Xian, Rena R.; Burns, Kathleen H.; Borowitz, Michael J.; Duffield, Amy S.; Taube, Janis M.

    2015-01-01

    Primary effusion lymphoma (PEL) is a rare and aggressive lymphoma that arises in the context of immunosuppression and is characterized by co-infection with Epstein–Barr virus (EBV) and human herpesvirus-8/Kaposi sarcoma-associated herpesvirus (HHV-8/KSHV). It was originally described as arising in body cavity effusions, but presentation as a mass lesion (extracavitary PEL) is now recognized. Here, we describe a case of PEL with an initial presentation as an intravascular lymphoma with associated skin lesions. The patient was a 53-year-old man with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) who presented with fevers, weight loss and skin lesions concerning for Kaposi sarcoma (KS). A skin biopsy revealed no evidence of KS; however, dermal vessels contained large atypical cells that expressed CD31 and plasma cell markers but lacked most B- and T-cell antigens. The atypical cells expressed EBV and HHV-8. The patient subsequently developed a malignant pleural effusion containing the same neoplastic cell population. The findings in this case highlight the potential for unusual intravascular presentations of PEL in the skin as well as the importance of pursuing microscopic diagnosis of skin lesions in immunosuppressed patients. PMID:25355615

  11. PRIMARY CUTANEOUS COCCIDIOIDOMYCOSIS—The Criteria for Diagnosis and a Report of a Case

    PubMed Central

    Wilson, J. Walter; Smith, Charles Edward; Plunkett, Orda A.

    1953-01-01

    Study was made of a case of coccidioidomycosis known to have resulted from primary inoculation of the organisms into the skin. Clinical observations and laboratory data were obtained at the time of clinical illness and for a period of five years thereafter. From the information thus obtained and correlation of it with what already was known of coccidioidomycosis, it was concluded that the disease originates very rarely as the result of primary cutaneous inoculation. In most instances lesions suspected to be of this type have actually resulted by dissemination of the organisms to the skin from a previously unrecognized pulmonary focus. Primary cutaneous coccidioidomycotic lesions closely resemble the primary cutaneous lesions (chancres) in other infectious granulomata, such as syphilis, tuberculosis and sporotrichosis. Spontaneous involution should occur within three months and then there should be immunity to reinfection in all but one or two per thousand instances. From these observations certain criteria were evolved by which to determine in a case of coccidioidomycosis with cutaneous manifestations whether or not the infecting organism entered through the skin. ImagesFigure 1.Figure 1. PMID:13082426

  12. Mucor circinelloides Was Identified by Molecular Methods as a Cause of Primary Cutaneous Zygomycosis▿

    PubMed Central

    Iwen, Peter C.; Sigler, Lynne; Noel, Rhonda K.; Freifeld, Alison G.

    2007-01-01

    A case of primary cutaneous zygomycosis caused by Mucor circinelloides is described. Histopathology showed typical hyphae along with chlamydospores. The isolate was identified by molecular and phenotypic methods. The utility of sequence analysis of the internal transcribed spacer region is highlighted; however, further studies are needed to assess species genetic heterogeneity. PMID:17122018

  13. 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.

  14. Primary cutaneous aspergillosis due to Aspergillus tamarii in an immunocompetent host

    PubMed Central

    Sharma, Sadhna; Yenigalla, Bindu Madhav; Naidu, Sujeet Kumar; Pidakala, Premalatha

    2013-01-01

    Primary cutaneous aspergillosis is a rare disease usually caused by Aspergillus fumigatus, Aspergillus flavus, Aspergillus terreus and Aspergillus ustus. It is usually seen in immunocompromised hosts, though some cases are also reported in immunocompetent hosts. We present a case of an immunocompetent farmer who presented with generalised nodules and plaques, mimicking erythema nodosum leprosum but turned out to be cutaneous aspergillosis caused by Aspergillus tamarii. The characteristic ascospores of Aspergillus species were found in skin lesions on fungus isolated in culture. The patient showed excellent response to antifungal therapy. PMID:23970496

  15. Primary cutaneous extranodal marginal zone B-cell lymphoma of the eyelid skin: Diagnostic clues and distinction from other ocular adnexal diseases.

    PubMed

    Stagner, Anna M; Jakobiec, Frederick A; Freitag, Suzanne K

    2016-01-01

    A 60-year-old man developed a rubbery thickening and erythema of his left lateral upper and lower eyelids and lateral canthus over several months. He was treated for an extended period of time for blepharitis and chalazia. Incisional biopsy eventually disclosed microscopically a hypercellular lymphoid population sparing the epidermis that surrounded adnexal structures and infiltrated between orbicularis muscle fibers. Immunohistochemically, the lesion was found to be composed of neoplastic, kappa-restricted B cells with an equal number of reactive T cells and small reactive follicles. The diagnosis was a primary cutaneous extranodal marginal zone B-cell lymphoma of the eyelid skin (EMZL). We review the distinguishing clinical, histopathologic, and immunohistochemical features of cutaneous EMZL and contrast those with EMZL of other ocular adnexal sites. Also offered is a differential diagnosis of cutaneous lymphomas of the eyelid skin, which are predominately T-cell lesions. PMID:26545575

  16. 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

  17. Cutaneous epitheliotropic T-cell lymphoma with systemic dissemination in a dog.

    PubMed

    Mineshige, Takayuki; Kawarai, Shinpei; Yauchi, Takahiro; Segawa, Kazuhito; Neo, Sakurako; Sugahara, Go; Kamiie, Junichi; Hisasue, Masaharu; Shirota, Kinji

    2016-05-01

    Cutaneous epitheliotropic T-cell lymphoma (CETL) is characterized by neoplastic T-cell infiltration of the epidermis, adnexal structures, and oral mucosa. The objective of this report was to describe the pathological findings of a canine case of terminal-stage CETL. A 10-year-old, mixed-breed, neutered male dog was presented with erosion of the oral mucosa and mucocutaneous junction. The dog was diagnosed with CETL with no evidence of metastasis. Despite chemotherapy, the dog was re-presented with oral pain, vomiting, and diarrhea, and died 17 months after the first visit to the hospital. A complete autopsy was performed. Histologic examination of the primary lesion and systemic organs was performed. Gross examination revealed an advanced-stage oral lesion. Distinct tumor formation was not observed in the primary sites and systemic organs. Histologically, the primary oral lesion was characterized by massive intraepithelial infiltration of a large number of neoplastic lymphocytes. The neoplastic cells in the metastatic sites also showed exclusive epitheliotropic proliferation in organs, including the trachea, tonsils, esophagus, stomach, small intestine, colon, anal mucosa, liver, pancreas, kidneys, urinary bladder, prostate gland, ear canals, and auricular and ventral skin. Immunohistochemically, the neoplastic cells were positive for CD3 and negative for CD20 as well as CD79α, supporting a diagnosis of CETL with systemic dissemination. In canine CETL with systemic signs, systemic metastasis should be considered even without evident mass formation. Neoplastic lymphocytes of CETL showed distinct epitheliotropism even in the systemic metastatic sites. PMID:26951331

  18. Lymphatic Invasion as a Prognostic Biomarker in Primary Cutaneous Melanoma

    PubMed Central

    Xu, Xiaowei; Gimotty, Phyllis A.; Guerry, DuPont; Karakousis, Giorgos; Elder, David E.

    2016-01-01

    Melanoma has a propensity for lymph node metastasis. However, the incidence of lymphatic invasion detected by histology alone in primary melanoma is disproportionately low in comparison to the incidence of positive sentinel lymph nodes (SLN). With the discovery of lymphatic endothelial cell markers, such as podoplanin and LYVE-1, lymphatic vessels can be reliably detected in formalin-fixed paraffin-embedded (FFPE) tissues. There is a now consensus that lymphatic invasion detected by immunohistochemical stains in primary melanoma is much more common than previously reported by histological examination alone. Immunohistochemical stains show that lymphangiogenesis and lymphatic invasion in primary melanoma may occur intratumorally or peritumorally, and lymphatic invasion is common across the range of tumor thicknesses in primary vertical growth phase (VGP) melanomas. A number of studies have shown that lymphatic invasion in primary melanoma is associated with a positive sentinel lymph node biopsy and a worse clinical outcome. Although not currently a part of the standard of care for staging of melanoma, the detection of lymphatic invasion in primary melanoma using immunohistochemical markers may be helpful in planning of therapy in some cases and may find a routine role in primary melanoma microscopic attributes in future. PMID:24258984

  19. A novel missense mutation in oncostatin M receptor beta causing primary localized cutaneous amyloidosis.

    PubMed

    Saeedi, Marjan; Ebrahim-Habibi, Azadeh; Haghighi, Alireza; Zarrabi, Fariba; Amoli, Mahsa M; Robati, Reza M

    2014-01-01

    Primary localized cutaneous amyloidosis (PLCA) is a chronic skin disorder, caused by amyloid material deposition in the upper dermis. Autosomal dominant PLCA has been mapped earlier to pathogenic missense mutations in the OSMR gene, which encodes the oncostatin M receptor ß subunit (OSMRß). OSMRß is interleukin-6 family cytokine receptors and possesses two ligands, oncostatin M and interleukin-31, which both have biologic roles in inflammation and keratinocyte cell proliferation, differentiation, and apoptosis. Here, we identified a new OSMR mutation in a Kurdish family for the first time. Blood samples were taken from all the affected individuals in the family. DNA extraction was performed using salting out technique. Primers were designed for intron flanking individual exons of OSMR gene which were subjected to direct sequencing after PCR amplification for each sample. Sequencing showed a C/T substitution at position 613 in the proband. This mutation results in an L613S (leucine 613 to serine) amino acid change. The identified mutation was observed in all affected family members but not in 100 ethnically matched healthy controls. Elucidating the molecular basis of familial PLCA provides new insight into mechanisms of itch in human skin and may lead to new therapeutic targets for pruritus. PMID:25054142

  20. 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

  1. 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.

  2. Estrogen and progesterone receptors in primary cutaneous melanoma.

    PubMed

    Ellis, D L; Wheeland, R G; Solomon, H

    1985-01-01

    Using a variety of techniques, estrogen and progesterone receptors have previously been identified in variable percentages of malignant melanomas. We examined 10 primary superficial spreading melanomas (SSM) with a fluorescent hormone-binding technique for estrogen and progesterone cytoplasmic receptors. Of these 6 SSM were markedly positive for estrogen and progesterone binding. Patients with dysplastic nevus syndrome (DNS) or a family history of DNS were markedly positive for estrogen and progesterone binding. A single patient with lentigo maligna and another patient with lentigo maligna melanoma were negative for estrogen and progesterone binding. None of the 21 control intradermal nevi examined for estrogen and progesterone binding exhibited marked positivity. PMID:3965520

  3. Primary localized cutaneous nodular amyloidosis of the feet: a case report and review of the literature.

    PubMed

    Ritchie, Simon A; Beachkofsky, Thomas; Schreml, Stephan; Gaspari, Anthony; Hivnor, Chad M

    2014-02-01

    Primary localized cutaneous nodular amyloidosis (PLCNA) is a rare disorder that manifests as the cutaneous formation of nodules composed of light-chain amyloid. Although the type of amyloid deposit is similar to primary systemic amyloidosis, there seems to be little, if any, crossover between the 2 diseases. Because reports of PLCNA are sparse, there is no established protocol for treating this disease. This case report presents a 42-year-old man with a visually striking presentation of PLCNA on both feet with some of the lesions possibly being secondary to trauma, a rare phenomenon. The lesions had been present for more than 4 years, and there were no signs or symptoms of systemic amyloidosis. The lesions responded well to a combination of complete curettage followed by CO2; laser ablation. Primary localized cutaneous nodular amyloidosis is rare and difficult to treat, with high rates of recurrence and a concern for progression to systemic amyloidosis. The diagnosis, workup, treatment, and monitoring of PLCNA also are discussed. PMID:24605345

  4. Nodular amyloidosis derived from keratinocytes: an unusual type of primary localized cutaneous nodular amyloidosis.

    PubMed

    Cornejo, Kristine M; Lagana, Frances J; Deng, April

    2015-11-01

    Primary, localized cutaneous amyloidosis includes macular, lichen, and nodular (tumefactive) types in which the amyloid deposits are limited to the dermis without systemic involvement. The material in lichen and macular amyloidosis is derived from epidermal keratinocytes [keratinocyte-derived amyloid (AK)], whereas that in nodular amyloidosis is derived from immunoglobulin light-chains amyloid (AL). Primary, localized cutaneous nodular amyloidosis (PLCNA) is a form of primary, localized cutaneous amyloidosis that has been associated with a risk of progression to systemic amyloidosis. We report an unusual case of nodular AK-type amyloid deposited in the dermis of the feet. The patient is a 60-year-old woman with asymptomatic verrucoid-like lesions present around the medial and lateral aspects of the bilateral heels for 1-2 years. A biopsy showed massive deposition of eosinophilic amorphous material in the papillary and reticular dermis. The material stained positive for Congo red with apple-green birefringence on polarized light. It was also positive for pan-cytokeratin and negative for kappa and lambda light-chain immunostains. An extensive workup was negative for systemic involvement. Lipid chromatography tandem mass spectrometry confirmed that the deposition was AK-type amyloid. We believe that this is the first case of PLCNA with AK deposition. This entity should be included in the differential diagnosis of PLCNA so that an extensive systemic workup may be avoided. PMID:26485243

  5. Primary Cutaneous Interdigitating Dendritic Cell Sarcoma: A Case Report and Review of the Literature.

    PubMed

    Nguyen, Catherine M; Cassarino, David

    2016-08-01

    Interdigitating dendritic cell sarcoma (IDCS) is a rare tumor of spindle to ovoid cells intermixed with lymphocytes and plasma cells. Primary cutaneous IDCS, with no nodal or other organ involvement is extremely rare, with less than 10 cases reported to date. Herein, the authors describe a case in which a 61-year-old man presented with scattered subcutaneous nodules on his left shoulder and right anterior thigh. A biopsy was performed, and the histopathologic findings revealed prominent, diffuse superficial, and deep dermal infiltration by an atypical epithelioid-shaped tumor forming sheets and cords infiltrating throughout the dermis. Immunohistochemical stains were strongly and diffusely positive for S100, CD45, CD68, and lysozyme, whereas CD21, CD23, CD3, CD20, CD30, CD34, and CD117 were all negative. The histologic and immunohistochemical findings were consistent with an IDCS. A positron emission tomography scan was negative for metastases, leading to the diagnosis of primary cutaneous IDCS. The patient was started on chemotherapy with gemcitabine and docetaxel, and was stable at 4 months follow-up. Our findings contribute to the limited existing literature on primary cutaneous IDCS. This is the first documented case in which chemotherapy with gemcitabine and docetaxel was implemented for treatment, helping to establish an optimal treatment protocol for clinical remission. PMID:27442049

  6. [Primary Sjögren's syndrome with cutaneous vasculitis manifested as leg ulcerations].

    PubMed

    Souza, Sonia Cristina de Magalhães; Kuruma, Katia Akemi Miyazato; Andrade, Danieli Castro Oliveira de; Azevedo, Pedro Ming; Figueiredo, Camille Pinto; Borba, Eduardo Ferreira; Gonçalves, Célio Rodrigues; Borges, Cláudia Teresa Lobato

    2004-04-01

    Primary Sjögren's Syndrome (pSS) is an autoimmune disease with a large spectrum of clinical manifestations extending from an organ-specific involvement to a systemic process. The skin is affected quite commonly and the estimated frequency of inflammatory vascular lesions is from 20% to 30%. Two specific, clinically recognizable forms of cutaneous vasculitis predominate, palpable purpura and chronic urticaria, but erythema multiforme, erythema perstans, erythema nodosum, erithematous macules and subcutaneous nodules have also been described. The authors report the case of a 46-year-old female patient, diagnosed as primary SS, who presented ocular and oral symptoms, poliarthritis and laboratory alterations (with a positive ANA, anti-SSA, rheumatoid factor, and hypergammaglobulinemia). Ten years after the diagnosis, she presented leg ulcers. The biopsy confirmed the presence of vasculitic process, and the ulcers improved rapidly after the treatment with endovenous cyclophosphamide. There are only two reports of chronic ulceration of the legs as cutaneous manifestation of SS. The authors stress the importance of considering ulcers in the differential diagnosis of cutaneous involvement of primary SS. PMID:21503546

  7. Skin-Directed Therapies in Cutaneous T-Cell Lymphoma.

    PubMed

    Nguyen, Cuong V; Bohjanen, Kimberly A

    2015-10-01

    Early stage mycosis fungoides represents the most common clinical presentation of cutaneous lymphoma, with skin-directed therapies long established in its treatment. These therapies continue to change as new treatment regimens emerge. Other skin-directed treatments include light and radiation therapy. Therapies with higher levels of evidence and less systemic toxicity are usually preferred as first-line treatment. However, even these established therapies, like topical corticosteroids and carmustine, lack randomized clinical trials to establish their efficacy. Research is also needed to further define the role of combination topical therapies and how skin-directed therapies can be used as adjuvants to systemic medications. PMID:26433841

  8. 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. PMID:27154316

  9. Durable Regression of Primary Cutaneous B-Cell Lymphoma Following Fever-inducing Mistletoe Treatment: Two Case Reports

    PubMed Central

    Lace, Aija; Fonseca, Maria P.; von Laue, Broder H.; Geider, Stefan; Kienle, Gunver S.

    2012-01-01

    Background: Mistletoe is a complementary cancer treatment that is widely used, usually in addition to and alongside recommended conventional cancer therapy. However, little is known about its use, effectiveness, and safety in the treatment of cutaneous lymphoma. Case Report: Two patients with primary cutaneous B-cell lymphoma (pT2bcNxM0 follicle center and pT2ac-NxM0 marginal zone) either declined or postponed recommended conventional treatment and received high-dose, fever-inducing mistletoe treatment; a combination of intratumoral, subcutaneous, and intravenous application was given; and one patient also underwent whole-body hyperthermia. The lymphoma regressed over a period of 12 and 8 months, respectively, and after administration of a cumulative dose of 12.98 g and 4.63 g mistletoe extract, respectively. The patients are in remission to date, 3.5 years after commencement of treatment. Neither patient received conventional cancer treatment during the entire observation period. PMID:24278797

  10. 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. PMID:25954764

  11. Telaprevir may induce adverse cutaneous reactions by a T cell immune-mediated mechanism.

    PubMed

    Federico, Alessandro; Aitella, Ernesto; Sgambato, Dolores; Savoia, Alfonso; De Bartolomeis, Fabio; Dallio, Marcello; Ruocco, Eleonora; Pezone, Luciano; Abbondanza, Ciro; Loguercio, Carmela; Astarita, Corrado

    2015-01-01

    The HCV protease inhibitor telaprevir associated with peginterferon-alpha and ribavirin, was widely used in the recent past as standard treatment in HCV genotype-1 infected patients. Telaprevir improves the sustained virology response rates, but at the same time increases the frequency of adverse cutaneous reactions. However, mechanisms through which telaprevir induces cutaneous lesions are not yet defined. A 50-year-old woman, affected by HCV genotype 1b, was admitted to our Department for a telaprevir-related severe cutaneous eruptions, eight weeks after starting a triple therapy (telaprevir associated with Peginterferon-alpha and ribavirin). Mechanisms of cutaneous reactions were investigated by skin tests with non-irritating concentrations of telaprevir and by activating in vitro T lymphocyte with different concentrations. Immediate and delayed responses to skin testing were negative, but the drug-induced lymphocytes activation was significantly higher as compared to patient's baseline values and to parallel results obtained in three healthy subjects (p < 0.05). In conclusion, adverse cutaneous reactions of our patient were caused by a telaprevir-induced T-cell dependent immune mechanism. PMID:25864225

  12. Mucin 1 is a potential therapeutic target in cutaneous T-cell lymphoma

    PubMed Central

    Stroopinsky, Dina; Yin, Li; Rosenblatt, Jacalyn; Alam, Maroof; Bhargava, Parul; Clark, Rachael A.; Kupper, Thomas S.; Palmer, Kristen; Coll, Maxwell D.; Rajabi, Hasan; Pyzer, Athalia; Bar-Natan, Michal; Luptakova, Katarina; Arnason, Jon; Joyce, Robin; Kufe, Donald; Avigan, David

    2015-01-01

    Cutaneous T-cell lymphoma (CTCL) is an aggressive neoplasm with limited treatments for patients with advanced disease. The mucin 1 C-terminal subunit (MUC1-C) oncoprotein plays a critical role in regulating cell proliferation, apoptosis, and protection from cytotoxic injury mediated by reactive oxygen species (ROS). Although CTCL cells exhibit resistance to ROS-induced apoptosis, the expression and functional significance of MUC1 in CTCL have not been previously investigated. Present studies demonstrate that MUC1-C is overexpressed in CTCL cell lines and primary CTCL cells but is absent in resting T cells from healthy donors and B-cell lymphoma cells. We have developed a cell-penetrating peptide that disrupts homodimerization of the MUC1-C subunit necessary for its nuclear translocation and downstream signaling. We show that treatment of CTCL cells with the MUC1-C inhibitor is associated with downregulation of the p53-inducible regulator of glycolysis and apoptosis and decreases in reduced NAD phosphate and glutathione levels. In concert with these results, targeting MUC1-C in CTCL cells increased ROS and, in turn, induced ROS-mediated late apoptosis/necrosis. Targeting MUC1-C in CTCL tumor xenograft models demonstrated significant decreases in disease burden. These findings indicate that MUC1-C maintains redox balance in CTCL cells and is thereby a novel target for the treatment of patients with CTCL. PMID:26048911

  13. Mucin 1 is a potential therapeutic target in cutaneous T-cell lymphoma.

    PubMed

    Jain, Salvia; Stroopinsky, Dina; Yin, Li; Rosenblatt, Jacalyn; Alam, Maroof; Bhargava, Parul; Clark, Rachael A; Kupper, Thomas S; Palmer, Kristen; Coll, Maxwell D; Rajabi, Hasan; Pyzer, Athalia; Bar-Natan, Michal; Luptakova, Katarina; Arnason, Jon; Joyce, Robin; Kufe, Donald; Avigan, David

    2015-07-16

    Cutaneous T-cell lymphoma (CTCL) is an aggressive neoplasm with limited treatments for patients with advanced disease. The mucin 1 C-terminal subunit (MUC1-C) oncoprotein plays a critical role in regulating cell proliferation, apoptosis, and protection from cytotoxic injury mediated by reactive oxygen species (ROS). Although CTCL cells exhibit resistance to ROS-induced apoptosis, the expression and functional significance of MUC1 in CTCL have not been previously investigated. Present studies demonstrate that MUC1-C is overexpressed in CTCL cell lines and primary CTCL cells but is absent in resting T cells from healthy donors and B-cell lymphoma cells. We have developed a cell-penetrating peptide that disrupts homodimerization of the MUC1-C subunit necessary for its nuclear translocation and downstream signaling. We show that treatment of CTCL cells with the MUC1-C inhibitor is associated with downregulation of the p53-inducible regulator of glycolysis and apoptosis and decreases in reduced NAD phosphate and glutathione levels. In concert with these results, targeting MUC1-C in CTCL cells increased ROS and, in turn, induced ROS-mediated late apoptosis/necrosis. Targeting MUC1-C in CTCL tumor xenograft models demonstrated significant decreases in disease burden. These findings indicate that MUC1-C maintains redox balance in CTCL cells and is thereby a novel target for the treatment of patients with CTCL. PMID:26048911

  14. 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.

  15. Synchronous Occurrence of Primary Cutaneous Anaplastic Large Cell Lymphoma and Squamous Cell Carcinoma

    PubMed Central

    Park, Ji-Hye; Lee, Jae Ho; Lim, Youngkyoung; Lee, You Jin

    2016-01-01

    CD30+ lymphoproliferative disorders (LPD) represent a spectrum of T-cell lymphoma including lymphomatoid papulosis and anaplastic large cell lymphoma (ALCL). Epidermis overlying cutaneous CD30+ LPD often shows epidermal hyperplasia, hyperkeratosis, crusting, and ulceration and it is difficult to distinguish from carcinoma such as keratoacanthoma (KA) or squamous cell carcinoma (SCC). Several cases of pseudocarcinomatous hyperplasia mimicking KA or SCC in CD30+ LPD have been reported. The relationship between CD30+ LPD and epithelial proliferations has not yet well understood. It was reported that a variety of mediators, including epidermal growth factor (EGF), transforming growth factor-α and EGFR from CD30+ LPD could attribute to epidermal hyperplasia. However, separate and distinct SCC occurring in CD30+ LPD has rarely been reported. Herein, we present a rare case of coexistence of SCC and cutaneous ALCL located on the same region. PMID:27489433

  16. Dermatitis artefacta in a 12-year-old girl mimicking cutaneous T-cell lymphoma.

    PubMed

    Angus, Janet; Affleck, Andrew G; Croft, Jane C Ravens; Leach, Iain H; Slater, David N; Millard, Leslie G

    2007-01-01

    Dermatitis artefacta or factitious disease may be unrecognized in children. We present a 12-year-old girl who had an unusual facial lesion on the chin, which was self-inflicted but histologically mimicked cutaneous T-cell lymphoma. Our report emphasizes both the potential diagnostic pitfalls and the importance of clinicopathologic correlation. PMID:17542895

  17. The Role of Systemic Retinoids in the Treatment of Cutaneous T-Cell Lymphoma.

    PubMed

    Huen, Auris O; Kim, Ellen J

    2015-10-01

    Retinoids are natural and synthetic vitamin A analogs with effects on cell proliferation, differentiation, and apoptosis. They have significant activity in hematologic malignancies and have been studied extensively in cutaneous T-cell lymphoma. Retinoids bind to nuclear receptors and exert their effects through moderation of gene expression. Retinoic acid receptor and retinoic X receptor exert regulatory activity in vivo, binding to distinct ligands. Studies investigating systemic retinoids as monotherapy and in combination with other agents active against cutaneous lymphoma are reviewed. Side effects associated with retinoids include teratogenicity, dyslipidemias, and hypothyroidism, which should be carefully monitored in patients receiving treatment. PMID:26433844

  18. Managing Patients with Cutaneous B-Cell and T-Cell Lymphomas Other Than Mycosis Fungoides.

    PubMed

    Kheterpal, Meenal; Mehta-Shah, Neha; Virmani, Pooja; Myskowski, Patricia L; Moskowitz, Alison; Horwitz, Steven M

    2016-06-01

    Cutaneous lymphomas (CL) are a heterogeneous group of neoplasms characterized with clinical and histopathological variation, as well as overlap with benign dermatoses. Diagnosis and treatment of CLs is challenging and often requires a multidisciplinary approach. However, prognostic knowledge of these conditions and awareness of treatment options can help optimize appropriate use of available regimens, thereby improving care for patients. Here, we review the most recent literature and outline treatment themes for managing patients with cutaneous B-cell and T-cell lymphomas other than mycosis fungoides. PMID:27101016

  19. Prognostic significance of periodic acid-Schiff-positive patterns in primary cutaneous melanoma.

    PubMed

    Warso, M A; Maniotis, A J; Chen, X; Majumdar, D; Patel, M K; Shilkaitis, A; Gupta, T K; Folberg, R

    2001-03-01

    The patterns of periodic acid-Schiff (PAS) staining of extracellular matrix in histological sections of certain melanomas may be predictive of outcome. Recent in vitro and molecular genetic data suggest that the appearance of these patterns in both uveal and cutaneous melanoma is a function of aggressive tumor cells. We studied 96 patients with primary cutaneous melanomas treated at the University of Illinois at Chicago who were monitored for disease-free survival. Survival probabilities were determined by Kaplan-Meier estimates, and prognostic factors were evaluated by multivariate analysis. By univariate analysis, there was a significant decrease in disease-free survival among patients whose tumors contained parallel with cross-linking or network patterns (PXNs; P = 0.0070). Stepwise regression with Cox models that included the combinations of the PAS-positive patterns, tumor thickness, female gender, ulceration, and age yielded a model with thickness and the PAS-positive parallel with cross-linking or networks. Despite the relatively small sample size in this study, the detection of the PAS-positive parallel with cross-linking or networking in cutaneous melanoma was associated with a decrease in disease-free outcome. Additional studies of the prognostic significance of these patterns is warranted on larger data sets. PMID:11297236

  20. MicroRNA Profiling of Primary Cutaneous Large B-Cell Lymphomas

    PubMed Central

    Koens, Lianne; Qin, Yongjun; Leung, Wai Y.; Corver, Willem E.; Jansen, Patty M.; Willemze, Rein; Vermeer, Maarten H.; Tensen, Cornelis P.

    2013-01-01

    Aberrant expression of microRNAs is widely accepted to be pathogenetically involved in nodal diffuse large B-cell lymphomas (DLBCLs). However, the microRNAs profiles of primary cutaneous large B-cell lymphomas (PCLBCLs) are not yet described. Its two main subtypes, i.e., primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL-LT) and primary cutaneous follicle center lymphoma (PCFCL) are characterized by an activated B-cell (ABC)-genotype and a germinal center B-cell (GCB)-genotype, respectively. We performed high-throughput sequencing analysis on frozen tumor biopsies from 19 cases of PCFCL and PCLBCL-LT to establish microRNA profiles. Cluster analysis of the complete microRNome could not distinguish between the two subtypes, but 16 single microRNAs were found to be differentially expressed. Single microRNA RT-qPCR was conducted on formalin-fixed paraffin-embedded tumor biopsies of 20 additional cases, confirming higher expression of miR-9-5p, miR-31-5p, miR-129-2-3p and miR-214-3p in PCFCL as compared to PCLBCL-LT. MicroRNAs previously described to be higher expressed in ABC-type as compared to GCB-type nodal DLBCL were not differentially expressed between PCFCL and PCLBCL-LT. In conclusion, PCFCL and PCLBCL-LT differ in their microRNA profiles. In contrast to their gene expression profile, they only show slight resemblance with the microRNA profiles found in GCB- and ABC-type nodal DLBCL. PMID:24358187

  1. MicroRNA profiling of primary cutaneous large B-cell lymphomas.

    PubMed

    Koens, Lianne; Qin, Yongjun; Leung, Wai Y; Corver, Willem E; Jansen, Patty M; Willemze, Rein; Vermeer, Maarten H; Tensen, Cornelis P

    2013-01-01

    Aberrant expression of microRNAs is widely accepted to be pathogenetically involved in nodal diffuse large B-cell lymphomas (DLBCLs). However, the microRNAs profiles of primary cutaneous large B-cell lymphomas (PCLBCLs) are not yet described. Its two main subtypes, i.e., primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL-LT) and primary cutaneous follicle center lymphoma (PCFCL) are characterized by an activated B-cell (ABC)-genotype and a germinal center B-cell (GCB)-genotype, respectively. We performed high-throughput sequencing analysis on frozen tumor biopsies from 19 cases of PCFCL and PCLBCL-LT to establish microRNA profiles. Cluster analysis of the complete microRNome could not distinguish between the two subtypes, but 16 single microRNAs were found to be differentially expressed. Single microRNA RT-qPCR was conducted on formalin-fixed paraffin-embedded tumor biopsies of 20 additional cases, confirming higher expression of miR-9-5p, miR-31-5p, miR-129-2-3p and miR-214-3p in PCFCL as compared to PCLBCL-LT. MicroRNAs previously described to be higher expressed in ABC-type as compared to GCB-type nodal DLBCL were not differentially expressed between PCFCL and PCLBCL-LT. In conclusion, PCFCL and PCLBCL-LT differ in their microRNA profiles. In contrast to their gene expression profile, they only show slight resemblance with the microRNA profiles found in GCB- and ABC-type nodal DLBCL. PMID:24358187

  2. 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

  3. Cutaneous metastasis of unknown primary presenting as massive and invasive abdominal lesion: an elective approach with electrochemotherapy.

    PubMed

    Lido, Paolo; Paolino, Giovanni; Feliziani, Andrea; Santurro, Letizia; Montuori, Mauro; Sanctis, Flavio de; Rossi, Piero; Petrella, Giuseppe; Ricciardi, Edoardo; Fusano, Giuseppe; Augusto, Orlandi; Polisca, Patrizio

    2015-01-01

    We describe herein what is to our knowledge the first reported case of an invasive cutaneous metastasis with unknown primary, electively treated solely with electrochemotherapy. We describe a female patient with a large, invasive and painful lesion in her hypogastric region, extending up to the pubic area. The cutaneous biopsy and instrumental and laboratory analyses, all failed to reveal the primary site. A final diagnosis of cutaneous metastasis with unknown primary was made and treatment was performed with electrochemotherapy. Our case highlights the importance of interdisciplinary choices in clinical practice to cope with the lack of a primary site and to improve quality of life, since no standardized therapy exists for these classes of patients. PMID:26734871

  4. Transcriptome Patterns from Primary Cutaneous Leishmania braziliensis Infections Associate with Eventual Development of Mucosal Disease in Humans

    PubMed Central

    Maretti-Mira, Ana Claudia; Bittner, Jaime; Oliveira-Neto, Manoel Paes; Liu, Minghsun; Kang, Dezhi; Li, Huiying; Pirmez, Claude; Craft, Noah

    2012-01-01

    Introduction Localized Cutaneous Leishmaniasis (LCL) and Mucosal Leishmaniasis (ML) are two extreme clinical forms of American Tegumentary Leishmaniasis that usually begin as solitary primary cutaneous lesions. Host and parasite factors that influence the progression of LCL to ML are not completely understood. In this manuscript, we compare the gene expression profiles of primary cutaneous lesions from patients who eventually developed ML to those that did not. Methods Using RNA-seq, we analyzed both the human and Leishmania transcriptomes in primary cutaneous lesions. Results Limited number of reads mapping to Leishmania transcripts were obtained. For human transcripts, compared to ML patients, lesions from LCL patients displayed a general multi-polarization of the adaptive immune response and showed up-regulation of genes involved in chemoattraction of innate immune cells and in antigen presentation. We also identified a potential transcriptional signature in the primary lesions that may predict long-term disease outcome. Conclusions We were able to simultaneously sequence both human and Leishmania mRNA transcripts in primary cutaneous leishmaniasis lesions. Our results suggest an intrinsic difference in the immune capacity of LCL and ML patients. The findings correlate the complete cure of L. braziliensis infection with a controlled inflammatory response and a balanced activation of innate and adaptive immunity. PMID:23029578

  5. 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.

  6. Cutaneous T-cell lymphoma in an African hedgehog (Atelerix albiventris).

    PubMed

    Spugnini, Enrico P; Pagotto, Annarita; Zazzera, Francesca; D'Avino, Alfredo; Caruso, Giovanni; Citro, Gennaro; Baldi, Alfonso

    2008-01-01

    A three-year-old male African hedgehog was presented for a non healing crusty proliferation on the left pinna. The lesion failed to respond to topical therapy and systemic antibiotic therapy. Whole body radiography and abdominal ultrasonograpy were within normal limits. The lesion was surgically removed. The patient recovered well from the procedure and remained in remission for nine months when he came back as an emergency case and died of an unrelated disease. The histopathology report enabled a diagnosis of completely excised cutaneous T-cell lymphoma. This report represents the first successful treatment of a cutanous T-cell lymphoma in this species and might help to plan future therapies. PMID:18396780

  7. Bcl-2 protein expression is the strongest independent prognostic factor of survival in primary cutaneous large B-cell lymphomas.

    PubMed

    Grange, Florent; Petrella, Tony; Beylot-Barry, Marie; Joly, Pascal; D'Incan, Michel; Delaunay, Michele; Machet, Laurent; Avril, Marie-Francoise; Dalac, Sophie; Bernard, Philippe; Carlotti, Agnes; Esteve, Eric; Vergier, Beatrice; Dechelotte, Pierre; Cassagnau, Elisabeth; Courville, Philippe; Saiag, Philippe; Laroche, Liliane; Bagot, Martine; Wechsler, Janine

    2004-05-15

    Bcl-2 protein expression has been associated with poor prognosis in patients with noncutaneous diffuse large B-cell lymphomas. In primary cutaneous large B-cell lymphomas, the location on the leg, the round-cell morphology defined as the predominance of centroblasts and immunoblasts over large centrocytes, and multiple skin lesions were identified as adverse prognostic factors. The prognostic value of bcl-2 protein expression has not been studied in large series of patients. We evaluated 80 primary cutaneous large B-cell lymphomas collected by the French Study Group on Cutaneous Lymphomas. The prognostic value of age, sex, number of lesions, cutaneous extent, location, serum lactate dehydrogenase (LDH) level, B symptoms, morphology, and bcl-2 protein expression was studied. The overall 5-year specific survival rate was 65%. In univariate analysis, advanced age, multiple skin lesions (n = 48), location on the leg (n = 25), round-cell morphology (n = 32), and bcl-2 expression (n = 39) were significantly related to death from lymphoma. In multivariate analysis, bcl-2 expression (P =.0003), multiple skin lesions (P =.004), and age remained independent prognostic factors. The 5-year specific survival rates in bcl-2-positive and bcl-2-negative patients were 41% and 89%, respectively (P <.0001). A new prognostic classification of primary cutaneous B-cell lymphoma should be based primarily on bcl-2 protein expression rather than the location of skin lesions. PMID:14726400

  8. Mogamulizumab for the treatment of cutaneous T-cell lymphoma: recent advances and clinical potential

    PubMed Central

    Duvic, Madeleine; Evans, Mark; Wang, Casey

    2016-01-01

    Mogamulizumab (KW-0761) is a humanized immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that targets CC chemokine receptor 4 (CCR4). It has shown promising therapeutic potential in phase I and II clinical trials and is currently being investigated for efficacy in treating cutaneous T-cell lymphoma (CTCL). We review the mechanism of action of mogamulizumab and its role in treating CTCL. We also discuss the results of major clinical trials. PMID:27247757

  9. 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. PMID:26667562

  10. Lack of lymphangiogenesis in human primary cutaneous melanoma. Consequences for the mechanism of lymphatic dissemination.

    PubMed Central

    de Waal, R. M.; van Altena, M. C.; Erhard, H.; Weidle, U. H.; Nooijen, P. T.; Ruiter, D. J.

    1997-01-01

    Cutaneous melanoma has an initial preference for lymphatic spread. Remarkably, melanoma progression toward this metastasizing phenotype is accompanied by intense blood vessel angiogenesis (hemangiogenesis), but lymphangiogenesis, the formation of new lymph vessels in the tumor, has never been reported. To investigate how primary melanoma cells interact with the existing lymphatic microvasculature, and whether lymphangiogenesis occurs, an immunostaining was developed that differentially decorates blood and lymph vessels in frozen tissue sections. The density and distribution of both these vessel types in and around thin (< or = 1.5 mm) and thick (> or = 1.5 mm) primary melanoma lesions and in normal and uninvolved skin were determined. Although especially in thick melanoma lesions a significant increase in blood vessel density was observed, lymphatic density remained unaltered, showing that lymphangiogenesis did not occur. Morphological analysis indicated, however, that melanoma progression is accompanied by a sequence of events that involves hemangiogenesis supporting tumor expansion, especially in the vertical growth phase. Often, stromal sepia are formed around the blood capillaries in the tumor neovasculature protecting them from invasion. Lymph vessels inside the tumor were infrequently observed. However, subepidermal lymph vessels often seemed to be entrapped and penetrated by the expanding tumor mass. In this way, hemangiogenesis, as the driving force behind tumor expansion, might indirectly increase the chance of lymphatic invasion in the absence of lymphangiogenesis. This model explains the paradox that, although melanoma metastasis seems to require angiogenesis, a consistent relation of prognosis with blood capillary density in primary cutaneous melanoma is lacking. Images Figure 1 Figure 2 Figure 3 PMID:9176389

  11. Autoimmunity in primary T-cell immunodeficiencies.

    PubMed

    Azizi, Gholamreza; Ghanavatinejad, Alireza; Abolhassani, Hassan; Yazdani, Reza; Rezaei, Nima; Mirshafiey, Abbas; Aghamohammadi, Asghar

    2016-09-01

    Primary immunodeficiency diseases (PID) are a genetically heterogeneous group of more than 270 disorders that affect distinct components of both humoral and cellular arms of the immune system. Primary T cell immunodeficiencies affect subjects at the early age of life. In most cases, T-cell PIDs become apparent as combined T- and B-cell deficiencies. Patients with T-cell PID are prone to life-threatening infections. On the other hand, non-infectious complications such as lymphoproliferative diseases, cancers and autoimmunity seem to be associated with the primary T-cell immunodeficiencies. Autoimmune disorders of all kinds (organ specific or systemic ones) could be subjected to this class of PIDs; however, the most frequent autoimmune disorders are immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA). In this review, we discuss the proposed mechanisms of autoimmunity and review the literature reported on autoimmune disorder in each type of primary T-cell immunodeficiencies. PMID:27063703

  12. Primary Cutaneous Coccidioidomycosis in an Italian Nun Working in South America and Review of Published Literature.

    PubMed

    Tortorano, A M; Carminati, G; Tosoni, A; Tintelnot, K

    2015-10-01

    Coccidioidomycosis is a systemic disease caused by the dimorphic fungus Coccidioides, endemic in parts of the Southwestern USA and Central and South America. Two species, Coccidioides immitis and Coccidioides posadasii, were differentiated. Primary cutaneous coccidioidomycosis (PCC) has been reported rarely. An unusual case of PCC characterized by a persistent solitary lesion diagnosed in Italy in an immunocompetent Italian nun living in Argentina is described. The isolate was identified by sequence analysis as C. posadasii. Antibody screening was negative. A total of 39 cases of PCC have been reported in the literature. Infections occurred as a consequence of traumatic implantation in a natural setting in endemic areas or of accidental inoculation in laboratory workers. Importance of accurate investigation of travel history and of occupational hazards to laboratory workers is outlined. PMID:25935662

  13. Disruption of CCL20-CCR6 interaction inhibits metastasis of advanced cutaneous T-cell lymphoma

    PubMed Central

    Ito, Mitsugu; Abe, Fumito; Nara, Miho; Watanabe, Atsushi; Takahashi, Naoto; Miyagaki, Tomomitsu; Sugaya, Makoto; Tagawa, Hiroyuki

    2016-01-01

    We recently demonstrated that upregulation of a chemokine receptor CCR6 and its ligand CCL20 led to metastasis of advanced cutaneous T-cell lymphoma (CTCL) cells, suggesting the involvement of CCL20-CCR6 interaction in initiating CTCL cell metastasis. In this study, we determined whether this interaction is functional in metastatic CTCL cells. We first demonstrated increased STAT3 expression during the progression of primary CTCL. STAT3 was spontaneously activated and mediated the transcription of CCL20 in CTCL cell lines. Next, to determine whether the transient knockdown of STAT3, CCL20, or CCR6 or treatment with neutralizing antibody against CCL20 (neutralizing CCL20 antibody) could reduce the migration ability of CTCL cells, we conducted an in vitro migration assay. All treatments reduced the nutrition-dependent migration activity of CTCL cells. Notably, treatment with neutralizing CCL20 antibody reduced the migration ability of the cells without decreasing the expression of CCL20 and CCR6. This demonstrated that the CCL20-CCR6 interaction is actually functional in metastatic CTCL cells. Finally, to examine the in vivo effect of neutralizing CCL20 antibody, we used NOD/Shi-scid IL-2γnul mice inoculated with CTCL cells. These mice were expected to die due to metastasis of CTCL cells into multiple organs. However, administration of neutralizing CCL20 antibody significantly prolonged the survival of the xenografted mice. These findings suggested that automatic activation of the STAT3/CCL20/CCR6 cascade was involved in CTCL lymphomagenesis and that disruption of CCL20-CCR6 interaction could be a key therapeutic strategy against advanced CTCL. PMID:26789110

  14. 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. PMID:26923912

  15. Aggressive primary cutaneous B-cell lymphomas show increased Angiopoietin-2-induced angiogenesis.

    PubMed

    Teichert, Martin; Stumpf, Christine; Booken, Nina; Wobser, Marion; Nashan, Dorothee; Hallermann, Christian; Mogler, Carolin; Müller, Cornelia S L; Becker, Jürgen C; Moritz, Rose K C; Andrulis, Mindaugas; Nicolay, Jan P; Goerdt, Sergij; Thomas, Markus; Klemke, Claus-Detlev; Augustin, Hellmut G; Felcht, Moritz

    2015-06-01

    Primary cutaneous large B-cell lymphomas, leg type (PCLBCL/LT) are primary cutaneous B-cell lymphoma (PCBCL) with an intermediate prognosis. Therefore, antracycline-based polychemotherapy combined with rituximab has been recommended as first-line treatment. Yet, despite this regimen, the 5-year survival rate remains 50-66% only. Angiogenesis, the formation of a vascular network, is essential for the pathogenesis of nodal lymphomas. So far, no study has analysed angiogenesis and its key factors in PCLBCL/LT. The present study was aimed at characterizing angiogenesis in PCLBCL/LT to identify the angiogenic molecules as potential therapeutic targets. The intra-tumoral microvessel density (MVD) was assessed by immunohistochemical studies of CD20 and CD31. The MVD was higher in PCLBCL/LT compared with indolent PCBCL. Analyses of open-source microarray data showed correlation between the angiogenic molecule angiopoietin-2 (Ang-2) and pan-endothelial cell markers. ELISA studies determined a shift between Ang-2 and Ang-1 towards Ang-2 in the peripheral blood of PCLBCL/LT patients. Immunofluorescence costainings against the Ang receptor Tie2/angiogenic integrins/CD34 revealed that the vasculature in both aggressive and indolent PCBCL tumors harbours an endothelial cell subpopulation with reduced expression of Tie2. In contrast, the alternative Ang-2 binding partners, angiogenic integrins, are strongly expressed in PCBCL. In line with these findings, downstream targets of Ang-2-integrin signalling, that is phosphorylation of focal adhesion kinase at Tyr397, and sprouting angiogenesis are enhanced in PCLBCL/LT. Our data present Ang-2 as a promising therapeutic target and anti-angiogenic therapy as a new line in treatment of PCLBCL/LT as a hitherto intractable disease. PMID:25776770

  16. 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.

  17. 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

  18. Expression of Human Endogenous Retrovirus-W Including Syncytin-1 in Cutaneous T-Cell Lymphoma

    PubMed Central

    Maliniemi, Pilvi; Vincendeau, Michelle; Mayer, Jens; Frank, Oliver; Hahtola, Sonja; Karenko, Leena; Carlsson, Emilia; Mallet, Francois; Seifarth, Wolfgang; Leib-Mösch, Christine; Ranki, Annamari

    2013-01-01

    The pathomechanism of mycosis fungoides (MF), the most common type of primary cutaneous T-cell lymphomas (CTCLs) and a malignancy of non-recirculating, skin-resident T-cells, is unknown albeit underlying viral infections have been sought for. Human endogenous retroviruses (HERVs) are ancient retroviral sequences in the human genome and their transcription is often deregulated in cancers. We explored the transcriptional activity of HERV sequences in a total of 34 samples comprising MF and psoriasis skin lesions, as well as corresponding non-malignant skin using a retrovirus-specific microarray and quantitative RT-PCR. To identify active HERV-W loci, we cloned the HERV-W specific RT-PCR products, sequenced the cDNA clones and assigned the sequences to HERV-W loci. Finally, we used immunohistochemistry on MF patient and non-malignant inflammatory skin samples to confirm specific HERV-encoded protein expression. Firstly, a distinct, skin-specific transcription profile consisting of five constitutively active HERV groups was established. Although individual variability was common, HERV-W showed significantly increased transcription in MF lesions compared to clinically intact skin from the same patient. Predominantly transcribed HERV-W loci were found to be located in chromosomes 6q21 and 7q21.2, chromosomal regions typically altered in CTCL. Surprisingly, we also found the expression of 7q21.2/ERVWE1-encoded Syncytin-1 (Env) protein in MF biopsies and expression of Syncytin-1 was seen in malignant lymphocytes, especially in the epidermotropic ones, in 15 of 30 cases studied. Most importantly, no Syncytin-1 expression was detected in inflammatory dermatosis (Lichen ruber planus) with skin-homing, non-malignant T lymphocytes. The expression of ERVWE1 mRNA was further confirmed in 3/7 MF lesions analyzed. Our observations strengthen the association between activated HERVs and cancer. The study offers a new perspective into the pathogenesis of CTCL since we demonstrate

  19. (18)FDG PET/CT appearance in primary cutaneous diffuse large B-cell lymphoma, leg type.

    PubMed

    Samarghandi, Amin; Gru, Alejandro Ariel; Natwa, Mona; Barker, David W

    2015-06-01

    We report the case of a 70-year-old woman who presented with a small and painless red skin nodule in the right lower leg, which rapidly and significantly increased in size over few weeks and developed a central eschar. Skin biopsy was consistent with primary cutaneous diffuse large B-cell lymphoma, leg type (PCDBCL-LT), an aggressive and rare cutaneous lymphoma. F-FDG PET/CT showed a hypermetabolic soft tissue mass in the right leg with no evidence of systemic involvement of disease. PMID:25742229

  20. BRAF and Epithelial-Mesenchymal Transition: Lessons From Papillary Thyroid Carcinoma and Primary Cutaneous Melanoma.

    PubMed

    Mitchell, Brendon; Dhingra, Jagdish K; Mahalingam, Meera

    2016-07-01

    The increased prevalence of BRAF mutations in thyroid carcinoma and primary cutaneous melanoma (PCM) hint that dysregulation of BRAF might contribute to the noted association between PCM and thyroid carcinoma. A recent study evaluating the rate of BRAFV600E mutations among patients who had been diagnosed with primary papillary thyroid carcinoma (PTC) and PCM showed that patients with either PCM or PTC were at an increased risk of developing the other as a second primary malignant neoplasm. Furthermore, the authors noted that samples from patients suffering from both malignancies exhibited a higher rate of incidence of the BRAFV600E mutation, compared with patients not suffering from both malignancies. These studies support the hypothesis that the pathogenesis of these 2 malignancies might share a conserved molecular pattern associated with dysregulation of the BRAF protein. One mechanism through which BRAF might contribute to PCM and thyroid carcinoma progression is through induction of epithelial-mesenchymal transition (EMT). Specifically, the Snail/E-cadherin axis has been demonstrated as a pathway dysregulated by BRAF, leading to EMT in both malignancies. Our analysis focuses on the results of these recent investigations, and through a review of select molecules relevant to EMT, looks to provide a context by which to better understand the relevance and role of stromal-parenchymal signaling and the BRAF mutation in the pathogenesis of PTC and PCM. PMID:27145091

  1. Retroviral Transduction of Murine Primary T Lymphocytes

    PubMed Central

    Lee, James; Sadelain, Michel; Brentjens, Renier

    2016-01-01

    Summary In comparison to human T cells, efficient retroviral gene transfer and subsequent expansion of murine primary T cells is more difficult to achieve. Herein, we describe an optimized gene transfer protocol utilizing an ecotropic viral vector to transduce primary murine T cells activated with magnetic beads coated with agonistic anti-CD3 and CD28 antibodies. Activated T cells are subsequently centrifuged (spinoculated) on RetroNectin-coated tissue culture plates in the context of retroviral supernatant. Variables found to be critical to high gene transfer and subsequent efficient T cell expansion included CD3/CD28 magnetic bead to cell ratio, time from T cell activation to initial spinoculation, frequency of T cell spinoculation, interleukin-2 concentration in the medium, and the initial purity of the T cell preparation. PMID:19110621

  2. Primary and Metastatic Cutaneous Melanomas Express ALK Through Alternative Transcriptional Initiation.

    PubMed

    Busam, Klaus J; Vilain, Ricardo E; Lum, Trina; Busam, Jonathan A; Hollmann, Travis J; Saw, Robyn P M; Coit, Daniel C; Scolyer, Richard A; Wiesner, Thomas

    2016-06-01

    A number of common driver mutations have been identified in melanoma, but other genetic or epigenetic aberrations are also likely to play a role in the pathogenesis of melanoma and present potential therapeutic targets. Translocations of the anaplastic lymphoma kinase (ALK), for example, have been reported in spitzoid melanocytic neoplasms leading to kinase-fusion proteins that result in immunohistochemically detectable ALK expression. In this study, we sought to determine whether ALK was also expressed in nonspitzoid primary and metastatic cutaneous melanomas. ALK immunohistochemistry was performed on 603 melanomas (303 primary and 300 metastatic tumors) from 600 patients. ALK immunohistochemistry expression was identified in 7 primary and 9 metastatic tumors. In 5 of 7 primary tumors and in 6 of 9 metastatic lesions, the majority of tumor cells were immunoreactive for ALK. In the other 2 primary and 3 metastatic lesions, positive staining was identified in less than half of the tumor cells. ALK positivity was found in the presence or absence of BRAF or NRAS mutations. In contrast to prior observations with ALK-positive Spitz tumors, none of the ALK-positive melanomas harbored a translocation. Instead, the ALK-positive melanomas predominantly expressed the recently described ALK isoform, ALK, which lacks the extracellular and transmembrane domains of wild-type ALK, consists primarily of the intracellular tyrosine kinase domain, and originates from an alternative transcriptional initiation site within the ALK gene. The findings are clinically relevant as patients with metastatic melanoma who have ALK expression may potentially benefit from treatment with ALK kinase inhibitors. PMID:26872010

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

    PubMed

    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; Odum, Niels

    2016-03-10

    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

  4. 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

  5. Vasculogenic mimicry has no prognostic significance in pT3 and pT4 cutaneous melanoma.

    PubMed

    Massi, Daniela; Franchi, Alessandro; Paglierani, Milena; Ketabchi, Sheyda; Borgognoni, Lorenzo; Reali, Umberto Maria; Santucci, Marco

    2004-04-01

    The concept of vasculogenic mimicry has been introduced to define periodic acid-Schiff (PAS)-positive channels and loops lined by tumor cells, instead of endothelium, able to contribute to microcirculation in uveal melanomas. Previous studies have shown that the PAS-positive patterns are associated with a poor prognosis in uveal melanoma. The aim of the current study was to investigate whether vasculogenic mimicry has a prognostic impact in pT3 and pT4 cutaneous melanoma. Fifteen patients with pT3 and pT4 cutaneous melanoma who did not experience progression after 10 years of follow-up and 30 matched controls who underwent progression were selected. Tumor sections were stained with PAS reaction, omitting the nuclear counterstaining. For immunohistochemistry, sections were stained with CD31, CD105 (endoglin), and laminin. Differences in the distribution of the PAS-positive patterns and a series of clinicopathological variables were evaluated by the Pearson chi(2) and Mann-Whitney U tests. We observed PAS-positive linear sheets, arcs, elliptical loops, and networks encircling roundish to oval aggregates of melanoma cells. The overall distribution of the PAS-positive patterns did not match with the blood microvessels' architecture as detected by immunohistochemical analysis. No statistically significant differences in the distribution of PAS-positive patterns were found between cases and controls. The presence of a parallel pattern correlated significantly with thickness (P = 0.04), whereas an inverse correlation was found with vessel area (P = 0.05). In conclusion, our results suggest that there is a mismatch between vasculogenic mimicry and tumor angiogenesis and do not support any prognostic role of vasculogenic mimicry in thick cutaneous melanoma. PMID:15116332

  6. 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. PMID:26112998

  7. A case of syringotropic cutaneous T-cell lymphoma treated with local radiotherapy.

    PubMed

    Jacob, Rojymon; Scala, Matthew; Fung, Maxwell A

    2009-01-01

    Syringotropic cutaneous T-cell lymphoma (SCTCL) is a variant of mycosis fungoides that is characterized by the presence of lymphocytic infiltration of eccrine glandular structures and the absence of the classic features of MF, such as epidermotropism and Pautrier's microabscesses. We report a patient with SCTCL who presented with multiple hypopigmented patches and localized alopecia who was treated with local radiotherapy with excellent local control. In our experience, local electron radiation offers local control in early stage SCTCL, and it may be possible to reserve systemic therapy for more advanced stages of the disease. PMID:19103368

  8. [Cutaneous lymphomas: new entities and rare variants].

    PubMed

    Kempf, W; Mitteldorf, C

    2015-02-01

    Primary cutaneous lymphomas are the second most common group of extranodal non-Hodgkin lymphomas. Recently several new variants and entities have been described but have not yet become part of the World Health Organization (WHO) classification. These forms include the granulomatous form of mycosis fungoides, which is associated with a poorer prognosis, as well as indolent CD8+ lymphoproliferations on the head and at acral localizations. Within the group of cutaneous CD30+ lymphoproliferative disorders, new histological types of lymphomatoid papulosis have been identified, such as type D (CD8+ epidermotropic) and type E (angioinvasive) which simulate aggressive lymphomas. Cutaneous peripheral T-cell lymphomas are a prognostically heterogeneous group of cutaneous lymphomas. The cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma and cutaneous gamma/delta T-cell lymphoma are very aggressive neoplasms, whereas cutaneous CD4+ small to medium-sized T-cell lymphoma in its solitary or localized form represents an indolent lymphoproliferation: the terminology, histogenesis and differentiation from nodular T-cell pseudolymphoma are still a matter of debate. Among B-cell lymphomas, disorders associated with Epstein-Barr virus (EBV) are discussed focusing on EBV diffuse large B-cell lymphoma of the elderly and EBV-associated mucocutaneous ulcer. This review describes the clinical, histological and immunophenotypic features of new and rare entities and variants of cutaneous lymphomas and highlights the impact of the clinicopathological correlation in the diagnostic process. PMID:25589355

  9. 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. PMID:26984345

  10. Primary Squamous Cell Carcinoma of Submandibular Salivary Gland with Sialo-Cutaneous Fistula: A Rare Case Report

    PubMed Central

    Thakur, Sanjiv S.

    2015-01-01

    Malignant tumours of the submandibular salivary glands are rare entities. Most common malignant tumour of submandibular gland is mucoepidermoid carcinoma. Histological finding of squamous cell carcinoma is very rare in submandibular salivary gland. Metastasis from distant primary squamous malignancy, direct invasion from cutaneous or mucosal squamous carcinoma, squamous component of mucoepidermoid carcinoma or primary squamous cell carcinoma of salivary origin are some of the possible causes. Of these, the latter is distinctly uncommon. Primary squamous malignancy is diagnosed only after ruling out other possible explanations. A positive mucin stain in the tumour or synchronous/ metachronous squamous carcinoma elsewhere excludes the diagnosis of a primary carcinoma. Primary squamous carcinoma is seen most commonly in parotid gland and rarely in submandibular gland. We present a case of primary squamous cell carcinoma of right submandibular salivary gland in a 45-year old-man. This case is presented for the rare entity of primary squamous cell carcinoma in submandibular salivary gland. PMID:26435997

  11. Primary cellulitis and cutaneous abscess caused by Yersinia enterocolitica in an immunocompetent host

    PubMed Central

    Kato, Hirofumi; Sasaki, Shugo; Sekiya, Noritaka

    2016-01-01

    Abstract 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

  12. Primary Uterine Peripheral T-cell Lymphoma

    PubMed Central

    Gong, Jing; Dong, Aisheng; Wang, Yang; Zhang, Xuefeng; Yang, Panpan; Wang, Li; Jing, Wei

    2016-01-01

    Abstract Primary uterine non-Hodgkin's lymphoma is extremely rare accounting for <1% of all extranodal non-Hodgkin's lymphomas. Imaging findings of primary uterine lymphoma have rarely been reported before. We present magnetic resonance imaging (MRI) and fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT findings in a patient with primary uterine peripheral T-cell lymphoma. A 27-year-old female presented with intermittent fever with neutropenia for 7 months. MRI showed an ill-defined mass involved both the uterine corpus and cervix, resulting in diffuse enlargement of the uterus. This mass showed inhomogeneous hypointensity on unenhanced T1-weighted images, hyperintensity on diffusion-weighted imaging, relative hypointensity compared to the surrounding myometrium on T2-weighted images and lower enhancement than the surrounding myometrium on enhanced T1-weighted images. FDG PET/CT showed intense FDG uptake in the thickened wall of the uterine corpus and cervix with SUVmax of 26.9. There were multiple hypermetabolic lymph nodes in the pelvis and retroperitoneum. Uterine curettage and CT-guided biopsy of the uterine mass revealed peripheral T-cell lymphoma. Bone marrow biopsy revealed no evidence of lymphomatous involvement. The imaging and pathologic findings were consistent with primary uterine lymphoma. After 3 circles of chemotherapy, follow-up enhanced MRI showed decreased thickness of the uterine wall. Despite its rarity, primary uterine non-Hodgkin's lymphoma should be taken into consideration when a uterine tumor shows large size, relative hypointesity on both T2-weighted images and enhanced T1-weighted images compared to the surrounding myometrium, and intense FDG uptake on PET/CT. MRI may be helpful for describing the relationship between the tumor and adjacent structures. FDG PET/CT may be useful for tumor detection and staging. PMID:27124063

  13. Nail Alterations in Cutaneous T-Cell Lymphoma: A Case Series and Review of Nail Manifestations

    PubMed Central

    Bishop, Brian E.; Wulkan, Adam; Kerdel, Francisco; El-Shabrawi-Caelen, Laila; Tosti, Antonella

    2015-01-01

    Background Cutaneous T-cell lymphoma (CTCL) encompasses a broad range of lymphoproliferative diseases affecting the skin and can be clinically misleading due to its variable presentation. Nail alterations commonly appear in advanced-stage mycosis fungoides and true Sézary syndrome; however, they may be present in any stage of the disease. Although proper recognition of nail involvement in CTCL has both clinical and therapeutic value, specific nail findings have been infrequently described in the current literature. Observations We describe 4 patients with CTCL who presented with clinically significant nail alterations. The most common findings were nail discoloration, thickening, crumbling, onycholysis, and onychomadesis. Other notable findings included splinter hemorrhages, subungual hyperkeratosis, and anonychia. Conclusions and Message The described cases illustrate many of the documented nail findings associated with CTCL and emphasize the variable nature of nail manifestations. The presence of specific nail alterations should increase the clinical suspicion of CTCL – especially in patients with concomitant systemic and/or cutaneous manifestations – and early biopsy specimens should be taken for diagnosis. Nail alterations should also be accurately described and monitored in all patients with biopsy-confirmed CTCL to help identify treatment response and detect disease recurrence. PMID:27170938

  14. Ectopic expression of B-lymphoid kinase in cutaneous T-cell lymphoma

    PubMed Central

    Krejsgaard, Thorbjørn; Vetter-Kauczok, Claudia S.; Woetmann, Anders; Kneitz, Hermann; Eriksen, Karsten W.; Lovato, Paola; Zhang, Qian; Wasik, Mariusz A.; Geisler, Carsten; Ralfkiaer, Elisabeth; Becker, Juergen C.

    2009-01-01

    B-lymphoid kinase (Blk) is exclusively expressed in B cells and thymocytes. Interestingly, transgenic expression of a constitutively active form of Blk in the T-cell lineage of mice results in the development of T-lymphoid lymphomas. Here, we demonstrate nuclear factor–kappa B (NF-κB)–mediated ectopic expression of Blk in malignant T-cell lines established from patients with cutaneous T-cell lymphoma (CTCL). Importantly, Blk is also expressed in situ in lesional tissue specimens from 26 of 31 patients with CTCL. Already in early disease the majority of epidermotropic T cells express Blk, whereas Blk expression is not observed in patients with benign inflammatory skin disorders. In a longitudinal study of an additional 24 patients biopsied for suspected CTCL, Blk expression significantly correlated with a subsequently confirmed diagnosis of CTCL. Blk is constitutively tyrosine phosphorylated in malignant CTCL cell lines and spontaneously active in kinase assays. Furthermore, targeting Blk activity and expression by Src kinase inhibitors and small interfering RNA (siRNA) inhibit the proliferation of the malignant T cells. In conclusion, this is the first report of Blk expression in CTCL, thereby providing new clues to the pathogenesis of the disease. PMID:19351960

  15. Hypopigmented interface T-cell dyscrasia: a form of cutaneous T-cell dyscrasia distinct from hypopigmented mycosis fungoides.

    PubMed

    Magro, Cynthia M; Hagen, Joshua W; Crowson, Arthur N; Liu, Yen Chen; Mihm, Martin; Drucker, Natalie M; Yassin, Aminah H

    2014-07-01

    Hypopigmentation in cutaneous T-cell lymphoproliferative disease should not always be equated with hypopigmented mycosis fungoides (MF). A form of hypopigmented pre-lymphomatous T-cell dyscrasia falling under the designation of the so-called hypopigmented interface variant of T-cell dyscrasia has recently been proposed. The aim of the present study was to establish hypopigmented interface T-cell dyscrasia as its own entity apart from other T-cell dyscrasias and MF using a patient case series. Twenty four cases of hypopigmented interface T-cell dyscrasia were identified in the dermatopathology database of Weill Medical College of Cornell University. There were 17 females and seven males (mean age, 36 years). In children and adolescents, the patients were most commonly of African American extraction. Truncal photo-protected areas manifesting as large solitary patches or multiple smaller macules were characteristic; disease progression to MF occurred in only one patient. The lesions responded to topical steroids and light therapy. The pathology was defined by a cell poor interface associated with degeneration of keratinocytes and melanocytes, and by lymphocytes whose nuclei showed low-grade cerebriform atypia, and which expressed a significant reduction in CD7 and CD62L expression. In 50% of the cases, the implicated cell type was of the CD8 subset. Clonality was not identified. Hypopigmented interface T-cell dyscrasia is a distinct entity separate from and rarely progressive to MF. PMID:24806661

  16. Analysis of the Clinical and Histopathological Patterns of 100 Consecutive Cases of Primary Cutaneous Melanoma and Correlation with Staging

    PubMed Central

    Nam, Kyung Wook; Bae, Seong Hwan; Song, Kyung Ho; Kim, Hoon Soo; Choi, Young Jin

    2015-01-01

    Background This study analyzed 100 consecutive patients with primary cutaneous melanoma over the course of 13 years to determine whether epidemiological differences correspond to different stages of the disease. We also investigated whether epidemiological characteristics affected the survival rate. Our results were compared with those of selected descriptive studies of melanoma in other East Asian populations, in order to determine whether cutaneous melanoma patterns are similar in East Asian populations. Methods The patients' medical records were reviewed retrospectively, and we analyzed the relationship of epidemiological characteristics to staging and survival rate. Additionally, papers from Hong Kong and Japan describing these phenomena in East Asian populations were subjected to a statistical comparison. Results The ratio of males to females was 1:1.8, and the foot was the most frequent tumor site (49%). Acral lentiginous melanoma occurred most frequently (55%). Nodular melanoma was associated with a higher stage. Stage III-IV tumors with Clark levels of IV-V were significantly associated with a low survival rate. A statistical analysis of comparable papers reported in Hong Kong and Japan showed similar results with regard to age, tumor location, and histopathological subtypes. Conclusions This study provides the first full epidemiological description of 100 consecutive cases of primary cutaneous melanoma in Korea, with results similar to those observed in other East Asian populations. Corresponding to previous findings, nodular melanoma tended to occur at a higher stage than other types, and tumors with high Clark levels and high stages showed a lower survival rate. PMID:26618123

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

    PubMed Central

    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. PMID:26813734

  18. 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. PMID:26813734

  19. Health-Related Quality of Life in Patients with Primary Cutaneous Amyloidosis

    PubMed Central

    Fang, Sheng; Shen, Xiao; Chen, Ai-Jun; Li, Shuang; Shan, Kui

    2015-01-01

    Background Primary cutaneous amyloidosis (PCA) is a relatively rare and itchy skin disorder characterized by amyloid deposits in the superficial dermis. The cosmetic disfigurement and severe pruritus dramatically affects the patient’s quality of life. In spite of the prevalence of the disease in China, the quality of life (QoL) impact of the PCA has not been well defined and is the focus of this study. Objective To examine the HRQoL of patients with PCA and to evaluate the association between HRQoL scores, disease, and socio-demographic determinants. Methods A total of 104 PCA patients and 101 healthy participants completed the questionnaires. HRQoL was measured using dermatology life quality index (DLQI) and SF-36. The socio demographic and clinical data such as age, sex, duration of disease and distribution of lesion pattern were analyzed mainly by hierarchical multiple regression analyses. Results Patients with PCA experienced significantly impaired health-related quality of life. The mean DLQI score was 9.05. Younger age, female gender, more pruritus and distribution pattern were independent predictor correlates of the high DLQI scores. The PCA group showed significantly decreasing average scores in several aspects of psychological symptoms, including SF, RE and MH. Conclusions PCA disease has a negative impact on the HRQoL of patients, and the HRQoL is associated with various disease characteristics. In conjunction with medical interventions, psychological and sociocultural assessment and intervention should be an essential part of the management of these cases. PMID:25799390

  20. 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

  1. 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

  2. Therapeutic advances in cutaneous T-cell lymphoma (CTCL): from retinoids to rexinoids.

    PubMed

    Stadler, Rudolf; Kremer, Almut

    2006-02-01

    Retinoids comprise a family of polyisoprenoid lipids that include vitamin A (retinol) and its various natural and synthetic analogues. Retinoids are compounds with multiple actions. They are involved in the control of cell proliferation, cell differentiation, and embryonic development. Each retinoid has its own profile of pharmacologic properties that determines its usefulness in clinical dermatology or oncology. Although numerous synthetic retinoids have been synthesized, their biological activities are usually associated with clinical disadvantages such as toxicity and teratogenicity. Retinoids that bind to both the retinoic acid receptor and retinoid X receptor subtypes have shown clinical activity in hematologic malignancies and can mediate genes associated with both growth and differentiation. Retinoid X receptor-specific rexinoids have also shown efficacy in the treatment of cutaneous T-cell lymphomas, but their exact mechanism of action is unclear. This article summarizes the clinical relevance of both groups of compounds in this important patient population. PMID:16516669

  3. 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.

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

    ClinicalTrials.gov

    2016-04-11

    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

  5. Differentiation between cutaneous form of adult T cell leukemia/lymphoma and cutaneous T cell lymphoma by in situ hybridization using a human T cell leukemia virus-1 DNA probe.

    PubMed Central

    Arai, E.; Chow, K. C.; Li, C. Y.; Tokunaga, M.; Katayama, I.

    1994-01-01

    Adult T cell leukemia/lymphoma (ATLL) shares overlapping clinicopathological features with cutaneous T cell lymphoma (CTCL), requiring detection of monoclonal integration of proviral DNA of type 1 human T cell leukemia virus for its differential diagnosis from the latter. We applied in situ hybridization (ISH) and polymerase chain reaction (PCR) to paraffin sections from 63 Japanese autopsy cases that had been diagnosed as CTCL in earlier years when ATLL was still not widely known. Eleven and two cases with confirmed diagnoses of ATLL and CTCL served as positive and negative controls, respectively. It was found that ISH was positive in 7 of 63 test cases and 10 of 11 positive controls, whereas PCR was positive in none of the test cases and eight of the positive control cases. Two negative controls were negative for both ISH and PCR. We conclude that ISH is superior to PCR for detecting type 1 human T cell leukemia virus proviral DNA on paraffin sections and that the ISH method is useful for differentiating CTCL from the cutaneous form of ATLL. Images Figure 1 PMID:8291605

  6. Retinoids Bias Integrin Expression and Function in Cutaneous T-Cell Lymphoma.

    PubMed

    Wang, Lei; DeMarco, Sebastian S; Chen, JianMing; Phillips, Charles M; Bridges, Lance C

    2015-08-01

    Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of malignancies characterized by accumulation of malignant T-cells within the skin. Retinoids, metabolic derivatives, and synthetic analogs of vitamin A embody an effective CTCL therapy with over three decades of clinical use. The established mechanism of action is induction of growth arrest and apoptosis. However, the natural role of retinoids in T-cell biology is imprinting gut-homing properties by inducing integrin α4β7 expression. How the natural role of retinoids relates to therapeutic effectiveness in CTCL has not been addressed and merits investigation. Here we provide evidence that retinoids, including Bexarotene, selectively induce CTCL lineages to increase integrin β7 expression and function prior to growth arrest and apoptosis. Interestingly, augmented CTCL cell adhesion obtained with retinoid exposure was potently attenuated by 1,25-dihydroxyvitamin D3, a metabolic vitamin derivative involved in prompting immune cell skin homing. The integrin-dependent adhesion changes in CTCL cells occurred through synergistic activation of RAR and RXR nuclear receptors. These data explore the early cellular changes induced by retinoids that may be pivotal to sensitizing CTCL cells to growth arrest and apoptosis. PMID:25826424

  7. The mutational landscape of cutaneous T-cell lymphoma and Sézary syndrome

    PubMed Central

    da Silva Almeida, Ana Carolina; Abate, Francesco; Khiabanian, Hossein; Martinez-Escala, Estela; Guitart, Joan; Tensen, Cornelis P.; Vermeer, Maarten H.; Rabadan, Raul; Ferrando, Adolfo; Palomero, Teresa

    2016-01-01

    Sézary syndrome is a leukemic and aggressive form of cutaneous T-cell lymphoma (CTCL) resulting from the malignant transformation of skin-homing central memory CD4 positive T cells. Here we performed whole-exome sequencing of tumor-normal sample pairs from 25 Sézary syndrome and 17 other CTCL patients. These analyses revealed a distinctive pattern of somatic copy number alterations in Sézary syndrome including highly prevalent chromosomal deletions involving the TP53, RB1, PTEN, DNMT3A and CDKN1B tumor suppressors. Mutation analysis identified a broad spectrum of somatic mutations in key genes involved in epigenetic regulation (TET2, CREBBP, MLL2, MLL3, BRD9, SMARCA4 and CHD3) and signaling, including MAPK1, BRAF, CARD11 and PRKG1 mutations driving increased MAPK, NFκB and NFAT activity upon T-cell receptor stimulation. Collectively, our findings provide new insights into the genetics of Sézary syndrome and CTCL and support the development of personalized therapies targeting key oncogenically activated signaling pathways for the treatment of these diseases. PMID:26551667

  8. Primary Cutaneous Follicle Center Lymphomas Expressing BCL2 Protein Frequently Harbor BCL2 Gene Break and May Present 1p36 Deletion: A Study of 20 Cases.

    PubMed

    Szablewski, Vanessa; Ingen-Housz-Oro, Saskia; Baia, Maryse; Delfau-Larue, Marie-Helene; Copie-Bergman, Christiane; Ortonne, Nicolas

    2016-01-01

    The classification of cutaneous follicular lymphoma (CFL) into primary cutaneous follicle center lymphoma (PCFCL) or secondary cutaneous follicular lymphoma (SCFL) is challenging. SCFL is suspected when tumor cells express BCL2 protein, reflecting a BCL2 translocation. However, BCL2 expression is difficult to assess in CFLs because of numerous BCL2+ reactive T cells. To investigate these issues and to further characterize PCFCL, we studied a series of 25 CFLs without any extracutaneous disease at diagnosis, selected on the basis of BCL2 protein expression using 2 BCL2 antibodies (clones 124 and E17) and BOB1/BCL2 double immunostaining. All cases were studied using interphase fluorescence in situ hybridization with BCL2, BCL6, IGH, IGK, IGL breakapart, IGH-BCL2 fusion, and 1p36/1q25 dual-color probes. Nineteen CFLs were BCL2 positive, and 6 were negative. After a medium follow-up of 24 (6 to 96) months, 5 cases were reclassified as SCFL and were excluded from a part of our analyses. Among BCL2+ PCFCLs, 60% (9/15) demonstrated a BCL2 break. BCL2-break-positive cases had a tendency to occur in the head and neck and showed the classical phenotype of nodal follicular lymphoma (CD10+, BCL6+, BCL2+, STMN+) compared with BCL2-break-negative PCFCLs. Del 1p36 was observed in 1 PCFCL. No significant clinical differences were observed between BCL2+ or BCL2- PCFCL. In conclusion, we show that a subset of PCFCLs harbor similar genetic alterations, as observed in nodal follicular lymphomas, including BCL2 breaks and 1p36 deletion. As BCL2 protein expression is usually associated with the presence of a BCL2 translocation, fluorescence in situ hybridization should be performed to confirm this hypothesis. PMID:26658664

  9. 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

  10. Cutaneous Borreliosis With a T-Cell-Rich Infiltrate and Simultaneous Involvement by B-Cell Chronic Lymphocytic Leukemia With t(14;18)(q32;q21).

    PubMed

    Kempf, Werner; Kazakov, Dmitry V; Hübscher, Eugen; Tinguely, Marianne

    2015-09-01

    Pseudolymphomatous infiltrates in Borrelia infection of the skin most commonly manifest with dense B-cell infiltrates and plasma cells. Cutaneous infiltrates of B-cell chronic lymphocytic leukemia (B-CLL) may accumulate at sites of infection, including Borrelia infection. We report an unusual constellation in a patient with synchronously diagnosed B-CLL and Borrelia infection of skin presenting with a dense dermal T-cell-rich infiltrate masking specific leukemic infiltrates of neoplastic B cells in the context of B-CLL harboring t(14;18)(q32;q21). Specific cutaneous involvement by B-CLL was confirmed by the detection of t(14;18)(q32;q21) (BCL2-IGH) using FISH in neoplastic B cells within the skin infiltrates. Borrelia burgdorferi (sensu lato) DNA detected by nested polymerase chain reaction in the skin biopsy and serological findings proved Borrelia infection. Complete resolution of the cutaneous infiltrates was observed after antibiotic treatment. This case demonstrates that Borrelia infection of the skin may present with dense T-cell-rich infiltrates mimicking cutaneous T-cell lymphoma and masking the synchronous presence of neoplastic B cells in the context of B-CLL. PMID:25171429

  11. Resimmune, an anti-CD3ε recombinant immunotoxin, induces durable remissions in patients with cutaneous T-cell lymphoma

    PubMed Central

    Frankel, Arthur E.; Woo, Jung H.; Ahn, Chul; Foss, Francine M.; Duvic, Madeleine; Neville, Paul H.; Neville, David M.

    2015-01-01

    Resimmune is a second-generation recombinant immunotoxin composed of the catalytic and translocation domains of diphtheria toxin fused to two single chain antibody fragments reactive with the extracellular domain of CD3ε. We gave intravenous infusions of Resimmune 2.5 – 11.25 μg/kg over 15 minutes to 30 patients (25 with cutaneous T-cell lymphoma, 3 with peripheral T-cell lymphoma, 1 with T-cell large granular lymphocytic leukemia and 1 with T-cell prolymphocytic leukemia) in an inter-patient dose escalation trial. The most common adverse events were fever, chills, hypotension, edema, hypoalbuminemia, hypophosphatemia, and transaminasemia. Among the 25 patients with cutaneous T-cell lymphoma, there were nine responses for a response rate of 36% (95% CI, 18%–57%) including four complete remissions (16%, 95% CI, 5%–36%). The durations of the complete remissions were 72+, 72+, 60+ and 38+ months. There were five partial remissions lasting 3, 3, 3+, 6+ and 14 months. Of 17 patients with a modified skin weighted assessment tool score <50, 17 patients with stage IB/IIB, and 11 patients with both a score <50 and stage IB/IIB, nine (53%), eight (47%), and eight (73%) had responses, respectively. Further studies of Resimmune in patients with low tumor burden, stage IB-IIB cutaneous T-cell lymphoma are warranted. This trial is registered at clinicaltrials.gov as #NCT00611208. PMID:25795722

  12. Primary Cutaneous Anaplastic Large-Cell Lymphoma With 6p25.3 Rearrangement in a Cardiac Transplant Recipient: A Case Report and Review of the Literature.

    PubMed

    Olson, Luke C; Cheng, Esther; Mathew, Susan; Torres-Quinones, Marta; Magro, Cynthia

    2016-06-01

    Posttransplant lymphoproliferative disorders define an important form of lymphoproliferative disease causally linked with a state of iatrogenic immune dysregulation inherent to the posttransplant setting. Most posttransplant lymphoproliferative disorders are in the context of Epstein-Barr virus-associated B-cell lymphoproliferative disease, most notably diffuse large-cell B-cell lymphoma. A less common variant falls under the rubric of posttransplant T-cell lymphoproliferative disease, which is largely unrelated to Epstein-Barr virus infection. Anaplastic large-cell lymphoma (ALCL) is the most recognized form of posttransplant T-cell lymphoproliferative disease. Although the 6p25.3 translocation is seen in a variety of B-cell lymphoproliferative disorders, this particular translocation in the spectrum of T-cell lymphoproliferative disease is a fairly specific finding pointing toward a diagnosis of primary cutaneous ALCL and a rare subset of lymphomatoid papulosis. This translocation in the peripheral T-cell lymphoma setting serves as a favorable prognostic predictor. We report a case of an 81-year-old heart transplant recipient who developed an expansile neck mass 17 years after his heart transplant. A diagnosis of cutaneous ALCL was subsequently made with cytogenetic analysis yielding the 6p25.3 translocation. The characteristic biphasic morphology of a small-cell epidermotropic neoplastic cell populace in concert with a dermal based large-cell infiltrate characteristic for those cases of ALCL harboring this translocation was seen. After excision of the nodule, his azathioprine was withheld. He is currently alive and well without evidence of disease. PMID:26863058

  13. Molecular analysis of tumor-promoting CD8+ T cells in two-stage cutaneous chemical carcinogenesis.

    PubMed

    Kwong, Bernice Y; Roberts, Scott J; Silberzahn, Tobias; Filler, Renata B; Neustadter, Jason H; Galan, Anjela; Reddy, Swapna; Lin, William M; Ellis, Peter D; Langford, Cordelia F; Hayday, Adrian C; Girardi, Michael

    2010-06-01

    T-pro are tumor-infiltrating TCRalphabeta(+)CD8(+) cells of reduced cytotoxic potential that promote experimental two-stage chemical cutaneous carcinogenesis. Toward understanding their mechanism of action, this study uses whole-genome expression analysis to compare T-pro with systemic CD8(+) T cells from multiple groups of tumor-bearing mice. T-pro show an overt T helper 17-like profile (high retinoic acid-related orphan receptor-(ROR)gammat, IL-17A, IL-17F; low T-bet and eomesodermin), regulatory potential (high FoxP3, IL-10, Tim-3), and transcripts encoding epithelial growth factors (amphiregulin, Gro-1, Gro-2). Tricolor flow cytometry subsequently confirmed the presence of TCRbeta(+) CD8(+) IL-17(+) T cells among tumor-infiltrating lymphocytes (TILs). Moreover, a time-course analysis of independent TIL isolates from papillomas versus carcinomas exposed a clear association of the "T-pro phenotype" with malignant progression. This molecular characterization of T-pro builds a foundation for elucidating the contributions of inflammation to cutaneous carcinogenesis, and may provide useful biomarkers for cancer immunotherapy in which the widely advocated use of tumor-specific CD8(+) cytolytic T cells should perhaps accommodate the cells' potential corruption toward the T-pro phenotype. The data are also likely germane to psoriasis, in which the epidermis may be infiltrated by CD8(+) IL-17-producing T cells. PMID:19924136

  14. 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.

  15. 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. PMID:25371972

  16. 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.

  17. Romidepsin: evidence for its potential use to manage previously treated cutaneous T cell lymphoma

    PubMed Central

    Poligone, Brian; Lin, Janet; Chung, Catherine

    2011-01-01

    Introduction: Cutaneous T cell lymphoma (CTCL) encompasses a heterogeneous group of neoplasms of skin-homing T cells, which includes mycosis fungoides, the most common form, and Sézary syndrome, the leukemia equivalent of mycosis fungoides. Histone deacetylase inhibitors are currently under investigation for their therapeutic value in a variety of conditions. Through multiple mechanisms, they induce apoptosis or inhibition of tumor cell growth. Some studies have also shown histone deacetylase inhibitors to have synergistic activity with existing therapeutic agents in selected conditions. Romidepsin is a histone deacetylase inhibitor with a promising efficacy and safety profile that may represent a valuable treatment alternative for patients with treatment-resistant mycosis fungoides and Sézary syndrome. Aims: To review emerging evidence regarding the use of romidepsin in the management of treatment-resistant CTCL. Evidence review: There is evidence that romidepsin can induce significant and durable responses in patients with refractory CTCL. In two independent Phase II trials including a total of 167 patients with CTCL, there was an overall response rate of 34% with a partial response of 28% and complete response rate of 6%. The most frequent toxicities reported from the Phase II trials were nausea, vomiting, fatigue, anorexia, and dysgeusia. Clinical potential: Romidepsin may be an effective therapeutic option for patients with CTCL who have had treatment failure with multiple standard treatment modalities. PMID:21468238

  18. 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.

  19. 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.

  20. Syndrome of selective IgM deficiency with severe T cell deficiency associated with disseminated cutaneous mycobacterium avium intracellulaire infection

    PubMed Central

    Gharib, Asal; Louis, Ankmalika Gupta; Agrawal, Sudhanshu; Gupta, Sudhir

    2015-01-01

    Cutaneous non-disseminated, non-tuberculous mycobacterial infections have been reported in both immunocompetent and immunocompromised subjects. Systemic Mycobacterium avium intracellulaire (MAI) have been reported in non-HIV patients with Idiopathic CD4 lymphocytopenia. We report a comprehensive immunological analysis in syndrome of selective IgM deficiency and T lymphocytopenia (both CD4+ and CD8+) with disseminated cutaneous MAI infection. Naïve (TN) and Central memory (TCM) subsets of both CD4+ and CD8+ T cells were decreased, whereas terminally differentiated effector memory (TEMRA) subset of CD4+ and CD8+ T cells were markedly increased. IFN-γ producing T cells were markedly decreased. Although CD14highCD16- proinflammatory monocytes were modestly increased, IFN-γR+ monocytes were markedly decreased. The expression of TLR3, TLR5, TLR7, and TLR9 on monocytes was decreased. Germinal center B cells (CD19+IgD-CD38+CD27lo) and B1 cells (CD20+CD27+CD43+CD70-) were markedly decreased. A role of immune alterations, including B cells and antibodies in disseminated cutaneous MAI infection is discussed. PMID:26550546

  1. Syndrome of selective IgM deficiency with severe T cell deficiency associated with disseminated cutaneous mycobacterium avium intracellulaire infection.

    PubMed

    Gharib, Asal; Louis, Ankmalika Gupta; Agrawal, Sudhanshu; Gupta, Sudhir

    2015-01-01

    Cutaneous non-disseminated, non-tuberculous mycobacterial infections have been reported in both immunocompetent and immunocompromised subjects. Systemic Mycobacterium avium intracellulaire (MAI) have been reported in non-HIV patients with Idiopathic CD4 lymphocytopenia. We report a comprehensive immunological analysis in syndrome of selective IgM deficiency and T lymphocytopenia (both CD4+ and CD8+) with disseminated cutaneous MAI infection. Naïve (TN) and Central memory (TCM) subsets of both CD4+ and CD8+ T cells were decreased, whereas terminally differentiated effector memory (TEMRA) subset of CD4+ and CD8+ T cells were markedly increased. IFN-γ producing T cells were markedly decreased. Although CD14(high)CD16- proinflammatory monocytes were modestly increased, IFN-γR+ monocytes were markedly decreased. The expression of TLR3, TLR5, TLR7, and TLR9 on monocytes was decreased. Germinal center B cells (CD19+IgD-CD38+CD27(lo)) and B1 cells (CD20+CD27+CD43+CD70-) were markedly decreased. A role of immune alterations, including B cells and antibodies in disseminated cutaneous MAI infection is discussed. PMID:26550546

  2. 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

  3. A new protoparvovirus in human fecal samples and cutaneous T cell lymphomas (mycosis fungoides).

    PubMed

    Phan, Tung G; Dreno, Brigitte; da Costa, Antonio Charlys; Li, Linlin; Orlandi, Patricia; Deng, Xutao; Kapusinszky, Beatrix; Siqueira, Juliana; Knol, Anne-Chantal; Halary, Franck; Dantal, Jacques; Alexander, Kathleen A; Pesavento, Patricia A; Delwart, Eric

    2016-09-01

    We genetically characterized seven nearly complete genomes in the protoparvovirus genus from the feces of children with diarrhea. The viruses, provisionally named cutaviruses (CutaV), varied by 1-6% nucleotides and shared ~76% and ~82% amino acid identity with the NS1 and VP1 of human bufaviruses, their closest relatives. Using PCR, cutavirus DNA was found in 1.6% (4/245) and 1% (1/100) of diarrhea samples from Brazil and Botswana respectively. In silico analysis of pre-existing metagenomics datasets then revealed closely related parvovirus genomes in skin biopsies from patients with epidermotropic cutaneous T-cell lymphoma (CTCL or mycosis fungoides). PCR of skin biopsies yielded cutavirus DNA in 4/17 CTCL, 0/10 skin carcinoma, and 0/21 normal or noncancerous skin biopsies. In situ hybridization of CTCL skin biopsies detected viral genome within rare individual cells in regions of neoplastic infiltrations. The influence of cutavirus infection on human enteric functions and possible oncolytic role in CTCL progression remain to be determined. PMID:27393975

  4. Inhibition of Histone Deacetylase 3 Causes Replication Stress in Cutaneous T Cell Lymphoma

    PubMed Central

    Wells, Christina E.; Bhaskara, Srividya; Stengel, Kristy R.; Zhao, Yue; Sirbu, Bianca; Chagot, Benjamin; Cortez, David; Khabele, Dineo; Chazin, Walter J.; Cooper, Andrew; Jacques, Vincent; Rusche, James; Eischen, Christine M.; McGirt, Laura Y.; Hiebert, Scott W.

    2013-01-01

    Given the fundamental roles of histone deacetylases (HDACs) in the regulation of DNA repair, replication, transcription and chromatin structure, it is fitting that therapies targeting HDAC activities are now being explored as anti-cancer agents. In fact, two histone deacetylase inhibitors (HDIs), SAHA and Depsipeptide, are FDA approved for single-agent treatment of refractory cutaneous T cell lymphoma (CTCL). An important target of these HDIs, histone deacetylase 3 (HDAC3), regulates processes such as DNA repair, metabolism, and tumorigenesis through the regulation of chromatin structure and gene expression. Here we show that HDAC3 inhibition using a first in class selective inhibitor, RGFP966, resulted in decreased cell growth in CTCL cell lines due to increased apoptosis that was associated with DNA damage and impaired S phase progression. Through isolation of proteins on nascent DNA (iPOND), we found that HDAC3 was associated with chromatin and is present at and around DNA replication forks. DNA fiber labeling analysis showed that inhibition of HDAC3 resulted in a significant reduction in DNA replication fork velocity within the first hour of drug treatment. These results suggest that selective inhibition of HDAC3 could be useful in treatment of CTCL by disrupting DNA replication of the rapidly cycling tumor cells, ultimately leading to cell death. PMID:23894374

  5. Panoptic clinical review of the current and future treatment of relapsed/refractory T-cell lymphomas: Cutaneous T-cell lymphomas.

    PubMed

    Zinzani, Pier Luigi; Bonthapally, Vijayveer; Huebner, Dirk; Lutes, Richard; Chi, Andy; Pileri, Stefano

    2016-03-01

    Primary cutaneous T-cell lymphomas (CTCLs), such as mycosis fungoides and Sézary syndrome, are a rare group of non-Hodgkin lymphomas, usually treated using a multimodal approach. Unfortunately, many patients go on to develop relapsed/refractory disease. Systemic treatment for relapsed/refractory CTCL has historically relied on chemotherapies and interferons, and while active, responses are often short-lived. Three drugs are now approved in the US to treat relapsed/refractory CTCL including the oral retinoid, bexarotene, and histone deacetylase inhibitors, romidepsin and vorinostat. Although response rates are typically <35%, romidepsin and vorinostat can induce some durable responses in heavily pretreated patients and alleviate bothersome symptoms, such as pruritus. New studies indicate that the anti-CD30 antibody-drug conjugate brentuximab vedotin, anti-CCR4 antibody mogamulizumab, and fusion protein immunotoxin A-dmDT390-bisFv(UCHT1) may be particularly active in this setting. In this paper, we present an exhaustive review of the clinical data on current and possible future drug treatment options for relapsed/refractory CTCL. PMID:26811014

  6. Decreased TNF-α synthesis by macrophages restricts cutaneous immunosurveillance by memory CD4+ T cells during aging

    PubMed Central

    Agius, Elaine; Lacy, Katie E.; Vukmanovic-Stejic, Milica; Jagger, Ann L.; Papageorgiou, Anna-Pia; Hall, Sue; Reed, John R.; Curnow, S. John; Fuentes-Duculan, Judilyn; Buckley, Christopher D.; Salmon, Mike; Taams, Leonie S.; Krueger, James; Greenwood, John; Klein, Nigel; Rustin, Malcolm H.A.

    2009-01-01

    Immunity declines during aging, however the mechanisms involved in this decline are not known. In this study, we show that cutaneous delayed type hypersensitivity (DTH) responses to recall antigens are significantly decreased in older individuals. However, this is not related to CC chemokine receptor 4, cutaneous lymphocyte-associated antigen, or CD11a expression by CD4+ T cells or their physical capacity for migration. Instead, there is defective activation of dermal blood vessels in older subject that results from decreased TNF-α secretion by macrophages. This prevents memory T cell entry into the skin after antigen challenge. However, isolated cutaneous macrophages from these subjects can be induced to secrete TNF-α after stimulation with Toll-like receptor (TLR) 1/2 or TLR 4 ligands in vitro, indicating that the defect is reversible. The decreased conditioning of tissue microenvironments by macrophage-derived cytokines may therefore lead to defective immunosurveillance by memory T cells. This may be a predisposing factor for the development of malignancy and infection in the skin during aging. PMID:19667063

  7. Current and emerging treatment strategies for cutaneous T-cell lymphoma.

    PubMed

    Lansigan, Frederick; Foss, Francine M

    2010-02-12

    Cutaneous T-cell lymphomas (CTCLs) are a rare group of mature T-cell lymphomas presenting primarily in the skin. The most common subtypes of CTCL are mycosis fungoides and its leukaemic variant Sézary's syndrome. Patients with early-stage disease frequently have an indolent clinical course; however, those with advanced stages have a shortened survival. For the treating physician, the question of how to choose a particular therapy in the management of CTCL is important. These diseases span the disciplines of dermatology, medical oncology and radiation oncology. Other than an allogeneic stem cell transplant, there are no curative therapies for this disease. Hence, many treatment modalities need to be offered to the patient over the course of their life. An accepted treatment approach has been to delay traditional chemotherapy, which can cause excessive toxicity without durable benefit. More conservative treatment strategies in the initial management of CTCL have led to the development of newer biological and targeted therapies. These therapies include biological immune enhancers such as interferon alpha and extracorporeal photopheresis that exert their effect by stimulating an immune response to the tumour cells. Retinoids such as bexarotene have been shown to be effective and well tolerated with predictable adverse effects. The fusion toxin denileukin diftitox targets the interleukin-2 receptor expressed on malignant T cells. Histone deacetylase inhibitors such as vorinostat and romidepsin (depsipeptide) may reverse the epigenetic states associated with cancer. Forodesine is a novel inhibitor of purine nucleoside phosphorylase and leads to apoptosis of malignant T cells. Pralatrexate is a novel targeted antifolate that targets the reduced folate carrier in cancer cells. Lastly, systemic chemotherapy including transplantation is used when rapid disease control is needed or if all other biological therapies have failed. As response rates to most of the biological

  8. 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. PMID:1858014

  9. Polish Lymphoma Research Group Experience With Bexarotene in the Treatment of Cutaneous T-Cell Lymphoma.

    PubMed

    Sokolowska-Wojdylo, Malgorzata; Florek, Aleksandra; Zaucha, Jan Maciej; Chmielowska, Ewa; Giza, Agnieszka; Knopinska-Posluszny, Wanda; Kulikowski, Waldemar; Prejzner, Witold; Romejko-Jarosinska, Joanna; Paszkiewicz-Kozik, Ewa; Osowiecki, Michal; Walewski, Jan; Rogowski, Wojciech; Grzanka, Aleksandra; Placek, Waldemar; Lugowska-Umer, Hanna; Kowalczyk, Anna; Nowicki, Roman; Jurczak, Wojciech

    2016-01-01

    Bexarotene, a synthetic retinoid licensed for the treatment of refractory cutaneous T-cell lymphoma (CTCL), has been used clinically in Poland since 2007 in 21 patients. The objective of our retrospective, multicenter study was to evaluate our experience with bexarotene therapy, including efficacy, safety, and survival outcomes. We retrospectively identified 21 adult patients who were treated with bexarotene between the years 2007 and 2012. Starting dose of bexarotene was 300 mg/m per day. The analysis included 3 patients with early-stage mycosis fungoides (MF), 16 patients with advanced-stage MF, and 2 patients with Sézary syndrome (SS). The mean duration of therapy with bexarotene was 14.5 months. Use of bexarotene resulted in an overall response rate of 81.0%, although the overall mortality rate was 52.8%. In our study, early-stage CTCL responded better than advanced-stage CTCL (100.0% vs. 77.8%, respectively). The mean time to observable response was 1.8 months, and the mean duration of the response was 16.4 months. Most significant side effects were hyperlipidemia, hypothyroidism, and a bleeding gastric ulcer. Based on the results of our analysis, bexarotene is a valuable tool in the treatment of refractory early-stage CTCL. Although a majority of patients initially responded to therapy, the high mortality rate in the advanced-stage group suggests that bexarotene does not completely resolve the therapeutic problems in all stages of CTCL. Patient stratification for bexarotene treatment may need a thorough reassessment, in that bexarotene may not be an effective drug in the very advanced stages of CTCL. PMID:24732904

  10. 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.

  11. Primary Cutaneous Nocardiosis in a Patient With Nephrotic Syndrome: A Case Report and Review of the Literature.

    PubMed

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

    2016-01-01

    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

  12. TOX expression in cutaneous B-cell lymphomas.

    PubMed

    Schrader, Anne M R; Jansen, Patty M; Willemze, Rein

    2016-08-01

    Thymocyte selection-associated high-mobility group box (TOX) is aberrantly expressed in cutaneous T-cell lymphomas. In a recent study, TOX expression was noted unexpectedly in the follicle center (germinal center) B-cells of reactive lymph nodes and tonsils, used as external controls. To evaluate whether TOX is also expressed by cutaneous B-cell lymphomas, TOX immunohistochemistry was performed on skin biopsies of 44 patients with primary and secondary cutaneous B-cell proliferations. TOX was expressed not only in the reactive follicle center cells of lymph nodes, tonsils, cutaneous lymphoid hyperplasia, and primary cutaneous marginal zone lymphomas, but also by the neoplastic follicle center cells of 16/17 patients with primary cutaneous follicle center lymphoma (PCFCL) and 7/7 patients with cutaneous manifestations of systemic follicular lymphoma (FL). Notably, TOX showed a very similar expression pattern as BCL6, a marker of germinal center B-cells. In 4/10 patients with a BCL6(+) primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL,LT) and in 2/2 patients with a secondary cutaneous BCL6(+) diffuse large B-cell lymphoma (DLBCL), TOX was expressed by more than 50 % of the neoplastic B-cells. In contrast, in 3/3 BCL6(-) PCDLBCL,LT, TOX was completely negative or weakly expressed by a minor proportion of the neoplastic B-cells. In conclusion, TOX is expressed not only by neoplastic T-cells, but also by both reactive and neoplastic follicle center (germinal center) B-cells and a proportion of BCL6(+) PCDLBCL,LT and secondary cutaneous BCL6(+) DLBCL. The functional significance of TOX expression in reactive and neoplastic B-cells remains to be elucidated. PMID:27180090

  13. Osteonecrosis of the Jaw in Association With Chemotherapy in the Setting of Cutaneous T-Cell Lymphoma.

    PubMed

    DeSesa, Christopher R; Appugounder, Suganya; Haberland, Christel; Johnson, Michael P

    2016-02-01

    T-cell lymphomas (TCLs) account for approximately 15 to 20% of all non-Hodgkin lymphomas in the United States. The most common form of TCL is cutaneous TCL (CTCL), with Sézary syndrome and mycosis fungoides being the most prevalent subtypes. Sézary syndrome is the more aggressive form and often is referred to as a late-stage variant of mycosis fungoides. Clinically, it is characterized by diffuse erythroderma, cutaneous edema, pruritus, nonhealing cutaneous ulcers, and lymphadenopathy. Patients also can present with changes to their nails, hyperpigmentation, alopecia, palmoplantar keratoderma, ectropion, and hepatosplenomegaly. The overall prognosis for patients with Sézary syndrome is poor. The literature regarding oral manifestations of CTCL mostly report those of mycosis fungoides because it is the most common subtype of CTCL. Currently, there are only 2 reports in the scientific literature of intraoral manifestations of Sézary syndrome. This case report describes a patient with Sézary syndrome who presented with rapidly progressing erythematous lesions of the gingiva and multifocal osteonecrosis of the maxilla and mandible. This is the third reported case of an intraoral manifestation of Sézary syndrome and the first reported case of osteonecrosis in the setting of CTCL. PMID:26296596

  14. 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. PMID:24516202

  15. Primary cutaneous epithelioid angiosarcoma: a clinicopathologic study of 13 cases of a rare neoplasm occurring outside the setting of conventional angiosarcomas and with predilection for the limbs.

    PubMed

    Suchak, Ravi; Thway, Khin; Zelger, Bernhard; Fisher, Cyril; Calonje, Eduardo

    2011-01-01

    Epithelioid angiosarcomas are rare aggressive neoplasms that occur most frequently in deep soft tissues. Primary cutaneous lesions are rare, and there are discrepant findings in the literature regarding their behavior. In this study, we report a series of 13 cases of primary cutaneous epithelioid angiosarcoma and analyze their clinicopathologic features. The tumors arising in the conventional settings for cutaneous angiosarcoma (ie, in the head and neck region of elderly patients, and those occurring postradiation or associated with lymphedema) were excluded. Primary cutaneous epithelioid angiosarcoma occurred in adults (mean age, 66 y) with an equal sex distribution, and presented as solitary (n=10) or multiple (n=3) nodules ranging in size from 8 to 80 mm, with a predilection for the limbs (n=10). Histopathologically, the tumors comprised infiltrative sheets of atypical epithelioid cells within the dermis with or without the involvement of the subcutis. Vascular channel formation and intracytoplasmic lumina were seen, at least focally, in most cases. Mitoses were readily identified and necrosis was seen in 40% of the cases. The tumors were immunoreactive for vascular markers, with CD31 and FLI-1 offering the highest sensitivity. Pancytokeratin was positive in two thirds of the cases, and epithelial membrane antigen was positive in one-quarter of the cases. There was rare focal expression of Melan-A (n=2) and smooth muscle actin (n=3). Follow-up information was available for 11 patients. Six patients died of metastatic disease after a median follow-up of 12 months (range, 3 to 36 mo), and 1 patient died of unrelated causes. These findings suggest that primary cutaneous epithelioid angiosarcoma occurring outside the conventional settings of angiosarcoma is a highly aggressive malignant tumor with mortality rates in excess of 55% after 3 years. PMID:21164288

  16. Fusariosis occurring in an ulcerated cutaneous CD8+ T cell lymphoma tumor.

    PubMed

    Hsu, Chao-Kai; Hsu, Mark Ming-Long; Lee, Julia Yu-Yun

    2006-01-01

    Fusarium species have recently emerged as the second most common pathogenic mold in immunocompromised patients, and they are moderately resistant to most antifungal agents. The skin lesions of disseminated fusariosis typically manifest as multiple red or violaceous macules or nodules, often ulcerated and covered by a black eschar. We report a case of cutaneous fusariosis in a patient with long-standing hypopigmented mycosis fungoides. The infection was successfully treated with a 3-month course of oral voriconazole. The present case is unusual in that the infection occurred within a pre-existing, ulcerated lesion of cutaneous CD8+ lymphoma, resulting clinically in confusion with pyoderma gangrenosum and necrosis of lymphoma. A high index of suspicion will prompt a timely biopsy as well as isolation of the fungus, and early institution of systemic antifungal therapy. PMID:16709499

  17. Angiotropism in primary cutaneous melanoma with brain metastasis: a study of 20 cases.

    PubMed

    Hung, Tawny; Morin, Jason; Munday, William R; Mackenzie, Ian R A; Lugassy, Claire; Barnhill, Raymond L

    2013-08-01

    Previous clinical and experimental studies suggested that invasion of the brain by metastatic melanoma may follow the external surfaces of vascular channels, that is, angiotropic extravascular migratory metastasis. Such angiotropic invasion seemss analogous to that of neoplastic glial invasion of the nervous system. We, therefore, have retrospectively investigated 20 primary melanoma cases and their respective metastatic brain lesions. The following parameters were analyzed in each primary melanoma: presence of angiotropism, Breslow thickness, Clark level, mitotic rate, sentinel lymph node (SLN) status, and time interval between the primary lesion and the metastasis. The metastatic brain lesions were examined for the presence of angiotropism. Of the 20 cases, 14 showed angiotropism in the primary lesion. The angiotropic group had a significantly deeper Breslow thickness (median 4.4 mm vs. 1.4 mm, P < 0.01) and was more mitotically active (median 11 vs. 4.7 mitoses/mm, P = 0.04). Interestingly, the angiotropic group had an average time lapse of 33 months from the primary lesion to the brain metastasis, whereas the nonangiotropic group had a 57-month time interval. Although the Kaplan-Meier analysis failed to show a survival difference in this small cohort (P = 0.235), there was a trend toward significance. Seven of 20 brain metastases showed angiotropism; however, no significant correlation between angiotropism in the primary melanomas and the corresponding metastatic lesions could be demonstrated. Indeed, angiotropism in the brain metastases was difficult to assess because the available material were generally small partial biopsy samplings and many showed conspicuous necrosis. Ten melanoma patients underwent SLN biopsy. The 3 of 6 positive cases in the angiotropic group had an average time lapse of 32 months from the primary lesion to the brain metastasis, whereas the 4 positive SLN biopsies in the nonangiotropic group had an average of 63 months. This preliminary

  18. Phase II study of gemcitabine and bexarotene (GEMBEX) in the treatment of cutaneous T-cell lymphoma

    PubMed Central

    Illidge, T; Chan, C; Counsell, N; Morris, S; Scarisbrick, J; Gilson, D; Popova, B; Patrick, P; Smith, P; Whittaker, S; Cowan, R

    2013-01-01

    Background: Both gemcitabine and bexarotene are established single agents for the treatment of cutaneous T-cell lymphoma (CTCL). We investigated the feasibility and efficacy of combining these drugs in a single-arm phase II study. Methods: Cutaneous T-cell lymphoma patients who had failed standard skin-directed therapy and at least one prior systemic therapy were given four cycles of gemcitabine and concurrent bexarotene for 12 weeks. Responders were continued on bexarotene maintenance until disease progression or unacceptable toxicity. Results: The median age was 65 years, stage IB (n=5), stage IIA (n=2), stage IIB (n=8), stage III (n=8) and stage IVA (n=12), 17 patients were erythrodermic, 17 patients were B1, and 10 patients were both erythrodermic and B1. Thirty (86%) patients completed four cycles of gemcitabine. In all, 80.0% of patients demonstrated a reduction in modified Severity-Weighted Assessment Tool (mSWAT) score although the objective disease response rate at 12 weeks was 31% (partial response (PR) 31%) and at 24 weeks 14% (PR 14%, stable disease (SD) 23%, progressive disease (PD) 54%, not evaluable 9%). Median progression-free survival was 5.3 months and median overall survival was 21.2 months. Conclusion: The overall response rate of the combination did not reach the specified target to proceed further and is lower than that previously reported for gemcitabine as a single agent. PMID:24136145

  19. Expression of cutaneous lymphocyte-associated antigen by CD8+ T cells specific for a skin-tropic virus

    PubMed Central

    Koelle, David M.; Liu, Zhi; McClurkan, Christopher M.; Topp, Max S.; Riddell, Stanley R.; Pamer, Eric G.; Johnson, Andrew S.; Wald, Anna; Corey, Lawrence

    2002-01-01

    Virus-specific CD8+ T cells traffic to infected tissues to promote clearance of infection. We used herpes simplex virus type 2 (HSV-2) as a model system to investigate CD8+ T cell trafficking to the skin in humans. Using human leukocyte antigen (HLA) class I tetramers, we observed that HSV-specific CD8+ T cells in the peripheral blood expressed high levels of cutaneous lymphocyte-associated antigen (CLA). In contrast, CD8+ T cells specific for non–skin-tropic herpesviruses lacked CLA expression. CLA-positive HSV-2–specific CD8+ T cells had the characteristics of central memory cells, expressing CCR7, CD62L, and CD28, and they proliferated briskly in response to antigen. CLA is related to a functional E-selectin ligand, and both E-selectin and CLA-positive cells were detected in HSV-2–infected skin. HSV-2–specific T cells adhered to cells transfected with E-selectin. A higher proportion of HSV-specific CD8+ T cells recovered from herpes lesions express CLA compared with blood, consistent with a role for CLA in skin homing. To our knowledge, this is the first report of expression of tissue-specific adhesion-associated molecules by virus-specific CD8+ T cells. The evaluation of vaccines for skin and mucosal pathogens should include study of the induction of appropriate tissue-specific homing molecules. PMID:12189248

  20. 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. PMID:25096163

  1. Cutaneous metastasis of cholangiocarcinoma

    PubMed Central

    Liu, Min; Liu, Bai-Long; Liu, Bin; Guo, Liang; Wang, Qiang; Song, Yan-Qiu; Dong, Li-Hua

    2015-01-01

    AIM: To investigate the clinical characteristics and prognostic factors of cutaneous metastasis of cholangiocarcinoma by a retrospective analysis of published cases. METHODS: An extensive search was conducted in the English literature within the PubMed database using the following keywords: cutaneous metastasis or skin metastasis and cholangiocarcinoma or bile duct. The data of 30 patients from 21 articles from 1978 to 2014 were analyzed. Patient data retrieved from the articles included the following: age, gender, time cutaneous metastasis occurred, number of cutaneous metastases throughout life, sites of initial cutaneous metastasis, anatomic site, pathology and differentiation of cholangiocarcinoma, and immunohistochemical results of the cutaneous metastasis. The assessment of overall survival after cutaneous metastasis (OSCM) was the primary endpoint. RESULTS: The median age at diagnosis of cutaneous metastasis of cholangiocarcinoma was 60.0 years (range: 35-77). This metastasis showed a predilection towards males, with a male to female ratio of 3.29. In 8 cases (27.6%), skin metastasis was the first sign of cholangiocarcinoma. Additionally, 18 cases (60.0%) manifested single cutaneous metastasis, while 12 cases (40.0%) demonstrated multiple skin metastases. In 50.0% of patients, the metastasis occurred in the drainage region, while 50.0% of patients had distant cutaneous metastases. The scalp was the most frequently involved region of distant skin metastasis, occurring in 36.7% of patients. The median OSCM of cholangiocarcinoma was 4.0 mo. Patient age and cutaneous metastatic sites showed no significant relation with OSCM, while male gender and single metastasis of the skin were associated with a poorer OSCM (hazard ratio: 0.168; P = 0.005, and hazard ratio: 0.296; P = 0.011, respectively). CONCLUSION: The prognosis of cutaneous metastasis of cholangiocarcinoma is dismal. Both male gender and single skin metastasis are associated with a poorer OSCM. PMID

  2. Pump-probe imaging of pigmented cutaneous melanoma primary lesions gives insight into metastatic potential

    PubMed Central

    Robles, Francisco E.; Deb, Sanghamitra; Wilson, Jesse W.; Gainey, Christina S.; Selim, M. Angelica; Mosca, Paul J.; Tyler, Douglas S.; Fischer, Martin C.; Warren, Warren S.

    2015-01-01

    Metastatic melanoma is associated with a poor prognosis, but no method reliably predicts which melanomas of a given stage will ultimately metastasize and which will not. While sentinel lymph node biopsy (SLNB) has emerged as the most powerful predictor of metastatic disease, the majority of people dying from metastatic melanoma still have a negative SLNB. Here we analyze pump-probe microscopy images of thin biopsy slides of primary melanomas to assess their metastatic potential. Pump-probe microscopy reveals detailed chemical information of melanin with subcellular spatial resolution. Quantification of the molecular signatures without reference standards is achieved using a geometrical representation of principal component analysis. Melanin structure is analyzed in unison with the chemical information by applying principles of mathematical morphology. Results show that melanin in metastatic primary lesions has lower chemical diversity than non-metastatic primary lesions, and contains two distinct phenotypes that are indicative of aggressive disease. Further, the mathematical morphology analysis reveals melanin in metastatic primary lesions has a distinct “dusty” quality. Finally, a statistical analysis shows that the combination of the chemical information with spatial structures predicts metastatic potential with much better sensitivity than SLNB and high specificity, suggesting pump-probe microscopy can be an important tool to help predict the metastatic potential of melanomas. PMID:26417529

  3. The most sensitive inputs to cutaneous representing regions of primary somatosensory cortex do not change with behavioral training.

    PubMed

    Blake, David T; Spingath, Elsie

    2015-12-01

    Learning a sensory detection task leads to an increased primary sensory cortex response to the detected stimulus, while learning a sensory discrimination task additionally leads to a decreased sensory cortex response to the distractor stimulus. Neural responses are scaled up, and down, in strength, along with concomitant changes in receptive field size. The present work considers neural response properties that are invariant to learning. Data are drawn from two animals that were trained to detect and discriminate spatially separate taps delivered to positions on the skin of their fingers. Each animal was implanted with electrodes positioned in area 3b, and responses were derived on a near daily basis over 84 days in animal 1 and 202 days in animal 2. Responses to taps delivered in the receptive field were quantitatively measured each day, and receptive fields were audiomanually mapped each day. In the subset of responses that had light cutaneous receptive fields, a preponderance of the days, the most sensitive region of the field was invariant to training. This skin region was present in the receptive field on all, or nearly all, occasions in which the receptive field was mapped, and this region constituted roughly half of the most sensitive region. These results suggest that maintaining the most sensitive inputs as dominant in cortical receptive fields provide a measure of stability that may be transformationally useful for minimizing reconstruction errors and perceptual constancy. PMID:26634900

  4. 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.

  5. 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. PMID:25565197

  6. 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

  7. 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.

  8. [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

    2016-02-16

    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. PMID:26763070

  9. 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. PMID:27040974

  10. Cutaneous leishmaniasis: co-ordinate expression of granzyme A and lymphokines by CD4+ T cells from susceptible mice.

    PubMed Central

    Frischholz, S; Röllinghoff, M; Moll, H

    1994-01-01

    We have recently demonstrated that the frequency of T cells expressing granzyme A is significantly higher in skin lesions and spleens of susceptible BALB/c mice compared with resistant C57BL/6 mice infected with Leishmania major, a cause of human cutaneous leishmaniasis. In the present study, we have performed in vitro studies to characterize the subpopulation, the antigen responsiveness and the lymphokine production pattern of granzyme A-expressing T cells in L. major-infected mice. Using a limiting dilution system for functional analysis of selected T cells at the clonal level, we could show that granzyme A activity in infected BALB/c mice can be assigned to L. major-reactive CD4+ T cells secreting interleukin-2 (IL-2) and IL-4. Granzyme A production was most pronounced in the early phase of infection. On the other hand, granzyme A expression could not be detected in C57BL/6-derived T cells responding to L. major. The data support the suggestion that granzyme A is produced by L. major-responsive CD4+ T cells facilitating lesion formation and the dissemination of infection. Images Figure 1 Figure 2 PMID:7927497

  11. 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. PMID:26056906

  12. Analysis and significance of the malignant 'eclipse' during the progression of primary cutaneous human melanomas.

    PubMed

    Kerbel, R S; Kobayashi, H; Graham, C H; Lu, C

    1996-04-01

    Why is it that primary melanomas which are less than 0.76 mm in thickness are almost always curable by surgery whereas thicker lesions are associated with a worse prognosis? Put in another way, why is it that such small increases in tumor thickness beyond 0.76 mm are often associated with the eventual formation of distant metastases and death? Part of the answer lies in the dramatic qualitative changes which can accompany small increases in the size of primary human melanomas. Thus, primary melanomas less than 0.76 mm in thickness usually contain very low proportions of metastatically competent tumor cells, whereas slightly thicker lesions can contain very high proportions of such cells, resulting from a selective growth advantage of the latter in the dermal mesenchyme. This overgrowth process is akin to a 'malignant eclipse' phenomenon (by analogy with a solar eclipse). We have been studying the causes of the malignant eclipse in melanoma, for which there are at least four possibilities: 1) an increase in autocrine, mitogenic growth factors by melanoma cells; 2) a decreased rate of apoptosis in the same population; 3) an acquired resistance to paracrine growth inhibitory factors; and 4) an increased ability to induce an angiogenic response. Evidence exists for all four possibilities. Our experimental approach to studying this problem has relied heavily on the use of cell lines obtained from early stage radial growth phase or vertical growth phase lesions which have a clinical-like inability to grow progressively in nude mice, and variants obtained from such lines which are aggressively tumorigenic. Using such paired lines, and other experimental systems, we have obtained evidence that shows early stage melanoma cell lines may be deficient in inducing angiogenesis, are highly sensitive to the growth inhibitory effects of a plethora of cytokines, including transforming growth factor beta, interleukin-6, and oncostatin M, and are more sensitive to undergoing

  13. 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. PMID:27622024

  14. Oxypurinol-Specific T Cells Possess Preferential TCR Clonotypes and Express Granulysin in Allopurinol-Induced Severe Cutaneous Adverse Reactions.

    PubMed

    Chung, Wen-Hung; Pan, Ren-You; Chu, Mu-Tzu; Chin, See-Wen; Huang, Yu-Lin; Wang, Wei-Chi; Chang, Jen-Yun; Hung, Shuen-Iu

    2015-09-01

    Allopurinol, a first-line drug for treating gout and hyperuricemia, is one of the leading causes of severe cutaneous adverse reactions (SCARs). To investigate the molecular mechanism of allopurinol-induced SCAR, we enrolled 21 patients (13 Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and 8 drug reaction with eosinophilia and systemic symptoms (DRESS)), 11 tolerant controls, and 23 healthy donors. We performed in vitro T-cell activation assays by culturing peripheral blood mononuclear cells (PBMCs) with allopurinol, oxypurinol, or febuxostat and measuring the expression of granulysin and IFN-γ in the supernatants of cultures. TCR repertoire was investigated by next-generation sequencing. Oxypurinol stimulation resulted in a significant increase in granulysin in the cultures of blood samples from SCAR patients (n=14) but not tolerant controls (n=11) or healthy donors (n=23). Oxypurinol induced T-cell response in a concentration- and time-dependent manner, whereas allopurinol or febuxostat did not. T cells from patients with allopurinol-SCAR showed no crossreactivity with febuxostat. Preferential TCR-V-β usage and clonal expansion of specific CDR3 (third complementarity-determining region) were found in the blister cells from skin lesions (n=8) and oxypurinol-activated T-cell cultures (n=4) from patients with allopurinol-SCAR. These data suggest that, in addition to HLA-B*58:01, clonotype-specific T cells expressing granulysin upon oxypurinol induction participate in the pathogenesis of allopurinol-induced SCAR. PMID:25946710

  15. Clinically significant responses achieved with romidepsin across disease compartments in patients with cutaneous T-cell lymphoma

    PubMed Central

    Kim, Ellen J.; Kim, Youn H.; Rook, Alain H.; Lerner, Adam; Duvic, Madeleine; Reddy, Sunil; Robak, Tadeusz; Becker, Jürgen C.; Samtsov, Alexey; McCulloch, William; Waksman, Joel; Whittaker, Sean

    2015-01-01

    Cutaneous T-cell lymphoma (CTCL) is a rare heterogeneous group of non-Hodgkin lymphomas that arises in the skin but can progress to systemic disease (lymph nodes, blood, viscera). Historically, in clinical trials of CTCL there has been little consistency in how responses were defined in each disease “compartment”; some studies only assessed responses in the skin. The histone deacetylase inhibitor romidepsin is approved by the US Food and Drug Administration for the treatment of CTCL in patients who have received at least one prior systemic therapy. Phase II studies that led to approval used rigorous composite end points that incorporated disease assessments in all compartments. The objective of this analysis was to thoroughly examine the activity of romidepsin within each disease compartment in patients with CTCL. Romidepsin was shown to have clinical activity across disease compartments and is suitable for use in patients with CTCL having skin involvement only, erythroderma, lymphadenopathy and/or blood involvement. PMID:25791237

  16. 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

  17. 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

  18. Cutaneous Metastases of the Synchronous Primary Endometrial and Bilateral Ovarian Cancer: An Infrequent Presentation and Literature Review

    PubMed Central

    Koc, Mehmet; Findik, Siddika

    2016-01-01

    There are limited data about the cutaneous metastases of gynecological malignancies in the literature. Based on this limited number of studies, cutaneous metastases from gynecological malignancies are uncommon occurrences. Cutaneous metastases from the synchronous endometrioid carcinoma of the uterine corpus and bilateral ovaries arising from endometriosis are extremely rare. Herein, we report a 51-year-old woman with FIGO Stage 1A Grade 1 endometrial endometrioid-type adenocarcinoma and synchronous bilateral Stage 1B ovarian endometrioid-type adenocarcinoma who presented 34 months following total abdominal hysterectomy and bilateral salpingo-oophorectomy with skin metastases. After the patient underwent an excisional biopsy, we applied a palliative radiotherapy. The patient received the combination therapy with cisplatin and doxorubicin after the completion of radiotherapy but the disease evolution was rapidly fatal and the patient died 4 months after her admission to our department due to widely disseminated disease. PMID:27597911

  19. Cutaneous Metastases of the Synchronous Primary Endometrial and Bilateral Ovarian Cancer: An Infrequent Presentation and Literature Review.

    PubMed

    Kanyilmaz, Gul; Aktan, Meryem; Koc, Mehmet; Findik, Siddika

    2016-01-01

    There are limited data about the cutaneous metastases of gynecological malignancies in the literature. Based on this limited number of studies, cutaneous metastases from gynecological malignancies are uncommon occurrences. Cutaneous metastases from the synchronous endometrioid carcinoma of the uterine corpus and bilateral ovaries arising from endometriosis are extremely rare. Herein, we report a 51-year-old woman with FIGO Stage 1A Grade 1 endometrial endometrioid-type adenocarcinoma and synchronous bilateral Stage 1B ovarian endometrioid-type adenocarcinoma who presented 34 months following total abdominal hysterectomy and bilateral salpingo-oophorectomy with skin metastases. After the patient underwent an excisional biopsy, we applied a palliative radiotherapy. The patient received the combination therapy with cisplatin and doxorubicin after the completion of radiotherapy but the disease evolution was rapidly fatal and the patient died 4 months after her admission to our department due to widely disseminated disease. PMID:27597911

  20. Progressive upregulation of PD-1 in primary and metastatic melanomas associated with blunted TCR signaling in infiltrating T lymphocytes.

    PubMed

    Chapon, Maxime; Randriamampita, Clotilde; Maubec, Eve; Badoual, Cécile; Fouquet, Stéphane; Wang, Shu-Fang; Marinho, Eduardo; Farhi, David; Garcette, Marylène; Jacobelli, Simon; Rouquette, Alexandre; Carlotti, Agnès; Girod, Angélique; Prévost-Blondel, Armelle; Trautmann, Alain; Avril, Marie-Françoise; Bercovici, Nadège

    2011-06-01

    Programmed death-1 (PD-1) is involved in T-cell tolerance to self-antigens. For some cancers, it has been suggested that the expression of a ligand of PD-1, namely PD-L1, could contribute to tumor escape from immune destruction. Nevertheless, the relationship between PD-1 expression on tumor-infiltrating T lymphocytes (TILs), disease stage, and TIL responsiveness is still poorly documented. In this study, we show that freshly isolated CD4(+) and CD8(+) TILs express substantial levels of PD-1 in primary melanomas. The expression of PD-1 was further increased at later stages in distant cutaneous metastases, especially on CD8(+) TILs. The expression of PD-1 ligands was frequent only in metastases, on both tumor cells and tumor-derived myeloid cells. TILs isolated from these cutaneous tumors are poorly reactive ex vivo, with blunted calcium response and IFN-γ production after TCR stimulation. Surprisingly, in distinct parts of a primary melanoma, either invasive or regressing, we show that TILs similarly express PD-1 and remain dysfunctional. The expressions of PD-1 and PD-L1 in metastatic melanoma lesions could be considered as witnesses of an unsuccessful anti-tumoral immune response, but the direct involvement of PD-1 in the severity of the disease, and the importance of TILs in tumor regression, remain to be established. PMID:21346771

  1. Importance of assessing nonattenuation-corrected positron emission tomography images in treatment response evaluation of primary cutaneous lymphoma

    PubMed Central

    Chandra, Piyush; Agrawal, Archi; Purandare, Nilendu; Shah, Sneha; Rangarajan, Venkatesh

    2016-01-01

    Studies have shown previously that nonattenuated corrected (AC) positron emission tomography (PET) images improve detection of superficial lesions when compared to AC images. We present a case of cutaneous lymphoma to demonstrate the importance of assessing nonattenuation-corrected PET images in treatment response evaluation. PMID:27385905

  2. Simultaneous aberrations of single CDKN2A network components and a high Rb phosphorylation status can differentiate subgroups of primary cutaneous B-cell lymphomas.

    PubMed

    Kaune, Kjell M; Neumann, Christine; Hallermann, Christian; Haller, Florian; Schön, Michael P; Middel, Peter

    2011-04-01

    The cyclin-dependent kinase inhibitor 2A (CDKN2A) gene on chromosome 9p21 encodes p16 (INK4A), the inhibitor of the CDK4/retinoblastoma (Rb) cell proliferation pathway, as well as p14 (ARF), which controls p53-dependent pathways. Inactivation of p16 has previously been associated with the prognostically unfavourable primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL, LT). In this work, we analysed 22 tumors [nine primary cutaneous follicle centre lymphomas (PCFCL), seven primary cutaneous marginal zone lymphomas (PCMZL) and six PCLBCL, LT] not only for alterations of the p16 gene but also for p14, p53 and Rb by fluorescence in situ hybridization (FISH) and immunohistochemistry. In most PCLBCL, LT (4/6) alterations of CDKN2A (two biallelic deletions, one monoallelic deletion and one trisomy 9) and in addition the highest frequency of deletions of p53 (3/6) and Rb (3/6) were detected. p16 was not expressed but very high levels of phosphorylated Rb, indicating a functional effect of genomic CDKN2A alterations on the protein level in PCLBCL, LT. Regarding the p14/p53 axis, PCLBCL, LT showed a variable expression. Neither PCFCL nor PCMZL showed alterations of CDKN2A and also deletions of p53 or Rb were extremely rare in these subtypes. Exclusively in PCMZL, p53 protein was consistently lacking. In conclusion, only PCLBCL, LT is characterized by a high frequency of aberrations of the CDKN2A network components in both important tumor suppressor pathways regulated by the CDKN2A gene. Moreover, PCLBCL, LT appears to be distinguishable from PCMZL not only by its level of p53 expression but also by its stage of Rb phosphorylation. The latter may also apply to a subgroup of PCFCL. PMID:21410763

  3. BRAF mutations in cutaneous melanoma are independently associated with age, anatomic site of the primary tumor and the degree of solar elastosis at the primary tumor site

    PubMed Central

    Bauer, Jürgen; Büttner, Petra; Murali, Rajmohan; Okamoto, Ichiro; Kolaitis, Nicholas A; Landi, Maria Teresa; Scolyer, Richard A.; Bastian, Boris C.

    2011-01-01

    SUMMARY Oncogenic BRAF mutations are more frequent in cutaneous melanoma from sites with little or moderate sun-induced damage than from sites with severe cumulative solar ultraviolet (UV) damage. We studied cutaneous melanomas from geographic regions with different levels of ambient UV radiation to delineate the relative effects of cumulative UV damage, age and anatomic site on the frequency of BRAF mutations. We show that BRAF-mutated melanomas occur in a younger age group on skin without marked solar elastosis, and less frequently affect the head and neck area, compared to melanomas without BRAF mutations. The findings indicate that BRAF-mutated melanomas arise early in life at low cumulative UV doses, whereas melanomas without BRAF mutations require accumulation of high UV doses over time. The effect of anatomic site on the mutation spectrum further suggests regional differences among cutaneous melanocytes. PMID:21324100

  4. MicroRNA-16 mediates the regulation of a senescence-apoptosis switch in cutaneous T-cell and other non-Hodgkin lymphomas.

    PubMed

    Kitadate, A; Ikeda, S; Teshima, K; Ito, M; Toyota, I; Hasunuma, N; Takahashi, N; Miyagaki, T; Sugaya, M; Tagawa, H

    2016-07-14

    Multiple sequential genetic and epigenetic alterations underlie cancer development and progression. Overcoming cellular senescence is an early step in cancer pathogenesis. Here, we demonstrate that a noncoding regulatory RNA, microRNA-16 (miR-16), has the potential to induce cellular senescence. First, we examined the expression of miR-16 in primary cutaneous T-cell lymphoma (CTCL) and other non-Hodgkin T/natural killer (NK)-cell lymphomas and found that miR-16 was downregulated than that in the corresponding normal cells. Notably, miR-16 expression was reduced as the primary CTCL progressed from the early stage to the advanced stage. Next, we transduced CTCL cells with miR-16 to examine whether this miRNA exhibited tumor-suppressive effects in CTCL cells. In CTCL cells expressing wild-type p53, forced expression of miR-16 enhanced p21 expression via downregulation of the polycomb group protein Bmi1, thereby inducing cellular senescence. Alternatively, in CTCL cells lacking functional p53, miR-16 induced compensatory apoptosis. The miR-16 transfection significantly decreased senescent cells and increased apoptotic cells in p21-knockdown CTCL cells expressing wild-type p53, suggesting that the presence or absence of p21 may be the most important condition in the senescence-apoptosis switch in CTCL lymphomagenesis. Furthermore, we found that the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) restored the expression of miR-16 and its essential targets, induced senescence in CTCL cells expressing wild-type p53 and promoted apoptosis in cells with nonfunctional p53. Moreover, we found that other T/NK-cell lymphoma cell lines showed similar tumor-suppressive effects in response to miR-16 and SAHA and that these effects were dependent on p53 status. These results suggested that epigenetic silencing of miR-16 may be a key step during lymphoma development. Elucidation of the essential targets of miR-16 and SAHA provides a basis for the clinical

  5. Cutaneous sarcoidosis and polycythemia vera.

    PubMed

    Pascual, J C; Belinchón, I; Albares, P; Vergara, G; Betlloch, I; Bañuls, J

    2004-11-01

    Polycythemia vera is classified with myelogenous leukaemia, agnogenic myeloid metaplasia and primary thrombocythemia as a myeloproliferative syndrome. Cutaneous symptoms have been reported with polycythemia vera, including facial plethora, aquagenic pruritus, urticaria, purpura, Sweet's syndrome and pyoderma gangrenosum. However, polycythemia vera associated with systemic sarcoidosis has been rarely reported. An unusual case of polycythemia vera associated with cutaneous sarcoidosis is described. PMID:15482300

  6. 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. PMID:16105841

  7. Intrahepatic Xenograft of Cutaneous T-Cell Lymphoma Cell Lines: A Useful Model for Rapid Biological and Therapeutic Evaluation.

    PubMed

    Andrique, Laetitia; Poglio, Sandrine; Prochazkova-Carlotti, Martina; Kadin, Marshall Edward; Giese, Alban; Idrissi, Yamina; Beylot-Barry, Marie; Merlio, Jean-Philippe; Chevret, Edith

    2016-07-01

    Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of diseases primarily involving the skin that could have an aggressive course with circulating blood cells, especially in Sézary syndrome and transformed mycosis fungoides. So far, few CTCL cell lines have been adapted for in vivo experiments and their tumorigenicity has not been adequately assessed, hampering the use of a reproducible model for CTCL biological evaluation. In fact, both patient-derived xenografts and cell line xenografts at subcutaneous sites failed to provide a robust tool, because engraftment was dependent on mice strain and cell line subtype. Herein, we describe an original method of intrahepatic injection into adult NOD.Cg-Prkdc(scid)Il2rg(tm1Wjl)/SzJ mice liver of both aggressive (My-La, HUT78, HH, MAC2A, and MAC2B) and indolent (FE-PD and MAC1) CTCL cell lines. Six of the seven CTCL cell lines were grafted with a high rate of success (80%). Moreover, this model provided a quick (15 days) and robust assay for in vivo evaluation of CTCL cell lines tumorigenicity and therapeutic response in preclinical studies. Such a reproducible model can be therefore used for further functional studies and in vivo drug testing. PMID:27181405

  8. Demographic patterns of cutaneous T-cell lymphoma incidence in Texas based on two different cancer registries

    PubMed Central

    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

    2015-01-01

    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. PMID:26136403

  9. Long-term outcome of patients with advanced-stage cutaneous T cell lymphoma treated with gemcitabine.

    PubMed

    Pellegrini, Cinzia; Stefoni, Vittorio; Casadei, Beatrice; Maglie, Roberto; Argnani, Lisa; Zinzani, Pier Luigi

    2014-11-01

    The choice of treatment for cutaneous T cell lymphoma (CTCL) is often determined by institutional experience, particularly as there is a paucity of data from phase III trials and a lack of consensus concerning treatment of the advanced stages. Among the several second-line and experimental drugs, gemcitabine could be considered one of the most suitable options for pretreated CTCL. Since it is difficult to find in literature the long-term outcome regarding the efficacy of a single-agent drug in pretreated patients and, in particular, in rare diseases such as CTCL, a retrospective observational study was conducted with the aim of evaluating the long-term outcome of CTCL patients treated with gemcitabine. Twenty-five patients with at least one therapy (range 1-8) performed prior to gemcitabine were found. After gemcitabine treatment, the overall response was 48 % with a 20 % of complete responses. At 15 years, the estimated overall survival is 47 %, progression-free survival 8.8 %, and disease-free survival 40 % (median reached at 2.9 years). All patients received at least three cycles and no grade 3-4 hematological adverse events occurred. At the latest follow-up, two patients are still in continuous complete response. This long-term update on the role of gemcitabine as a single agent in pretreated advanced-stage CTCL confirms this monotherapy as effective and safe. PMID:24908331

  10. Biological modifiers (etretinate (changed from etetrinate) and alfa 2a) in the treatment of refractory cutaneous T-cell lymphoma.

    PubMed

    Avilés, A; Guzmán, R; García, E L; Díaz-Maqueo, J C

    1996-02-01

    To assess the efficacy and toxicity of biological modifiers in combination etetrinate, 0.8 mg/kg/day, po and interferon alfa 2a 9.0 MU, three times at week) in the treatment of refractory cutaneous T-cell lymphoma (CTLC) we began a clinical study on 12 heavily treated patients. After 1 year on treatment 10/12 patients (83%) achieved complete response. Two patients were considered failures with disease progression. After a median follow-up of 3 years, seven patients (56%) remained in complete remission. Toxicity was mild. All patients received 93% of the planned dose of etetrinate and interferon. We feel that biological modifiers, as etetrinate and interferons, are agents with limited hematological toxicity even in higher doses. The combination of two agents, with different mechanisms of action, could improve the outcome in patients with refractory CTCL. Controlled trials are necessary to define the roles of this type of therapy as first line of treatment. PMID:10851517

  11. A unique phenotype of skin-associated lymphocytes in humans. Preferential expression of the HECA-452 epitope by benign and malignant T cells at cutaneous sites.

    PubMed Central

    Picker, L. J.; Michie, S. A.; Rott, L. S.; Butcher, E. C.

    1990-01-01

    It has been proposed that the skin is a functionally unique compartment of the immune system, although little direct evidence supporting this hypothesis has been presented. Here we show that lymphocyte populations at cutaneous sites can be differentiated from otherwise similar populations at noncutaneous sites by their preferential expression of an epitope defined by the MAb HECA-452. This MAb recognizes a predominantly 200-kd cell-surface glycoprotein present on about 16% of peripheral blood T cells, including both CD4+ and CD8+ T cells (17% and 11% HECA-452+, respectively), as well as TCR-delta-bearing T cells (32%+). Most thymocytes (99%) lacked HECA-452 antigen expression, and essentially all the HECA-452+ peripheral blood T cells were found in the adhesion molecule high, CD45R low putative memory cell subset, findings suggesting that HECA-452 expression develops peripherally as a consequence of antigenic stimulation. However, the HECA-452 antigen is not a conventional activation antigen because it was not upregulated with mitogen stimulation of peripheral blood T cells. Most significantly, among 54 diverse specimens of normal/reactive lymphoid tissues and sites of chronic inflammation, there was a clear association of lymphocyte HECA-452 expression and cutaneous location. In extracutaneous sites (n = 38) only about 5% of lymphocytes within the T-cell areas of these tissues expressed this antigen, whereas in inflammatory skin lesions (n = 16), 85% were HECA-452+. The association of HECA-452 expression and cutaneous location was also seen in a series of T-cell lymphomas. The malignant cells of 16 of 18 cases of epidermotropic (patch/plaque) stage mycosis fungoides were HECA-452+, as well as 2 of 7 nonmycosis fungoides peripheral T-cell lymphomas in skin. In contrast, this antigen was not expressed in thymic (lymphoblastic) lymphomas (n = 14), nonepidermotropic (tumor) stage mycosis fungoides (n = 5), and noncutaneous peripheral T-cell lymphomas (n = 15). Among

  12. Expression of Cutaneous Lymphocyte–Associated Antigen and E-selectin Ligand by Circulating Human Memory CD4+ T Lymphocytes Specific for Herpes Simplex Virus Type 2

    PubMed Central

    González, Julio C.; Kwok, William W.; Wald, Anna; McClurkan, Christopher L.; Huang, Jay; Koelle, David M.

    2005-01-01

    Virus-specific memory T lymphocytes traffic to sites of viral infection. Herpes simplex virus (HSV) type 2–specific CD4+ and CD8+ T lymphocytes differ with regard to their homing kinetics to infected tissues. We studied the expression of cutaneous lymphocyte–associated antigen (CLA) and E-selectin ligand (ESL) by HSV-2–specific CD4+ T lymphocytes. Virus-reactive T lymphocytes were identified ex vivo by CD154 or interferon-γ up-regulation. We detected selective expression of CLA by HSV-2–reactive CD4+ T lymphocytes, but at levels lower than those we previously observed for CD8+ T lymphocytes. Short-term HSV-2–reactive CD4+ lines generated from peripheral-blood mononuclear cells preferentially express CLA, compared with cytomegalovirus- or influenza-specific cells. CLA is expressed by HSV-2–reactive cells that are initially CLA negative before restimulation. Short-term culture-expanded HSV-2–specific CD4+ T lymphocytes also selectively express ESL. These findings have implications for the optimization of vaccines for HSV and other cutaneous pathogens. PMID:15609235

  13. 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.

  14. Cutaneous cryosurgery.

    PubMed

    Zimmerman, Ethan E; Crawford, Paul

    2012-12-15

    Cutaneous cryosurgery refers to localized application of freezing temperatures to achieve destruction of skin lesions. It can be used to treat a broad range of benign and premalignant skin conditions, and certain malignant skin conditions, with high cure rates. Cellular destruction is accomplished by delivery of the cryogen via dipstick, probe, or spray techniques. It is widely used in primary care because of its safety, effectiveness, low cost, ease of use, good cosmetic results, and lack of need for anesthesia. Cryosurgery is as effective as alternative therapies for most cases of molluscum contagiosum, dermatofibromas, keloids, and plantar or genital warts. It is a more effective cure for common warts than salicylic acid or observation. Cryosurgery is generally the treatment of choice for actinic keratosis. Contraindications to cryosurgery include cryofibrinogenemia, cryoglobulinemia, Raynaud disease, agammaglobulinemia, and multiple myeloma. Complications from cryosurgery include hypopigmentation and alopecia, and can be avoided by limiting freeze times to less than 30 seconds. Referral to a dermatologist should be considered in cases of diagnostic uncertainty or for treatment of skin cancer, which requires larger amounts of tissue destruction, resulting in higher complication rates. PMID:23316984

  15. Cutaneous Small/Medium CD4+ Pleomorphic T-Cell Lymphoma-Like Nodule in a Patient With Erythema Chronicum Migrans.

    PubMed

    Celebi Cherukuri, Nil; Roth, Christine G; Aggarwal, Nidhi; Ho, Jonhan; Gehris, Robin; Akilov, Oleg E

    2016-06-01

    CD4+ small/medium pleomorphic T-cell lymphoma is a relatively rare subtype of cutaneous lymphoproliferative disorder with an indolent clinical behavior. The place of this condition among lymphomas is debatable. The authors describe a rare case of the direct association of CD4 small/medium pleomorphic T-cell lymphoma-like solitary nodule with Borrelia burgdorferi infection in a 5-year-old boy, discuss the reactive nature of this condition, and emphasize the importance of clinicopathological correlation. PMID:27097344

  16. Excellent Outcome of Immunomodulation or Bruton’s Tyrosine Kinase Inhibition in Highly Refractory Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type

    PubMed Central

    Accurso, Joseph; Sluzevich, Jason; Menke, David M.; Tun, Han W.

    2015-01-01

    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. PMID:26788279

  17. Primary Cutaneous Cryptococcosis Treated with Debridement and Fluconazole Monotherapy in an Immunosuppressed Patient: A Case Report and Review of the Literature

    PubMed Central

    Wang, Jennifer; Bartelt, Luther; Yu, Deborah; Joshi, Anjali; Weinbaum, Bradley; Pierson, Tiffany; Patrizio, Michael; Warren, Cirle A.; Hughes, Molly A.; Donowitz, Gerald

    2015-01-01

    Cryptococcus neoformans is an opportunistic yeast present in the environment. Practitioners are familiar with the presentation and management of the most common manifestation of cryptococcal infection, meningoencephalitis, in patients with AIDS or other conditions of immunocompromise. There is less awareness, however, of uncommon presentations where experience rather than evidence guides therapy. We report a case of primary cutaneous cryptococcosis (PCC) in a patient who had been immunosuppressed by chronic high-dose corticosteroid for the treatment of severe asthma. This case highlights the importance of early recognition of aggressive cellulitis that fails standard empiric antibiotic treatment in an immunocompromised patient. It also demonstrates successful treatment of PCC with a multispecialty approach including local debridement and fluconazole monotherapy. PMID:25722900

  18. Periodic acid-Schiff-positive organisms in primary cutaneous Bacillus cereus infection. Case report and an investigation of the periodic acid-Schiff staining properties of bacteria.

    PubMed

    Khavari, P A; Bolognia, J L; Eisen, R; Edberg, S C; Grimshaw, S C; Shapiro, P E

    1991-04-01

    Primary cutaneous Bacillus cereus infection frequently presents as a single necrotic bulla on the extremity of an immunocompromised patient. In lesional biopsy specimens and smears, the large gram-positive rods of B cereus may be mistaken for Clostridium species. This is a potentially serious error, as Bacillus species are resistant to penicillin and other beta-lactam antibiotics. We studied a case in which large periodic acid-Schiff-staining organisms were seen in the biopsy specimen from a necrotic bulla on the finger of a neutropenic patient with diffuse large cell lymphoma. The tissue biopsy specimen subsequently yielded a pure culture of B cereus. Staining with periodic acid-Schiff was then performed on a series of bacterial species in human tissue and from smears of culture colonies. The following bacterial species were found to be consistently periodic acid-Schiff positive after diastase digestion: B cereus, Corynebacterium diphtheriae, Propionibacterium acnes, Klebsiella pneumoniae, and Micrococcus luteus. PMID:1900984

  19. Cutaneous metastasis of breast adenoid cystic carcinoma to the scalp.

    PubMed

    Little, Anthony J; Seline, Alison E; Swick, Brian L; Wanat, Karolyn A

    2016-08-01

    Adenoid cystic carcinoma (ACC) is a tumor that can be of primary cutaneous origin or secondary to metastatic disease, most commonly salivary origin. Aside from primary cutaneous and salivary types, ACC of the breast is a rare, more indolent variant. Cutaneous metastases secondary to breast ACC is exceedingly uncommon and not previously reported to our knowledge. We present the case of a 67-year-old woman who developed cutaneous metastasis from primary breast ACC. PMID:26968987

  20. No evidence of HTLV-I proviral integration in lymphoproliferative disorders associated with cutaneous T-cell lymphoma.

    PubMed Central

    Wood, G. S.; Schaffer, J. M.; Boni, R.; Dummer, R.; Burg, G.; Takeshita, M.; Kikuchi, M.

    1997-01-01

    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. Images Figure 1 Figure 2

  1. 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

  2. Cutaneous protothecosis.

    PubMed

    Hillesheim, Paul B; Bahrami, Soon

    2011-07-01

    Prototheca species are an achlorophyllic algae that cause infections primarily in immunocompromised individuals. At least one-half of infectious cases are cutaneous. Because protothecosis is seldom suspected clinically, patients may be subjected to various treatment modalities for extended periods without satisfactory results. Cutaneous protothecosis shares similar clinical and pathologic findings with deep tissue fungal mycoses. The typical presentation occurs most commonly on the face and extremities as erythematous plaques, nodules, or superficial ulcers. Prototheca spp are spherical, unicellular, nonbudding organisms that are sometimes noted on routine hematoxylin-eosin staining but are best visualized with periodic acid-Schiff and Gomori methenamine-silver histochemical stains. Although protothecosis can be diagnosed on biopsy, culture of the organism on a medium such as Sabouraud dextrose agar is required for definitive diagnosis. Treatment may require a combination of surgical excision and antifungal agents. Therefore, cutaneous protothecosis should be considered in a lesion that appears suspicious for the more-common fungal infections. PMID:21732787

  3. [Perspective of cutaneous lymphoma reserach].

    PubMed

    Dummer, Reinhard; Urosevic, Mirjana; Cozzio, Antonio; Asagoe, Kenji; Döbbeling, Udo; Burg, Günter

    2006-06-01

    Primary cutaneous lymphomas are characterized by an expansion of hematopoietic cells in the special microenvironment of the skin. They represent a special challenge both for researches and for clinicians who treat patients with these disorders. New research data concerning the biology of lymphocytes and the cutaneous microenvironment have increased our knowledge of these diseases in the last decades. The new WHO/EORTC classification definitely will facilitate a more detailed investigation of the various subtypes. PMID:16734840

  4. T-cell Landscape in a Primary Melanoma Predicts the Survival of Patients with Metastatic Disease after Their Treatment with Dendritic Cell Vaccines.

    PubMed

    Vasaturo, Angela; Halilovic, Altuna; Bol, Kalijn F; Verweij, Dagmar I; Blokx, Willeke A M; Punt, Cornelis J A; Groenen, Patricia J T A; van Krieken, J Han J M; Textor, Johannes; de Vries, I Jolanda M; Figdor, Carl G

    2016-06-15

    Tumor-infiltrating lymphocytes appear to be a predictor of survival in many cancers, including cutaneous melanoma. We applied automated multispectral imaging to determine whether density and distribution of T cells within primary cutaneous melanoma tissue correlate with survival of metastatic melanoma patients after dendritic cell (DC) vaccination. CD3(+) T cell infiltration in primary tumors from 77 metastatic melanoma patients was quantified using the ratio of intratumoral versus peritumoral T-cell densities (I/P ratio). Patients with longer survival after DC vaccination had stronger T-cell infiltration than patients with shorter survival in a discovery cohort of 19 patients (P = 0.000026) and a validation cohort of 39 patients (P = 0.000016). I/P ratio was the strongest predictor of survival in a multivariate analysis including M substage and serum lactate dehydrogenase level. To evaluate I/P ratio as a predictive biomarker, we analyzed 19 chemotherapy-treated patients. Longer survival times of DC-vaccinated compared with chemotherapy-treated patients was observed for high (P = 0.000566), but not low (P = 0.154) I/P ratios. In conclusion, T-cell infiltration into primary melanoma is a strong predictor of survival after DC vaccination in metastatic melanoma patients who, on average, started this therapy several years after primary tumor resection. The infiltration remains predictive even after adjustment for late-stage prognostic markers. Our findings suggest that the I/P ratio is a potential predictive biomarker for treatment selection. Cancer Res; 76(12); 3496-506. ©2016 AACR. PMID:27197179

  5. Cutaneous Sarcoidosis.

    PubMed

    Wanat, Karolyn A; Rosenbach, Misha

    2015-12-01

    The skin is the second most common organ affected in sarcoidosis, which can affect patients of all ages and races, with African American women having the highest rates of sarcoidosis in the United States. The cutaneous manifestations are protean and can reflect involvement of sarcoidal granulomas within the lesion or represent reactive non-specific inflammation, as seen with erythema nodosum. Systemic work-up is necessary in any patient with cutaneous involvement of sarcoidal granulomas, and treatment depends on other organ involvement and severity of clinical disease. Skin-directed therapies are first line for mild disease, and immunomodulators or immunosuppressants may be necessary. PMID:26593142

  6. Phase 1/2 study of mogamulizumab, a defucosylated anti-CCR4 antibody, in previously treated patients with cutaneous T-cell lymphoma.

    PubMed

    Duvic, Madeleine; Pinter-Brown, Lauren C; Foss, Francine M; Sokol, Lubomir; Jorgensen, Jeffrey L; Challagundla, Pramoda; Dwyer, Karen M; Zhang, Xiaoping; Kurman, Michael R; Ballerini, Rocco; Liu, Li; Kim, Youn H

    2015-03-19

    This phase 1/2 study evaluated the efficacy of mogamulizumab, a defucosylated, humanized, anti-CC chemokine receptor 4 monoclonal antibody, in 41 pretreated patients with cutaneous T-cell lymphoma. No dose-limiting toxicity was observed and the maximum tolerated dose was not reached in phase 1 after IV infusion of mogamulizumab (0.1, 0.3, and 1.0 mg/kg) once weekly for 4 weeks followed by a 2-week observation. In phase 2, patients were dosed with 1.0 mg/kg mogamulizumab according to the same schedule for the first course followed by infusion every 2 weeks during subsequent courses until disease progression. The most frequent treatment-emergent adverse events were nausea (31.0%), chills (23.8%), headache (21.4%), and infusion-related reaction (21.4%); the majority of events were grade 1/2. There were no significant hematologic effects. Among 38 evaluable patients, the overall response rate was 36.8%: 47.1% in Sézary syndrome (n = 17) and 28.6% in mycosis fungoides (n = 21). Eighteen of 19 (94.7%) patients with ≥B1 blood involvement had a response in blood, including 11 complete responses. Given the safety and efficacy of mogamulizumab, phase 3 investigation of mogamulizumab is warranted in cutaneous T-cell lymphoma patients. This trial was registered at www.clinicaltrials.gov as #NCT00888927. PMID:25605368

  7. Phase 1/2 study of mogamulizumab, a defucosylated anti-CCR4 antibody, in previously treated patients with cutaneous T-cell lymphoma

    PubMed Central

    Pinter-Brown, Lauren C.; Foss, Francine M.; Sokol, Lubomir; Jorgensen, Jeffrey L.; Challagundla, Pramoda; Dwyer, Karen M.; Zhang, Xiaoping; Kurman, Michael R.; Ballerini, Rocco; Liu, Li; Kim, Youn H.

    2015-01-01

    This phase 1/2 study evaluated the efficacy of mogamulizumab, a defucosylated, humanized, anti-CC chemokine receptor 4 monoclonal antibody, in 41 pretreated patients with cutaneous T-cell lymphoma. No dose-limiting toxicity was observed and the maximum tolerated dose was not reached in phase 1 after IV infusion of mogamulizumab (0.1, 0.3, and 1.0 mg/kg) once weekly for 4 weeks followed by a 2-week observation. In phase 2, patients were dosed with 1.0 mg/kg mogamulizumab according to the same schedule for the first course followed by infusion every 2 weeks during subsequent courses until disease progression. The most frequent treatment-emergent adverse events were nausea (31.0%), chills (23.8%), headache (21.4%), and infusion-related reaction (21.4%); the majority of events were grade 1/2. There were no significant hematologic effects. Among 38 evaluable patients, the overall response rate was 36.8%: 47.1% in Sézary syndrome (n = 17) and 28.6% in mycosis fungoides (n = 21). Eighteen of 19 (94.7%) patients with ≥B1 blood involvement had a response in blood, including 11 complete responses. Given the safety and efficacy of mogamulizumab, phase 3 investigation of mogamulizumab is warranted in cutaneous T-cell lymphoma patients. This trial was registered at www.clinicaltrials.gov as #NCT00888927. PMID:25605368

  8. Wide versus narrow excision margins for high-risk, primary cutaneous melanomas: long-term follow-up of survival in a randomised trial

    PubMed Central

    Hayes, Andrew J; Maynard, Lauren; Coombes, Gillian; Newton-Bishop, Julia; Timmons, Michael; Cook, Martin; Theaker, Jeffrey; Bliss, Judith M; Thomas, J Meirion

    2016-01-01

    Summary Background The necessary margin of excision for cutaneous melanomas greater than 2 mm in thickness is controversial. At a median follow-up of 5 years, findings from our previously published randomised trial of narrow (1 cm) versus wide (3 cm) excision margins in patients with thick cutaneous melanomas showed that narrow margins were associated with an increased frequency of locoregional relapse, but no significant difference in overall survival was apparent. We now report a long-term survival analysis of that trial. Methods We did a randomised, open-label multicentre trial in 59 hospitals—57 in the UK, one in Poland, and one in South Africa. Patients with one primary localised cutaneous melanoma greater than 2 mm in Breslow thickness on the trunk or limbs (excluding palms or soles) were randomly assigned (1:1) centrally to receive surgery with either a 1 cm or 3 cm excision margin following an initial surgery. The randomisation lists were generated with random permuted blocks and stratified by centre and extent of initial surgery. The endpoints of this analysis were overall survival and melanoma-specific survival. Analyses were done in the intention-to-treat population. This trial was not registered because it predated mandatory trial registration. Findings Between Dec 16, 1992, and May 22, 2001, we randomly assigned 900 patients to surgery with either a 1 cm excision margin (n=453) or a 3 cm excision margin (n=447). At a median follow-up of 8·8 years (106 months [IQR 76–135], 494 patients had died, with 359 of these deaths attributed to melanoma. 194 deaths were attributed to melanoma in the 1 cm group compared with 165 in the 3 cm group (unadjusted hazard ratio [HR] 1·24 [95% CI 1·01–1·53]; p=0·041). Although a higher number of deaths overall occurred in the 1 cm group compared with the 3 cm group (253 vs 241), the difference was not significant (unadjusted HR 1·14 [95% CI 0·96–1·36]; p=0·14). Surgical complications were reported in 35 (8

  9. Novel primary thymic defect with T lymphocytes expressing gamma delta T cell receptor.

    PubMed

    Geisler, C; Pallesen, G; Platz, P; Odum, N; Dickmeiss, E; Ryder, L P; Svejgaard, A; Plesner, T; Larsen, J K; Koch, C

    1989-07-01

    Flow cytometric analysis of the peripheral blood mononuclear cells in a six year old girl with a primary cellular immune deficiency showed a normal fraction of CD3 positive T cells. Most (70%) of the CD3 positive cells, however, expressed the gamma delta and not the alpha beta T cell receptor. Immunoprecipitation and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that most of the gamma delta T cell receptors existed as disulphide-linked heterodimers. Proliferative responses to mitogens were severely reduced, but specific antibody responses after vaccination could be detected. A thymic biopsy specimen showed severe abnormalities of both the thymic lymphoid and epithelial component with abortive medullary differentiation and almost an entire lack of Hassall's corpuscles. This patient represents a case of primary immune deficiency syndrome not previously described. Thymic deficiency associated with a high proportion of T cells expressing the gamma delta T cell receptor has been described in nude mice, and it is suggested that the immune deficiency of this patient may represent a human analogue. PMID:2527256

  10. 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

  11. 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.

  12. Cutaneous Horn

    MedlinePlus

    ... fair-skinned individuals with a history of significant sun exposure. Signs and Symptoms A cutaneous horn most often ... radiation therapy. Trusted Links MedlinePlus: Skin Conditions MedlinePlus: Sun Exposure References Bolognia, Jean L., ed. Dermatology , pp.1715. ...

  13. Global Patterns of Methylation in Sézary Syndrome Provide Insight into the Role of Epigenetics in Cutaneous T-Cell Lymphoma.

    PubMed

    Whittaker, Sean

    2016-09-01

    van Doorn et al. have defined the DNA methylomes of Sézary cells based on a genome-wide methylation analysis using the Illumina 450K array platform (Illumina, San Diego, CA). Their results show aberrant DNA methylation patterns in CD4-enriched T cells from peripheral blood samples, patterns that are distinct from those of patients with inflammatory erythroderma and from healthy volunteers. Whereas 7.8% of 473,921 5'-cytosine-phosphate-guanine-3' (CpG) sites were hypomethylated, 3.2% showed marked enrichment and selection for hypermethylated CpG sites within the proximal region of gene promoters, including some genes that have previously been shown to be hypermethylated in cutaneous T-cell lymphomas (CTCLs), using standard bisulfite modification techniques. PMID:27542296

  14. Cutaneous lymphoid hyperplasias.

    PubMed

    Gilliam, A C; Wood, G S

    2000-06-01

    Benign hyperplastic lymphoid infiltrates of the skin (pseudolymphoma, older term) simulate lymphoma clinically and histologically. They can be divided into B-cell predominant (typical cutaneous lymphoid hyperplasia (CLH), angiolymphoid hyperplasia, Kimura's disease, and Castleman's disease) and T-cell predominant (T-cell CLH, lymphomatoid contact dermatitis, and lymphomatoid drug eruption). Both types may represent exaggerated reactions to diverse external antigens (insect bite, tattoo, zoster, trauma, among others). A composite assessment of clinical presentation and behavior, routine histology, immunophenotyping, and molecular studies is essential for the diagnosis of benign cutaneous lymphoid infiltrates. Treatment includes antibiotics, intralesional and systemic corticosteroids, excision, radiotherapy, and immunosuppressants. Treatment depends on the assessment and biologic behavior, which is usually benign. Molecular biologic analysis has shown that a significant proportion of cases harbor occult B- or T-cell clones (clonal CLH). Progression to overt cutaneous lymphoma has been observed in a minority of cases. Patients with clonal populations of B or T cells and persistent lesions should be closely observed for emergence of a lymphoma. PMID:10892716

  15. Isolated cutaneous involvement in a child with nodal anaplastic large cell lymphoma.

    PubMed

    Mendiratta, Vibhu; Gandhi, Nikita; Rana, Shiwangi; Shukla, Shailaja

    2016-01-01

    Non-Hodgkin lymphoma is a common childhood T-cell and B-cell neoplasm that originates primarily from lymphoid tissue. Cutaneous involvement can be in the form of a primary extranodal lymphoma, or secondary to metastasis from a non-cutaneous location. The latter is uncommon, and isolated cutaneous involvement is rarely reported. We report a case of isolated secondary cutaneous involvement from nodal anaplastic large cell lymphoma (CD30 + and ALK +) in a 7-year-old boy who was on chemotherapy. This case is reported for its unusual clinical presentation as an acute febrile, generalized papulonodular eruption that mimicked deep fungal infection, with the absence of other foci of systemic metastasis. PMID:26728811

  16. Annular subacute cutaneous lupus erythematosus lesions and polymyositis onset in a patient with primary Sjogren's syndrome: how should this unusual association be classified?

    PubMed

    Bernacchi, E; Neri, R; Caproni, M; Loggini, B; Fabbri, P; Bombardieri, S

    2013-03-01

    Classification of the wide variety of autoimmune diseases that can occur before or after the onset of Sjögren's syndrome (SS) is currently debated within the conventional SS criteria or as primary SS (pSS) developing autoimmune disease or as 'associated-overlap' with other systemic autoimmune diseases. There is also debate on whether or not to consider annular polycyclic subacute cutaneous lupus erythematosus (SCLE) and annular erythema associated with Sjögren's syndrome (AESS) as a spectrum linked to Ro-SSA and/or La-SSB auto-antibodies (SSA/SSB auto-ab). We present the case of a 55-year-old female patient, with pSS positive for SSA and SSB auto-ab, who developed chronic relapsing polymyositis and atypical annular non-polycyclic SCLE lesions resembling AESS, which seemed to suggest a common spectrum. While a chronic-progressive polymyositis may be generally accepted as a relatively rare myositis complicating pSS, interpretation of annular lesions of non-systemic SCLE in SS patients might actually be underestimated as pSS skin manifestation likely related to SSA/SSB auto-ab. PMID:23358869

  17. Solitary (primary) uveal T-cell lymphoma in a horse.

    PubMed

    Trope, Gareth D; McCowan, Christina I; Tyrrell, Dayle; Lording, Peter M; Maggs, David J

    2014-03-01

    A 22-year-old Australian stockhorse gelding was presented with anterior uveitis in the right eye which was nonresponsive to anti-inflammatory therapy. Clinical examination revealed corneal edema and vascularization, marked hypopyon, and thickening of the dorsal iris, which was confirmed by ultrasonography. Hematologic and biochemical analyses, abdominal and thoracic ultrasonography, and abdominocentesis with cytologic and biochemical analysis revealed no significant abnormalities. Cytological examination of an aqueous humor sample revealed a population of predominantly large lymphoblasts with high nuclear-to-cytoplasmic ratio, round or irregular nuclei, clumped nuclear chromatin, multiple large prominent nucleoli, and a small volume of basophilic cytoplasm. The cytologic diagnosis was intraocular lymphoma. Biopsy of the right submandibular lymph node revealed no evidence of neoplastic invasion. Euthanasia and a complete necropsy were performed and revealed no evidence of neoplasia in any tissue other than the right eye, which had an extensive, well-defined infiltrate of neoplastic lymphocytes expanding the ciliary body and iris, infiltrating the ciliary epithelium, and extending into the pars plana and peripheral choroid. Immunohistochemistry confirmed that neoplastic cells expressed the T-cell marker CD3. To the authors' knowledge, this is the first description of primary, solitary uveal T-cell lymphoma in a horse. Although apparently rare, lymphoma should be considered in horses with uveitis, even when inflammation is unilateral and in the absence of extraocular signs of neoplasia. Aqueocentesis and cytological examination provided an antemortem diagnosis in this case and should be considered as a diagnostic tool for investigation of uveal thickening and hypopyon. PMID:23802547

  18. P16 protein expression in primary cutaneous melanoma with positive and negative lymph node biopsies: Particular aspects of a study performed at the Hospital de Clinicas de Porto Alegre, Brazil

    PubMed Central

    Fauri, JAC; Ricardi, F; Diehl, ES; Cartell, A; Furian, R; Bakos, L; Edelweiss, MI

    2011-01-01

    BACKGROUND: Cutaneous melanoma dermal invasion, identified through measurement of maximum tumour thickness and sentinel lymph node (SLN) biopsy, is important to establish melanoma prognosis and progression. P16 protein expression has been shown to be a predictive factor for melanoma evolution and prognosis. OBJECTIVE: To investigate p16 protein expression in cutaneous melanomas with and without SLN metastasis. PATIENTS AND METHODS: Sixty-seven paraffin-embedded cutaneous melanoma specimens of patients who had undergone SLN investigation were evaluated from 1995 to 2007. SLN biopsy was negative for metastasis in 34 of these patients (controls); in the remaining 33 patients, SLN biopsy was positive (cases). The expression of p16 protein in the primary tumour was measured using an immunohistochemical assay. The samples were classified according to their nuclear expression. RESULTS: P16 nuclear expression was absent in 14 cases and in 15 controls; P=0.812. There was no statistically significant difference in p16 nuclear expression between cases and controls. CONCLUSIONS: The present study does not support the findings of other studies that suggest p16 protein expression is important in the prognosis of cutaneous melanoma. PMID:22942654

  19. Cutaneous Myiasis.

    PubMed

    Solomon, Michal; Lachish, Tamar; Schwartz, Eli

    2016-09-01

    Myiasis is defined as the infestation of live vertebrates, either humans or animals, with dipterous larvae. Many organs can be infested by these larvae with cutaneous myiasis being the most common form. Cutaneous myiasis can be divided into three categories: localized furuncular myiasis, migratory myiaisis and wound myiasis, which occurs when fly larvae infest the open wounds of the host. Human myiasis has worldwide distribution, with more species and a heavier burden in tropical and subtropical countries. In recent years with increased travel to the tropics, myiasis has become common in returning travelers from these regions, Furuncular myiasis, mainly Dermatobia homonis becomes the most common form seen among them. Treatment is based on full extraction of the larva and no antibiotic treatment is needed. Understanding the mode of transmission of each type of myiasis may help to prevent the infestation. PMID:27443558

  20. Cutaneous Listeriosis

    PubMed Central

    Godshall, Casey E.; Suh, Gina

    2013-01-01

    Cutaneous infections due to Listeria monocytogenes are rare. Typically, infections manifest as nonpainful, nonpruritic, self-limited, localized, papulopustular or vesiculopustular eruptions in healthy persons. Most cases follow direct inoculation of the skin in veterinarians or farmers who have exposure to animal products of conception. Less commonly, skin lesions may arise from hematogenous dissemination in compromised hosts with invasive disease. Here, we report the first case in a gardener that occurred following exposure to soil and vegetation. PMID:23966491

  1. 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,…

  2. Characterization of dynamic actin associations with T-cell receptor microclusters in primary T cells

    PubMed Central

    Smoligovets, Alexander A.; Smith, Adam W.; Wu, Hung-Jen; Petit, Rebecca S.; Groves, Jay T.

    2012-01-01

    T cell triggering through T-cell antigen receptors (TCRs) results in spatial assembly of the receptors on multiple length scales. This assembly is mediated by the T cell actin cytoskeleton, which reorganizes in response to TCR phosphorylation and then induces the coalescence of TCRs into microclusters, followed by their unification into a micrometer-scale structure. The exact outcomes of the association of TCRs with a dynamic and fluctuating actin network across these length scales are not well characterized, but it is clear that weak and transient interactions at the single-molecule level sum to yield significant receptor rearrangements at the plasma membrane. We used the hybrid live cell–nanopatterned supported lipid bilayer system to quantitatively probe the actin–TCR interaction in primary T cells. A specialized tracking algorithm revealed that actin slows as it passes over TCR clusters in a direction-dependent manner with respect to the resistance against TCR motion. We also observed transient actin enrichments at sites corresponding to putative TCR clusters that far exceeded pure stochastic fluctuations and described an image time-autocorrelation analysis method to quantify these accumulations. PMID:22389407

  3. 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. PMID:25233487

  4. The Spectrum of Cutaneous Lymphomas in HIV infection: a study of 21 cases.

    PubMed

    Beylot-Barry, M; Vergier, B; Masquelier, B; Bagot, M; Joly, P; Souteyrand, P; Vaillant, L; Avril, M F; Franck, N; Fraitag, S; Delaunay, M; Laroche, L; Estève, E; Courville, P; Dechelotte, P; Beylot, C; De Mascarel, A; Wechsler, J; Merlio, J P

    1999-10-01

    We studied 21 HIV-associated lymphomas with cutaneous presentation to determine whether they showed features of primary cutaneous lymphoma arising fortuitously or whether they represented the cutaneous involvement of AIDS systemic lymphoma. Besides rare mycosis fungoides (n = 3), which shared typical clinicopathologic lesions, nonepidermotropic large-cell lymphomas (n = 18) were predominant. They frequently presented as a solitary nodule or tumor. Seven of the eight large T-cell lymphomas had a CD30-positive (CD30+) phenotype but did not express ALK protein. Overexpression of p53 protein was observed in six cases. Although EBV-EBER transcripts were detected in two of them, LMP1 protein was absent. Except for their original prevalence, the features of these T-cell CD30+ cutaneous lymphomas were the same as in immunocompetent patients. The 10 B-cell cutaneous lymphoma were immunoblastic or centroblastic lymphomas, with a differential expression of BCL-6 and Syndecan. Four of them expressed CD30, EBER-EBV transcripts, and LMP1 and p53 proteins. This B-cell CD30+ EBV+ phenotype contrasts with cutaneous lymphoma in immunocompetent patients. Human herpesvirus 8 was not involved in lymphomagenesis since its sequences were detected in a single patient with Kaposi's sarcoma and Castleman's disease. These lymphomas occurred in severely immunocompromised patients with a low CD4 count. Death was due to immunodepression rather than to lymphoma spread, suggesting avoiding aggressive immunosuppressive treatment in such patients. PMID:10524521

  5. Characterization of cutaneous antigen presentation in partially inbred miniature swine.

    PubMed

    Grabbe, S; Fishbein, J M; Sachs, D H; Flotte, T J; Granstein, R D

    1994-12-01

    MHC class I and II-defined, partially inbred miniature swine have recently become available as a large animal model in transplantation immunology. To investigate cutaneous immunocompetence in this model, cutaneous antigen presenting cell (APC) function was assessed. For morphologic analysis, punch biopsies were examined by electron microscopy. By this technique, epidermal Langerhans cells bearing typical Birbeck granules could be detected. For functional studies, epidermal cell (EC) suspensions were prepared from split thickness skin specimens. Using FACS analysis, freshly prepared epidermal cell suspensions contained 1.8-4.7% MHC class II-positive cells. These EC potently stimulated allogeneic nylon wool-enriched peripheral blood T cells in the primary mixed EC-lymphocyte reaction. For in vivo assessment of cutaneous APC function, EC suspensions enriched for or depleted of class II-positive EC were generated by panning of class II-positive EC using mouse anti-MHC class II antibodies and anti-mouse IgG-coated petri dishes. EC were then coupled to the hapten trinitrophenol (TNP) and injected s.c. into autologous or MHC-mismatched pigs twice at a one week interval. One week later, pigs were challenged by s.c.-injection of 0.5-1 x 10(7) TNP-coupled or uncoupled EC. Autologous unseparated EC as well as EC enriched for MHC class II-positive cells were able to sensitize naive animals against TNP, whereas neither TNP-coupled EC depleted of class II-positive APC, MHC-mismatched EC coupled to TNP, nor uncoupled EC induced immunity to TNP. Our data indicate that inbred miniature swine possess competent cutaneous APC which are able to induce cutaneous APC which are able to induce cutaneous immunity in a matter similar to Langerhans cells in murine or human skin. PMID:7749572

  6. The effect of extracorporeal photopheresis alone or in combination therapy on circulating CD4+Foxp3+CD25- T-cells in patients with leukemic cutaneous T-cell lymphoma

    PubMed Central

    Shiue, Lisa H.; Couturier, Jacob; Lewis, Dorothy E.; Wei, Caimiao; Ni, Xiao; Duvic, Madeleine

    2015-01-01

    Purpose Extracorporeal photopheresis (ECP) alone or in combination therapy is effective for treatment of leukemic cutaneous T-cell lymphoma (L-CTCL), but its mechanism(s) of action remain unclear. This study was designed to investigate the effect of ECP on regulatory T-cell and CD8+ T-cells in L-CTCL patients. Experimental Design Peripheral blood from 18 L-CTCL patients at baseline, Day 2, 1-month, 3-month, and 6-month post-ECP therapy were analyzed by flow cytometry for CD4+CD25+/high, CD4+Foxp3+CD25+/-, CD3+CD8+, CD3+CD8+CD69+, and CD3+CD8+IFN-γ+ T-cells. Clinical responses were assessed and correlated with changes in these T-cell subsets. Results Twelve of 18 patients achieved clinical responses. The average baseline number of CD4+CD25+/high T-cells of PBMCs in L-CTCL patients was normal (2.2%), but increased at 6-month post-therapy (4.3%, p<0.01). The average baseline number of CD4+Foxp3+ T-cells out of CD4+ T-cells in 9 evaluable patients was high (66.8±13.7%), mostly CD25 negative. The levels of CD4+Foxp3+ T cells in responders were higher (n=6, 93.1±5.7%) than non-responders (n=3, 14.2±16.0%, p<0.01), and they declined in parallel with malignant T-cells. The numbers of CD3+CD8+CD69+ and CD3+CD8+ IFN-γ+ T-cells increased at 3-month post-therapy in 5 of 6 patients studied. Conclusions ECP alone or in combination therapy might be effective in L-CTCL patients whose malignant T-cells have a CD4+Foxp3+CD25- phenotype. PMID:25772268

  7. Cutaneous manifestations associated with melanoma.

    PubMed

    Vyas, Ritva; Selph, Jacqueline; Gerstenblith, Meg R

    2016-06-01

    Melanoma is a malignancy most commonly arising from the skin; therefore, primary melanoma characteristics are usually the first cutaneous manifestations of melanoma. Cutaneous metastases, which can occur locally or diffusely, are important to detect in a timely manner as treatments for advanced melanoma that impact survival are now available. Melanoma can be associated with local or diffuse pigmentation changes, including depigmentation associated with the leukodermas and hyperpigmentation associated with diffuse melanosis cutis. The leukodermas occur frequently, illustrate the immunogenic nature of melanoma, and may impact prognosis. Paraneoplastic syndromes in association with melanoma are rare, though can occur. PMID:27178692

  8. Cutaneous manifestations of lupus erythematosus.

    PubMed

    Laman, S D; Provost, T T

    1994-02-01

    Lupus erythematosus is an autoimmune disease that demonstrates cutaneous, systemic, or both cutaneous and systemic manifestations. This article reviews the cutaneous manifestations of lupus erythematosus. PMID:8153399

  9. 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

  10. Chronic reparative changes in medium-sized vessels in a case of primary cutaneous anaplastic large-cell lymphoma with angioinvasive features and cytotoxic phenotype: new histopathological findings in line with indolent clinical behavior.

    PubMed

    Macarenco, Ricardo S; de Oliveira, Deilson Elgui

    2015-05-01

    Angioinvasion/angiodestruction has been reported in a small subset of primary cutaneous anaplastic large-cell lymphomas (PCALCL). Recently, PCALCL with angioinvasive features and cytotoxic phenotype has been characterized as a variant associated with good clinical outcomes despite worrisome histopathologic features. We report a case of PCALCL with angioinvasive features and cytotoxic phenotype associated with reparative changes on the wall of medium-sized vessels involved by the neoplasm, including intimal fibroblastic proliferation and luminal obliteration. This vascular pattern, although previously unreported in PCALCL, is in accordance with the indolent behavior observed in this entity and provides a further link with lymphomatoid papulosis type E. PMID:25365499