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Sample records for nevoid basal-cell carcinoma

  1. Nevoid basal cell carcinoma syndrome

    MedlinePlus

    NBCC syndrome; Gorlin-Goltz syndrome; Basal cell nevus syndrome; BCNS; Basal cell cancer - nevoid basal cell carcinoma syndrome ... Nevoid basal cell carcinoma nevus syndrome is a rare genetic condition. The gene linked to the syndrome is known as PTCH (" ...

  2. Nevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome).

    PubMed

    Bresler, Scott C; Padwa, Bonnie L; Granter, Scott R

    2016-06-01

    Nevoid basal cell carcinoma syndrome, or basal cell nevus syndrome (Gorlin syndrome), is a rare autosomal dominantly inherited disorder that is characterized by development of basal cell carcinomas from a young age. Other distinguishing clinical features are seen in a majority of patients, and include keratocystic odontogenic tumors (formerly odontogenic keratocysts) as well as dyskeratotic palmar and plantar pitting. A range of skeletal and other developmental abnormalities are also often seen. The disorder is caused by defects in hedgehog signaling which result in constitutive pathway activity and tumor cell proliferation. As sporadic basal cell carcinomas also commonly harbor hedgehog pathway aberrations, therapeutic agents targeting key signaling constituents have been developed and tested against advanced sporadically occurring tumors or syndromic disease, leading in 2013 to FDA approval of the first hedgehog pathway-targeted small molecule, vismodegib. The elucidation of the molecular pathogenesis of nevoid basal cell carcinoma syndrome has resulted in further understanding of the most common human malignancy.

  3. Nevoid basal cell carcinoma syndrome (Gorlin syndrome)

    PubMed Central

    Lo Muzio, Lorenzo

    2008-01-01

    Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, is a hereditary condition characterized by a wide range of developmental abnormalities and a predisposition to neoplasms. The estimated prevalence varies from 1/57,000 to 1/256,000, with a male-to-female ratio of 1:1. Main clinical manifestations include multiple basal cell carcinomas (BCCs), odontogenic keratocysts of the jaws, hyperkeratosis of palms and soles, skeletal abnormalities, intracranial ectopic calcifications, and facial dysmorphism (macrocephaly, cleft lip/palate and severe eye anomalies). Intellectual deficit is present in up to 5% of cases. BCCs (varying clinically from flesh-colored papules to ulcerating plaques and in diameter from 1 to 10 mm) are most commonly located on the face, back and chest. The number of BBCs varies from a few to several thousand. Recurrent jaw cysts occur in 90% of patients. Skeletal abnormalities (affecting the shape of the ribs, vertebral column bones, and the skull) are frequent. Ocular, genitourinary and cardiovascular disorders may occur. About 5–10% of NBCCS patients develop the brain malignancy medulloblastoma, which may be a potential cause of early death. NBCCS is caused by mutations in the PTCH1 gene and is transmitted as an autosomal dominant trait with complete penetrance and variable expressivity. Clinical diagnosis relies on specific criteria. Gene mutation analysis confirms the diagnosis. Genetic counseling is mandatory. Antenatal diagnosis is feasible by means of ultrasound scans and analysis of DNA extracted from fetal cells (obtained by amniocentesis or chorionic villus sampling). Main differential diagnoses include Bazex syndrome, trichoepithelioma papulosum multiplex and Torre's syndrome (Muir-Torre's syndrome). Management requires a multidisciplinary approach. Keratocysts are treated by surgical removal. Surgery for BBCs is indicated when the number of lesions is limited; other treatments include laser ablation, photodynamic

  4. Nevoid basal cell carcinoma syndrome (Gorlin syndrome).

    PubMed

    Lo Muzio, Lorenzo

    2008-11-25

    Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, is a hereditary condition characterized by a wide range of developmental abnormalities and a predisposition to neoplasms. The estimated prevalence varies from 1/57,000 to 1/256,000, with a male-to-female ratio of 1:1. Main clinical manifestations include multiple basal cell carcinomas (BCCs), odontogenic keratocysts of the jaws, hyperkeratosis of palms and soles, skeletal abnormalities, intracranial ectopic calcifications, and facial dysmorphism (macrocephaly, cleft lip/palate and severe eye anomalies). Intellectual deficit is present in up to 5% of cases. BCCs (varying clinically from flesh-colored papules to ulcerating plaques and in diameter from 1 to 10 mm) are most commonly located on the face, back and chest. The number of BBCs varies from a few to several thousand. Recurrent jaw cysts occur in 90% of patients. Skeletal abnormalities (affecting the shape of the ribs, vertebral column bones, and the skull) are frequent. Ocular, genitourinary and cardiovascular disorders may occur. About 5-10% of NBCCS patients develop the brain malignancy medulloblastoma, which may be a potential cause of early death. NBCCS is caused by mutations in the PTCH1 gene and is transmitted as an autosomal dominant trait with complete penetrance and variable expressivity. Clinical diagnosis relies on specific criteria. Gene mutation analysis confirms the diagnosis. Genetic counseling is mandatory. Antenatal diagnosis is feasible by means of ultrasound scans and analysis of DNA extracted from fetal cells (obtained by amniocentesis or chorionic villus sampling). Main differential diagnoses include Bazex syndrome, trichoepithelioma papulosum multiplex and Torre's syndrome (Muir-Torre's syndrome). Management requires a multidisciplinary approach. Keratocysts are treated by surgical removal. Surgery for BBCs is indicated when the number of lesions is limited; other treatments include laser ablation, photodynamic

  5. New mutation of the PTCH gene in nevoid basal-cell carcinoma syndrome with West syndrome.

    PubMed

    Tachi, Nobutada; Fujii, Katsunori; Kimura, Mitsugu; Seki, Kouhei; Hirakai, Masahisa; Miyashita, Toshiyuki

    2007-11-01

    Neurologic involvement in nevoid basal-cell carcinoma syndrome includes intracranial calcification, congenital hydrocephalus, intracranial neoplasms, and mental retardation. A few cases of epilepsy with nevoid basal-cell carcinoma syndrome were reported. We report on a patient with nevoid basal-cell carcinoma syndrome and West syndrome. The patient had a heterozygous mutation (insertion of TGGC) in the PTCH gene. This mutation causes a shift of the reading frame, and creates a stop codon predicting the truncation of the PTCH protein. This mutation was not found in previously described patients with nevoid basal-cell carcinoma syndrome.

  6. Undifferentiated sinonasal carcinoma in a patient with nevoid basal cell carcinoma syndrome.

    PubMed

    Sobota, Amy; Pena, Maria; Santi, Mariarita; Ali Ahmed, Atif

    2007-07-01

    Nevoid basal cell carcinoma syndrome is an autosomal dominant multisystem disorder characterized by developmental anomalies and occurrence of multiple basal cell carcinomas and other tumors in early childhood. In this article, the authors report a case of a 19-year-old African American male with nevoid basal cell carcinoma syndrome and a history of medulloblastoma at age 2, meningioma at age 14, thyroid follicular adenomas with papillary carcinoma at age 15, and 2 basal cell carcinomas at ages 16 and 18. Recently, he developed sinonasal undifferentiated carcinoma (SNUC). The radiology and pathology of the sinonasal carcinoma are presented in this report. Review of the literature reveals that this is the first case of SNUC occurring in a patient with nevoid basal cell carcinoma syndrome.

  7. Treatment of nevoid basal cell carcinoma syndrome: a case report

    PubMed Central

    2016-01-01

    Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, is characterized by various embryological deformities and carcinoma formation. It is caused by PTCHI gene mutations and is autosomal dominantly inherited. Some of the main symptoms of NBCCS are multiple basal cell carcinomas, multiple keratocystic odontogenic tumors (KCOTs) of the mandible, hyperkeratosis of the palmar and plantar, skeletal deformity, calcification of the falx cerebri, and facial defomity. Recurrent KCOT is the main symptom of NBCCS and is present in approximately 90% of patients. In NBCCS, KCOTs typically occur in multiples. KCOTs can be detected in patients under the age of 10, and new and recurring cysts develop until approximately the age of 30. The postoperation recurrence rate is approximately 60%. This case report presents a 14-year-old female patient with a chief complaint of a cyst found in the maxilla and mandible. The patient was diagnosed with NBCCS, and following treatment of marsupialization and enucleation, the clinical results were satisfactory. PMID:27847737

  8. Brain morphology in children with nevoid basal cell carcinoma syndrome.

    PubMed

    Shiohama, Tadashi; Fujii, Katsunori; Miyashita, Toshiyuki; Mizuochi, Hiromi; Uchikawa, Hideki; Shimojo, Naoki

    2017-04-01

    Brain morphology is tightly regulated by diverse signaling pathways. Hedgehog signaling is a candidate pathway considered responsible for regulating brain morphology. Nevoid basal cell carcinoma syndrome (NBCCS), caused by a PTCH1 mutation in the hedgehog signaling pathway, occasionally exhibits macrocephaly and medulloblastoma. Although cerebellar enlargement occurs in ptch1 heterozygous-deficient mice, its impact on human brain development remains unknown. We investigated the brain morphological characteristics of children with NBCCS. We evaluated brain T1-weighted images from nine children with NBCCS and 15 age-matched normal control (NC) children (mean [standard deviation], 12.2 [2.8] vs. 11.6 [2.3] years old). The diameters of the cerebrum, corpus callosum, and brain stem and the cerebellar volume were compared using two-tailed t-tests with Welch's correction. The transverse diameters (150.4 [9.9] vs. 136.0 [5.5] mm, P = 0.002) and longitudinal diameters (165.4 [8.0] vs. 151.3 [8.7] mm, P = 0.0007) of the cerebrum, cross-sectional area of the cerebellar vermis (18.7 [2.6] vs. 11.8 [1.7] cm(2) , P = 0.0001), and total volume of the cerebellar hemispheres (185.1 [13.0] vs. 131.9 [10.4] cm(3) , P = 0.0001) were significantly larger in the children with NBCCS than in NC children. Thinning of the corpus callosum and ventricular enlargement were also confirmed in children with NBCCS. We demonstrate that, on examination of the brain morphology, an increase in the size of the cerebrum, cerebellum, and cerebral ventricles is revealed in children with NBCCS compared to NC children. This suggests that constitutively active hedgehog signaling affects human brain morphology and the PI3K/AKT and RAS/MAPK pathways.

  9. Nevoid Basal Cell Carcinoma Syndrome - Clinical and Radiological Findings of Three Cases

    PubMed Central

    Ali, Ibrahim K; Karjodkar, Freny R; Sansare, Kaustubh; Salve, Prashant; Goyal, Shikha

    2016-01-01

    Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder, characterized by skeletal anomalies and multiple keratocystic odontogenic tumors of the jaws. The skeletal anomalies of this syndrome are mandibular prognathism, bossing of frontal and parietal bones, high-arched palate, and bifid rib. We report three cases with NBCCS, emphasizing the clinical and radiographic findings, the importance of the early diagnosis of NBCCS, and a preventive multidisciplinary approach in the management of NBCCS. PMID:27630800

  10. Germline mutations of the PTCH gene in Japanese patients with nevoid basal cell carcinoma syndrome.

    PubMed

    Minami, M; Urano, Y; Ishigami, T; Tsuda, H; Kusaka, J; Arase, S

    2001-09-01

    Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by developmental and skeletal anomalies, palmo-plantar pits, odontogenic keratocysts, ectopic calcification, and occurrence of various types of tumors including basal cell carcinoma. Recent evidence has indicated that the human homologue of a Drosophila segment polarity gene, PTCH, is a NBCCS susceptibility gene. In the study presented here, we detected two novel mutations of the PTCH gene, I805X/2395delC and Y93X/C297A, in two unrelated Japanese patients. Early protection of the skin from the sunlight is important to the prevention of BCC development in NBCCS patients. Genetic analysis of the PTCH gene is essential for the early, definitive diagnosis of NBCCS, especially before the expression of clinical manifestations is complete.

  11. Review of Ocular Manifestations of Nevoid Basal Cell Carcinoma Syndrome: What an Ophthalmologist Needs to Know

    PubMed Central

    Chen, Judy J.; Sartori, Juliana; Aakalu, Vinay K.; Setabutr, Pete

    2015-01-01

    Nevoid basal cell carcinoma syndrome (NBCCS) is a rare, autosomal dominant disorder characterized by multiple basal cell carcinomas (BCCs), odontogenic keratocysts, palmar and/or plantar pits, and ectopic calcifications of the falx cerebri. Myriad ophthalmologic findings are associated with NBCCS, including periocular BCCs, hypertelorism, strabismus, myelinated nerve fibers, and disorders of the retina and retinal pigment epithelium. We performed a literature search in PubMed for articles on the ophthalmologic manifestations of Gorlin syndrome, published between 1984 and 2014. Of 33 papers, 31 were included. Although Gorlin syndrome is due to mutations in a single gene, it displays variable phenotypic expressivity. Therefore, familiarity with this disorder across clinical specialties is necessary to avoid misdiagnosis. The ophthalmologist should be included in the multidisciplinary team for the management of Gorlin syndrome in order to prevent visual loss and improve the quality of life of these patients. PMID:26692711

  12. Ameloblastoma: a neglected criterion for nevoid basal cell carcinoma (Gorlin) syndrome.

    PubMed

    Ponti, Giovanni; Pastorino, Lorenza; Pollio, Annamaria; Nasti, Sabina; Pellacani, Giovanni; Mignogna, Michele D; Tomasi, Aldo; Del Forno, Corrado; Longo, Caterina; Bianchi-Scarrà, Giovanna; Ficarra, Guido; Seidenari, Stefania

    2012-09-01

    Ameloblastomas are considered to be aggressive and locally invasive neoplasms derived from odontogenic epithelium with a tendency for recurrence and bone destruction. Although the relationship between nevoid basal cell carcinoma syndrome (NBCCS) and ameloblastoma is less frequent, it might constitute a peculiar stigmata of this hereditary disorder. The objective of the current study was to evaluate whether a combined clinical and biomolecular approach could be useful for the identification of NBCCS among patients with a diagnosis of ameloblastoma. The authors collected ameloblastoma tumors recorded in the databases of the Pathology Departments of the University of Modena during the period 1991-2011. Family trees were drawn for all 41 patients affected by these specific odontogenic tumors. Two patients with ameloblastoma were also affected by multiple basal cell carcinomas and odontogenic keratocysts tumors (OKCTs) achieving the requested clinical criteria for the diagnosis of NBCCS. The clinical diagnoses were confirmed by the identification of two different novel PTCH1 germline mutations (c.2186A > T [p.K729 M]; c.931insA) in those unrelated patients. Clinical ameloblastoma findings can be used as screening for the identification of families at risk of NBCCS. Ameloblastomas diagnosis warrants the search for associated cutaneous basal cell carcinomas and other benign and malignant tumors related to NBCCS. Thus, we propose the inclusion of ameloblasoma as criterion for the identification of NBCCS.

  13. Gorlin syndrome (nevoid basal cell carcinoma syndrome): update and literature review.

    PubMed

    Fujii, Katsunori; Miyashita, Toshiyuki

    2014-10-01

    Gorlin syndrome, also called nevoid basal cell carcinoma syndrome, is an autosomal dominant neurocutaneous disease characterized by developmental anomalies such as palmar pits and rib anomaly, and tumorigenesis such as medulloblastoma and basal cell carcinoma. This syndrome is mainly caused by a mutation of PTCH1, a human homologue of Drosophila patched, including frameshift, missense, or nonsense mutations. Genotype-phenotype correlation has not been established. PTCH1 is a member of hedgehog signaling, which is a highly conserved pathway in vertebrates, composed of hedgehog, SMO, and GLI proteins as well as PTCH1. Given that hedgehog signaling regulates cell growth and development, disorder of this pathway gives rise to not only developmental anomalies but also diverse tumors such as those seen in Gorlin syndrome. We recently reported, for the first time, a nationwide survey of Gorlin syndrome in Japan, noting that the frequency was 1/235,800 in the Japanese population, and that the frequency of basal cell carcinomas was significantly lower in Japan than in the USA and Europe, suggesting that ethnicity and genetic background contribute to these differences. Given that many clinical trials using newly discovered molecular inhibitors are still ongoing, these agents should become the new therapeutic options for hedgehog pathway-dependent tumors in patients with or without Gorlin syndrome.

  14. Analysis of mutation in exon 17 of PTCH in patients with nevoid basal cell carcinoma syndrome.

    PubMed

    Li, Jichen; Wang, Jinhui; Liu, Yingqun; Wang, Wei

    2010-01-01

    Abnormalities in sonic hedgehog (SHH) signaling pathway components are major contributing factors in the development of nevoid basal cell carcinoma syndromes (NBCCS) that include SHH, PTCH, SMO and GLI. The novel patched homologue (PTCH) mutation and clinical manifestations with NBCCS links PTCH haplosufficiency and aberrant activation of the sonic hedgehog/Patched/smoothened pathway. To investigate further the molecular genetics of NBCCS, we performed mutation analysis of PTCH gene in a family case with five affected members. These clinical manifestations might be associated with a novel constitutional mutation of the PTCH gene, 3146A-->T (1049N-->I), in exon 17. The analyzed results of tumor tissue show a high expression of GLI. Our findings suggested that the mutation of 3146A-->T may be the cause of high expression of GLI and permit SMO to transmit signal to the nucleus through SHH/PTCH/SMO pathway.

  15. Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome

    SciTech Connect

    Kimonis, V.E.; Yang, M.L.; Bale, S.J.

    1997-03-31

    Nevoid basal cell carcinoma syndrome (NBCC; Gorlin syndrome), an autosomal dominant disorder linked to 9q22.3-q31, and caused by mutations in PTC, the human homologue of the Drosophila patched gene, comprises multiple basal cell carcinomas, keratocysts of the jaw, palmar/plantar pits, spine and rib anomalies and calcification of the falx cerebri. We reviewed the findings on 105 affected individuals examined at the NIH since 1985. The data included 48 males and 57 females ranging in age from 4 months to 87 years. Eighty percent of whites (71/90) and 38% (5/13) of African-Americans had at least one basal cell carcinoma (BCC), with the first tumor occurring at a mean age of 23 (median 20) years and 21 (median 20) years, respectively. Excluding individuals exposed to radiation therapy, the number of BCCs ranged from 1 to >1,000 (median 8) and 1 to 3 (median 2), respectively, in the 2 groups. Jaw cysts occurred in 78/105 (74%) with the first tumor occurring in 80% by the age of 20 years. The number of total jaw cysts ranged from 1 to 28 (median 3). Palmar pits and plantar pits were seen in 87%. Ovarian fibromas were diagnosed by ultrasound in 9/52 (17%) at a mean age of 30 years. Medulloblastoma occurred in 4 patients at a mean age of 2.3 years. Three patients had cleft lip or palate. Physical findings include {open_quotes}coarse face{close_quotes} in 54%, relative macrocephaly in 50%, hypertelorism in 42%, frontal bossing in 27%, pectus deformity in 13%, and Sprengel deformity in 11%. This study delineates the frequency of the clinical and radiological anomalies in NBCC in a large population of US patients and discusses guidelines for diagnosis and management. 48 refs., 3 figs., 5 tabs.

  16. Spectrum of PTCH mutations in Italian nevoid basal cell-carcinoma syndrome patients: identification of thirteen novel alleles.

    PubMed

    Savino, Maria; d'Apolito, Maria; Formica, Vincenza; Baorda, Filomena; Mari, Francesca; Renieri, Alessandra; Carabba, Enrico; Tarantino, Enrico; Andreucci, Elena; Belli, Serena; Lo Muzio, Lorenzo; Dallapiccola, Bruno; Zelante, Leopoldo; Savoia, Anna

    2004-11-01

    The nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant genetic disease characterized by numerous basal cell carcinomas, odontogenic keratocysts of the jaws, palmar and plantal pits, skeletal abnormalities, and calcification of the falx cerebri. The gene responsible for this syndrome is the PTCH tumor suppressor gene encoding for the sonic hedgehog receptor. In this paper, we report thirteen novel mutations identified in the first screening of NBCCS patients in Italy. Except for p.T230P and p.F505_L506delinsLR, all the other mutations are predicted to determine a premature truncation of the protein.

  17. Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome.

    PubMed

    Kimonis, V E; Goldstein, A M; Pastakia, B; Yang, M L; Kase, R; DiGiovanna, J J; Bale, A E; Bale, S J

    1997-03-31

    Nevoid basal cell carcinoma syndrome (NBCC; Gorlin syndrome), an autosomal dominant disorder linked to 9q22.3-q31, and caused by mutations in PTC, the human homologue of the Drosophila patched gene, comprises multiple basal cell carcinomas, keratocysts of the jaw, palmar/plantar pits, spine and rib anomalies and calcification of the falx cerebri. We reviewed the findings on 105 affected individuals examined at the NIH since 1985. The data included 48 males and 57 females ranging in age from 4 months to 87 years. Eighty percent of whites (71/90) and 38% (5/13) of African-Americans had at least one basal cell carcinoma (BCC), with the first tumor occurring at a mean age of 23 (median 20) years and 21 (median 20) years, respectively. Excluding individuals exposed to radiation therapy, the number of BCCs ranged from 1 to > 1,000 (median 8) and 1 to 3 (median 2), respectively, in the 2 groups. Jaw cysts occurred in 78/105 (74%) with the first tumor occurring in 80% by the age of 20 years. The number of total jaw cysts ranged from 1 to 28 (median 3). Palmar pits and plantar pits were seen in 87%. Ovarian fibromas were diagnosed by ultrasound in 9/52 (17%) at a mean age of 30 years. Medulloblastoma occurred in 4 patients at a mean age of 2.3 years. Three patients had cleft lip or palate. Physical findings include "coarse face" in 54%, relative macrocephaly in 50%, hypertelorism in 42%, frontal bossing in 27%, pectus deformity in 13%, and Sprengel deformity in 11%. Important radiological signs included calcification of the falx cerebri in 65%, of the tentorium cerebelli in 20%, bridged sella in 68%, bifid ribs in 26%, hemivertebrae in 15%, fusion of the vertebral bodies in 10%, and flame shaped lucencies of the phalanges, metacarpal, and carpal bones of the hands in 30%. Several traits previously considered components of the syndrome (including short fourth metacarpal, scoliosis, cervical ribs and spina bifida occulta) were not found to be significantly increased in the

  18. Germline mutations of the PTCH gene in Japanese patients with nevoid basal cell carcinoma syndrome.

    PubMed

    Tanioka, Miki; Takahashi, Katsu; Kawabata, Tomohiro; Kosugi, Shinji; Murakami, Kenichiro; Miyachi, Yoshiki; Nishigori, Chikako; Iizuka, Tadahiko

    2005-01-01

    We identified seven novel germline mutations of the PTCH gene in eight unrelated Japanese patients with nevoid basal cell carcinoma syndrome (NBCCS). In order to ensure genetic diagnosis, all 23 coding exons of the PTCH gene were amplified from genomic DNA by polymerase chain reaction (PCR) and sequenced. Mutations were found in all eight patients with NBCCS. The mutations detected in this study include one insertion/deletion mutation, one 1-bp insertion, two 1-bp deletions, one nonsense mutation and two missense mutations. None of the mutations have been previously reported. Five mutations caused premature stop codons that are predicted to result in a truncated protein. In the two missense mutations, the strong basic residue arginine was substituted by serine or glycine in highly conserved components of the putative transmembrane domain of PTCH, and these mutations may therefore affect the conformation and function of the PTCH protein. No phenotype-genotype relationships were found in the Japanese NBCCS patients, consistent with results of previous studies on NBCCS in African-American and Caucasian patients.

  19. Nevoid Basal cell carcinoma syndrome: a cephalometric study of patients and controls.

    PubMed

    Leonardi, Rosalia; Licciardello, Valeria; Santarelli, Andrea; Ciavarella, Domenico; Bolouri, Susanne; Härle, Franz; Caltabiano, Mario; Lo Muzio, Lorenzo

    2009-01-01

    Craniofacial morphology of patients with nevoid basal cell carcinoma syndrome (NBCCS) has sometimes been reported at clinical examination, but any investigation has described it on the basis of cephalometric measurements.The purpose of this study was to conduct a cephalometric analysis of patients with NBCCS and to compare measurements with non-NBCCS subjects of similar ages, to elucidate if there is any relationship between NBCCS and craniofacial morphology.The study population consisted of 14 adult patients (9 men and 5 women), ranging in age from 18.2 to 56.8 years, with the diagnosis of NBCCS, with good-quality lateral cephalometric radiographs, and 14 adult healthy patients matched for age and sex to the NBCCS group. Cephalometric measurements were carried out on radiographs, and measurements of angles and distances were performed.Statistical differences between NBCCS subjects and controls were observed. Data analysis displayed that the measurements of the anterior cranial base (P

  20. PTCH mutations and deletions in patients with typical nevoid basal cell carcinoma syndrome and in patients with a suspected genetic predisposition to basal cell carcinoma: a French study.

    PubMed

    Soufir, N; Gerard, B; Portela, M; Brice, A; Liboutet, M; Saiag, P; Descamps, V; Kerob, D; Wolkenstein, P; Gorin, I; Lebbe, C; Dupin, N; Crickx, B; Basset-Seguin, N; Grandchamp, B

    2006-08-21

    The patched (PTCH) mutation rate in nevoid basal cell carcinoma syndrome (NBCCS) reported in various studies ranges from 40 to 80%. However, few studies have investigated the role of PTCH in clinical conditions suggesting an inherited predisposition to basal cell carcinoma (BCC), although it has been suggested that PTCH polymorphisms could predispose to multiple BCC (MBCC). In this study, we therefore performed an exhaustive analysis of PTCH (mutations detection and deletion analysis) in 17 patients with the full complement of criteria for NBCCS (14 sporadic and three familial cases), and in 48 patients suspected of having a genetic predisposition to BCC (MBCC and/or age at diagnosis < or =40 years and/or familial BCC). Eleven new germline alterations of the PTCH gene were characterised in 12 out of 17 patients harbouring the full complement of criteria for the syndrome (70%). These were frameshift mutations in five patients, nonsense mutations in five patients, a small inframe deletion in one patient, and a large germline deletion in another patient. Only one missense mutation (G774R) was found, and this was in a patient affected with MBCC, but without any other NBCCS criterion. We therefore suggest that patients harbouring the full complement of NBCCS criteria should as a priority be screened for PTCH mutations by sequencing, followed by a deletion analysis if no mutation is detected. In other clinical situations that suggest genetic predisposition to BCC, germline mutations of PTCH are not common.

  1. A new germline mutation of the PTCH gene in a Japanese patient with nevoid basal cell carcinoma syndrome associated with meningioma.

    PubMed

    Tate, Genshu; Li, Min; Suzuki, Takao; Mitsuya, Toshiyuki

    2003-01-01

    We employed polymerase chain reaction and DNA sequencing analysis to characterize the PTCH gene in a Japanese nevoid basal cell carcinoma syndrome (NBCCS) patient suffering from meningioma, multiple basal cell carcinoma and epidermal cysts. Direct sequence analyses revealed a novel single base deletion at nucleotide 2613 in exon 16 (2613delC) in one PTCH allele, resulting in the frame shift and the introduction of a premature termination codon in this mutated allele.

  2. Multiple nevoid basal cell carcinoma syndrome associated with congenital orbital teratoma, caused by a PTCH1 frameshift mutation.

    PubMed

    Rodrigues, A L; Carvalho, A; Cabral, R; Carneiro, V; Gilardi, P; Duarte, C P; Puente-Prieto, J; Santos, P; Mota-Vieira, L

    2014-07-25

    Gorlin-Goltz syndrome, or nevoid basal cell carcinoma syndrome (NBCCS), is a rare autosomal dominant disorder caused by mutations in the PTCH1 gene and shows a high level of penetrance and variable expressivity. The syndrome is characterized by developmental abnormalities or neoplasms and is diagnosed with 2 major criteria, or with 1 major and 2 minor criteria. Here, we report a new clinical manifestation associated with this syndrome in a boy affected by NBCCS who had congenital orbital teratoma at birth. Later, at the age of 15 years, he presented with 4 major and 4 minor criteria of NBCCS, including multiple basal cell carcinoma and 2 odontogenic keratocysts of the jaw, both confirmed by histology, more than 5 palmar pits, calcification of the cerebral falx, extensive meningeal calcifications, macrocephaly, hypertelorism, frontal bosses, and kyphoscoliosis. PTCH1 mutation analysis revealed the heterozygous germline mutation c.290dupA. This mutation generated a frameshift within exon 2 and an early premature stop codon (p.Asn97LysfsX43), predicting a truncated protein with complete loss of function. Identification of this mutation is useful for genetic counseling. Although the clinical symptoms are well-known, our case contributes to the understanding of phenotypic variability in NBCCS, highlighting that PTCH1 mutations cannot be used for predicting disease burden and reinforces the need of a multidisciplinary team in the diagnosis, treatment, and follow-up of NBCCS patients.

  3. Nevoid basal cell carcinoma syndrome with cleft lip and palate associated with the novel PTCH gene mutations.

    PubMed

    Sasaki, Ryo; Saito, Kayoko; Watanabe, Yorikatsu; Takayama, Yoshinaga; Fujii, Katsunori; Agawa, Kaori; Miyashita, Toshiyuki; Ando, Tomohiro; Akizuki, Tanetaka

    2009-07-01

    Nevoid basal cell carcinoma syndrome (NBCCS) is a rare autosomal dominant disorder characterized by developmental abnormalities and a predisposition to cancers. Two unrelated patients, 21- and 16-year-old males, with cleft lip and palate and multiple jaw cysts, were diagnosed according to clinical criteria. To confirm a diagnosis of NBCCS, we undertook a molecular genetic analysis of the PTCH gene. Their PTCH genes were analyzed by direct sequencing of the PCR product from their DNA, and previously unreported mutations were identified. A heterozygous duplication at the nucleotide position between 3325 and 3328 of the PTCH gene (c.3325_3328dupGGCG) was detected in the 21-year-old patient. It caused a frameshift mutation, resulting in a premature termination of the PTCH protein. A point mutation (G to C) in intron 7 of the PTCH gene (c.1067+1G>C) was detected in the 16-year-old patient. This caused an aberrant splicing of PTCH. It is interesting to note that the non-canonical cryptic splice-donor site was activated, which did not conform to the GT-AG rule.

  4. Sensitivity of cultured lymphocytes from patients with nevoid basal cell carcinoma syndrome to ultraviolet light and phytohemagglutinin stimulation

    SciTech Connect

    Ferraro, P.; Celotti, L.; Furlan, D.; Pattarello, I.; Peserico, A. )

    1990-01-01

    DNA repair and replication after in vitro UV irradiation were determined in cultured peripheral blood lymphocytes from 6 patients with nevoid basal cell carcinoma syndrome (NBCCS) and from a group of control donors. DNA repair synthesis (UDS) was measured in unstimulated lymphocytes by incubation with 3H-TdR in the presence of hydroxyurea for 3 and 6 h after UV irradiation (6-48 J/m2). DNA replication was measured in PHA-stimulated lymphocytes, UV-irradiated or mock-irradiated, by incubation with 3H-TdR for 24 h. The effect of the mitogen was followed during 5 days after stimulation by determining the incorporation of 3H-TdR, the increase of cell number, and the mitotic index. NBCCS and control lymphocytes showed equal sensitivity to UV light in terms of UDS and reduced response to PHA. On the contrary, the mitotic index and the number of cells in stimulated cultures were significantly lower in the affected subjects. These data suggest an altered progression along the cell cycle, which could be characteristic of stimulated NBCCS lymphocytes.

  5. Basal Cell Carcinoma

    MedlinePlus

    ... Kids’ zone Video library Find a dermatologist Basal cell carcinoma Overview Basal cell carcinoma: This skin cancer ... that has received years of sun exposure. Basal cell carcinoma: Overview Basal cell carcinoma (BCC) is the ...

  6. Further localization of the gene for nevoid basal cell carcinoma syndrome (NBCCS) in 15 Australasian families: Linkage and loss of heterozygosity

    SciTech Connect

    Chenevix-Trench, G.; Wicking, C.; Berkman, J.; Sharpe, H.; Hockey, A.; Haan, E.; Oley, C.; Ravine, D.; Turner, A.; Searle, J.

    1993-09-01

    Nevoid basal cell carcinoma syndrome (NBCCS; basal cell nevus syndrome or Gorlin syndrome) is a cancer-predisposition syndrome characterized by multiple basal cell carcinomas (BCCs) and diverse developmental defects. The gene for NBCCS has been mapped to 9q23.1-q31 in North Americal and European families. In addition, loss of heterozygosity (LOH) for genetic markers in this region has been detected in sporadic BCCs, indicating that the NBCCs gene is probably a tumor-suppressor gene. In this study the authors have determined that the NBCCS gene is also linked to this region in Australasian pedigrees and that there is no significant evidence of heterogeneity. They have defined the localization of the gene by multipoint and haplotype analysis of 15 families, using four microsatellite markers. LOH at these loci was detected in 50% of sporadic BCCs, a rate that is significantly higher than that in other skin lesions used as controls. 21 refs., 3 figs., 2 tabs.

  7. DHPLC analysis of patients with Nevoid Basal Cell Carcinoma Syndrome reveals novel PTCH missense mutations in the sterol-sensing domain.

    PubMed

    Marsh, A; Wicking, C; Wainwright, B; Chenevix-Trench, G

    2005-09-01

    Nevoid Basal Cell Carcinoma Syndrome (NBCCS) is an autosomal dominant disorder characterised by multiple basal cell carcinomas, palmar and plantar pitting, odontogenic keratocysts of the jaws and bilamellar calcification of the falx. Mutations in the PTCH gene are responsible for NBCCS but most studies have found mutations in less than half of the cases tested. We used denaturing high performance liquid chromatography (DHPLC) to screen for PTCH mutations in 28 NBCCS cases, most of whom had been previously evaluated by single stranded conformation polymorphism analysis but found to be negative. Protein truncating (n = 10) and missense or indel (n = 4) mutations were found in 14/28 (50%) cases and one additional case carried an unclassified variant, c.2777G>C. Thirteen of the variants were novel. The mutation frequency was similar in inherited and de novo cases. Three of the missense and indel mutations were in the sterol-sensing domain, and one was in the sixth transmembrane domain.

  8. Nevoid basal cell carcinoma syndrome with medulloblastoma in an African-American boy: A rare case illustrating gene-environment interaction

    SciTech Connect

    Korczak, J.F.; Goldstein, A.M.; Kase, R.G.

    1997-03-31

    We present an 8-year-old African-American boy with medulloblastoma and nevoid basal cell carcinoma syndrome (NBCCS) who exhibited the radiosensitive response of basal cell carcinoma (BCC) formation in the area irradiated for medulloblastoma. Such a response is well-documented in Caucasian NBCCS patients with medulloblastoma. The propositus was diagnosed with medulloblastoma at the age of 2 years and underwent surgery, chemotherapy, and craniospinal irradiation. At the age of 6 years, he was diagnosed with NBCCS following his presentation with a large odontogenic keratocyst of the mandible, pits of the palms and soles and numerous BCCs in the area of the back and neck that had been irradiated previously for medulloblastoma. Examination of other relatives showed that the propositus mother also had NBCCS but was more mildly affected; in particular, she had no BCCs. This case illustrates complex gene-environment interaction, in that increased skin pigmentation in African-Americans is presumably protective against ultraviolet, but not ionizing, radiation. This case and other similar cases in the literature show the importance of considering NBCCS in the differential diagnosis of any patient who presents with a medulloblastoma, especially before the age of 5 years, and of examining other close relatives for signs of NBCCS to determine the patient`s at-risk status. Finally, for individuals who are radiosensitive, protocols that utilize chemotherapy in lieu of radiotherapy should be considered. 27 refs., 4 figs.

  9. A YAC contig spanning the nevoid basal cell carcinoma syndrome, Fanconi anaemia group C, and xeroderma pigmentosum group A loci on chromosome 9q

    SciTech Connect

    Morris, D.J.; Reis, A.

    1994-09-01

    Nevoid basal cell carcinoma syndrome (NBCCS, Gorlin syndrome) is an autosomal dominant disorder, characterized primarily by multiple basal cell carcinomas, epithelium-lined jaw cysts, and palmar and plantar pits, as well as various other features. Loss of heterozygosity studies and linkage analysis have mapped the NBCCS gene to chromosome 9q and suggested that it is a tumor suppressor. The apparent sensitivity of NBCCS patients to UV and X-irradiation raises the possibility of hypersensitivity to DNA-damaging reagents or defective DNA repair being etiological in the disorder. The recent mapping of the Fanconi anaemia group C (FACC) and xeroderma pigmentosum complementing group A (XPAC) genes to the same region on 9q has led us to begin the molecular dissection of the 9q22-q31 region. PCR analysis of the presence or absence of 10 microsatellite markers and exons 3 and 4 of the XPAC and FACC genes, respectively, allowed us to order 12 YACs into an overlapping contig and to order the markers as follows: D9S151/D9S12P1-D9S12P2-D9S197-D9S196-D9S280-FACC-D9S287/XPAC-D9S180-D9S6-D9S176. Sizing of the YACs has provided an initial estimate of the size of the NBCCS candidate region between D9S12 and D9S180 to be less than 1.65 Mb. 45 refs., 1 fig., 1 tab.

  10. Peri-gestational Dietary Folic Acid Deficiency Protects Against Medulloblastoma Formation in a Mouse Model of Nevoid Basal Cell Carcinoma Syndrome

    PubMed Central

    Been, Raha A.; Nagel, Christian W.; Hooten, Anthony J.; Langer, Erica K.; DeCoursin, Krista J.; Marek, Courtney A.; Janik, Callie L.; Linden, Michael A.; Reed, Robyn C.; Schutten, Melissa M.; Largaespada, David A.; Johnson, Kimberly J.

    2013-01-01

    Hereditary nevoid basal cell carcinoma syndrome (NBCCS) is caused by PTCH1 gene mutations that result in diverse neoplasms including medulloblastoma (MB). Epidemiological studies report reduced pediatric brain tumor risks associated with maternal intake of prenatal vitamins containing folic acid (FA) and FA supplements specifically. We hypothesized that low maternal FA intake during the peri-gestational period would increase MB incidence in a transgenic NBCCS mouse model, which carries an autosomal dominant mutation in the Ptch1 gene. Female wild-type C57BL/6 mice (n=126) were randomized to one of three diets with differing FA amounts: 0.3 mg/kg (low), 2.0 mg/kg (control), and 8.0 mg/kg (high) one month prior to mating with Ptch1+/− C57BL/6 males. Females were maintained on the diet until pup weaning; the pups were then aged for tumor development. Compared to the control group, offspring MB incidence was significantly lower in the low FA group (Hazard Ratio (HR)=0.47; 95% confidence interval (CI) 0.27–0.80) at one year. No significant difference in incidence was observed between the control and high FA groups. Low maternal peri-gestational FA levels may decrease MB incidence in mice genetically predisposed to tumor development. Our results could have implications for prenatal FA intake recommendations in the presence of cancer syndromes. PMID:23909730

  11. Basal Cell Carcinoma

    PubMed Central

    Lanoue, Julien

    2016-01-01

    Basal cell carcinoma is the most commonly occurring cancer in the world and overall incidence is still on the rise. While typically a slow-growing tumor for which metastases is rare, basal cell carcinoma can be locally destructive and disfiguring. Given the vast prevalence of this disease, there is a significant overall burden on patient well-being and quality of life. The current mainstay of basal cell carcinoma treatment involves surgical modalities, such as electrodessication and curettage, excision, cryosurgery, and Mohs micrographic surgery. Such methods are typically reserved for localized basal cell carcinoma and offer high five-year cure rates, but come with the risk of functional impairment, disfigurement, and scarring. Here, the authors review the evidence and indications for nonsurgical treatment modalities in cases where surgery is impractical, contraindicated, or simply not desired by the patient. PMID:27386043

  12. Characterisation of the Nevoid basal cell carcinoma (Gorlin`s) syndrome (NBCCS) gene region on chromosome 9q22-q31

    SciTech Connect

    Morris, D.J.; Digweed, M.; Sperling, K.

    1994-09-01

    Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominantly inherited malignancy-associated disease of unknown etiology. The gene has been mapped to chromosome 9q22-q31 by us and other groups, using linkage analysis and loss of heterozygosity studies. Subsequent linkage and haplotype analyses from 133 meioses in NBCCS families has refined the position of the gene between D9S12 and D9S287. Since the gene for Fanconi`s Anaemia type C (FAAC) has been assigned to the same 9q region, we have performed linkage analysis between FACC and NBCCCS in NBCCS families. No recombination has been observed between NBCCS and FACC and maximum lod scores of 34.98 and 11.94 occur for both diseases at the markers D9S196/D9S197. Southern blot analysis using an FACC cDNA probe has revealed no detectable rearrangements in our NBCCS patients. We have established a YAC contig spanning the region from D9S12 to D9S176 and STS content mapping in 22 YACs has allowed the ordering of 12 loci in the region, including the xeroderma pigmentosum type A (XPAC) gene, as follows: D9S151/D9S12P1 - D9S12P2 - D9S197 - D9S196 - D9S280 - FACC - D9S287/XPAC - D9S180 - D9S6 - D9S176. Using the contig we have been able to eliminate the {alpha}1 type XV collagen gene and the markers D9S119 and D9S297 from the NBCCS candidate region. Twelve YACs have been used to screen a chromosome 9 cosmid library and more than 1000 cosmids from the region have been identified to be used for the construction of a cosmid contig. A selection of these cosmids will be used for the isolation of coding sequencing from the region.

  13. Nevoid Basal Cell Carcinoma Syndrome

    MedlinePlus

    ... removed and fertilized in a laboratory. When the embryos reach a certain size, 1 cell is removed ... question. The parents can then choose to transfer embryos which do not have the mutation. PGD has ...

  14. Vismodegib in basal cell carcinoma.

    PubMed

    Amaria, R N; Bowles, D W; Lewis, K D; Jimeno, A

    2012-07-01

    Vismodegib is a novel, small-molecule inhibitor of smoothened, a key component of the hedgehog signaling pathway. Increased hedgehog pathway signaling is critical in the development of hereditary and spontaneous basal cell carcinomas of the skin, and has been implicated in the development of a number of other tumors. In preclinical models, vismodegib demonstrated potent antitumor activity in hedgehog-dependent tumors, particularly basal cell carcinomas. Clinically, phase I and II studies showed dramatic anticancer activity in patients with advanced basal cell carcinomas. In January 2012, vismodegib was approved by the FDA for the treatment of unresectable or metastatic basal cell carcinomas of the skin.

  15. Analysis of 133 meioses places the genes for nevoid basal cell carcinoma (gorlin) syndrome and fanconi anemia group C in a 2.6-cM interval and contributes to the fine map of 9q22.3

    SciTech Connect

    Farndon, P.A.; Hardy, C.; Kilpatrick, M.W.

    1994-09-15

    Four disease genes (NBCCS, ESS1, XPAC, FACC) map to 9q22.3-q31. A fine map of this region was produced by linkage and haplotype analysis using 12 DNA markers. The gene for nevoid basal cell carcinoma syndrome (NBCCS, Gorlin) has an important role in congenital malformations and carcinogenesis. Phase-known recombinants in a study of 133 meioses place NBCCS between (D9S12/D9S151) and D9S176. Haplotype analysis in a two-generation family suggests that NBCCS lies in a smaller interval of 2.6 cM centromeric to D9S287. These flanking markers will be useful clinically for gene tracking. Recombinants also map FACC (Fanconi anemia, group C) to the same region, between (D9S12/D9S151) and D9S287. The recombination rate between (D9S12/D9S151) and D9S53 in males is 8.3% and 13.2% in females, giving a sex-specific male:female ratio of 1:1.6 and a sex-averaged map distance of 10.4 cM. No double recombinants were detected, in agreement with the apparently complete level of interference predicted from the male chiasmata map. 19 refs., 2 figs., 1 tab.

  16. Photodynamic therapy for basal cell carcinoma.

    PubMed

    Fargnoli, Maria Concetta; Peris, Ketty

    2015-11-01

    Topical photodynamic therapy is an effective and safe noninvasive treatment for low-risk basal cell carcinoma, with the advantage of an excellent cosmetic outcome. Efficacy of photodynamic therapy in basal cell carcinoma is supported by substantial research and clinical trials. In this article, we review the procedure, indications and clinical evidences for the use of photodynamic therapy in the treatment of basal cell carcinoma.

  17. [Basal cell carcinoma with matrical differentiation].

    PubMed

    Goldman-Lévy, Gabrielle; Frouin, Eric; Soubeyran, Isabelle; Maury, Géraldine; Guillot, Bernard; Costes, Valérie

    2015-04-01

    Basal cell carcinoma with matrical differentiation is a very rare variant of basal cell carcinoma. To our knowledge, less than 30 cases have been reported. This tumor is composed of basaloid lobules showing a differentiation toward the pilar matrix cells. Recently, it has been demonstrated that beta-catenin would interfer with physiopathogenesis of matrical tumors, in particular pilomatricomas, but also basal cell carcinomas with matrical differentiation. This is a new case, with immunohistochemical and molecular analysis of beta-catenin, in order to explain its histogenesis.

  18. Metastatic Basal cell carcinoma accompanying gorlin syndrome.

    PubMed

    Bilir, Yeliz; Gokce, Erkan; Ozturk, Banu; Deresoy, Faik Alev; Yuksekkaya, Ruken; Yaman, Emel

    2014-01-01

    Gorlin-Goltz syndrome or basal cell nevus syndrome is an autosomal dominant syndrome characterized by skeletal anomalies, numerous cysts observed in the jaw, and multiple basal cell carcinoma of the skin, which may be accompanied by falx cerebri calcification. Basal cell carcinoma is the most commonly skin tumor with slow clinical course and low metastatic potential. Its concomitance with Gorlin syndrome, resulting from a mutation in a tumor suppressor gene, may substantially change morbidity and mortality. A 66-year-old male patient with a history of recurrent basal cell carcinoma was presented with exophthalmus in the left eye and the lesions localized in the left lateral orbita and left zygomatic area. His physical examination revealed hearing loss, gapped teeth, highly arched palate, and frontal prominence. Left orbital mass, cystic masses at frontal and ethmoidal sinuses, and multiple pulmonary nodules were detected at CT scans. Basal cell carcinoma was diagnosed from biopsy of ethmoid sinus. Based on the clinical and typical radiological characteristics (falx cerebri calcification, bifid costa, and odontogenic cysts), the patient was diagnosed with metastatic skin basal cell carcinoma accompanied by Gorlin syndrome. Our case is a basal cell carcinoma with aggressive course accompanying a rarely seen syndrome.

  19. Basal cell carcinoma of the nail unit.

    PubMed

    Forman, Seth B; Ferringer, Tammie C; Garrett, Algin B

    2007-05-01

    We report a case of a 70-year-old white male with a basal cell carcinoma of the left thumb nail unit. Excision of the tumor via Mohs micrographic surgery was completed in 2 stages. The defect was repaired with a full thickness skin graft. Five months later the nail unit healed without complications. Prior to this report, 21 cases of basal cell carcinoma have been reported in the world literature. This case, as well as the prior reports, are reviewed with a focus on time to diagnosis, location, excisional technique, and method of repair.

  20. Metastatic giant basal cell carcinoma: a case report

    PubMed Central

    Bellahammou, Khadija; Lakhdissi, Asmaa; Akkar, Othman; Rais, Fadoua; Naoual, Benhmidou; Elghissassi, Ibrahim; M’rabti, Hind; Errihani, Hassan

    2016-01-01

    Basal cell carcinoma is the most common skin cancer, characterised by a slow growing behavior, metastasis are extremely rare, and it occurs in less than 0, 1% of all cases. Giant basal cell carcinoma is a rare form of basal cell carcinoma, more aggressive and defined as a tumor measuring more than 5 cm at its largest diameter. Only 1% of all basal cell carcinoma develops to a giant basal cell carcinoma, resulting of patient's negligence. Giant basal cell carcinoma is associated with higher potential of metastasis and even death, compared to ordinary basal cell carcinoma. We report a case of giant basal cell carcinoma metastaticin lung occurring in a 79 years old male patient, with a fatal evolution after one course of systemic chemotherapy. Giant basal cell carcinoma is a very rare entity, early detection of these tumors could prevent metastasis occurrence and improve the prognosis of this malignancy. PMID:27795755

  1. Metastatic giant basal cell carcinoma: a case report.

    PubMed

    Bellahammou, Khadija; Lakhdissi, Asmaa; Akkar, Othman; Rais, Fadoua; Naoual, Benhmidou; Elghissassi, Ibrahim; M'rabti, Hind; Errihani, Hassan

    2016-01-01

    Basal cell carcinoma is the most common skin cancer, characterised by a slow growing behavior, metastasis are extremely rare, and it occurs in less than 0, 1% of all cases. Giant basal cell carcinoma is a rare form of basal cell carcinoma, more aggressive and defined as a tumor measuring more than 5 cm at its largest diameter. Only 1% of all basal cell carcinoma develops to a giant basal cell carcinoma, resulting of patient's negligence. Giant basal cell carcinoma is associated with higher potential of metastasis and even death, compared to ordinary basal cell carcinoma. We report a case of giant basal cell carcinoma metastaticin lung occurring in a 79 years old male patient, with a fatal evolution after one course of systemic chemotherapy. Giant basal cell carcinoma is a very rare entity, early detection of these tumors could prevent metastasis occurrence and improve the prognosis of this malignancy.

  2. Advanced treatment for basal cell carcinomas.

    PubMed

    Atwood, Scott X; Whitson, Ramon J; Oro, Anthony E

    2014-07-01

    Basal cell carcinomas (BCCs) are very common epithelial cancers that depend on the Hedgehog pathway for tumor growth. Traditional therapies such as surgical excision are effective for most patients with sporadic BCC; however, better treatment options are needed for cosmetically sensitive or advanced and metastatic BCC. The first approved Hedgehog antagonist targeting the membrane receptor Smoothened, vismodegib, shows remarkable effectiveness on both syndromic and nonsyndromic BCCs. However, drug-resistant tumors frequently develop, illustrating the need for the development of next-generation Hedgehog antagonists targeting pathway components downstream from Smoothened. In this article, we will summarize available BCC treatment options and discuss the development of next-generation antagonists.

  3. Advanced Treatment for Basal Cell Carcinomas

    PubMed Central

    Atwood, Scott X.; Whitson, Ramon J.; Oro, Anthony E.

    2014-01-01

    Basal cell carcinomas (BCCs) are very common epithelial cancers that depend on the Hedgehog pathway for tumor growth. Traditional therapies such as surgical excision are effective for most patients with sporadic BCC; however, better treatment options are needed for cosmetically sensitive or advanced and metastatic BCC. The first approved Hedgehog antagonist targeting the membrane receptor Smoothened, vismodegib, shows remarkable effectiveness on both syndromic and nonsyndromic BCCs. However, drug-resistant tumors frequently develop, illustrating the need for the development of next-generation Hedgehog antagonists targeting pathway components downstream from Smoothened. In this article, we will summarize available BCC treatment options and discuss the development of next-generation antagonists. PMID:24985127

  4. Multiphoton imaging of basal cell carcinoma (BCC)

    NASA Astrophysics Data System (ADS)

    Cicchi, R.; Carli, P.; Massi, D.; Sestini, S.; Stambouli, D.; Pavone, F. S.

    2006-02-01

    We used two-photon microscopy towards the imaging of cutaneous basal cell carcinoma (BCC). Our aim was to evaluate the morphology of BCC using two-photon fluorescence excitation and to establish a correlation with histopathology. We built a custom two-photon microscope and we measured the system capabilities. The system allowed to perform a preliminary measurement on a fresh human skin tissue sample. A human skin tissue sample of BCC excised during dermatological surgery procedures were used. The clinical diagnosis of BCC was confirmed by subsequent histopathological examination. The sample was imaged using endogenous tissue fluorescence within 2-3 hours from the excision with a two photon laser scanning fluorescence microscope. The acquired images allowed an obvious discrimination of the neoplastic areas toward normal tissue, based on morphological differences and aberrations of the intensity of the fluorescence signal. Our results showed that BCC tissue has a more homogeneous structure in comparison to normal tissue as well as a higher fluorescent response. The images obtained by two photon microscopy were further compared to the images acquired by an optical microscope after the conventional histopathological examination on one part of the respective sample. Our suggested method may represent a new diagnostic tool that improves the diagnostic accuracy of clinical examination alone, enabling the accurate discrimination of basal cell carcinoma from normal tissue.

  5. Pigmented basal cell carcinoma mimicking a superficial spreading melanoma.

    PubMed

    Hasbún Acuña, Paula; Cullen Aravena, Roberto; Maturana Donaire, César; Ares Mora, Raúl; Porras Kusmanic, Ninoska

    2016-12-20

    Basal cell carcinoma is the most common form of skin cancer, especially in elderly people. Pigmented basal cell carcinoma is a rare subtype and has been described in the literature as a nodular and hyperpigmented lesion; rarely, it can appear as an extensive pigmented plate, which may be clinically indistinguishable from superficial spreading melanoma and Bowen disease. Dermatoscopy has a high sensitivity in the diagnosis of basal cell carcinoma. When Menzies criteria are used; however, the final diagnosis is made by histopathology. The objective of the present report is to analyze the case of a patient with pigmented basal cell carcinoma simulating a superficial spreading melanoma.

  6. The dermatoscopic universe of basal cell carcinoma.

    PubMed

    Lallas, Aimilios; Apalla, Zoe; Argenziano, Giuseppe; Longo, Caterina; Moscarella, Elvira; Specchio, Francesca; Raucci, Margaritha; Zalaudek, Iris

    2014-07-01

    Following the first descriptions of the dermatoscopic pattern of basal cell carcinoma (BCC) that go back to the very early years of dermatoscopy, the list of dermatoscopic criteria associated with BCC has been several times updated and renewed. Up to date, dermatoscopy has been shown to enhance BCC detection, by facilitating its discrimination from other skin tumors and inflammatory skin diseases. Furthermore, upcoming evidence suggests that the method is also useful for the management of the tumor, since it provides valuable information about the histopathologic subtype, the presence of clinically undetectable pigmentation, the expansion of the tumor beyond clinically visible margins and the response to non-ablative treatments. In the current article, we provide a summary of the traditional and latest knowledge on the value of dermatoscopy for the diagnosis and management of BCC.

  7. A Prognostic Dilemma of Basal Cell Carcinoma with Intravascular Invasion

    PubMed Central

    Niumsawatt, Vachara; Castley, Andrew

    2016-01-01

    Summary: Basal cell carcinoma is the most common malignancy; however, it very rarely metastasizes. Despite the low mortality caused by this cancer, once it spreads, it has dim prognosis. We report a case of basal cell carcinoma with rare intravascular invasion and review the literature for risk factors and management of metastasis. PMID:27757356

  8. Vismodegib hedgehog-signaling inhibition and treatment of basal cell carcinomas as well as keratocystic odontogenic tumors in Gorlin syndrome.

    PubMed

    Booms, Patrick; Harth, Marc; Sader, Robert; Ghanaati, Shahram

    2015-01-01

    Vismodegib hedgehog signaling inhibition treatment has potential for reducing the burden of multiple skin basal cell carcinomas and jaw keratocystic odontogenic tumors. They are major criteria for the diagnosis of Gorlin syndrome, also called nevoid basal cell carcinoma syndrome. Clinical features of Gorlin syndrome are reported, and the relevance of hedgehog signaling pathway inhibition by oral vismodegib for maxillofacial surgeons is highlighted. In summary, progressed basal cell carcinoma lesions are virtually inoperable. Keratocystic odontogenic tumors have an aggressive behavior including rapid growth and extension into adjacent tissues. Interestingly, nearly complete regression of multiple Gorlin syndrome-associated keratocystic odontogenic tumors following treatment with vismodegib. Due to radio-hypersensitivity in Gorlin syndrome, avoidance of treatment by radiotherapy is strongly recommended for all affected individuals. Vismodegib can help in those instances where radiation is contra-indicated, or the lesions are inoperable. The effect of vismodegib on basal cell carcinomas was associated with a significant decrease in hedgehog-signaling and tumor proliferation. Vismodegib, a new and approved drug for the treatment of advanced basal cell carcinoma, is a specific oncogene inhibitor. It also seems to be effective for treatment of keratocystic odontogenic tumors and basal cell carcinomas in Gorlin syndrome, rendering the surgical resections less challenging.

  9. [Basal-cell nevomatosis associated with multifocal fetal rhabdomyoma. A case].

    PubMed

    Klijanienko, J; Caillaud, J M; Micheau, C; Flamant, F; Schwaab, G; Avril, M F; Ponzio-Prion, A

    1988-11-26

    Nevoid basal-cell carcinoma is a hereditary syndrome. Its major features are a multiple basal-cell carcinoma which appears early in childhood, skeletal and genital abnormalities and ectopic calcifications. It may be associated with malignant schwannoma, medulloblastoma and lymphoma. We report one case of nevoid basal-cell carcinoma syndrome associated with foetal rhabdomyoma, thyroid gland polyadenoma and benign schwannoma. The first case of foetal rhabdomyoma associated with this syndrome was described in 1976.

  10. Rippled-pattern basal cell carcinoma.

    PubMed

    Misago, Noriyuki; Tsuruta, Noriko; Narisawa, Yutaka

    2012-07-01

    Basal cell carcinoma (BCC) is the most common malignant cutaneous neoplasm, however, there have been few studies on BCC with a "rippled pattern" so far. We reviewed the 650 BCC specimens from the archives of our institution, and only one example of BCC with a rippled pattern was found. We herein report the histopathological characteristics of this case. Within the lesion, which showed the typical histopathological features of nodular BCC, there was a noticeable area composed of 10-15 basaloid aggregations, which showed the rippled pattern. The rippled pattern was characterized by alternating bands of epithelial cords of spindle-shaped basaloid cells and mucinous spaces. Characteristically, around the rippled-pattern area, neoplastic aggregations with a mucinous reticulated or cystic pattern (pseudo-tubular structures), and many cord-like structures were seen. A review of the published work and the present case suggested that the histopathological characteristics of rippled-pattern BCC are: (i) a nodular type of BCC; (ii) considerably rare; (iii) have frequent intervention by mucinous spaces between the epithelial cords; and (iv) no apparent divergent differentiation with folliculosebaceous-apocrine lineage. The last three characteristics contrasted with those of the rippled-pattern sebaceoma/trichoblastoma. However, neoplastic germinative cells in rippled-pattern BCC may naturally form cord-like structures in a manner similar to rippled-pattern sebaceoma/trichoblastoma.

  11. New basal cell carcinoma susceptibility loci

    PubMed Central

    Stacey, Simon N.; Helgason, Hannes; Gudjonsson, Sigurjon A.; Thorleifsson, Gudmar; Zink, Florian; Sigurdsson, Asgeir; Kehr, Birte; Gudmundsson, Julius; Sulem, Patrick; Sigurgeirsson, Bardur; Benediktsdottir, Kristrun R.; Thorisdottir, Kristin; Ragnarsson, Rafn; Fuentelsaz, Victoria; Corredera, Cristina; Gilaberte, Yolanda; Grasa, Matilde; Planelles, Dolores; Sanmartin, Onofre; Rudnai, Peter; Gurzau, Eugene; Koppova, Kvetoslava; Nexø, Bjørn A.; Tjønneland, Anne; Overvad, Kim; Jonasson, Jon G.; Tryggvadottir, Laufey; Johannsdottir, Hrefna; Kristinsdottir, Anna M.; Stefansson, Hreinn; Masson, Gisli; Magnusson, Olafur T.; Halldorsson, Bjarni V.; Kong, Augustine; Rafnar, Thorunn; Thorsteinsdottir, Unnur; Vogel, Ulla; Kumar, Rajiv; Nagore, Eduardo; Mayordomo, José I.; Gudbjartsson, Daniel F.; Olafsson, Jon H.; Stefansson, Kari

    2015-01-01

    In an ongoing screen for DNA sequence variants that confer risk of cutaneous basal cell carcinoma (BCC), we conduct a genome-wide association study (GWAS) of 24,988,228 SNPs and small indels detected through whole-genome sequencing of 2,636 Icelanders and imputed into 4,572 BCC patients and 266,358 controls. Here we show the discovery of four new BCC susceptibility loci: 2p24 MYCN (rs57244888[C], OR=0.76, P=4.7 × 10−12), 2q33 CASP8-ALS2CR12 (rs13014235[C], OR=1.15, P=1.5 × 10−9), 8q21 ZFHX4 (rs28727938[G], OR=0.70, P=3.5 × 10−12) and 10p14 GATA3 (rs73635312[A], OR=0.74, P=2.4 × 10−16). Fine mapping reveals that two variants correlated with rs73635312[A] occur in conserved binding sites for the GATA3 transcription factor. In addition, expression microarrays and RNA-seq show that rs13014235[C] and a related SNP rs700635[C] are associated with expression of CASP8 splice variants in which sequences from intron 8 are retained. PMID:25855136

  12. New basal cell carcinoma susceptibility loci.

    PubMed

    Stacey, Simon N; Helgason, Hannes; Gudjonsson, Sigurjon A; Thorleifsson, Gudmar; Zink, Florian; Sigurdsson, Asgeir; Kehr, Birte; Gudmundsson, Julius; Sulem, Patrick; Sigurgeirsson, Bardur; Benediktsdottir, Kristrun R; Thorisdottir, Kristin; Ragnarsson, Rafn; Fuentelsaz, Victoria; Corredera, Cristina; Gilaberte, Yolanda; Grasa, Matilde; Planelles, Dolores; Sanmartin, Onofre; Rudnai, Peter; Gurzau, Eugene; Koppova, Kvetoslava; Nexø, Bjørn A; Tjønneland, Anne; Overvad, Kim; Jonasson, Jon G; Tryggvadottir, Laufey; Johannsdottir, Hrefna; Kristinsdottir, Anna M; Stefansson, Hreinn; Masson, Gisli; Magnusson, Olafur T; Halldorsson, Bjarni V; Kong, Augustine; Rafnar, Thorunn; Thorsteinsdottir, Unnur; Vogel, Ulla; Kumar, Rajiv; Nagore, Eduardo; Mayordomo, José I; Gudbjartsson, Daniel F; Olafsson, Jon H; Stefansson, Kari

    2015-04-09

    In an ongoing screen for DNA sequence variants that confer risk of cutaneous basal cell carcinoma (BCC), we conduct a genome-wide association study (GWAS) of 24,988,228 SNPs and small indels detected through whole-genome sequencing of 2,636 Icelanders and imputed into 4,572 BCC patients and 266,358 controls. Here we show the discovery of four new BCC susceptibility loci: 2p24 MYCN (rs57244888[C], OR=0.76, P=4.7 × 10(-12)), 2q33 CASP8-ALS2CR12 (rs13014235[C], OR=1.15, P=1.5 × 10(-9)), 8q21 ZFHX4 (rs28727938[G], OR=0.70, P=3.5 × 10(-12)) and 10p14 GATA3 (rs73635312[A], OR=0.74, P=2.4 × 10(-16)). Fine mapping reveals that two variants correlated with rs73635312[A] occur in conserved binding sites for the GATA3 transcription factor. In addition, expression microarrays and RNA-seq show that rs13014235[C] and a related SNP rs700635[C] are associated with expression of CASP8 splice variants in which sequences from intron 8 are retained.

  13. [Vismodegib Therapy for Periocular Basal Cell Carcinoma].

    PubMed

    Keserü, M; Green, S; Dulz, S

    2017-01-01

    Background Basal cell carcinoma (BCC) is the commonest periorbital tumour. Mohs' micrographic surgery and secondary reconstruction is the therapeutic gold standard for periorbital BCC. In cases of inoperability for any reason, therapeutic alternatives are needed. Since the approval of vismodegib, an orally administered, targeted BCC therapy is available. Nevertheless there is little information on the use of vismodegib for periorbital BCC. Patients and Methods In a retrospective study, we analysed the data of 4 patients treated with vismodegib since 2014. The patients' mean age before starting therapy was 87 years. The mean maximum tumour diameter was 22.0 mm. Results The median follow-up was 17 months. The median treatment duration was 7.5 months. In 75 % of patients, complete clinical remission of BCC was achieved. In 25 % of patients, interim stabilisation of tumour growth was possible. The most common side effect of therapy was muscle spasm. Conclusion Vismodegib is an effective treatment option for patients with periorbital BCC, in whom surgical treatment is not possible for any reason.

  14. Basal cell epithelioma (carcinoma) in children and teenagers

    SciTech Connect

    Rahbari, H.; Mehregan, A.H.

    1982-01-15

    Among over 390,000 routine dermatopathologic specimens there were 85 cases diagnosed as basal cell epithelioma (carcinoma) (BCE) in persons 19 years old or younger. This number was refined to 40 cases de novo BCE in children and teenagers. Basal cell epithelioma unrelated to other conditions is rare in the young and it should be differentiated from similar fibroepithelial growths.

  15. Vismodegib (ERIVEDGE°) In basal cell carcinoma: too many unknowns.

    PubMed

    2015-01-01

    Basal cell carcinomas are the most common skin cancers. They are usually localised and carry a good prognosis. There is no standard treatment for the rare patients with metastatic basal cell carcinoma or very extensive basal cell carcinoma for whom surgery or radiotherapy is inappropriate. Vismodegib, a cytotoxic drug, is claimed to prevent tumour growth by inhibiting a pathway involved in tissue repair and embryogenesis. It has been authorised in the European Union for patients with metastatic or locally advanced and extensive basal cell carcinoma. Clinical evaluation of vismodegib is based on a non-comparative clinical trial involving 104 patients, providing only weak evidence. Twenty-one months after the start of the trial, 7 patients with metastases (21%) and 6 patients with advanced basal cell carcinoma (10%) had died. Given the lack of a placebo group, there is no way of knowing whether vismodegib had any effect, positive or negative, on survival. There were no complete responses among patients with metastases, but about one-third of them had partial responses. Among the 63 patients with locally advanced basal cell carcinoma, there were 14 complete responses and 16 partial responses. The recurrence rate in patients with complete responses was not reported. Similar results were reported in two other uncontrolled trials available in mid-2014. Vismodegib has frequent and sometimes serious adverse effects, including muscle spasms, fatigue and severe hyponatraemia. Cases of severe weight loss, alopecia, ocular disorders, other cancers (including squamous cell carcinoma) and anaemia have also been reported. More data are needed on possible hepatic and cardiovascular adverse effects. A potent teratogenic effect was seen in experimental animals. As vismodegib enters semen, contraception is mandatory for both men (condoms) and women. In practice, vismodegib has frequent and varied adverse effects, some of which are serious, while its benefits are poorly documented

  16. Current diagnosis and treatment of basal cell carcinoma.

    PubMed

    Alter, Mareike; Hillen, Uwe; Leiter, Ulrike; Sachse, Michael; Gutzmer, Ralf

    2015-09-01

    Basal cell carcinoma represents is most common tumor in fair-skinned individuals. In Germany, age-standardized incidence rates are 63 (women) and 80 (men) per 100,000 population per year. Early lesions may be difficult to diagnose merely on clinical grounds. Here, noninvasive diagnostic tools such as optical coherence tomography and confocal laser scanning microscopy may be helpful. The clinical diagnosis is usually confirmed by histology. Standard therapy consists of complete excision with thorough histological examination, either by means of micrographic surgery or, depending on tumor size and location as well as infiltration, using surgical margins of 3-5 mm or more. In particular, multiple basal cell carcinomas (such as in Gorlin-Goltz syndrome) and locally advanced as well as rarely also metastatic basal cell carcinoma may pose a therapeutic challenge. In superficial basal cell carcinoma, nonsurgical therapies such as photodynamic therapy or topical agents may be considered. In case of locally advanced or metastatic basal cell carcinoma, an interdisciplinary tumor board should issue therapeutic recommendations. These include radiation therapy as well as systemic therapy with a hedgehog inhibitor.

  17. Nuclear morphometry and chromatin textural characteristics of basal cell carcinoma.

    PubMed

    Mendaçolli, Paola Jung; Brianezi, Gabrielli; Schmitt, Juliano Vilaverde; Marques, Mariângela Esther Alencar; Miot, Hélio Amante

    2015-01-01

    Histological subtypes of basal cell carcinoma have biological, evolutionary and distinct prognostic behavior. The analysis of characteristics of the nucleus can provide data on their cellular physiology and behavior. The authors of this study evaluated nuclear morphological parameters and textural patterns of chromatin from different subtypes of basal cell carcinoma: nodular (n=37), superficial (n=28) and sclerodermiform (n=28). The parameters were compared between neoplasms' subtypes and with unaffected adjacent basal epithelium. Nuclear area and diameter of sclerodermiform neoplasms were superior to the other subtypes. Chromatin's color intensity and fractal dimension were less intense in superficial subtypes. Nuclear roundness and chromatin's entropy presented lower values in tumors than in normal epithelium. There was significant correlation between morphological and textural variables of normal skin and tumors. Morphometric elements and textural chromatin's homogeneity of basal cell carcinomas may be related to evolutionary, biological and behavior particularities related to each histotype.

  18. UV-specific p53 and PTCH mutations in sporadic basal cell carcinoma of sun-exposed skin.

    PubMed

    Ratner, D; Peacocke, M; Zhang, H; Ping, X L; Tsou, H C

    2001-02-01

    UVB irradiation is known to produce DNA damage at mutation hotspots in the p53 tumor suppressor gene, leading to the development of skin cancers. Mutations in the PTCH tumor suppressor gene, which is known to be responsible for the development of nevoid basal cell carcinoma syndrome, have also been identified in sporadic basal cell carcinomas (BCCs). We describe the case of an 80-year-old welder in whom 3 novel p53 mutations, as well as UV-specific PTCH mutations, were detected in two BCC samples from sun-exposed skin. The simultaneous presence of UV-specific p53 and PTCH mutations in the same BCC sample has not previously been reported.

  19. Vismodegib resistance in basal cell carcinoma: not a smooth fit.

    PubMed

    Ridky, Todd W; Cotsarelis, George

    2015-03-09

    In this issue of Cancer Cell, two complementary papers by Atwood and colleagues and Sharpe and colleagues show that basal cell carcinomas resistant to the Smoothened (SMO) inhibitor vismodegib frequently harbor SMO mutations that limit drug binding, with mutations at some sites also increasing basal SMO activity.

  20. [Successful therapy of metastatic basal cell carcinoma with vismodegib].

    PubMed

    Zutt, M; Mazur, F; Bergmann, M; Lemke, A J; Kaune, K M

    2014-11-01

    A 71-year-old man presented with giant basal cell carcinoma on the abdomen which had metastasized. He was treated with oral vismodegib. Both the primary ulcerated tumor on the abdomen and the metastases responded. Vismodegib was well tolerated without significant side effects. The tumor recurred promptly after vismodegib was discontinued, and then was resistant to therapy when vismodegib was re-administered.

  1. Follicular atrophoderma with multiple basal cell carcinomas (Bazex).

    PubMed

    Gould, D J; Barker, D J

    1978-10-01

    Five patients from a single family are reported who have an inherited condition of which the main features are follicular atrophoderma, abnormalities of scalp hair and multiple basal cell carcinomas. Thes abnormalities are consistent with the syndrome described by Bazex et al. (1964). The pattern of inheritance of this condition is discussed.

  2. Terahertz pulse imaging of ex vivo basal cell carcinoma.

    PubMed

    Woodward, Ruth M; Wallace, Vincent P; Pye, Richard J; Cole, Bryan E; Arnone, Donald D; Linfield, Edmund H; Pepper, Michael

    2003-01-01

    Terahertz pulse imaging has been used for the first time to study basal cell carcinoma ex vivo, the most common form of skin cancer. This noninvasive technique uses part of the electromagnetic spectrum in the frequency range 0.1-2.7 THz. A total of 21 samples were imaged; the study was performed blind and results were compared to histology. Each image consisted of possible diseased tissue and normal tissue from the same patient. The diseased tissue showed an increase in absorption compared to normal tissue, which is attributed to either an increase in the interstitial water within the diseased tissue or a change in the vibrational modes of water molecules with other functional groups. Seventeen of the images showed a significant difference between the normal and the diseased tissue. These were confirmed by histology to be basal cell carcinomas. Of the remaining four cases, three showed no contrast and were confirmed as blind controls of normal tissue; the fourth case was a suspected basal cell carcinoma but showed no contrast, and histology showed no tumor. Cross-sections of the terahertz images, showing the terahertz absorption, were compared to histology. Regions of increased terahertz absorption agreed well with the location of the tumor sites. Resolutions at 1 THz of 350 microm laterally and 40 microm axially in skin were attainable with our system. These results demonstrate the ability of terahertz pulse imaging to distinguish basal cell carcinoma from normal tissue, and this macroscopic technique may, in the future, help plan surgery.

  3. Basal Cell Carcinoma of the Umbilicus: A Comprehensive Literature Review

    PubMed Central

    Cohen, Philip R

    2016-01-01

    Basal cell carcinoma (BCC) typically occurs in sun-exposed sites. Only 16 individuals with umbilical BCC have been described in the literature, and the characteristics of patients with umbilical BCC are summarized. PubMed was used to search the following terms: abdomen, basal cell carcinoma, basal cell nevus syndrome, and umbilicus. Papers with these terms and references cited within these papers were reviewed. BCC of the umbilicus has been reported in five men and 11 women; one man had two tumors. Two patients had basal cell nevus syndrome (BCNS). Other risk factors for BCC were absent. The tumor most commonly demonstrated nodular histology (64%, 9/14); superficial and fibroepithelioma of Pinkus variants were noted in three and two patients, respectively. The tumor was pigmented in eight individuals. Treatment was conventional surgical excision (87%, 13/15) or Mohs micrographic surgery (13%, 2/15); either adjuvant laser ablation or radiotherapy was performed in two patients. The prognosis after treatment was excellent with no recurrence or metastasis (100%, 16/16). In conclusion, BCC of the umbilicus is rare. It usually presents as a tumor with a non-aggressive histologic subtype in an individual with no risk factors for this malignancy. There has been no recurrence or metastasis following excision of the cancer. PMID:27738570

  4. Basal Cell Carcinoma on the Sole: An Easily Missed Cancer

    PubMed Central

    Hone, Natalie L.; Grandhi, Radhika; Ingraffea, Adam A.

    2016-01-01

    Basal cell carcinoma (BCC) is the most common skin cancer, and solar ultraviolet ray exposure is the most significant risk factor for its development. The plantar foot is infrequently exposed to the sun, thus the presence of BCC on the sole is rare. We report a case of BCC on the sole of the foot and its treatment in the hope to facilitate its detection. PMID:27920679

  5. Subconjunctival "ring" recurrence of Basal cell carcinoma of the globe.

    PubMed

    Lee, Scott; Cnaan, Ran Ben; Paramanathan, Nirosha; Davies, Michael; Benger, Ross; Ghabrial, Raf

    2010-01-01

    Basal cell carcinoma is the most common indication for orbital exenteration. The recurrence rate of BCC removed with microscopically controlled histology sections is up to 6%. The authors describe the recurrence of a lower eyelid BCC resected with microscopic control that did not manifest itself until 15 years later as a subconjunctival lesion, encircling the globe, and without apparent skin involvement. BCC can present in any manner following surgery, and therefore, judicious follow-up is necessary even after microscopically controlled resection.

  6. Autofluorescence imaging of basal cell carcinoma by smartphone RGB camera

    NASA Astrophysics Data System (ADS)

    Lihachev, Alexey; Derjabo, Alexander; Ferulova, Inesa; Lange, Marta; Lihacova, Ilze; Spigulis, Janis

    2015-12-01

    The feasibility of smartphones for in vivo skin autofluorescence imaging has been investigated. Filtered autofluorescence images from the same tissue area were periodically captured by a smartphone RGB camera with subsequent detection of fluorescence intensity decreasing at each image pixel for further imaging the planar distribution of those values. The proposed methodology was tested clinically with 13 basal cell carcinoma and 1 atypical nevus. Several clinical cases and potential future applications of the smartphone-based technique are discussed.

  7. Expression of ZNF396 in basal cell carcinoma.

    PubMed

    Bai, Juncheng; Kito, Yusuke; Okubo, Hiroshi; Nagayama, Tomoko; Takeuchi, Tamotsu

    2014-05-01

    Zfp191 represses differentiation and keeps various cells in the stem/progenitor stage. Here, we report that a Zfp191 homolog protein, ZNF396, is expressed in basal cell carcinoma (BCC) and possibly represses the expression of a Notch system effector molecule, Hes1 (hairy and enhancer of split-1), and prevents BCC cells from undergoing Notch-mediated squamous cell differentiation. ZNF396 immunoreactivity was found in the nucleus of 35 of 38 cutaneous BCC and 4 of 74 squamous cell carcinoma tissue specimens. In non-tumorous epidermal tissues, ZNF396 immunoreactivity was restricted in basal cells. siRNA-mediated silencing of ZNF396 induced the expression of Notch2, Hes1, and involucrin in cultured BCC cells. Finally, we found that siRNA-mediated silencing of ZNF396 gene inhibited the proliferation of TE354.T basal cell carcinoma cells. ZNF396 might repress Notch-Hes1 signaling axis and prevent tumor cells from undergoing squamous differentiation in BCC.

  8. Basal Cell Carcinoma Arising in a Breast Augmentation Scar.

    PubMed

    Edwards, Lisa R; Cresce, Nicole D; Russell, Mark A

    2017-04-01

    We report a case of a 46-year-old female who presented with a persistent lesion on the inferior right breast. The lesion was located within the scar from a breast augmentation procedure 12 years ago. The lesion had been treated as several conditions with no improvement. Biopsy revealed a superficial and nodular basal cell carcinoma, and the lesion was successfully removed with Mohs micrographic surgery. Basal cell carcinoma arising in a surgical scar is exceedingly rare with only 13 reported cases to date. This is the first reported case of basal cell carcinoma arising in a breast augmentation scar. We emphasize the importance of biopsy for suspicious lesions or those refractory to treatment, particularly those lesions that form within a scar. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

  9. Mutations in the human homologue of Drosophila patched (PTCH) in basal cell carcinomas and the Gorlin syndrome: different in vivo mechanisms of PTCH inactivation.

    PubMed

    Unden, A B; Holmberg, E; Lundh-Rozell, B; Stähle-Bäckdahl, M; Zaphiropoulos, P G; Toftgård, R; Vorechovsky, I

    1996-10-15

    The nevoid basal cell carcinoma (Gorlin) syndrome (NBCCS) is an autosomal dominant disorder characterized by multiple developmental defects and cancer susceptibility, in particular to basal cell carcinoma. The human homologue of Drosophila patched (PTCH) was recently identified, mapped to the NBCCS locus on chromosome 9q22.3, and found mutated in patients with NBCCS and also in sporadic basal cell carcinomas. Here we show germ-line PTCH mutations in three families with NBCCS. We demonstrate that a germ-line PTCH frameshift deletion in one patient with NBCCS was accompanied by loss of the normal copy of PTCH in a tumor developed in the same patient. Another basal cell carcinoma from this patient did not show the loss of the normal copy of PTCH, instead a missense mutation in a highly conserved residue was identified in the nondeleted allele, illustrating two different mechanisms of PTCH inactivation in different tumors derived from the same NBCCS patient. We also show somatic PTCH mutations in 4 basal cell carcinomas identified by analyzing 18 non-NBCCS patients with sporadic tumors. These data provide further support for PTCH as an important tumor suppressor gene in the development of the most common human cancer.

  10. Basal Cell Carcinoma in Gorlin's Patients: a Matter of Fibroblasts-Led Protumoral Microenvironment?

    PubMed

    Gache, Yannick; Brellier, Florence; Rouanet, Sophie; Al-Qaraghuli, Sahar; Goncalves-Maia, Maria; Burty-Valin, Elodie; Barnay, Stéphanie; Scarzello, Sabine; Ruat, Martial; Sevenet, Nicolas; Avril, Marie-Françoise; Magnaldo, Thierry

    2015-01-01

    Basal cell carcinoma (BCC) is the commonest tumor in human. About 70% sporadic BCCs bear somatic mutations in the PATCHED1 tumor suppressor gene which encodes the receptor for the Sonic Hedgehog morphogen (SHH). PATCHED1 germinal mutations are associated with the dominant Nevoid Basal Cell Carcinoma Syndrome (NBCCS), a major hallmark of which is a high susceptibility to BCCs. Although the vast majority of sporadic BCCs arises exclusively in sun exposed skin areas, 40 to 50% BCCs from NBCCS patients develop in non photo-exposed skin. Since overwhelming evidences indicate that microenvironment may both be modified by- and influence the- epithelial tumor, we hypothesized that NBCCS fibroblasts could contribute to BCCs in NBCCS patients, notably those developing in non photo-exposed skin areas. The functional impact of NBCCS fibroblasts was then assessed in organotypic skin cultures with control keratinocytes. Onset of epidermal differentiation was delayed in the presence of primary NBCCS fibroblasts. Unexpectedly, keratinocyte proliferation was severely reduced and showed high levels of nuclear P53 in both organotypic skin cultures and in fibroblast-led conditioning experiments. However, in spite of increased levels of senescence associated β-galactosidase activity in keratinocytes cultured in the presence of medium conditioned by NBCCS fibroblasts, we failed to observe activation of P16 and P21 and then of bona fide features of senescence. Constitutive extinction of P53 in WT keratinocytes resulted in an invasive phenotype in the presence of NBCCS fibroblasts. Finally, we found that expression of SHH was limited to fibroblasts but was dependent on the presence of keratinocytes. Inhibition of SHH binding resulted in improved epidermal morphogenesis. Altogether, these data suggest that the repertoire of diffusible factors (including SHH) expressed by primary NBCCS fibroblasts generate a stress affecting keratinocytes behavior and epidermal homeostasis. Our findings

  11. Expression of heparanase in basal cell carcinoma and squamous cell carcinoma*

    PubMed Central

    Pinhal, Maria Aparecida Silva; Almeida, Maria Carolina Leal; Costa, Alessandra Scorse; Theodoro, Thérèse Rachell; Serrano, Rodrigo Lorenzetti; Machado Filho, Carlos D'Apparecida Santos

    2016-01-01

    Background Heparanase is an enzyme that cleaves heparan sulfate chains. Oligosaccharides generated by heparanase induce tumor progression. Basal cell carcinoma and squamous cell carcinoma comprise types of nonmelanoma skin cancer. Objectives Evaluate the glycosaminoglycans profile and expression of heparanase in two human cell lines established in culture, immortalized skin keratinocyte (HaCaT) and squamous cell carcinoma (A431) and also investigate the expression of heparanase in basal cell carcinoma, squamous cell carcinoma and eyelid skin of individuals not affected by the disease (control). Methods Glycosaminoglycans were quantified by electrophoresis and indirect ELISA method. The heparanase expression was analyzed by quantitative RT-PCR (qRTPCR). Results The A431 strain showed significant increase in the sulfated glycosaminoglycans, increased heparanase expression and decreased hyaluronic acid, comparing to the HaCaT lineage. The mRNA expression of heparanase was significantly higher in Basal cell carcinoma and squamous cell carcinoma compared with control skin samples. It was also observed increased heparanase expression in squamous cell carcinoma compared to the Basal cell carcinoma. Conclusion The glycosaminoglycans profile, as well as heparanase expression are different between HaCaT and A431 cell lines. The increased expression of heparanase in Basal cell carcinoma and squamous cell carcinoma suggests that this enzyme could be a marker for the diagnosis of such types of non-melanoma cancers, and may be useful as a target molecule for future alternative treatment. PMID:27828631

  12. Management of superficial basal cell carcinoma: focus on imiquimod

    PubMed Central

    Raasch, Beverly

    2009-01-01

    Superficial basal cell carcinoma comprise up to 25% of all histological sub-types. They are more likely to occur on younger persons and females and although generally more common on the trunk, also occur frequently on the exposed areas of the head and neck especially in areas of high sun exposure. In the last decade, new treatment options such as topical applications that modify the immune response have been trialed for effectiveness in treating these lesions. Imiquimod 5% cream has been shown to stimulate the innate and cell mediated immune system. The short-term success of imiquimod 5% cream in randomized controlled trials comparing different treatment regimes and dosing as a treatment for small superficial basal cell carcinoma (BCC) not on the face or neck is in the range of 82% for 5 times per week application. A high proportion of participants with good response rates to topical treatment (58%–92%) experience local side effects such as itching and burning, less commonly erosion and ulceration, but the proportion of participants ceasing treatment has not been high. To date one long-term study indicates a treatment success rate of 78%–81% and that initial response is a predictor of long-term outcome. Recurrences tend to occur within the first year after treatment. Future research will compare this preparation to the gold standard treatment for superficial BCC – surgical excision. PMID:21436969

  13. Basal cell carcinoma of the nipple - an unusual location in a male patient.

    PubMed

    Avci, Oktay; Pabuççuoğlu, Uğur; Koçdor, M Ali; Unlü, Mehtat; Akin, Ciler; Soyal, Cüneyt; Canda, Tülay

    2008-02-01

    Although basal cell carcinoma is extremely common, it only rarely occurs on the nipple. Men are affected more often than women. Basal cell carcinoma of the nipple-areola complex may be more aggressive as metastases to regional lymph nodes have been reported. We report a basal cell carcinoma of the nipple with features of a fibroepithelioma of Pinkus in a man and review the literature.

  14. Basal cell carcinoma, squamous cell carcinoma and melanoma of the head and face.

    PubMed

    Feller, L; Khammissa, R A G; Kramer, B; Altini, M; Lemmer, J

    2016-02-05

    Ultraviolet light (UV) is an important risk factor for cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and cutaneous melanoma of the skin. These cancers most commonly affect persons with fair skin and blue eyes who sunburn rather than suntan. However, each of these cancers appears to be associated with a different pattern of UV exposure and to be mediated by different intracellular molecular pathways.Some melanocortin 1 receptor (MC1R) gene variants play a direct role in the pathogenesis of cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and cutaneous melanoma apart from their role in determining a cancer-prone pigmentory phenotype (fair skin, red hair, blue eyes) through their interactions with other genes regulating immuno-inflammatory responses, DNA repair or apoptosis.In this short review we focus on the aetiological role of UV in cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and cutaneous melanoma of the skin, and on some associated biopathological events.

  15. Advances in the management of basal cell carcinoma

    PubMed Central

    Carucci, John A.

    2015-01-01

    Basal cell carcinoma (BCC), a malignant neoplasm derived from non-keratinizing cells that originate in the basal layer of the epidermis, is the most common cancer in humans. Several factors such as anatomic location, histologic features, primary or recurrent tumors, and patient characteristics influence the choice of treatment modality for BCC. Mohs micrographic surgery (MMS) facilitates optimal margin control and conservation of normal tissue for the management of BCC; however, other treatment modalities may also be implemented in the correct clinical scenario. Other treatment modalities that will be reviewed include simple excision, electrodesiccation and curettage, cryotherapy, topical immunotherapy and chemotherapy, photodynamic therapy, and radiation therapy. In addition, targeted molecular therapeutic options for the treatment of advanced or metastatic BCC will be discussed in this informal review based on recent literature obtained by using PubMed with relevant search terms. PMID:26097726

  16. Novel Hedgehog pathway targets against basal cell carcinoma

    SciTech Connect

    Tang, Jean Y. So, P.-L.; Epstein, Ervin H.

    2007-11-01

    The Hedgehog signaling pathway plays a key role in directing growth and patterning during embryonic development and is required in vertebrates for the normal development of many structures, including the neural tube, axial skeleton, skin, and hair. Aberrant activation of the Hedgehog (Hh) pathway in adult tissue is associated with the development of basal cell carcinoma (BCC), medulloblastoma, and a subset of pancreatic, gastrointestinal, and other cancers. This review will provide an overview of what is known about the mechanisms by which activation of Hedgehog signaling leads to the development of BCCs and will review two recent papers suggesting that agents that modulate sterol levels might influence the Hh pathway. Thus, sterols may be a new therapeutic target for the treatment of BCCs, and readily available agents such as statins (HMG-CoA reductase inhibitors) or vitamin D might be helpful in reducing BCC incidence.

  17. Management of periorbital basal cell carcinoma with orbital invasion.

    PubMed

    Sun, Michelle T; Wu, Albert; Figueira, Edwin; Huilgol, Shyamala; Selva, Dinesh

    2015-11-01

    Basal cell carcinoma (BCC) is the most common eyelid malignancy; however, orbital invasion by periocular BCC is rare, and management remains challenging. Established risk factors for orbital invasion by BCC include male gender, advanced age, medial canthal location, previous recurrences, large tumor size, aggressive histologic subtype and perineural invasion. Management requires a multidisciplinary approach with orbital exenteration remaining the treatment of choice. Globe-sparing treatment may be appropriate in selected patients and radiotherapy and chemotherapy are often used as adjuvant therapies for advanced or inoperable cases, although the evidence remains limited. We aim to summarize the presentation and treatment of BCC with orbital invasion to better guide the management of this complex condition.

  18. Vismodegib: the Proof of Concept in Basal Cell Carcinoma

    PubMed Central

    Berrada, Narjiss; Lkhoyali, Siham; Mrabti, Hind; Errihani, Hassan

    2014-01-01

    Although basal cell carcinoma (BCC) is the most common cancer worldwide, its metastatic dissemination is exceptional. Before 2012, we had a few treatment options available for metastatic or locally advanced cases. Management of these patients was complicated due to the lack of scientific data, the deterioration of a patient’s general status, the patient’s advanced age, and the presence of multiple comorbidities. The hedgehog signaling pathway is dysregulated in BCC. The exploration of this signaling pathway yielded to a major milestone in the treatment of advanced BCC. Vismodegib (GDC-0449), an oral small-molecule agent that targets the Hedgehog signaling pathway, demonstrates high levels of activity in clinical trials. It was approved in January 2012 for the treatment of locally advanced or metastatic BCC. Vismodegib confirms, once again, the interest in exploring the signal transduction pathways in cancers. PMID:24932107

  19. Ameloblastoma vs basal cell carcinoma: an immunohistochemical comparison.

    PubMed

    Jawad, Salam N; Abdullah, Bashar H

    2016-12-01

    Despite behavioral mimicry of ameloblastoma (AB) and basal cell carcinoma (BCC), they are classified at 2 extremes within pertinent WHO classifications with respect to benign and malignant designation. This study aims to appraise the current allocation of AB in the classification through an immunohistochemical comparison of some aspects of behavior with BCC. Sections from retrospectively retrieved formalin-fixed, paraffin-embedded tissue blocks of AB (n = 37) and BCC (n = 34) were comparatively examined for the immunohistochemical expression for Ki-67, Bcl-2, MMP-2, MMP-9, CD31, and D2-40 monoclonal antibodies. No statistically significant differences between the tumors were found regarding the immunoexpressions of Bcl-2 (P = .252), CD31 microvessel density (P = .895), lymphatic vessel density (P = .642), and MMP-9 stromal expression (P = .083). MMP-2 expression was significantly higher in epithelial and stromal regions of AB (P = .009 and P = .001, respectively), whereas Ki-67 and MMP-9 epithelial expressions were significantly higher in BCC (P < .000 and P = .026, respectively). Within the studied immunohistochemical attributes for tumor behavior, the study accentuated the overall behavioral mimicry of the tumors and indicated that BCCs surmount ABs by the proliferative rate only.

  20. Morphological Spectrum of Basal Cell Carcinoma in Southern Karnataka

    PubMed Central

    Lobo, Flora Dorothy; Naik, Ramdas; Khadilkar, Urmila Niranjan; Kini, Hema; Kini, Ullal Anand

    2016-01-01

    Introduction Basal Cell Carcinoma (BCC) is the most common skin cancer worldwide, which appears over sun-exposed skin as slow-growing, locally invasive lesion that rarely metastasizes. Many phenotypic presentations are possible. BCCs are more common in males and tend to occur in older people. Majority is found on the head and neck. Many histopathological subtypes have been defined including nodular, micronodular, cystic, superficial, pigmented, adenoid, infiltrating, sclerosing, keratotic, infundibulocystic, metatypical, basosquamous and fibroepitheliomatous. Mixed patterns are common. Aim The aim was to study morphological spectrum of BCC in a tertiary care hospital in southern Karnataka. Materials and Methods This was a retrospective analysis of 100 cases of BCCs reported in the Department of Pathology over a 9-year period from 2006 to 2014. Results The mean age of presentation was 62 years. There was slight female preponderance (56%). The most common location was face (65%) and the most common presentation was ulceration (45%). Of the 100 BCCs, 50% were nodular, 13% infiltrating, 6% basosquamous, 4% superficial, 3% keratotic, 3% multinodular and 1% mixed. Conclusion BCC, besides being the commonest cutaneous cancer, is also known for its numerous histological patterns which are shown to have prognostic implications. This study reveals the frequency of the various histological patterns of BCC in southern Karnataka, where it has been rarely studied before. PMID:27504291

  1. Ionizing Radiation Exposure and Basal Cell Carcinoma Pathogenesis

    PubMed Central

    Li, Changzhao; Athar, Mohammad

    2016-01-01

    This commentary summarizes studies showing risk of basal cell carcinoma (BCC) development in relationship to environmental, occupational and therapeutic exposure to ionizing radiation (IR). BCC, the most common type of human cancer, is driven by the aberrant activation of hedgehog (Hh) signaling. Ptch, a tumor suppressor gene of Hh signaling pathway, and Smoothened play a key role in the development of radiation-induced BCCs in animal models. Epidemiological studies provide evidence that humans exposed to radiation as observed among the long-term, large scale cohorts of atomic bomb survivors, bone marrow transplant recipients, patients with tinea capitis and radiologic workers enhances risk of BCCs. Overall, this risk is higher in Caucasians than other races. People who were exposed early in life develop more BCCs. The enhanced IR correlation with BCC and not other common cutaneous malignancies is intriguing. The mechanism underlying these observations remains undefined. Understanding interactions between radiation-induced signaling pathways and those which drive BCC development may be important in unraveling the mechanism associated with this enhanced risk. Recent studies showed that Vismodegib, a Smoothened inhibitor, is effective in treating radiation-induced BCCs in humans, suggesting that common strategies are required for the intervention of BCCs development irrespective of their etiology. PMID:26930381

  2. Regressing basal-cell carcinoma masquerading as benign lichenoid keratosis

    PubMed Central

    Kulberg, Aleksandra; Weyers, Wolfgang

    2016-01-01

    Background Benign lichenoid keratosis (BLK, LPLK) is often misdiagnosed clinically as superficial basal-cell carcinoma (BCC), especially when occurring on the trunk. However, BCCs undergoing regression may be associated with a lichenoid interface dermatitis that may be misinterpreted as BLK in histopathologic sections. Methods In order to assess the frequency of remnants of BCC in lesions interpreted as BLK, we performed step sections on 100 lesions from the trunk of male patients that had been diagnosed as BLK. Results Deeper sections revealed remnants of superficial BCC in five and remnants of a melanocytic nevus in two specimens. In the original sections of cases in which a BCC showed up, crusts tended to be more common, whereas vacuolar changes at the dermo-epidermal junction and melanophages in the papillary dermis tended to be less common and less pronounced. Conclusions Lesions from the trunk submitted as BCC and presenting histopathologically as a lichenoid interface dermatitis are not always BLKs. Although no confident recommendations can be given on the basis of this limited study, deeper sections may be warranted if lesions are crusted and/or associated with only minimal vacuolar changes at the dermo-epidermal junction and no or few melanophages in the papillary dermis. PMID:27867740

  3. Susceptibility to basal cell carcinoma: associations with PTCH polymorphisms.

    PubMed

    Strange, R C; El-Genidy, N; Ramachandran, S; Lovatt, T J; Fryer, A A; Smith, A G; Lear, J T; Wong, C; Jones, P W; Ichii-Jones, F; Hoban, P R

    2004-11-01

    Loss of function of the human patched gene (PTCH) is common and critical in basal cell carcinoma (BCC) development. Indirect evidence suggests polymorphism in PTCH mediates BCC risk. We studied 659 BCC cases and 300 controls to determine if exon 2(318), 3(429), 11(1552), 12(1665), 12(1686), 14(2199) and 23(3944) and intron 9(1336-135) and 15(2560+9)PTCH variants were sufficiently common for use in case-control studies, and if selected markers were associated with risk. Intron 15(2560+9) and exon 23(3944) variants were studied further. Their genotype frequencies were not significantly different in controls and cases, though frequency of the G(2560+9)-C(3944) haplotype was lower in all cases (odds ratio=0.44, p=0.009) and those stratified by BCC site and rate of development of further tumours. This association was not mediated by the extent of UVR exposure. We confirmed the robustness of these findings by showing these associations demonstrated similar odds ratios in two groups of randomly selected cases and controls, and using the false positive report probability (FPRP) approach described by Wacholder et al. (2004). The FPRP value (0.168) was in the noteworthy category. These data, showing for the first time that PTCH polymorphism mediates susceptibility, are compatible with reports showing that PTCH haploinsufficiency influences development of BCC precursor lesions.

  4. Survey among patients with basal cell carcinoma in The Netherlands.

    PubMed

    Gerritsen, M J P; De Rie, M A; Beljaards, R C; Thissen, M R T M; Kuipers, M V

    2009-01-01

    This paper describes the findings of a survey distributed among Dutch patients with basal cell carcinoma (BCC). The questionnaire comprised a list of questions related to demographic characteristics, features of BCC, reason for consulting a dermatologist, anxiety, type of treatment and the satisfaction with this treatment and desired benefits of treatment. In total, 220 patients completed the survey. The age of these responders varied between 27 and 89 years (mean 64.6 years). Half of the patient group had already previously experienced a BCC. Most patients (52%) indicated that the diagnosis 'skin cancer' frightened them, but that they knew it could be treated. Accordingly, most patients (70%) indicated that BCC had no or hardly any influence on their quality of life. From the patient's perspective, efficacy, low recurrence rate and no or minor scarring are important features of a BCC treatment. Surgery was the most popular therapy. The number of BCC patients is growing, which will lead to a definite burden for dermatologists in the near future. Our survey demonstrated that patients are mostly interested in the efficacy, low recurrence rates and cosmetic outcome of their therapies. Newly efficacious and non-invasive therapies, such as the recently introduced photodynamic therapy or home treatment with imiquimod, can help to overcome these concerns.

  5. Vismodegib: in locally advanced or metastatic basal cell carcinoma.

    PubMed

    Keating, Gillian M

    2012-07-30

    Vismodegib is the first Hedgehog pathway inhibitor to be approved in the US, where it is indicated for the treatment of adults with metastatic basal cell carcinoma (BCC), or with locally advanced BCC that has recurred following surgery or who are not candidates for surgery, and who are not candidates for radiation. Vismodegib selectively and potently inhibits the Hedgehog signalling pathway by binding to Smoothened, thereby inhibiting the activation of Hedgehog target genes. Oral vismodegib was effective in the treatment of patients with locally advanced (n = 63) or metastatic (n = 33) BCC, according to the results of an ongoing, noncomparative, multinational, pivotal, phase II trial (ERIVANCE BCC). In this trial (using a clinical cutoff date of 26 November 2010), the independent review facility overall response rate was 42.9% in patients with locally advanced BCC and 30.3% in patients with metastatic BCC. In both patients with locally advanced BCC and those with metastatic BCC, the median duration of response was 7.6 months and median progression-free survival was 9.5 months. Oral vismodegib had an acceptable tolerability profile in patients with advanced BCC.

  6. E-cadherin expression in basal cell carcinoma.

    PubMed Central

    Pizarro, A.; Benito, N.; Navarro, P.; Palacios, J.; Cano, A.; Quintanilla, M.; Contreras, F.; Gamallo, C.

    1994-01-01

    E-cadherin (E-CD) is a calcium-dependent cell-cell adhesion molecule which is expressed in almost all epithelial tissues. E-CD expression is involved in epidermal morphogenesis and is reduced during tumour progression of mouse epidermal carcinogenesis. It has been suggested that E-CD could play a role as an invasion-suppressor molecule. In the present work we have studied the E-CD expression in 31 patients with basal cell carcinoma (BCC) using an immunohistochemical technique with a monoclonal antibody (HECD-1) specific for human E-CD. E-CD expression was preserved in all specimens of superficial and nodular BCC, and was reduced in 10 of 15 infiltrative BCCs. A heterogeneous distribution of cells with different immunostaining intensity was more frequently observed in specimens of infiltrative BCC. These results suggest that E-CD might be related to the growth pattern and the local aggressive behaviour of BCC, and support the idea that E-CD might play a role as an invasion-suppressor molecule in vivo. Images Figure 1 PMID:8286199

  7. Chemopreventive opportunities to control basal cell carcinoma: Current perspectives.

    PubMed

    Tilley, Cynthia; Deep, Gagan; Agarwal, Rajesh

    2015-09-01

    Basal cell carcinoma (BCC) is a major health problem with approximately 2.8 million new cases diagnosed each year in the United States. BCC incidences have continued to rise due to lack of effective chemopreventive options. One of the key molecular characteristics of BCC is the sustained activation of hedgehog signaling through inactivating mutations in the tumor suppressor gene patch (Ptch) or activating mutations in Smoothened. In the past, several studies have addressed targeting the activated hedgehog pathway for the treatment and prevention of BCC, although with toxic effects. Other studies have attempted BCC chemoprevention through targeting the promotional phase of the disease especially the inflammatory component. The compounds that have been utilized in pre-clinical and/or clinical studies include green and black tea, difluoromethylornithine, thymidine dinucleotide, retinoids, non-steroidal anti-inflammatory drugs, vitamin D3, and silibinin. In this review, we have discussed genetic and epigenetic modifications that occur during BCC development as well as the current state of BCC pre-clinical and clinical chemoprevention studies.

  8. Mechanisms and efficacy of vismodegib in the treatment of basal cell carcinoma.

    PubMed

    Amin, Shivan H; Motamedi, Kevin K; Ochsner, Matthew C; Song, Tara E; Hybarger, C Patrick

    2013-11-01

    Historically patients with advanced basal cell carcinoma have been subjected to large surgical resections for the treatment of their disease. However, with the development of vismodegib, a first in class molecule that acts to inhibit the hedgehog pathway, patients with advanced and metastatic basal cell carcinoma may have renewed hope in limiting the morbidity involved with surgery. Preliminary data shows a relatively good safety profile and promising results, although further research remains to be conducted. Current progress on utilization of vismodegib for the treatment of advanced basal cell carcinoma is reviewed in this article. Only literature with objective clinical evidence was included in this review.

  9. TERT promoter mutations are frequent in cutaneous basal cell carcinoma and squamous cell carcinoma.

    PubMed

    Griewank, Klaus G; Murali, Rajmohan; Schilling, Bastian; Schimming, Tobias; Möller, Inga; Moll, Iris; Schwamborn, Marion; Sucker, Antje; Zimmer, Lisa; Schadendorf, Dirk; Hillen, Uwe

    2013-01-01

    Activating mutations in the TERT promoter were recently identified in up to 71% of cutaneous melanoma. Subsequent studies found TERT promoter mutations in a wide array of other major human cancers. TERT promoter mutations lead to increased expression of telomerase, which maintains telomere length and genomic stability, thereby allowing cancer cells to continuously divide, avoiding senescence or apoptosis. TERT promoter mutations in cutaneous melanoma often show UV-signatures. Non-melanoma skin cancer, including basal cell carcinoma and squamous cell carcinoma, are very frequent malignancies in individuals of European descent. We investigated the presence of TERT promoter mutations in 32 basal cell carcinomas and 34 cutaneous squamous cell carcinomas using conventional Sanger sequencing. TERT promoter mutations were identified in 18 (56%) basal cell carcinomas and in 17 (50%) cutaneous squamous cell carcinomas. The recurrent mutations identified in our cohort were identical to those previously described in cutaneous melanoma, and showed a UV-signature (C>T or CC>TT) in line with a causative role for UV exposure in these common cutaneous malignancies. Our study shows that TERT promoter mutations with UV-signatures are frequent in non-melanoma skin cancer, being present in around 50% of basal and squamous cell carcinomas and suggests that increased expression of telomerase plays an important role in the pathogenesis of these tumors.

  10. Basal cell carcinoma of the prostate: unusual subtype of prostatic carcinoma.

    PubMed

    Komura, Kazumasa; Inamoto, Teruo; Tsuji, Motomu; Ibuki, Naokazu; Koyama, Kohei; Ubai, Takanobu; Azuma, Haruhito; Katsuoka, Yoji

    2010-12-01

    Basal cell carcinoma of the prostate, which has been generally considered to be indolent, is an unusual histological type of prostatic carcinoma and is extremely rare. This tumor has been classified according to the prevalent pattern of growth as adenoid cystic carcinoma or basaloid cell carcinoma (BCC), with the former growth pattern being considered to be the main feature of this entity. A 67-year-old Japanese man was admitted to a general hospital with obstructive urinary symptoms. His prostate was slightly enlarged, stony hard, and with a rough surface on digital rectal examination, while serum prostate-specific antigen and prostatic acid phosphatase concentrations were within the normal ranges (0.007 and 0.9 ng/mL, respectively). 2-Fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) exhibited multiple accumulations suspicious for cancer metastases. Specimens obtained by prostatic needle biopsy showed immunohistochemical reactivity for cytokeratin 34βE12 and P63, findings that were identical to those seen in basal cell carcinoma. Basal cell carcinoma of the prostate is a rare tumor, reported in 56 cases so far, and among all these, the pure form of BCC is extremely rare. Immunohistochemistry is indispensable to distinguish this neoplasm from other unusual histological types of prostatic carcinomas. Our findings reveal that tumors with a basaloid cell-predominant pattern have significant potential for a poor prognosis, in contrast with the conventional understanding regarding this neoplasm.

  11. In Vivo Multiphoton Microscopy of Basal Cell Carcinoma

    PubMed Central

    Balu, Mihaela; Zachary, Christopher B.; Harris, Ronald M.; Krasieva, Tatiana B.; König, Karsten; Tromberg, Bruce J.; Kelly, Kristen M.

    2015-01-01

    Importance Basal cell carcinomas (BCCs) are diagnosed by clinical evaluation, which can include dermoscopic evaluation, biopsy, and histopathologic examination. Recent translation of multiphoton microscopy (MPM) to clinical practice raises the possibility of noninvasive, label-free in vivo imaging of BCCs that could reduce the time from consultation to treatment. Objectives To demonstrate the capability of MPM to image in vivo BCC lesions in human skin, and to evaluate if histopathologic criteria can be identified in MPM images. Design, Setting, and Participants Imaging in patients with BCC was performed at the University of California–Irvine Health Beckman Laser Institute & Medical Clinic, Irvine, between September 2012 and April 2014, with a clinical MPM-based tomograph. Ten BCC lesions were imaged in vivo in 9 patients prior to biopsy. The MPM images were compared with histopathologic findings. Main Outcomes and Measures MPM imaging identified in vivo and noninvasively the main histopathologic feature of BCC lesions: nests of basaloid cells showing palisading in the peripheral cell layer at the dermoepidermal junction and/or in the dermis. Results The main MPM feature associated with the BCC lesions involved nests of basaloid cells present in the papillary and reticular dermis. This feature correlated well with histopathologic examination. Other MPM features included elongated tumor cells in the epidermis aligned in 1 direction and parallel collagen and elastin bundles surrounding the tumors. Conclusions and Relevance This study demonstrates, in a limited patient population, that noninvasive in vivo MPM imaging can provide label-free contrast that reveals several characteristic features of BCC lesions. Future studies are needed to validate the technique and correlate MPM performance with histopathologic examination. PMID:25909650

  12. Laser ablation of basal cell carcinomas guided by confocal microscopy

    NASA Astrophysics Data System (ADS)

    Sierra, Heidy; Cordova, Miguel; Nehal, Kishwer; Rossi, Anthony; Chen, Chih-Shan Jason; Rajadhyaksha, Milind

    2016-02-01

    Laser ablation offers precise and fast removal of superficial and early nodular types of basal cell carcinomas (BCCs). Nevertheless, the lack of histological confirmation has been a limitation. Reflectance confocal microscopy (RCM) imaging combined with a contrast agent can offer cellular-level histology-like feedback to detect the presence (or absence) of residual BCC directly on the patient. We conducted an ex vivo bench-top study to provide a set of effective ablation parameters (fluence, number of passes) to remove superficial BCCs while also controlling thermal coagulation post-ablation to allow uptake of contrast agent. The results for an Er:YAG laser (2.9 um and pulse duration 250us) show that with 6 passes of 25 J/cm2, thermal coagulation can be effectively controlled, to allow both the uptake of acetic acid (contrast agent) and detection of residual (or absence) BCCs. Confirmation was provided with histological examination. An initial in vivo study on 35 patients shows that the uptake of contrast agent aluminum chloride) and imaging quality is similar to that observed in the ex vivo study. The detection of the presence of residual tumor or complete clearance was confirmed in 10 wounds with (additional) histology and in 25 lesions with follow-up imaging. Our results indicate that resolution is sufficient but further development and use of appropriate contrast agent are necessary to improve sensitivity and specificity. Advances in RCM technology for imaging of lateral and deep margins directly on the patient may provide less invasive, faster and less expensive image-guided approaches for treatment of BCCs.

  13. Clinicopathological analysis of basal cell carcinoma of the anal region and its distinction from basaloid squamous cell carcinoma.

    PubMed

    Patil, Deepa T; Goldblum, John R; Billings, Steven D

    2013-10-01

    Basal cell carcinoma of the anal region is rare and morphologically difficult to distinguish from basaloid squamous cell carcinoma, particularly on biopsies. This distinction has therapeutic and prognostic implications. We reviewed morphological features of 9 basal cell carcinomas and 15 basaloid squamous cell carcinomas from the anal region diagnosed during 1993-2011 and determined the utility of Ber-EP4, BCL2, TP63, CK5/6, CDKN2A, and SOX2 as diagnostic tools. Immunostains were scored in a semi-quantitative manner (1+-1-10%, 2+-11-50%, 3+->50%). All basal cell carcinomas were located in the perianal region, while all basaloid squamous cell carcinomas originated in the anal canal/anorectum. Nodular subtype of basal cell carcinoma was the most common subtype. Retraction artifact was the only significant distinguishing histological feature of basal cell carcinoma compared with basaloid squamous cell carcinoma (88% vs 26%; P=0.04). Atypical mitoses were more common in basaloid squamous cell carcinomas (71% vs 11%; P=0.05). An in situ component was only present in basaloid squamous cell carcinomas, and was noted in 6/15 cases. Basal cell carcinomas had 2-3+ Ber-EP4 (basal cell carcinoma 100% vs basaloid squamous cell carcinoma 40%; P<0.001) and BCL2 immunoreactivity (basal cell carcinomas 100% vs basaloid squamous cell carcinoma 33%; P<0.001). Diffuse CDKN2A and SOX2 expression was seen only in basaloid squamous cell carcinomas (basal cell carcinoma 0% vs basaloid squamous cell carcinoma 93%; P<0.001). There was no difference in TP63 and CK5/6 expression. Perianal location, retraction artifact, and lack of atypical mitoses are histological features that help distinguish basal cell carcinoma from basaloid squamous cell carcinoma. An in situ component, when present, supports the diagnosis of basaloid squamous cell carcinoma. Immunostains are extremely helpful as diffuse Ber-EP4 and BCL2 expression is a feature of basal cell carcinoma and basaloid squamous cell carcinoma

  14. Partial relapse of Bell's palsy following superficial radiotherapy to a basal cell carcinoma in the temple.

    PubMed

    Brincat, S; Mantell, B S

    1986-07-01

    A patient who developed a partial relapse of Bell's palsy following superficial radiotherapy to a basal cell carcinoma in the temple is reported. Nerves injured by Bell's palsy may be more susceptible to radiation induced damage.

  15. Imaging of basal cell carcinoma tissue using en-face OCT

    NASA Astrophysics Data System (ADS)

    Penmetsa, Bhanu Rakesh; Khandwala, Mona; Bradu, Adrian; Hughes, Michael; Jones, Carole A.; Schofield, John; Podoleanu, Adrian Gh.

    2008-09-01

    We have investigated the applicability of en-face OCT in imaging freshly excised biopsies of Basal Cell Carcinoma. Encouraging results have been obtained in identifying tumor features and abnormal skin architecture.

  16. Successful imiquimod treatment of multiple basal cell carcinomas after radiation therapy for Hodgkin's disease.

    PubMed

    Beyeler, Mirjam; Urosevic, Mirjana; Pestalozzi, Bernhard; Dummer, Reinhard

    2005-01-01

    We present a case of a 55-year-old male patient who developed five basal cell carcinomas 23 years after radiation therapy of Hodgkin's disease. In 1980 he received radiation therapy twice. Due to relapses, he was treated with aggressive polychemotherapy and underwent autologous stem cell transplantation, which then led to complete remission. Until now he is in complete remission. However, multiple superficial basal cell carcinomas have developed on irradiation fields that have been successfully treated by imiquimod.

  17. Primary basal cell carcinoma of the caruncle: case report and review of the literature.

    PubMed

    Ugurlu, Seyda; Ekin, Meryem Altin; Altinboga, Aysegul Aksoy

    2014-01-01

    A case of primary basal cell carcinoma of the caruncle is presented and patients presented in the literature reviewed. Clinical features and outcome of a patient with primary basal cell carcinoma of the caruncle is described. Review of 8 other cases identified through literature search with the keywords of "basal cell carcinoma" and "caruncle" is presented.A 67-year-old male patient presented with a 12 months' history of a lesion over the caruncular region. Incisional biopsy of the lesion revealed primary basal cell carcinoma of nodular type. MRI of the orbit identified extension of the lesion into the medial orbit. The tumor was excised, and reconstructive surgery was performed. The patient declined subsequent radiotherapy. No recurrence was detected during the follow up of 33 months. The current patient and 8 other patients with primary basal cell carcinoma of the caruncle were reviewed.The main therapeutic approach for primary basal cell carcinoma of the caruncle is complete excision with tumor-free surgical margins. Adjuvant radiotherapy or chemotherapy may be administered when deemed necessary.

  18. Basal cell cancer (image)

    MedlinePlus

    Basal cell cancer is a malignant skin tumor involving cancerous changes of basal skin cells. Basal cell skin cancers ... biopsy is needed to prove the diagnosis of basal cell carcinoma. Treatment varies depending on the size, depth, and ...

  19. Basal cell carcinoma with matrical differentiation: expression of beta-catenin [corrected] and osteopontin.

    PubMed

    Del Sordo, Rachele; Cavaliere, Antonio; Sidoni, Angelo

    2007-10-01

    Basal cell carcinoma with matrical differentiation is an extremely rare variant. To date, only 12 cases have been described in the literature. This tumor is a typical basal cell carcinoma with basaloid nests containing shadow cells identical to those of pilomatricoma and pilomatrical carcinoma. We present two additional cases and have investigated the immunoprofile of .-catenin and osteopontin with the aim of determining both their biological significance and possible diagnostic utility. The morphological and immunohistochemical features of these cases that we have found suggest that basal cell carcinomas with matrical differentiation belong to a spectrum of lesions deriving from hair follicles in which .-catenin plays an important role in the tumor development, differentiation, and behavior.

  20. An Interesting Case of Basal Cell Carcinoma with Raynaud's Phenomenon Following Chronic Arsenic Exposure.

    PubMed

    Gulshan, S; Rahman, M J; Sarkar, R; Ghosh, S; Hazra, R

    2016-01-01

    Arsenic is commonly known to be associated with squamous cell carcinoma. Among the lesser known associations is basal cell carcinoma and even rarer is its effect on blood vessels causing peripheral vascular disease. Here we present a case of a 55 yr old man with ulceroproliferative lesions on scalp and forehead along with several hyperpigmented patches on trunk and extremities. He had symptoms suggestive of Raynaud's phenomenon that eventually led to digital gangrene. FNAC was done which was suggestive of basal cell carcinoma. On further enquiry, he was found to reside in an arsenic endemic zone and was investigated for blood arsenic level which was elevated. Punch biopsy from different lesions from body confirmed nodular basal cell carcinoma. Presently the patient has stopped drinking water from the local tubewell. On follow-up he shows improvement of Raynaud's phenomenon and skin lesions.

  1. Photodynamic therapy with 5-aminoolevulinic acid-induced porphyrins and DMSO/EDTA for basal cell carcinoma

    NASA Astrophysics Data System (ADS)

    Warloe, Trond; Peng, Qian; Heyerdahl, Helen; Moan, Johan; Steen, Harald B.; Giercksky, Karl-Erik

    1995-03-01

    Seven hundred sixty three basal cell carcinomas (BCCs) in 122 patients were treated by photodynamic therapy by 5-aminolevulinic acid (ALA) in cream topically applied, either alone, in combination with dimethyl sulphoxide (DMSO) and ethylenediaminetetraacetic acid disodium salt (EDTA), or with DMSO as a pretreatment. After 3 hours cream exposure 40 - 200 Joules/cm2 of 630 nm laser light was given. Fluorescence imaging of biopsies showed highly improved ALA penetration depth and doubled ALA-induced porphyrin production using DMSO/EDTA. Treatment response was recorded after 3 months. After a single treatment 90% of 393 superficial lesions responded completely, independent of using DMSO/EDTA. In 363 nodulo-ulcerative lesions the complete response rate increased from 67% to above 90% with DMSO/EDTA for lesions less than 2 mm thickness and from 34% to about 50% for lesions thicker than 2 mm. Recurrence rate observed during a follow-up period longer than 12 months was 2 - 5%. PDT of superficial thin BCCs with ALA-induced porphyrins and DMSO/EDTA equals surgery and radiotherapy with respect to cure rate and recurrence. Cosmetic results of ALA-based PDT seemed to be better than those after other therapies. In patients with the nevoid BCC syndrome the complete response rate after PDT was far lower.

  2. [A case of squamous cell carcinoma of the hard palate in a patient with basal cell nevus syndrome].

    PubMed

    Matsuo, Mioko; Rikimaru, Fumihide; Higaki, Yuichiro; Masuda, Muneyuki

    2014-06-01

    Basal cell nevus syndrome is an autosomal dominant disorder characterized by the developmental malformations and its carcinogenic nature. This syndrome shows various symptoms of multiple cutaneous basal cell carcinoma, ketatocystic odontogenic tumors, and inborn abnormalities in the bone and skin. Although basal cell nevus syndrome itself is a rare disorder, we experienced a very rare case in which squamous cell carcinoma of the oral cavity developed, and not cutaneous basal cell carcinoma. Only 4 similar cases have been reported in the English literature. The patient was a 33-year-old woman. She was diagnosed as having squamous cell carcinoma of the hard palate, and basal cell nevus syndrome in our hospital. The patient underwent surgery for squamous cell carcinoma of the hard palate, with postoperative chemoradiothetrapy. Since patients with this syndrome tend to form basal cell carcinoma when exposed to X-ray radiation, we perform radiotherapy with care.

  3. Perianal basal cell carcinoma: a comparative histologic, immunohistochemical, and flow cytometric study with basaloid carcinoma of the anus.

    PubMed

    Alvarez-Cañas, M C; Fernández, F A; Rodilla, I G; Val-Bernal, J F

    1996-08-01

    Perianal basal cell carcinoma is a very rare tumor accounting for only 0.2% of the anorectal tumors. It must be distinguished from basaloid carcinoma of the anus, which resembles it histologically but shows a much more aggressive behavior, metastasizes early, and often proves fatal, thus requiring different therapy. Differential diagnosis of both entities by light microscopy may be difficult. Five cases of perianal basal cell carcinoma and five cases of basaloid carcinoma were studied by means of immunohistochemistry and flow cytometry. Some immunohistochemical markers, such as epithelial membrane antigen, carcinoembrionic antigen, and keratins, as well as the lectin Ulex europaeus agglutinin I stained basaloid carcinoma and were negative for basal cell carcinoma. In contrast, the monoclonal antibody Ber-EP4 seems to be a good marker for perianal basal cell carcinoma and useful in differentiating it from basaloid carcinoma of the anus. Basaloid carcinomas are associated with a significantly higher S-phase fraction than are perianal basal cell carcinomas (p < 0.01).

  4. Reporting basal cell carcinoma: a survey of the attitudes of histopathologists.

    PubMed Central

    Milroy, C J; Richman, P I; Wilson, G D; Sanders, R

    1999-01-01

    AIMS: To investigate the histopathological reporting of basal cell carcinoma. METHODS: Methods of classification and attitudes to excision margins were ascertained from histopathologists in 130 centres; 82 replies were obtained (63% response rate). RESULTS: 24% of those replying did not use any classification system for basal cell carcinoma. The remainder (76%) used a wide variety of different classification systems. A small number (9%) of those questioned felt reporting on completeness of excision was not important. The majority of histopathologists considered the excision margin was worth reporting but there were differences in methods of processing and reporting biopsies. CONCLUSIONS: There is considerable variation in histopathological reporting of basal cell carcinoma. There is a need for uniformity of histopathological reporting to allow both improved management decisions and comparative audit of this extremely common skin cancer. Images PMID:10690185

  5. [Exclusive radiotherapy for a facial basal cell carcinoma with trigeminal ganglion involvement].

    PubMed

    Longeac, M; Lapeyre, M; Delbet Dupas, C; Barthélémy, I; Pham Dang, N

    2016-06-01

    Basal cell carcinomas with symptomatic perineural invasion are rare entities. We report the case of a 60year-old man (with a grafted kidney), surgically treated in 2007 for a sclerodermiform basal cell carcinoma infiltrating the left nostril. Five years later, a painful left hemifacial hypoesthesia associated with an ulcus rodens of the nasolabial fold appeared. A biopsy confirmed a recurrence. MRI showed an enhancement of the trigeminal ganglion. The patient had a trigeminal perineural invasion secondary to a cutaneous basal cell carcinoma. He received a local intensity-modulated radiotherapy alone (70Gy in 33 sessions), administered from the skin tumour to the skull base. Three years after the end of treatment, the patient is in radiological and clinical remission, with partial recovery of the hypoesthesia. Evolution was marked by iterative corneal ulcers and decreased visual acuity. Modalities of treatment by surgery and/or radiation therapy and complications are poorly described in the literature.

  6. Hedgehog pathway inhibition in advanced basal cell carcinoma: latest evidence and clinical usefulness

    PubMed Central

    Silapunt, Sirunya; Chen, Leon; Migden, Michael R.

    2016-01-01

    Treatment of locally advanced basal cell carcinomas (laBCCs) with large, aggressive, destructive, and disfiguring tumors, or metastatic disease is challenging. Dysregulation of the Hedgehog (Hh) signaling pathway has been identified in the vast majority of basal cell carcinomas (BCCs). There are two United States Food and Drug Administration (US FDA)-approved Hh pathway inhibitors (HPIs) that exhibit antitumor activity in advanced BCC with an acceptable safety profile. Common adverse effects include muscle spasms, dysgeusia, alopecia, fatigue, nausea and weight loss. PMID:27583029

  7. Basal cell carcinoma and breast carcinoma following repeated fluoroscopic examinations of the chest

    SciTech Connect

    Myskowski, P.L.; Gumpertz, E.; Safai, B.

    1985-03-01

    A 69-year-old white Italian woman was first seen at Memorial Sloan-Kettering Cancer Center in 1981 concerning several skin growths on her back. The patient had had several basal cell carcinomas surgically removed from her back during the preceding 5 years. There was no history of arsenic ingestion or prolonged sun exposure and her family history was negative for skin cancer. The patient had developed pulmonary tuberculosis in 1938 and was treated with pneumothorax therapy. She had had more than 50 fluoroscopic examinations of the chest following this therapy, as well as multiple diagnostic x-ray films since that time. On the back, clustered in the interscapular region, were multiple scars and nine erythematous nodules with pearly borders, telangiectasia, and translucent surfaces. Within several nodules there were areas of light and dark brown pigmentation. Biopsy of all lesions revealed basal cell carcinoma, some of which were pigmented, without evidence of chronic radiodermatitis. All lesions were treated with curettage and electrodesiccation three times with good cosmetic results.

  8. Analysis of effectiveness of a surgical treatment algorithm for basal cell carcinoma*

    PubMed Central

    Luz, Flávio Barbosa; Ferron, Camila; Cardoso, Gilberto Perez

    2016-01-01

    BACKGROUND Surgical excision is the treatment of choice for basal cell carcinoma and micrographic surgery considered the gold standard, however not yet used routinely worldwide available, as in Brazil. Considering this, a previously developed treatment guideline, which the majority of tumors were treated by conventional technique (not micrographic) was tested. OBJECTIVE To establish the recurrence rate of basal cell carcinomas treated according to this guideline. METHOD Between May 2001 and July 2012, 919 basal cell carcinoma lesions in 410 patients were treated according to the proposed guideline. Patients were followed-up and reviewed between September 2013 and February 2014 for clinical, dermatoscopic and histopathologic detection of possible recurrences. RESULTS After application of exclusion criteria, 520 lesions were studied, with 88.3% primary and 11.7% recurrent tumors. Histological pattern was indolent in 85.5%, 48.6% were located in high risk areas and 70% small tumors. Only 7.3% were treated by Mohs micrographic surgery. The recurrence rate, in an average follow-up period of 4.37 years, was 1.3% for primary and 1.63% for recurrent tumors. Study limitations: unicenter study, with all patients operated on by the same surgeon. CONCLUSION The treatment guideline utilized seems a helpful guide for surgical treatment of basal cell carcinoma, especially if micrographic surgery is not available. PMID:28099591

  9. [Current recommendations in the treatment of basal cell carcinoma and squamous cell carcinoma of the skin].

    PubMed

    Kunte, C; Konz, B

    2007-05-01

    The incidence of the most common tumors of the skin, basal cell carcinoma and squamous cell carcinoma, has risen rapidly in recent years. Dermatologists see in their daily practice many different clinical and histological variants of these tumors. They must be able to develop therapeutic strategies adapted to the tumor and the patient. Surgical excision remains the standard treatment. Micrographic histological evaluation should be employed in difficult locations, for large tumors and when there is increased risk of recurrence or metastasis. For initial or superficial lesions, other approaches such as radiation therapy, as well as curettage, cryosurgery, laser therapy and photodynamic therapy can be employed. An additional option is topical treatment with imiquimod or 5-flourouracil.

  10. Pigmented Basal cell carcinoma of nipple and areola in a male breast - a case report with review of literature.

    PubMed

    Kalyani, R; Vani, B R; Srinivas, Murthy V; Veda, P

    2014-03-01

    Basal cell carcinoma is a common skin cancer worldwide. However basal cell carcinoma of nipple and areola complex is rare, commonly seen in males in elderly age group. The tumor has aggressive behavior with increased tendency for metastasis. We present a case in a 78 year male in the left breast.

  11. Diagnostic utility of immunohistochemistry in distinguishing trichoepithelioma and basal cell carcinoma: evaluation using tissue microarray samples.

    PubMed

    Tebcherani, Antonio José; de Andrade, Heitor Franco; Sotto, Mirian N

    2012-10-01

    Trichoepithelioma is a benign neoplasm that shares both clinical and histological features with basal cell carcinoma. It is important to distinguish these neoplasms because they require different clinical behavior and therapeutic planning. Many studies have addressed the use of immunohistochemistry to improve the differential diagnosis of these tumors. These studies present conflicting results when addressing the same markers, probably owing to the small number of basaloid tumors that comprised their studies, which generally did not exceed 50 cases. We built a tissue microarray with 162 trichoepithelioma and 328 basal cell carcinoma biopsies and tested a panel of immune markers composed of CD34, CD10, epithelial membrane antigen, Bcl-2, cytokeratins 15 and 20 and D2-40. The results were analyzed using multiple linear and logistic regression models. This analysis revealed a model that could differentiate trichoepithelioma from basal cell carcinoma in 36% of the cases. The panel of immunohistochemical markers required to differentiate between these tumors was composed of CD10, cytokeratin 15, cytokeratin 20 and D2-40. The results obtained in this work were generated from a large number of biopsies and resulted in the confirmation of overlapping epithelial and stromal immunohistochemical profiles from these basaloid tumors. The results also corroborate the point of view that trichoepithelioma and basal cell carcinoma tumors represent two different points in the differentiation of a single cell type. Despite the use of panels of immune markers, histopathological criteria associated with clinical data certainly remain the best guideline for the differential diagnosis of trichoepithelioma and basal cell carcinoma.

  12. Basal cell carcinoma arising in a congenital melanocytic naevus in an adult.

    PubMed

    Cooper, Lillian; Srinivasan, Karthik; Nugent, Nora

    2017-02-13

    Congenital melanocytic naevi (CMN) are common skin lesions. They harbour a risk of malignant transformation, and various lesions have been described as developing within them. A basal cell cancer occurring within a CMN has never previously been described. A case is described of a woman aged 52 years presenting with a slow-growing, symptomatic 3 cm lesion in the centre of a 10×5 cm CMN on her right upper back. Diagnostic core biopsy revealed an ulcerated, infiltrative basal cell carcinoma which was then further excised. The scar has healed with no evidence of local recurrence at 1-year follow-up.

  13. Basal cell carcinoma of the skin (part 1): epidemiology, pathology and genetic syndromes.

    PubMed

    Correia de Sá, Tiago Ribeiro; Silva, Roberto; Lopes, José Manuel

    2015-11-01

    Basal cell carcinoma (BCC) is the most common skin cancer worldwide with increasing incidence, but difficult to assess due to the current under registration practice. Despite the low mortality rate, BCC is a cause of great morbidity and an economic burden to health services. There are several risk factors that increase the risk of BCC and partly explain its incidence. Low-penetrance susceptibility alleles, as well as genetic alterations in signaling pathways, namely SHH pathway, also contribute to the carcinogenesis. BCC associate with several genetic syndromes, of which basal cell nevus syndrome is the most common.

  14. A subset of prostatic basal cell carcinomas harbor the MYB rearrangement of adenoid cystic carcinoma.

    PubMed

    Bishop, Justin A; Yonescu, Raluca; Epstein, Jonathan I; Westra, William H

    2015-08-01

    Adenoid cystic carcinoma (ACC) is a basaloid tumor consisting of myoepithelial and ductal cells typically arranged in a cribriform pattern. Adenoid cystic carcinoma is generally regarded as a form of salivary gland carcinoma, but it can arise from sites unassociated with salivary tissue. A rare form of prostate carcinoma exhibits ACC-like features; it is no longer regarded as a true ACC but rather as prostatic basal cell carcinoma (PBCC) and within the spectrum of basaloid prostatic proliferations. True ACCs often harbor MYB translocations resulting in the MYB-NFIB fusion protein. MYB analysis could clarify the true nature of prostatic carcinomas that exhibit ACC features and thus help refine the classification of prostatic basaloid proliferations. Twelve PBCCs were identified from the pathology consultation files of Johns Hopkins Hospital. The histopathologic features were reviewed, and break-apart fluorescence in situ hybridization for MYB was performed. All 12 cases exhibited prominent basaloid histology. Four were purely solid, 7 exhibited a cribriform pattern reminiscent of salivary ACC, and 1 had a mixed pattern. The MYB rearrangement was detected in 2 (29%) of 7 ACC-like carcinomas but in none (0%) of the 5 PBCCs with a prominent solid pattern. True ACCs can arise in the prostate as is evidenced by the presence of the characteristic MYB rearrangement. When dealing with malignant basaloid proliferations in the prostate, recommendations to consolidate ACCs with other tumor types may need to be reassessed, particularly in light of the rapidly advancing field of biologic therapy where the identification of tumor-specific genetic alterations presents novel therapeutic targets.

  15. Perineural Infiltration of Cutaneous Squamous Cell Carcinoma and Basal Cell Carcinoma Without Clinical Features

    SciTech Connect

    Lin, Charles; Tripcony, Lee; Keller, Jacqui; Poulsen, Michael; Martin, Jarad; Jackson, James; Dickie, Graeme

    2012-01-01

    Purpose: To review the factors that influence outcome and patterns of relapse in patients with cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) with perineural infiltration (PNI) without clinical or radiologic features, treated with surgery and radiotherapy. Methods and Materials: Between 1991 and 2004, 222 patients with SCC or BCC with PNI on pathologic examination but without clinical or radiologic PNI features were identified. Charts were reviewed retrospectively and relevant data collected. All patients were treated with curative intent; all had radiotherapy, and most had surgery. The primary endpoint was 5-year relapse-free survival from the time of diagnosis. Results: Patients with SCC did significantly worse than those with BCC (5-year relapse-free survival, 78% vs. 91%; p < 0.01). Squamous cell carcinoma with PNI at recurrence did significantly worse than de novo in terms of 5-year local failure (40% vs. 19%; p < 0.01) and regional relapse (29% vs. 5%; p < 0.01). Depth of invasion was also a significant factor. Of the PNI-specific factors for SCC, focal PNI did significantly better than more-extensive PNI, but involved nerve diameter or presence of PNI at the periphery of the tumor were not significant factors. Conclusions: Radiotherapy in conjunction with surgery offers an acceptable outcome for cutaneous SCC and BCC with PNI. This study suggests that focal PNI is not an adverse feature.

  16. Differential senescence capacities in meibomian gland carcinoma and basal cell carcinoma.

    PubMed

    Zhang, Leilei; Huang, Xiaolin; Zhu, Xiaowei; Ge, Shengfang; Gilson, Eric; Jia, Renbing; Ye, Jing; Fan, Xianqun

    2016-03-15

    Meibomian gland carcinoma (MGC) and basal cell carcinoma (BCC) are common eyelid carcinomas that exhibit highly dissimilar degrees of proliferation and prognoses. We address here the question of the differential mechanisms between these two eyelid cancers that explain their different outcome. A total of 102 confirmed MGC and 175 diagnosed BCC cases were analyzed. Twenty confirmed MGC and twenty diagnosed BCC cases were collected to determine the telomere length, the presence of senescent cells, and the expression levels of the telomere capping shelterin complex, P53, and the E3 ubiquitin ligase Siah1. Decreased protein levels of the shelterin subunits, shortened telomere length, over-expressed Ki-67, and Bcl2 as well as mutations in P53 were detected both in MGC and BCC. It suggests that the decreased protein levels of the shelterin complex and the shortened telomere length contribute to the tumorigenesis of MGC and BCC. However, several parameters distinguish MGC from BCC samples: (i) the mRNA level of the shelterin subunits decreased in MGC but it increased in BCC; (ii) P53 was more highly mutated in MGC; (iii) Siah1 mRNA was over-expressed in BCC; (iv) BCC samples contain a higher level of senescent cells; (v) Ki-67 and Bcl2 expression were lower in BCC. These results support a model where a preserved P53 checkpoint in BCC leads to cellular senescence and reduced tumor proliferation as compared to MGC.

  17. Photodynamic therapy by topical meso-tetraphenylporphinesulfonate tetrasodium salt administration in superficial basal cell carcinomas

    SciTech Connect

    Santoro, O.; Bandieramonte, G.; Melloni, E.; Marchesini, R.; Zunino, F.; Lepera, P.; De Palo, G. )

    1990-08-01

    The efficacy of an originally developed photodynamic approach, using topical administration of tetraphenylporphinesulfonate as the photosensitizer, was evaluated in a series of 292 basal cell carcinoma lesions (less than 2-mm thick) in 50 treated patients. The lack of indication for conventional therapies was the main selection criterion. The photosensitizing agent (2% solution) was topically applied at 0.1 ml/cm2, followed by light irradiation with a dye laser emitting at 645 nm (120 or 150 J/cm2). After initial treatment, all lesions responded, with 273 (93.5%) complete responses. Recurrences were observed in 29 (10.6%). A second application of photoradiation was performed in 15 persistent lesions and 11 relapsed lesions, producing 19/26 complete responses. Our results suggest that this technique can be considered a promising alternative treatment modality in selected cases of superficial basal cell carcinomas.

  18. Managing adverse events associated with vismodegib in the treatment of basal cell carcinoma.

    PubMed

    Fife, Kate; Herd, Robert; Lalondrelle, Susan; Plummer, Ruth; Strong, Amy; Jones, Sarah; Lear, John T

    2017-01-01

    Basal cell carcinomas are the most common form of skin cancer. Some develop into advanced cases not suitable for standard therapy. Vismodegib is the first-in-class oral hedgehog pathway inhibitor (which is dysregulated in 90% of basal cell carcinomas), and has demonstrated efficacy for advanced disease in clinical trials. An UK expert panel met to discuss management strategies for adverse events associated with vismodegib (most commonly taste disturbances, muscle cramps and alopecia). Managing patient expectations and implementing treatment breaks were considered important strategies. Quinine was useful to alleviate muscle cramps. For taste disturbances, food swaps alongside dietician referral were suggested. The experts concluded that these common adverse events can be successfully managed to allow optimum treatment duration of vismodegib.

  19. Dynamic focus optical coherence tomography: feasibility for improved basal cell carcinoma investigation

    NASA Astrophysics Data System (ADS)

    Nasiri-Avanaki, M. R.; Aber, Ahmed; Hojjatoleslami, S. A.; Sira, Mano; Schofield, John B.; Jones, Carole; Podoleanu, A. Gh.

    2012-03-01

    Basal cell carcinoma (BCC) is the most common form of skin cancer. To improve the diagnostic accuracy, additional non-invasive methods of making a preliminary diagnosis have been sought. We have implemented an En-Face optical coherence tomography (OCT) for this study in which the dynamic focus was integrated into it. With the dynamic focus scheme, the coherence gate moves synchronously with the peak of confocal gate determined by the confocal interface optics. The transversal resolution is then conserved throughout the depth range and an enhanced signal is returned from all depths. The Basal Cell Carcinoma specimens were obtained from the eyelid a patient. The specimens under went analysis by DF-OCT imaging. We searched for remarkable features that were visualized by OCT and compared these findings with features presented in the histology slices.

  20. Recurrence rate of basal cell carcinoma with positive histopathological margins and related risk factors*

    PubMed Central

    Lara, Fernanda; Santamaría, Jesus Rodriguez; Garbers, Luiz Eduardo Fabricio de Melo

    2017-01-01

    BACKGROUND The best way to approach surgically removed basal cell carcinoma with positive histopathological margins is a controversial issue. Some authors believe that the more appropriate treatment is an immediate reoperation while others prefer a periodic follow up. The rates of recurrence are variable in literature, between 10% and 67%. OBJECTIVE To define the recurrence rate of basal cell carcinoma with positive margins after surgery. Secondarily, identify morphological aspects that can suggest a more frequent tumoral recurrence. METHODS This was a retrospective and observational study made by analysis of medical records of 487 patients between January 2003 and December 2009 in Hospital de Clínicas da Universidade Federal do Paraná (HC-UFPR). From 402 basal cell carcinomas surgically treated, 41 fulfilled inclusion criteria and were evaluated for five years or more. Recurrence rate of these tumors was analyzed in all patients and clinical characteristics such as sex, age, tumor size, tumor site, ulceration, and histological type were evaluated in order to find if they were related to more common tumoral recurrence. RESULTS The rate of positive margins after surgery was 12.18%. There were five cases of tumoral recurrence in the observation group and three cases in the re-excision group. Tumor size, site, histological type, ulceration and type of positive margin did not differ statistically between groups. It was not possible to consider if these factors were important in recurrence rates. STUDY LIMITATIONS Ideally, a prospective study with a larger sample would be more accurate. CONCLUSION The treatment of choice in basal cell carcinoma with positive margins must be individualized to reduce recurrence rates. PMID:28225958

  1. Basal Cell Carcinoma: Pathogenesis, Epidemiology, Clinical Features, Diagnosis, Histopathology, and Management

    PubMed Central

    Marzuka, Alexander G.; Book, Samuel E.

    2015-01-01

    Basal cell carcinoma (BCC) is the most common malignancy. Exposure to sunlight is the most important risk factor. Most, if not all, cases of BCC demonstrate overactive Hedgehog signaling. A variety of treatment modalities exist and are selected based on recurrence risk, importance of tissue preservation, patient preference, and extent of disease. The pathogenesis, epidemiology, clinical features, diagnosis, histopathology, and management of BCC will be discussed in this review. PMID:26029015

  2. Vismodegib: a guide to its use in locally advanced or metastatic basal cell carcinoma.

    PubMed

    Lyseng-Williamson, Katherine A; Keating, Gillian M

    2013-02-01

    Vismodegib is the first Hedgehog pathway inhibitor to be approved in the USA, where it is indicated for the treatment of adults with metastatic basal cell carcinoma (BCC), or with locally advanced BCC that has recurred following surgery or who are not candidates for surgery, and who are not candidates for radiation. In an ongoing, noncomparative, phase II trial, oral vismodegib was effective in and had an acceptable tolerability profile in the treatment of patients with locally advanced or metastatic BCC.

  3. Which histological characteristics of basal cell carcinomas influence the quality of optical coherence tomography imaging?

    NASA Astrophysics Data System (ADS)

    Mogensen, M.; Thrane, L.; Joergensen, T. M.; Nürnberg, B. M.; Jemec, G. B. E.

    2009-07-01

    We explore how histopathology parameters influence OCT imaging of basal cell carcinomas (BCC) and address whether such parameters correlate with the quality of the recorded OCT images. Our results indicate that inflammation impairs OCT imaging and that sun-damaged skin can sometimes provide more clear-cut images of skin cancer lesions using OCT imaging when compared to skin cancer surrounded by skin without sun-damage.

  4. Thorium X treatment: multiple basal cell carcinomas within a port-wine stain.

    PubMed

    Natkunarajah, J; Cliff, S

    2009-07-01

    Thorium X is an ionizing radiation treatment that was commonly used by dermatologists in the 1930 s to 1950 s to treat a variety of benign dermatoses and vascular lesions including port-wine stains. By the 1960 s, thorium X was discontinued due to poor clinical results and the carcinogenic potential. We report a 64-year-old man with a history of multiple basal cell carcinomas in a facial port wine stain, which had previously been treated with thorium X.

  5. Dermatoscopy-guided therapy of pigmented basal cell carcinoma with imiquimod*

    PubMed Central

    Husein-ElAhmed, Husein; Fernandez-Pugnaire, Maria Antonia

    2016-01-01

    BACKGROUND Dermatoscopy is a non-invasive diagnostic tool used to examine skin lesions with an optical magnification. It has been suggested as a useful tool for monitoring therapeutic response in lentigo maligna patients treated with imiquimod. OBJECTIVE To examine the accuracy of dermatoscopy as a tool to monitor the therapeutic response of pigmented basal cell carcinoma treated with imiquimod. METHOD The authors designed a prospective study. Patients with pigmented basal cell carcinoma were included and data regarding the dermatoscopy features were collected following the Menzies criteria, prior to initiating the imiquimod treatment. Subsequent dermatoscopic evaluations were performed at weeks 4 and 8, following imiquimod discontinuation. RESULTS Twenty lesions were included. The most common pigmented dermatoscopy features were large blue-grey ovoid nests (80%), followed by blue-grey globules (50%) and leaf-like areas (30%). No spoke wheel areas were observed. In 17 out of 20 patients, a response was noted during the first evaluation at 4 weeks, while the clearance was noted at the second check-up after 8 weeks. In two patients, the clearance was found at the initial evaluation at 4 weeks, while in one patient, the response remained unchanged. Blue-grey globules were the fastest to exhibit clearance (50% at week 4), followed by leaf-like areas (15%) and large blue-grey ovoid nests (6.25%). CONCLUSION According to our results, dermatoscopic evaluation enhances the accuracy in the assessment of the clinical response to imiquimod in pigmented basal cell carcinoma. PMID:28099598

  6. Cationic Phosphorus Dendrimer Enhances Photodynamic Activity of Rose Bengal against Basal Cell Carcinoma Cell Lines.

    PubMed

    Dabrzalska, Monika; Janaszewska, Anna; Zablocka, Maria; Mignani, Serge; Majoral, Jean Pierre; Klajnert-Maculewicz, Barbara

    2017-04-06

    In the last couple of decades, photodynamic therapy emerged as a useful tool in the treatment of basal cell carcinoma. However, it still meets limitations due to unfavorable properties of photosensitizers such as poor solubility or lack of selectivity. Dendrimers, polymers widely studied in biomedical field, may play a role as photosensitizer carriers and improve the efficacy of photodynamic treatment. Here, we describe the evaluation of an electrostatic complex of cationic phosphorus dendrimer and rose bengal in such aspects as singlet oxygen production, cellular uptake, and phototoxicity against three basal cell carcinoma cell lines. Rose bengal-cationic dendrimer complex in molar ratio 5:1 was compared to free rose bengal. Obtained results showed that the singlet oxygen production in aqueous medium was significantly higher for the complex than for free rose bengal. The cellular uptake of the complex was 2-7-fold higher compared to a free photosensitizer. Importantly, rose bengal, rose bengal-dendrimer complex, and dendrimer itself showed no dark toxicity against all three cell lines. Moreover, we observed that phototoxicity of the complex was remarkably enhanced presumably due to high cellular uptake. On the basis of the obtained results, we conclude that rose bengal-cationic dendrimer complex has a potential in photodynamic treatment of basal cell carcinoma.

  7. 980nm laser for difficult-to-treat basal cell carcinoma

    NASA Astrophysics Data System (ADS)

    Derjabo, A. D.; Cema, I.; Lihacova, I.; Derjabo, L.

    2013-06-01

    Begin basal cell carcinoma (BCC) is most common skin cancer over the world. There are around 20 modalities for BCC treatment. Laser surgery is uncommon option. We demonstrate our long term follow up results. Aim: To evaluate long term efficacy of a 980nm diode laser for the difficult-to-treat basal cell carcinoma. Materials and Methods: 167 patients with 173 basal cell carcinoma on the nose were treated with a 980 nm diode laser from May 1999 till May 2005 at Latvian Oncology center. All tumors were morphologically confirmed. 156 patients were followed for more than 5 years. Results: The lowest recurrence rate was observed in cases of superficial BCC, diameter<6mm bet the highest recurrence rate was in cases of infiltrative BCC and nodular recurrent BCC. Conclusions: 980 nm diode laser is useful tool in dermatology with high long term efficacy, good acceptance by the patients and good cosmetics results.

  8. Basal cell carcinoma vs basaloid squamous cell carcinoma of the skin: an immunohistochemical reappraisal.

    PubMed

    Webb, David V; Mentrikoski, Mark J; Verduin, Lindsey; Brill, Louis B; Wick, Mark R

    2015-04-01

    Typical cutaneous basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are morphologically dissimilar. It is well known, however, that poorly differentiated SCC may assume a basaloid phenotype, complicating the histologic distinction between these 2 neoplasms. Selected immunohistochemical stains have been used in the past to aid in that differential diagnosis. In the current study, additional markers were evaluated to determine whether they would be helpful in that regard. Twenty-nine cases of metatypical (squamoid) BCC (MBCC) and 25 examples of basaloid SCC (BSCC) were studied using the antibodies Ber-EP4 and MOC-31 as well as a plant lectin preparation from Ulex europaeus I (UEA-1). The resulting immunostains were interpreted independently by 3 pathologists, and the results showed that MBCCs demonstrated strong and diffuse staining for Ber-EP4 (25/29) and MOC-31 (29/29). In contrast, BSCCs tended to be only sporadically reactive for both markers (4/25 and 1/25 cases, respectively). Labeling for UEA-1 was observed in almost all BSCCs (24/25), but only 6 of 29 cases of MBCC showed limited, focal staining with that lectin. These data suggest that MOC-31 is a useful marker in the specified differential diagnosis, especially when used together with UEA-1.

  9. Basaloid squamous cell carcinoma with 'monster' cells: a mimic of pleomorphic basal cell carcinoma.

    PubMed

    Defty, Clare L; Segen, Joseph; Carter, Jonathan J; Ahmed, Imtiaz; Carr, Richard A

    2011-04-01

    Pleomorphic giant or 'monster' cells represent a well-recognized yet uncommon finding associated with basal cell carcinoma (BCC), usually of nodular type. We present a case of basaloid squamous cell carcinoma (basaloid SCC) with 'monster' cells that closely mimicked those described in pleomorphic nodular BCC. Clinically, the lesion presented as a fleshy, hyperkeratotic nodule in an 82-year-old woman. Histopathology revealed a basaloid lesion with lobulated borders and focal retraction artifact but a lack of prominent palisading or stromal mucin. There were areas of necrosis and small foci of keratinization. Striking bizarre monstrous pleomorphic nuclei were widely scattered throughout the lesion. Ber-EP4 immunohistochemistry proved to be negative and epithelial membrane antigen (EMA) expression was moderate to strong in 70% of the basaloid epithelium. Monster cells have not previously been highlighted in cutaneous SCC or in its uncommon cutaneous basaloid variant. The prognostic significance of monster cells is unknown but, given the relative paucity of keratinization in basaloid SCC, these lesions should probably be regarded as poorly differentiated. We have not previously encountered an SCC that so closely resembles nodular BCC with pleomorphic monster cells and believe that this is the first such report in the literature.

  10. Expression of p75 neurotrophin receptor in desmoplastic trichoepithelioma, infiltrative basal cell carcinoma, and microcystic adnexal carcinoma.

    PubMed

    Jedrych, Jaroslaw; McNiff, Jennifer M

    2013-05-01

    The histological discrimination between desmoplastic trichoepithelioma, infiltrative basal cell carcinoma, and microcystic adnexal carcinoma encountered in small biopsies is challenging when only morphological criteria are applied. The objective of this study is to test the use of p75 neurotrophin receptor (p75NTR) as an adjunct aid in classification of these tumors. Immunohistochemistry for p75NTR antigen was performed on routinely processed biopsies of 37 desmoplastic trichoepitheliomas, 11 infiltrative basal cell carcinomas, and 9 microcystic adnexal carcinomas diagnosed by morphological criteria in conjunction with results of CK20 immunostains. Cases were analyzed for the extent and intensity of p75NTR expression. Diffuse immunoreactivity was defined as involving >90% of tumor cells. Of the 37 desmoplastic trichoepitheliomas, 35 (94%) displayed strong diffuse immunoreactivity of tumor cells, proving high sensitivity of the marker to detect this tumor. However, despite the fact that diffuse p75NTR expression reached statistical significance in differentiating desmoplastic trichoepithelioma from infiltrative basal cell carcinoma (Fisher exact test P < 0.0001) and microcystic adnexal carcinoma (P < 0.0016), specificity of the stain is unsatisfactory because strong diffuse expression of p75NTR by neoplastic cells was observed in 4 (36%) cases of infiltrative basal cell carcinomas and 4 (44%) cases of microcystic adnexal carcinoma. This study demonstrates a significant difference in p75NTR expression in selected sclerosing neoplasms of the skin. Nevertheless, the practical value of p75NTR as an adjunct marker in the differential diagnosis of these tumors seems to be limited because of significant overlap in amount of p75NTR immunoreactivity.

  11. Systemic treatments for basal cell carcinoma (BCC): the advent of dermato-oncology in BCC.

    PubMed

    Ali, F R; Lear, J T

    2013-07-01

    Basal cell carcinoma (BCC) is the most common cancer in the U.K. and its incidence is increasing. Vismodegib, a hedgehog pathway inhibitor, has recently been licensed by the U.S. Food and Drug Administration for treatment of advanced BCC. Phase 2 trials have demonstrated efficacy in cases of locally advanced and metastatic BCC, as well as cases of hereditary basal cell naevus (Gorlin) syndrome. Side-effects are frequent and considerable and include myalgia, taste disturbance, alopecia, weight loss and fatigue. Further research is needed to investigate means of circumventing these side-effects, and longitudinal data are required to assess the long-term benefits of, and the nature of resistance to, this novel class of agents. Alternative hedgehog inhibitors are currently in clinical development. We review the current data pertaining to this novel treatment modality and discuss its likely future role in the management of BCC.

  12. A massive neglected giant basal cell carcinoma in a schizophrenic patient treated successfully with vismodegib.

    PubMed

    Andersen, Rosa Marie; Lei, Ulrikke

    2015-01-01

    The small molecule vismodegib is a great treatment alternative to patients challenged, e.g. psychiatric disorders, suffering from severe basal cell carcinoma of the skin in which surgery or other treatment modalities is not possible because of patient's wish or condition. We present a case of a 73-year-old schizophrenic patient with a 15-year history of a neglected tumour located at the forehead and scalp, admitted to hospital in a state of inanition because of tumour expansion to the meninges and severe anaemia caused by bleeding, treated successfully with vismodegib.

  13. Confocal and dermoscopic features of basal cell carcinoma in Gorlin-Goltz syndrome: A case report.

    PubMed

    Casari, Alice; Argenziano, Giuseppe; Moscarella, Elvira; Lallas, Aimilios; Longo, Caterina

    2016-01-14

    Gorlin-Goltz (GS) syndrome is an autosomal dominant disease linked to a mutation in the PTCH gene. Major criteria include the onset of multiple basal cell carcinoma (BCC), keratocystic odontogenic tumours in the jaws and bifid ribs. Dermoscopy and reflectance confocal microscopy represent imaging tools that are able to increase the diagnostic accuracy of skin cancer in a totally noninvasive manner, without performing punch biopsies. Here we present a case of a young woman in whom the combined approach of dermoscopy and RCM led to the identification of multiple small inconspicuous lesions as BCC and thus to the diagnosis of GS syndrome.

  14. Giant Anterior Chest Wall Basal Cell Carcinoma: An Approach to Palliative Reconstruction

    PubMed Central

    Prendergast, Christina; Leis, Amber

    2016-01-01

    Anterior chest wall giant basal cell carcinoma (GBCC) is a rare skin malignancy that requires a multidisciplinary treatment approach. This case report demonstrates the challenges of anterior chest wall GBCC reconstruction for the purpose of palliative therapy in a 72-year-old female. Surgical resection of the lesion included the manubrium and upper four ribs. The defect was closed with bilateral pectoral advancement flaps, FlexHD, and pedicled VRAM. The palliative nature of this case made hybrid reconstruction more appropriate than rigid sternal reconstruction. In advanced metastatic cancers, the ultimate goals should be to avoid risk for infection and provide adequate coverage for the defect. PMID:28083152

  15. Vismodegib: a promising drug in the treatment of basal cell carcinomas.

    PubMed

    Dirix, Luc; Rutten, Annemie

    2012-08-01

    Hedgehog pathway signaling is important for embryonic development; however, inappropriate reactivation of this pathway in adults has been linked to several forms of cancer. Vismodegib (Erivedge™), a first-in-class hedgehog pathway inhibitor, blocks the pathway by inhibiting the activity of the signaling protein SMO. Preclinical studies have provided promising indications of potential tumor-reducing activity in several cancers. Thus far, clinical pharmacology and Phase I studies have demonstrated the unique pharmacokinetic profile of vismodegib, its efficacy in certain types of tumors and a generally tolerable adverse-event profile. A pivotal Phase II clinical trial confirmed the favorable benefit:risk profile of vismodegib in advanced basal cell carcinoma.

  16. Analysis and diagnosis of basal cell carcinoma (BCC) via infrared imaging

    NASA Astrophysics Data System (ADS)

    Flores-Sahagun, J. H.; Vargas, J. V. C.; Mulinari-Brenner, F. A.

    2011-09-01

    In this work, a structured methodology is proposed and tested through infrared imaging temperature measurements of a healthy control group to establish expected normality ranges and of basal cell carcinoma patients (a type of skin cancer) previously diagnosed through biopsies of the affected regions. A method of conjugated gradients is proposed to compare measured dimensionless temperature difference values (Δ θ) between two symmetric regions of the patient's body, that takes into account the skin, the surrounding ambient and the individual core temperatures and doing so, the limitation of the results interpretation for different individuals become simple and nonsubjective. The range of normal temperatures in different regions of the body for seven healthy individuals was determined, and admitting that the human skin exhibits a unimodal normal distribution, the normal range for each region was considered to be the mean dimensionless temperature difference plus/minus twice the standard deviation of the measurements (Δθ±2σ) in order to represent 95% of the population. Eleven patients with previously diagnosed basal cell carcinoma through biopsies were examined with the method, which was capable of detecting skin abnormalities in all cases. Therefore, the conjugated gradients method was considered effective in the identification of the basal cell carcinoma through infrared imaging even with the use of a low optical resolution camera (160 × 120 pixels) and a thermal resolution of 0.1 °C. The method could also be used to scan a larger area around the lesion in order to detect the presence of other lesions still not perceptible in the clinical exam. However, it is necessary that a temperature differences mesh-like mapping of the healthy human body skin is produced, so that the comparison of the patient Δ θ could be made with the exact region of such mapping in order to possibly make a more effective diagnosis. Finally, the infrared image analyzed through the

  17. Sonidegib, a novel smoothened inhibitor for the treatment of advanced basal cell carcinoma.

    PubMed

    Doan, Hung Q; Silapunt, Sirunya; Migden, Michael R

    2016-01-01

    Basal cell carcinoma (BCC) is the most common nonmelanoma skin cancer. If left untreated, BCCs can become locally aggressive or even metastasize. Currently available treatments include local destruction, surgery, and radiation. Systemic options for advanced disease are limited. The Hedgehog (Hh) pathway is aberrantly activated in a majority of BCCs and in other cancers. Hh pathway inhibitors are targeted agents that inhibit the aberrant activation of the Hh pathway, with smoothened being a targeted component. Sonidegib is a novel smoothened inhibitor that was recently approved by the US Food and Drug Administration. This review focuses on BCC pathogenesis and the clinical efficacy of sonidegib for the treatment of advanced BCC.

  18. Facial Basal Cell Carcinoma Treated with Topical 5% Imiquimod Cream with Dermoscopic Evaluation

    PubMed Central

    Singal, Archana; Daulatabad, Deepashree; Pandhi, Deepika; Arora, VK

    2016-01-01

    Basal cell carcinoma (BCC) is the most common skin cancer worldwide. Surgical excision is considered to be the primary therapeutic modality wherever possible. For inoperable cases, 5% imiquimod seems to be a good alternative. We present two cases of nodular pigmented BCCs on the face in elderly women successfully treated with 5% imiquimod cream application resulting in complete clinical clearance of lesion as well as on histology and dermatoscopy. There was no recurrence of the lesion on 2 years follow-up for the first and 1.5 years for the second patient. PMID:27398014

  19. Sonidegib, a novel smoothened inhibitor for the treatment of advanced basal cell carcinoma

    PubMed Central

    Doan, Hung Q; Silapunt, Sirunya; Migden, Michael R

    2016-01-01

    Basal cell carcinoma (BCC) is the most common nonmelanoma skin cancer. If left untreated, BCCs can become locally aggressive or even metastasize. Currently available treatments include local destruction, surgery, and radiation. Systemic options for advanced disease are limited. The Hedgehog (Hh) pathway is aberrantly activated in a majority of BCCs and in other cancers. Hh pathway inhibitors are targeted agents that inhibit the aberrant activation of the Hh pathway, with smoothened being a targeted component. Sonidegib is a novel smoothened inhibitor that was recently approved by the US Food and Drug Administration. This review focuses on BCC pathogenesis and the clinical efficacy of sonidegib for the treatment of advanced BCC. PMID:27695345

  20. Concurrent Paget’s disease and basal cell carcinoma of the vulva; a case report

    PubMed Central

    Abdelbaqi, Maisoun; Shackelford, Rodney E; Quigley, Brian C; Hakam, Ardeshir

    2012-01-01

    An 82-year-old Caucasian woman had a long-standing history of recurrent Paget’s disease of the right perianal region that was documented by multiple skin biopsies. Histological examination of a skin biopsy from an erythematous raised right perianal area revealed large rounded cells with ample pale staining cytoplasm scattered throughout the epidermis in multifocal nests and a flattened basal layer. A second lesion showed tongues of basaloid cells with peripheral palisading in continuity with the undersurface of the epidermis at multiple points. The individual tumor nests had cytoplasmic melanization and slit-like stromal separation. The tumor cells in the epidermis showed positive immunoreactivity for carcinoembryonic antigen while the basaloid cells were negative. A diagnosis of combined vulvar Paget’s disease and basal cell carcinoma of an infundibulocystic type was rendered. Concurrent involvement of the same area by Paget’s disease and Basal cell carcinoma (BCC) has been reported only once. Here we report a second case of BCC concurrent with vulvar Paget’s disease. PMID:22949943

  1. Detection of Basal Cell Carcinoma Using Color and Histogram Measures of Semitranslucent Areas

    PubMed Central

    Stoecker, William V.; Gupta, Kapil; Shrestha, Bijaya; Wronkiewiecz, Mark; Chowdhury, Raeed; Stanley, R. Joe; Xu, Jin; Moss, Randy H.; Celebi, M. Emre; Rabinovitz, Harold S.; Oliviero, Margaret; Malters, Joseph M.; Kolm, Isabel

    2009-01-01

    Background Semitranslucency, defined as a smooth, jelly-like area with varied, near-skin-tone color, can indicate a diagnosis of basal cell carcinoma (BCC) with high specificity. This study sought to analyze potential areas of semitranslucency with histogram-derived texture and color measures to discriminate BCC from non-semitranslucent areas in non-BCC skin lesions. Methods For 210 dermoscopy images, the areas of semitranslucency in 42 BCCs and comparable areas of smoothness and color in 168 non-BCCs were selected manually. Six color measures and six texture measures were applied to the semitranslucent areas of the BCC and the comparable areas in the non-BCC images. Results Receiver operating characteristic (ROC) curve analysis showed that the texture measures alone provided greater separation of BCC from non-BCC than the color measures alone. Statistical analysis showed that the four most important measures of semitranslucency are three histogram measures: contrast, smoothness, and entropy, and one color measure: blue chromaticity. Smoothness is the single most important measure. The combined 12 measures achieved a diagnostic accuracy of 95.05% based on area under the ROC curve. Conclusion Texture and color analysis measures, especially smoothness, may afford automatic detection of basal cell carcinoma images with semitranslucency. PMID:19624424

  2. Safety and efficacy of vismodegib in patients aged ≥65 years with advanced basal cell carcinoma.

    PubMed

    Chang, Anne Lynn S; Lewis, Karl D; Arron, Sarah T; Migden, Michael R; Solomon, James A; Yoo, Simon; Day, Bann-Mo; McKenna, Edward F; Sekulic, Aleksandar

    2016-11-15

    Because many patients with unresectable basal cell carcinoma (BCC) are aged ≥65 years, this study explores the efficacy and safety of vismodegib in these patients with locally advanced (la) or metastatic (m) basal cell carcinoma (BCC) in the ERIVANCE BCC trial and the expanded access study (EAS).We compared patients aged ≥65 years to patients aged <65 years taking vismodegib 150 mg/day, using descriptive statistics for response and safety. Patients aged ≥65 years (laBCC/mBCC) were enrolled in ERIVANCE BCC (33/14) and EAS (27/26). Investigator-assessed best overall response rate in patients ≥65 and <65 years was 46.7%/35.7% and 72.7%/52.6% (laBCC/mBCC), respectively, in ERIVANCE BCC and 45.8%/33.3% and 46.9%/28.6%, respectively, in EAS. These differences were not clinically meaningful. Safety was similar in both groups, although those aged ≥65 years had a higher percentage of grade 3-5 adverse events than those aged <65 years. Vismodegib demonstrated similar clinical activity and adverse events regardless of age.

  3. Safety and efficacy of vismodegib in patients aged ≥65 years with advanced basal cell carcinoma

    PubMed Central

    Chang, Anne Lynn S.; Lewis, Karl D.; Arron, Sarah T.; Migden, Michael R.; Solomon, James A.; Yoo, Simon; Day, Bann-Mo; McKenna, Edward F.; Sekulic, Aleksandar

    2016-01-01

    Because many patients with unresectable basal cell carcinoma (BCC) are aged ≥65 years, this study explores the efficacy and safety of vismodegib in these patients with locally advanced (la) or metastatic (m) basal cell carcinoma (BCC) in the ERIVANCE BCC trial and the expanded access study (EAS).We compared patients aged ≥65 years to patients aged <65 years taking vismodegib 150 mg/day, using descriptive statistics for response and safety. Patients aged ≥65 years (laBCC/mBCC) were enrolled in ERIVANCE BCC (33/14) and EAS (27/26). Investigator-assessed best overall response rate in patients ≥65 and <65 years was 46.7%/35.7% and 72.7%/52.6% (laBCC/mBCC), respectively, in ERIVANCE BCC and 45.8%/33.3% and 46.9%/28.6%, respectively, in EAS. These differences were not clinically meaningful. Safety was similar in both groups, although those aged ≥65 years had a higher percentage of grade 3-5 adverse events than those aged <65 years. Vismodegib demonstrated similar clinical activity and adverse events regardless of age. PMID:27764798

  4. An unusual infiltrative basal cell carcinoma with osteoclastic stromal changes mimicking carcinosarcoma: a case report.

    PubMed

    Gamsizkan, Mehmet; Naujokas, Agne; Simsek, Hasan Aktug; McCalmont, Timothy H

    2015-01-01

    A 91-year-old man presented with an ulcerated nodule on his left lower eyelid. The tumor showed an epithelial component composed of basaloid and clear cells and a stroma that contained many osteoclastic giant cells. Strong, diffuse expression for cytokeratin 17 and p63 was noted in the epithelial component, whereas no staining was present in the sarcomatoid stroma, suggesting that the osteoclast-rich stromal component represented an unusual benign stromal reaction to the carcinoma rather than a manifestation of carcinosarcoma. Further supporting this interpretation was the absence of mitotic figures and low Ki-67 proliferation index (of approximately 1%) in the stromal cells. We herein reported a case of unusual infiltrative basal cell carcinoma, accompanied by a clear cell carcinomatous features and concurrent benign osteoclastic stromal changes.

  5. Hybrid image representation learning model with invariant features for basal cell carcinoma detection

    NASA Astrophysics Data System (ADS)

    Arevalo, John; Cruz-Roa, Angel; González, Fabio A.

    2013-11-01

    This paper presents a novel method for basal-cell carcinoma detection, which combines state-of-the-art methods for unsupervised feature learning (UFL) and bag of features (BOF) representation. BOF, which is a form of representation learning, has shown a good performance in automatic histopathology image classi cation. In BOF, patches are usually represented using descriptors such as SIFT and DCT. We propose to use UFL to learn the patch representation itself. This is accomplished by applying a topographic UFL method (T-RICA), which automatically learns visual invariance properties of color, scale and rotation from an image collection. These learned features also reveals these visual properties associated to cancerous and healthy tissues and improves carcinoma detection results by 7% with respect to traditional autoencoders, and 6% with respect to standard DCT representations obtaining in average 92% in terms of F-score and 93% of balanced accuracy.

  6. Excision repair of pyrimidine dimers induced by simulated solar radiation in the skin of patients with basal cell carcinoma

    SciTech Connect

    Alcalay, J.; Freeman, S.E.; Goldberg, L.H.; Wolf, J.E. )

    1990-11-01

    One prominent lesion induced in DNA by ultraviolet (UV) radiation is the cyclobutyl pyrimidine dimer formed between adjacent pyrimidines on the same DNA strand. We investigated whether people who have developed basal cell carcinoma on sun-exposed skin have an altered ability to repair UV-induced pyrimidine dimers in DNA. Twenty-two patients with at least one basal cell carcinoma, aged 31-84 years, and 19 healthy volunteers, aged 25-61 years, took part in the study. Both groups were given one minimal erythema dose (MED) of simulated solar radiation on the lower back. DNA was extracted from the irradiated skin 0 to 6 h later, and the number of UV-induced pyrimidine dimers was determined using a dimer-specific endonuclease. At time 0, the average number of dimers per unit of DNA was similar in the two groups. After 6 h, an average of 22 +/- 4% of the dimers were removed in the group with basal cell carcinoma compared to 33 +/- 4% in the cancer-free group. In the basal cell carcinoma group, only 23% of the patients repaired more than 30% of the dimers after 6 h, compared with 53% of the cancer-free subjects (p less than 0.05). We conclude that patients who develop basal cell carcinoma on sun-exposed skin may have a decreased ability to repair pyrimidine dimers induced in skin exposed to simulated solar radiation.

  7. Isolation (from a basal cell carcinoma) of a functionally distinct fibroblast-like cell type that overexpresses Ptch.

    PubMed

    Dicker, Anthony J; Serewko, Magdalena M; Russell, Terry; Rothnagel, Joseph A; Strutton, Geoff M; Dahler, Alison L; Saunders, Nicholas A

    2002-05-01

    In this study we report on the isolation and characterization of a nonepithelial, nontumorigenic cell type (BCC1) derived from a basal cell carcinoma from a patient. The BCC1 cells share many characteristics with dermal fibroblasts, such as the expression of vimentin, lack of expression of cytokeratins, and insensitivity to agents that cause growth inhibition and differentiation of epithelial cells; however, significant differences between BCC1 cells and fibroblasts also exist. For example, BCC1 cells are stimulated to undergo DNA synthesis in response to interferon-gamma, whereas dermal fibroblasts are not. More over, BCC1 cells overexpress the basal cell carcinoma-specific genes ptch and ptch2. These data indicate that basal cell carcinomas are associated with a functionally distinct population of fibroblast-like cells that overexpress known tumor-specific markers (ptch and ptch2).

  8. Comparison between mALA- and ALA-PDT in the treatment of basal cell carcinomas

    NASA Astrophysics Data System (ADS)

    Schleier, Peter; Zenk, Witold; Hyckel, Peter; Berndt, Alexander

    2006-02-01

    Introduction: The external application of aminoleavulinic acid (ALA), which is a substrate of physiologic cell metabolism, represents a possible treatment option in superficial basal cell carcinomas (BCC). The development of new ALA-esters (mALA) with potential for higher penetration depths promises higher therapeutic success. This research aimed to prove the following hypothesis: The cytotoxic effect of the mALA- photodynamic therapy (mALA-PDT), when compared to the ALA-PDT, leads to a higher clinical success rate. Material and Methods: 24 patients with multiple facial tumors, after having received several local surgical excisions with known histology, were treated with either ALA- or mALA-PDT, during the past two years. In total, 89 basal cell carcinoma, 45 actinic keratoses, 6 keratoacanthoma, and 2 squamous cell carcinomas were treated. ALA-PDT: A thermo gel with 40 % mALA or ALA was applied from a cooled syringe. Three to five hours after gel application the skin was cleaned from any gel residues. Irradiation was done with a diode laser and was performed in two sessions, each 10 min long. After intervals of 2, 4 and 12 weeks, the patients were recalled to assess therapeutic efficacy. This was followed by photographic documentation. Results: More than 80% of the tumors treated primarily were resolved successfully. A recurrence rate of approximately 15% was observed. Three per cent of the tumors showed no reaction to therapy. There were no statistically significant differences between the two therapeutic groups. Discussion: The advantage of the use of ALA lies foremost in the fast metabolic use of the body's own photosensitizer PpIX. There are no known side effects of this therapy. Moreover, external application is superior to systemic application with regard to patient management. The method can be combined with other therapies. Although the mALA should have a better penetration in tumor tissue, the therapeutic outcome is similar to the use of ALA.

  9. GREM1 is expressed in the cancer-associated myofibroblasts of basal cell carcinomas

    PubMed Central

    Kim, Hye Sung; Shin, Myung Soo; Cheon, Min Seok; Kim, Jae Wang; Lee, Cheol; Kim, Woo Ho; Kim, Young Sill

    2017-01-01

    Cancer-associated fibroblasts (CAFs) play important roles in cancer progression through their complex interactions with cancer cells. The secreted bone morphogenetic protein antagonist, gremlin1 (GREM1) is expressed by the CAFs of basal cell carcinomas (BCCs), and promotes the growth of cancer cells. In this study, we investigated the expression of GREM1 mRNAs in various benign and malignant skin tumors, including various BCC subtypes. Analysis by RNA in situ hybridization (ISH) revealed that fibroblasts in the scar tissue expressed GREM1 and α-smooth muscle actin (α-SMA), whereas resident fibroblasts in the dermis of the normal skin did not express GREM1. Real-time polymerase chain reaction analysis showed significantly higher GREM1 expression in skin cancers and pilomatricomas (PMCs) than in other benign skin tumors. Tissue microarrays analyzed by RNA ISH for GREM1 expression also demonstrated that 23% of BCCs, 42% of squamous cell carcinomas, 20% of melanomas, and 90% of PMCs were positive for GREM1 expression, whereas trichoepitheliomas, eccrine poromas, hidradenomas, and spiradenomas were negative for GREM1 expression. Most BCCs that were GREM1 expression positive were of desmoplastic or mixed subtypes, and GREM1 expression was localized to activated myofibroblasts at the tumoral-stromal interface. Interestingly, most PMCs harbored GREM1-expressing fibroblasts, probably because of the inflammatory responses caused by foreign body reactions to keratin. Additionally, in BCCs, stromal GREM1 expression had a strong correlation with CD10 expression. In conclusion, GREM1 is frequently expressed by myofibroblasts in scars or in the stroma of basal cell carcinomas, suggesting that GREM1 expression can be a marker for activated myofibroblasts in the cancer stroma or in scar tissue. PMID:28346486

  10. Relation between sonic hedgehog pathway gene polymorphisms and basal cell carcinoma development in the Polish population.

    PubMed

    Lesiak, Aleksandra; Sobolewska-Sztychny, Dorota; Majak, Paweł; Sobjanek, Michał; Wodz, Karolina; Sygut, Karolina Przybyłowska-; Majsterek, Ireneusz; Wozniacka, Anna; Narbutt, Joanna

    2016-01-01

    In recent decades, increases have been observed in the incidence of nonmelanoma skin cancers, including basal cell carcinoma (BCC) and squamous cell carcinoma. BCC is the most common neoplasm in Caucasian populations. Sonic hedgehog (Shh) pathway impairment plays a key role in BCC pathogenesis, and there is evidence that Shh pathway genetic variations may predispose to BCC development. We genotyped 22 single-nucleotide polymorphisms (SNPs) in 4 Shh pathway genes: SHH, GLI, SMO, and PTCH. The study group consisted of 142 BCC patients and 142 age-matched, sex-matched healthy subjects (controls). SNPs were assessed using the PCR-RFLP method. The genotype distribution for the polymorphisms in the rs104894049 331 A/T SHH, rs104894040 349 T/C SHH, and rs41303402 385 G/A SMO genes differed significantly between the BCC patients and the controls. The presence of CC genotype in the SHH rs104894040 349 T/C polymorphism was linked to the highest risk of BCC development (OR 87.9, p < 0.001). Other genotypes, such as the TT in SHH rs104894049 331 A/T and the GG in SMO rs41303402 385 G/A also statistically raised the risk of BCC, but these associations were weaker. Other investigated polymorphisms showed no statistical differences between patients and controls. The results obtained testify to the importance of the SHH and SMO gene polymorphisms in skin cancerogenesis. These results mainly underline the potential role of SHH3 rs104894040 349 T/C gene polymorphism in the development of skin basal cell carcinomas in patients of Polish origin.

  11. Diffuse large B-cell lymphoma mimicking advanced basal cell carcinoma.

    PubMed Central

    Akinyemi, Emmanuel; Mai, Le; Matin, Abu; Maini, Archana

    2007-01-01

    Primary cutaneous B-cell lymphomas (PCBCLs) are made up of a heterogenous group of B-cell lymphoproliferative diseases confined to the skin at the time of diagnosis with no evidence of extracutaneous involvement. With early diagnosis and adequate treatment, PCBCLs as a group has excellent prognosis, with about a 95% survival rate at five years. We report a case of diffuse large B-cell lymphoma (DLBCL) in a 52-year-old woman presenting as a fungating skin ulcer mimicking advanced basal cell carcinoma. Review of available literature showed most studies of PCBCLs being done on Europeans with no universally acceptable system of classification. Clinical findings, diagnostic evaluations and treatment outcomes of PCBCLs are discussed with emphasis on comparison of European Organization for Research and Treatment of Cancer (EORTC) and the World Health Organization (WHO) Classification of Neoplasms of the Hematopoietic and Lymphoid Tissue classification systems. Images Figure 1 Figure 2 PMID:17722675

  12. Diffuse large B-cell lymphoma mimicking advanced basal cell carcinoma.

    PubMed

    Akinyemi, Emmanuel; Mai, Le; Matin, Abu; Maini, Archana

    2007-08-01

    Primary cutaneous B-cell lymphomas (PCBCLs) are made up of a heterogenous group of B-cell lymphoproliferative diseases confined to the skin at the time of diagnosis with no evidence of extracutaneous involvement. With early diagnosis and adequate treatment, PCBCLs as a group has excellent prognosis, with about a 95% survival rate at five years. We report a case of diffuse large B-cell lymphoma (DLBCL) in a 52-year-old woman presenting as a fungating skin ulcer mimicking advanced basal cell carcinoma. Review of available literature showed most studies of PCBCLs being done on Europeans with no universally acceptable system of classification. Clinical findings, diagnostic evaluations and treatment outcomes of PCBCLs are discussed with emphasis on comparison of European Organization for Research and Treatment of Cancer (EORTC) and the World Health Organization (WHO) Classification of Neoplasms of the Hematopoietic and Lymphoid Tissue classification systems.

  13. Basal cell carcinoma with halo phenomenon in a young female: significance of dermatoscopy in early diagnosis.

    PubMed

    Basak, Pinar Yuksel; Meric, Gonca; Ciris, Metin

    2015-01-01

    Halo phenomenon of nevus may be observed as a circular reaction, although it is unusual around tumors. A 29-year-old woman presented with a pigmented lesion on the cheek since three years. She noted whitening of the skin around the lesion almost after a year following its appearance. Dermatologic examination revealed a pigmented nodular lesion with a hypopigmented halo on the left infraorbital region. The clinical impression was halo nevus, whereas basal cell carcinoma (BCC) was considered in dermatoscopic differential diagnosis. The diagnosis was infiltrative-type BCC histopathologically. The persistence of a perilesional halo around an enlarging pigmented lesion should be carefully examined with accompanying dermatoscopic findings even in young patients for early diagnosis of tumoral lesions.

  14. Basal Cell Carcinoma or Trichoblastoma? Dermoscopic Examination of Black Macules Developing in the Same Nevus Sebaceus

    PubMed Central

    Kitamura, Shinya; Hata, Hiroo; Imafuku, Keisuke; Shimizu, Hiroshi

    2016-01-01

    Nevus sebaceus (NS) is a common congenital birthmark, and various tumors have been reported to develop in NS. Basal cell carcinoma (BCC) seldom occurs in NS, and it is very important to be able to clinicopathologically distinguish BCC from trichoblastoma. Herein, we describe a case of BCC and trichoblastoma occurring simultaneously in the same NS, including the differential dermoscopic features. BCC is clinically difficult to distinguish from trichoblastoma because the clinical manifestations are similar. In a dermoscopic examination of BCC, arborizing vessels are one of the diagnostically significant features. In our case, the BCC showed ‘multiple’ black structures, and the trichoblastoma showed a ‘single’ black structure without arborizing vessels. To the best of our knowledge, there have been no reports on the dermoscopic findings of secondary tumors on NS. PMID:27293402

  15. Multiple facial basal cell carcinomas in xeroderma pigmentosum treated with topical imiquimod 5% cream.

    PubMed

    Yang, Jian-Qiang; Chen, Xian-Yu; Engle, Michelle Yixiao; Wang, Jian-You

    2015-01-01

    Xeroderma pigmentosum (XP) is an autosomal recessive disease characterized by solar sensitivity, photophobia, early onset of freckling, and solar-induced cutaneous neoplastic changes. Management of patients with XP is a therapeutic challenge as they usually develop multiple cutaneous malignancies, making surgical therapy difficult, and continue to form skin malignancies at a high rate. We describe a 30-year-old Chinese man with XP who had been previously treated with excision and dermatoplasty. Upon recurrence of multiple superficial, ulcerative, and pigmented lesions, imiquimod 5% cream was recommended for 4 months. His multiple facial lesions demonstrated an excellent response to topical imiquimod 5% cream with minor side effects. This favorable response indicates that topical application of imiquimod 5% cream is an effective means of treating multiple basal cell carcinomas in XP.

  16. Treatment of basal cell carcinoma of the nasal pyramid with intralesional interferon alfa-2b.

    PubMed

    Fernández-Vozmediano, José Manuel; Armario-Hita, José Carlos

    2010-04-01

    For patients with basal cell carcinoma (BCC) in whom surgical intervention is not optimal, local treatment with interferon alfa-2b is an alternative. In this study, patients with BCC of the nasal pyramid were treated with intralesional interferon alfa-2b (five million international units three times per week) for four to eight weeks. Cutaneous biopsies were performed before and after treatment for histologic examination. Twelve patients, primarily with the infiltrative histologic form (80%), were treated. Complete clinical and histologic regression was confirmed in all cases, and the aesthetic results were excellent. After four years' follow-up, no tumor persistence was observed in any patient. The most frequent adverse events were transient, mild-to-moderate flu-like symptoms in 95% of patients and asymptomatic leukopenia or neutropenia in 25%. These results suggest that intralesional interferon alfa-2b is a safe and effective nonsurgical alternative approach to treat BCC of the nasal pyramid.

  17. Involvement of p16 and PTCH in pathogenesis of melanoma and basal cell carcinoma.

    PubMed

    Cretnik, Maja; Poje, Gorazd; Musani, Vesna; Kruslin, Bozo; Ozretic, Petar; Tomas, Davor; Situm, Mirna; Levanat, Sonja

    2009-04-01

    The involvement of two tumor suppressors p16 and Ptch in pathogenesis of cutaneous melanomas and basal cell carcinomas (BCCs) was studied through expression of Ptch and p16 and genetic alterations in 9p21 region (p16) and in 9q22.3 region (PTCH) of chromosome 9. Immunohistochemical analyses of paraffin-embedded tissues with Ptch and p16 antibodies, typing for 9q22-q31 and 9p21 region with polymorphic markers and p16 and Ptch mutation detection was done. Higher expression of p16 and Ptch in melanoma and BCC of the skin was frequently detected in studied cases. However, allelic loss of PTCH region occurs more frequently in BCCs than loss of heterozygosity of p16 region. Both types of tumors, BCCs and melanomas, suggest involvement of Hh-Gli signaling pathway, but using different mechanisms.

  18. Superficial basal cell carcinoma treated with 70% trichloroacetic acid applied topically: a case study

    PubMed Central

    Chiriac, Anca; Brzezinski, Piotr; Moldovan, Cosmin; Podoleanu, Cristian; Coros, Marius Florin; Stolnicu, Simona

    2017-01-01

    Background Basal cell carcinoma (BCC) is the most common form of skin cancer, affecting millions of people worldwide. The treatment concept for BCCs is the surgical one, but it is costly, as such, searching for alternative medical therapeutics is justified. Aim To highlight the efficacy of high concentration (70%) trichloroacetic acid (TCA) as a choice therapy for low-risk BCC. Method and patient Authors present, for the first time, the use of a high concentration TCA applied once a week for 2 consecutive weeks with a toothpick, on a patient with BCC on the right preauricular area. Results On examination 4 weeks later, the lesion was not clinically and dermatoscopically evidenced. Conclusion High concentration TCA could be an effective and safe, non-invasive choice of therapy for low-risk BCC, easy to perform, not expensive, with good cosmetic results, especially for patients who are not likely to undergo invasive or expensive treatments. PMID:28260938

  19. Vismodegib: the first drug approved for advanced and metastatic basal cell carcinoma.

    PubMed

    Dubey, A K; Dubey, S; Handu, S S; Qazi, M A

    2013-01-01

    Treatment of basal cell carcinoma (BCC) usually involves surgical interventions and laser ablation, but in locally advanced BCC, which arise either from earlier untreated lesions or from recurrence of aggressive BCC, surgery and radiotherapy are not helpful. Vismodegib, the first oral-targeted therapy for locally advanced and metastatic BCC, unsuitable for surgery or radiotherapy, was recently approved by US Food and Drug Administration (FDA). The drug was under the priority review program of FDA and was approved on the basis of promising results of phase II trial. Vismodegib acts by targeting the hedgehog pathway, which is activated abnormally in most BCCs. Approval of vismodegib is a big step ahead in the treatment of advanced BCC, where there was no other effective drug therapy till now.

  20. Identifying locally advanced basal cell carcinoma eligible for treatment with vismodegib: an expert panel consensus.

    PubMed

    Peris, Ketty; Licitra, Lisa; Ascierto, Paolo A; Corvò, Renzo; Simonacci, Marco; Picciotto, Franco; Gualdi, Giulio; Pellacani, Giovanni; Santoro, Armando

    2015-01-01

    Basal cell carcinoma (BCC) is the most common skin cancer worldwide. Most occur on the head and neck, where cosmetic and functional outcomes are critical. BCC can be locally destructive if not diagnosed early and treated appropriately. Surgery is the treatment of choice for the majority of high-risk lesions. Aggressive, recurrent or unresectable tumors can be difficult to manage. Until recently, no approved systemic therapy was available for locally advanced or metastatic BCC inappropriate for surgery or radiotherapy. Vismodegib provides a systemic treatment option. However, a consensus definition of advanced BCC is lacking. A multidisciplinary panel with expertise in oncology, dermatology, dermatologic surgery and radiation oncology proposes a consensus definition based on published evidence and clinical experience.

  1. Vismodegib in the treatment of basal cell carcinoma: indications for clinical practice.

    PubMed

    Calzavara Pinton, Piergiacomo; Licitra, Lisa; Peris, Katia; Santoro, Armando; Ascierto, Paolo Antonio

    2015-01-01

    Basal cell carcinoma (BCC) is a frequent skin cancer which can cause substantial morbidity due to its location on the face, its frequency of relapse and its capacity to invade local tissues. The primary treatment of BCC usually involves surgery or radiotherapy. In patients who have exhausted surgical and radiotherapy options or with metastatic BCC, guidelines recommend the use of the Hedgehog pathway inhibitor vismodegib. This molecule is indicated for the treatment of adults with metastatic BCC, or with locally advanced BCC which has recurred following surgery or who are not eligible to surgery or radiation. This paper aims to provide suggestions on the optimal management of BCC patients treated with vismodegib in clinical practice, according to the large experience gained by a group of Italian dermatologists and oncologists. In particular, the focus of this paper will be on the monitoring of patients and the management of adverse events.

  2. Depletion of cutaneous macrophages and dendritic cells promotes growth of basal cell carcinoma in mice.

    PubMed

    König, Simone; Nitzki, Frauke; Uhmann, Anja; Dittmann, Kai; Theiss-Suennemann, Jennifer; Herrmann, Markus; Reichardt, Holger M; Schwendener, Reto; Pukrop, Tobias; Schulz-Schaeffer, Walter; Hahn, Heidi

    2014-01-01

    Basal cell carcinoma (BCC) belongs to the group of non-melanoma skin tumors and is the most common tumor in the western world. BCC arises due to mutations in the tumor suppressor gene Patched1 (Ptch). Analysis of the conditional Ptch knockout mouse model for BCC reveals that macrophages and dendritic cells (DC) of the skin play an important role in BCC growth restraining processes. This is based on the observation that a clodronate-liposome mediated depletion of these cells in the tumor-bearing skin results in significant BCC enlargement. The depletion of these cells does not modulate Ki67 or K10 expression, but is accompanied by a decrease in collagen-producing cells in the tumor stroma. Together, the data suggest that cutaneous macrophages and DC in the tumor microenvironment exert an antitumor effect on BCC.

  3. Locally advanced and metastatic basal cell carcinoma: molecular pathways, treatment options and new targeted therapies.

    PubMed

    Ruiz Salas, Veronica; Alegre, Marta; Garcés, Joan Ramón; Puig, Lluis

    2014-06-01

    The hedgehog (Hh) signaling pathway has been identified as important to normal embryonic development in living organisms and it is implicated in processes including cell proliferation, differentiation and tissue patterning. Aberrant Hh pathway has been involved in the pathogenesis and chemotherapy resistance of different solid and hematologic malignancies. Basal cell carcinoma (BCC) and medulloblastoma are two well-recognized cancers with mutations in components of the Hh pathway. Vismodegib has recently approved as the first inhibitor of one of the components of the Hh pathway (smoothened). This review attempts to provide current data on the molecular pathways involved in the development of BCC and the therapeutic options available for the treatment of locally advanced and metastatic BCC, and the new targeted therapies in development.

  4. Basal cell carcinoma preferentially arises from stem cells within hair follicle and mechanosensory niches.

    PubMed

    Peterson, Shelby C; Eberl, Markus; Vagnozzi, Alicia N; Belkadi, Abdelmadjid; Veniaminova, Natalia A; Verhaegen, Monique E; Bichakjian, Christopher K; Ward, Nicole L; Dlugosz, Andrzej A; Wong, Sunny Y

    2015-04-02

    Basal cell carcinoma (BCC) is characterized by frequent loss of PTCH1, leading to constitutive activation of the Hedgehog pathway. Although the requirement for Hedgehog in BCC is well established, the identity of disease-initiating cells and the compartments in which they reside remain controversial. By using several inducible Cre drivers to delete Ptch1 in different cell compartments in mice, we show here that multiple hair follicle stem cell populations readily develop BCC-like tumors. In contrast, stem cells within the interfollicular epidermis do not efficiently form tumors. Notably, we observed that innervated Gli1-expressing progenitors within mechanosensory touch dome epithelia are highly tumorigenic. Sensory nerves activate Hedgehog signaling in normal touch domes, while denervation attenuates touch dome-derived tumors. Together, our studies identify varying tumor susceptibilities among different stem cell populations in the skin, highlight touch dome epithelia as "hot spots" for tumor formation, and implicate cutaneous nerves as mediators of tumorigenesis.

  5. Photodynamic therapy of nodular basal cell carcinoma with multifiber contact light delivery.

    PubMed

    Thompson, Marcelo Soto; Andersson-Engels, Stefan; Svanberg, Sune; Johansson, T; Palsson, Sara; Bendsoe, Niels; Derjabo, A; Kapostins, J; Stenram, Unne; Spigulis, J; Svanberg, Katarina

    2006-01-01

    To overcome the limited treatment depth of superficial photodynamic therapy we investigate interstitial light delivery. In the present work the treatment light was delivered using a system in which three or six clear-cut fibers were placed in direct contact with the tumor area. This placement was thought to represent a step toward general purpose interstitial PDT. Twelve nodular basal cell carcinomas were treated employing delta-aminolevulinic acid and 635 nm laser irradiation. Fluorescence measurements were performed monitoring the buildup and subsequent bleaching of the produced sensitizer protoporphyrin IX. The treatment efficacy, judged at a 28-month follow-up, showed a 100% complete response. Two punch excisions at 7 months converted two partial responses to complete responses. One patient failed to appear at all follow-up sessions. The outcome of the treatments was comparable to superficial photodynamic therapy in terms of histological, clinical, and cosmetic results.

  6. Genome-wide association study identifies 14 novel risk alleles associated with basal cell carcinoma

    PubMed Central

    Chahal, Harvind S.; Wu, Wenting; Ransohoff, Katherine J.; Yang, Lingyao; Hedlin, Haley; Desai, Manisha; Lin, Yuan; Dai, Hong-Ji; Qureshi, Abrar A.; Li, Wen-Qing; Kraft, Peter; Hinds, David A.; Tang, Jean Y.; Han, Jiali; Sarin, Kavita Y.

    2016-01-01

    Basal cell carcinoma (BCC) is the most common cancer worldwide with an annual incidence of 2.8 million cases in the United States alone. Previous studies have demonstrated an association between 21 distinct genetic loci and BCC risk. Here, we report the results of a two-stage genome-wide association study of BCC, totalling 17,187 cases and 287,054 controls. We confirm 17 previously reported loci and identify 14 new susceptibility loci reaching genome-wide significance (P<5 × 10−8, logistic regression). These newly associated SNPs lie within predicted keratinocyte regulatory elements and in expression quantitative trait loci; furthermore, we identify candidate genes and non-coding RNAs involved in telomere maintenance, immune regulation and tumour progression, providing deeper insight into the pathogenesis of BCC. PMID:27539887

  7. Smoothened variants explain the majority of drug resistance in basal cell carcinoma.

    PubMed

    Atwood, Scott X; Sarin, Kavita Y; Whitson, Ramon J; Li, Jiang R; Kim, Geurim; Rezaee, Melika; Ally, Mina S; Kim, Jinah; Yao, Catherine; Chang, Anne Lynn S; Oro, Anthony E; Tang, Jean Y

    2015-03-09

    Advanced basal cell carcinomas (BCCs) frequently acquire resistance to Smoothened (SMO) inhibitors through unknown mechanisms. Here we identify SMO mutations in 50% (22 of 44) of resistant BCCs and show that these mutations maintain Hedgehog signaling in the presence of SMO inhibitors. Alterations include four ligand binding pocket mutations defining sites of inhibitor binding and four variants conferring constitutive activity and inhibitor resistance, illuminating pivotal residues that ensure receptor autoinhibition. In the presence of a SMO inhibitor, tumor cells containing either class of SMO mutants effectively outcompete cells containing the wild-type SMO. Finally, we show that both classes of SMO variants respond to aPKC-ι/λ or GLI2 inhibitors that operate downstream of SMO, setting the stage for the clinical use of GLI antagonists.

  8. The first experience in estimation of basal cell carcinoma cryoresistence using noninvasive spectrophotometry

    NASA Astrophysics Data System (ADS)

    Andrukhina, V. V.; Litvinova, K. S.; Nikitin, A. A.; Spiridonova, N. Z.; Rogatkin, D. A.

    2009-10-01

    The urgency of BCC study affecting maxillofacial area and neck is not only caused by high prevalence of this disease, but also insufficient efficiency of existing treatment methods which lead to full or partial recovery only in 60-80% of cases. We analyzed the results of 198 BCC cases cryosurgical treatment. 33 (16,6%) patients showed continued tumor growth. It has been hypothesized that the behavior and character of microcirculation changes during patient's testing have to correlate with damaging rate of tumors that will allow to develop indications for surgical treatment with local destruction - cryosurgery or cryolaser treatment. We have tested the new group of 33 patients with primary and recurrence types of basal cell carcinoma (BCC) by means of Laser Doppler Flowmetry, Tissues Reflectance Oximetry, Laser Fluorescence Diagnostics before operation. It was shown that the microcirculatory data indicates the presence of cryoresistance.

  9. The first experience in estimation of basal cell carcinoma cryoresistence using noninvasive spectrophotometry

    NASA Astrophysics Data System (ADS)

    Andrukhina, V. V.; Litvinova, K. S.; Nikitin, A. A.; Spiridonova, N. Z.; Rogatkin, D. A.

    2010-02-01

    The urgency of BCC study affecting maxillofacial area and neck is not only caused by high prevalence of this disease, but also insufficient efficiency of existing treatment methods which lead to full or partial recovery only in 60-80% of cases. We analyzed the results of 198 BCC cases cryosurgical treatment. 33 (16,6%) patients showed continued tumor growth. It has been hypothesized that the behavior and character of microcirculation changes during patient's testing have to correlate with damaging rate of tumors that will allow to develop indications for surgical treatment with local destruction - cryosurgery or cryolaser treatment. We have tested the new group of 33 patients with primary and recurrence types of basal cell carcinoma (BCC) by means of Laser Doppler Flowmetry, Tissues Reflectance Oximetry, Laser Fluorescence Diagnostics before operation. It was shown that the microcirculatory data indicates the presence of cryoresistance.

  10. In vitro effects of tetraiodothyroacetic acid combined with X-irradiation on basal cell carcinoma cells.

    PubMed

    Leith, John T; Davis, Paul J; Mousa, Shaker A; Hercbergs, Aleck A

    2017-02-16

    We investigated radiosensitization in an untreated basal cell carcinoma (TE.354.T) cell line and post-pretreatment with tetraiodothyroacetic acid (tetrac) X 1 h at 37°C, 0.2 and 2.0 µM tetrac. Radioresistant TE.354.T cells were grown in modified medium containing fibroblast growth factor-2, stem cell factor-1 and a reduced calcium level. We also added reproductively inactivated (30 Gy) "feeder cells" to the medium. The in vitro doubling time was 34.1 h, and the colony forming efficiency was 5.09 percent. These results were therefore suitable for clonogenic radiation survival assessment. The 250 kVp X-ray survival curve of control TE.354.T cells showed linear-quadratic survival parameters of αX-ray = 0.201 Gy(-1) and βX-ray = 0.125 Gy(-2). Tetrac concentrations of either 0.2 or 2.0 µM produced αX-ray and βX-ray parameters of 2.010 and 0.282 Gy(-1) and 2.050 and 0.837 Gy(-2), respectively. The surviving fraction at 2 Gy (SF2) for control cells was 0.581, while values for 0.2 and 2.0 µM tetrac were 0.281 and 0.024. The SF2 data show that tetrac concentrations of 0.2 and 2.0 µM sensitize otherwise radioresistant TE.354.T cells by factors of 2.1 and 24.0, respectively. Thus, radioresistant basal cell carcinoma cells may be radiosensitized pharmacologically by exposure to tetrac.

  11. In vitro effects of tetraiodothyroacetic acid combined with X-irradiation on basal cell carcinoma cells

    PubMed Central

    Leith, John T.; Davis, Paul J.; Mousa, Shaker A.; Hercbergs, Aleck A.

    2017-01-01

    ABSTRACT We investigated radiosensitization in an untreated basal cell carcinoma (TE.354.T) cell line and post-pretreatment with tetraiodothyroacetic acid (tetrac) X 1 h at 37°C, 0.2 and 2.0 µM tetrac. Radioresistant TE.354.T cells were grown in modified medium containing fibroblast growth factor-2, stem cell factor-1 and a reduced calcium level. We also added reproductively inactivated (30 Gy) “feeder cells” to the medium. The in vitro doubling time was 34.1 h, and the colony forming efficiency was 5.09 percent. These results were therefore suitable for clonogenic radiation survival assessment. The 250 kVp X-ray survival curve of control TE.354.T cells showed linear-quadratic survival parameters of αX-ray = 0.201 Gy−1 and βX-ray = 0.125 Gy−2. Tetrac concentrations of either 0.2 or 2.0 µM produced αX-ray and βX-ray parameters of 2.010 and 0.282 Gy−1 and 2.050 and 0.837 Gy−2, respectively. The surviving fraction at 2 Gy (SF2) for control cells was 0.581, while values for 0.2 and 2.0 µM tetrac were 0.281 and 0.024. The SF2 data show that tetrac concentrations of 0.2 and 2.0 µM sensitize otherwise radioresistant TE.354.T cells by factors of 2.1 and 24.0, respectively. Thus, radioresistant basal cell carcinoma cells may be radiosensitized pharmacologically by exposure to tetrac. PMID:28113001

  12. Pharmacologic retinoid signaling and physiologic retinoic acid receptor signaling inhibit basal cell carcinoma tumorigenesis

    PubMed Central

    So, Po-Lin; Fujimoto, Michele A.; Epstein, Ervin H.

    2015-01-01

    Basal cell carcinoma (BCC) is the most common human cancer. Patients with basal cell nevus syndrome (Gorlin syndrome) are highly susceptible to developing many BCCs as a result of a constitutive inactivating mutation in one allele of PATCHED 1, which encodes a tumor suppressor that is a major inhibitor of Hedgehog signaling. Dysregulated Hedgehog signaling is a common feature of both hereditary and sporadic BCCs. Recently, we showed remarkable anti-BCC chemopreventive efficacy of tazarotene, a retinoid with retinoic acid receptor (RAR) β/γ specificity, in Ptch1 +/− mice when treatment was commenced before carcinogenic insults. In this study, we assessed whether the effect of tazarotene against BCC carcinogenesis is sustained after its withdrawal and whether tazarotene is effective against preexisting microscopic BCC lesions. We found that BCCs did not reappear for at least 5 months after topical drug treatment was stopped and that already developed, microscopic BCCs were susceptible to tazarotene inhibition. In vitro, tazarotene inhibited a murine BCC keratinocyte cell line, ASZ001, suggesting that its effect in vivo is by direct action on the actual tumor cells. Down-regulation of Gli1, a target gene of Hedgehog signaling and up-regulation of CRABPII, a target gene of retinoid signaling, were observed with tazarotene treatment. Finally, we investigated the effects of topical applications of other retinoid-related compounds on BCC tumorigenesis in vivo. Tazarotene was the most effective of the preparations studied, and its effect most likely was mediated by RARγ activation. Furthermore, inhibition of basal RAR signaling in the skin promoted BCC carcinogenesis, suggesting that endogenous RAR signaling restrains BCC growth. PMID:18483315

  13. Molecular classification of basal cell carcinoma of skin by gene expression profiling.

    PubMed

    Jee, Byul A; Lim, Hyoseob; Kwon, So Mee; Jo, Yuna; Park, Myong Chul; Lee, Il Jae; Woo, Hyun Goo

    2015-12-01

    Non-melanoma skin cancers (NMSC) including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are more common kinds of skin cancer. Although these tumors share common pathological and clinical features, their similarity and heterogeneity at molecular levels are not fully elaborated yet. Here, by performing comparative analysis of gene expression profiling of BCC, SCC, and normal skin tissues, we could classify the BCC into three subtypes of classical, SCC-like, and normal-like BCCs. Functional enrichment and pathway analyses revealed the molecular characteristics of each subtype. The classical BCC showed the enriched expression and transcription signature with the activation of Wnt and Hedgehog signaling pathways, which were well known key features of BCC. By contrast, the SCC-like BCC was enriched with immune-response genes and oxidative stress-related genes. Network analysis revealed the PLAU/PLAUR as a key regulator of SCC-like BCC. The normal-like BCC showed prominent activation of metabolic processes particularly the fatty acid metabolism. The existence of these molecular subtypes could be validated in an independent dataset, which demonstrated the three subgroups of BCC with distinct functional enrichment. In conclusion, we suggest a novel molecular classification of BCC providing insights on the heterogeneous progression of BCC.

  14. Expression of drebrin, an actin binding protein, in basal cell carcinoma, trichoblastoma and trichoepithelioma.

    PubMed

    Mizutani, Yoko; Iwamoto, Ikuko; Kanoh, Hiroyuki; Seishima, Mariko; Nagata, Koh-ichi

    2014-06-01

    Drebrin, an F-actin binding protein, is known to play important roles in cell migration, synaptogenesis and neural plasticity. Although drebrin was long thought to be specific for neuronal cells, its expression has recently been reported in non-neuronal cells. As for skin-derived cells, drebrin was shown to be enriched at adhering junctions (AJs) in cultured primary keratinocytes and also be highly expressed in basal cell carcinoma (BCC) cells. Since BCC and two types of benign neoplasm, trichoblastoma and trichoepithelioma, are considered to derive from the same origin, follicular germinative cells, it is sometimes difficult to morphologically distinguish BCC from trichoblastoma and trichoepithelioma. In this study, we performed immunohistochemical staining of drebrin in BCC, trichoblastoma and trichoepithelioma, to examine whether drebrin could serve as a biomarker for BCC diagnosis. In western blotting, drebrin was detected highly and moderately in the lysates from a squamous cell carcinoma cell line, DJM-1, and normal human epidermis, respectively. In immunofluorescence analyses, drebrin was colocalized with markers of AJs and tight junctions in DJM-1 cells and detected at cell-cell junction areas of human normal epidermis tissue. We then examined the distribution patterns of drebrin in BCC, trichoblastoma and trichoepithelioma. In BCC tissues, intense and homogeneous drebrin expression was observed mainly at tumor cell-cell boundaries. In contrast, drebrin was stained only weakly and non-homogeneously in trichoblastoma and trichoepthelioma tissue samples. For differential diagnosis of BCC, drebrin may be a novel and useful marker.

  15. First-in-human trial of nanoelectroablation therapy for basal cell carcinoma: proof of method.

    PubMed

    Nuccitelli, Richard; Wood, Ryan; Kreis, Mark; Athos, Brian; Huynh, Joanne; Lui, Kaying; Nuccitelli, Pamela; Epstein, Ervin H

    2014-02-01

    This nanoelectroablation therapy effectively treats subdermal murine allograft tumors, autochthonous basal cell carcinoma (BCC) tumors in Ptch1+/-K14-Cre-ER p53 fl/fl mice, and UV-induced melanomas in C57/BL6 HGF/SF mice. Here, we described the first human trial of this modality. We treated 10 BCCs on three subjects with 100-1000 electric pulses 100 ns in duration, 30 kV/cm in amplitude, applied at 2 pulses per second. Seven of the 10 treated lesions were completely free of basaloid cells when biopsied and two partially regressed. Two of the 7 exhibited seborrheic keratosis in the absence of basaloid cells. One of the 10 treated lesions recurred by week 10 and histologically had the appearance of a squamous cell carcinoma. No scars were visible at the healed sites of any of the successfully ablated lesions. One hundred pulses were sufficient for complete ablation of BCCs with a single, 1-min nanoelectroablation treatment.

  16. Invasive urothelial carcinoma exhibiting basal cell immunohistochemical markers: A variant of urothelial carcinoma associated with aggressive features.

    PubMed

    Mai, Kien T; Truong, Luan D; Ball, Christopher G; Williams, Phillip; Flood, Trevor A; Belanger, Eric C

    2015-08-01

    We characterize invasive urothelial carcinoma (UC) exhibiting urothelial basal cell immunohistochemical markers. Consecutive invasive UCs were immunostained with CK20 and urothelial basal cell markers, cytokeratin 5 (CK5)/CD44. Immunostaining for CK5 and CD44 was scored as follows: positive for staining of more than 25% thickness of the epithelial nest or epithelium and low for lesser immunoreactivity. Invasive urothelial carcinoma (UC) exhibiting positive CK5/CD44 staining was designated as basal-like UC (BUC). In this study, of 251 invasive UC (pT1 in 57% and pT2-4 in 43%), BUC accounted for 40% of cases (accounting for most pT2-4 UC) and often presented as non-papillary UC without previous history of UC. In addition, BUC exhibited uniform nuclei with lesser degree of atypia than non BUC and decreased or negative cytokeratin 20 reactivity. Nested and microcystic variants of UC immunohistochemically stained as BUCs. Invasive non-BUCs were often papillary with marked cytologic atypia and pleomorphism, and accounted for most pT1 UC. The rates of perivesical invasion, lymph node and distant metastases were higher for BUC than non-BUC. All nine cases with absent/minimal residual in situ UC in 102 radical cystectomy specimens were from invasive non-BUC. BUC is distinguished from non-BUC due to this aggressive behavior, distinct immunohistochemical profile, and predominant non-papillary architecture. Our findings are consistent with recent studies identifying a subtype of muscle-invasive UC with molecular expression of basal cell and luminal cell molecular profiles. Our study further supports categorizing invasive UCs into these subtypes with different biological behaviors, possibly contributing to better therapeutic strategies.

  17. Master/slave optical coherence tomography imaging of eyelid basal cell carcinoma.

    PubMed

    Chin, Catherine; Bradu, Adrian; Lim, Rongxuan; Khandwala, Mona; Schofield, John; Leick, Lasse; Podoleanu, Adrian

    2016-09-10

    Optical coherence tomography (OCT) is fast emerging as an additional non-interventional modality for skin tumor detection and diagnosis. A master/slave flying spot OCT configuration was assembled to detect periocular basal cell carcinomas (BCC). A swept source at 1300 nm and sweeping speed of 50 kHz were used. A three-step process was involved. First, 384 channeled spectra using a mirror were stored for 384 optical path differences at the master stage. Then, the stored channeled spectra (masks) were correlated with the channeled spectrum from the BCC tissue to produce 384 en face OCT images (200×200 pixels) for the optical path difference values used to acquire the masks. Finally, these en face slices were stacked to form a volume to cross-reference BCC tumor margins in the orthogonal plane. Per each eyelid sample, several en face images of 200×200 lateral pixels are produced in the time to scan laterally a complete raster of 1.6 s. Combination of the en face views with the cross-sectioning views allow for better discrimination of BCCs comparable to using cross-sectional imaging alone, as previously reported using the conventional fast-Fourier-transform-based OCT techniques.

  18. Gene Expression and Proteome Analysis as Sources of Biomarkers in Basal Cell Carcinoma

    PubMed Central

    Ghita, Mihaela Adriana; Voiculescu, Suzana; Rosca, Adrian E.; Moraru, Liliana; Greabu, Maria

    2016-01-01

    Basal cell carcinoma (BCC) is the world's leading skin cancer in terms of frequency at the moment and its incidence continues to rise each year, leading to profound negative psychosocial and economic consequences. UV exposure is the most important environmental factor in the development of BCC in genetically predisposed individuals, this being reflected by the anatomical distribution of lesions mainly on sun-exposed skin areas. Early diagnosis and prompt management are of crucial importance in order to prevent local tissue destruction and subsequent disfigurement. Although various noninvasive or minimal invasive techniques have demonstrated their utility in increasing diagnostic accuracy of BCC and progress has been made in its treatment options, recurrent, aggressive, and metastatic variants of BCC still pose significant challenge for the healthcare system. Analysis of gene expression and proteomic profiling of tumor cells and of tumoral microenvironment in various tissues strongly suggests that certain molecules involved in skin cancer pathogenic pathways might represent novel predictive and prognostic biomarkers in BCC. PMID:27578920

  19. No Evidence of Human Papilloma Virus Infection in Basal Cell Carcinoma

    PubMed Central

    Nahidi, Yalda; Meibodi, Naser Tayyebi; Meshkat, Zahra; Esmaili, Habibollah; Jahanfakhr, Samaneh

    2015-01-01

    Background: Basal cell carcinoma (BCC) is the most common skin cancer among whites, and several risk factors have been discussed in itsdevelopment and progress. Detection of human papilloma virus (HPV) deoxyribonucleic acid (DNA) BCCs in some studies suggests that the virus may play a role in the pathogenesis of this disease. Several molecular studies showed conflicting reports. Aims: The purpose of this study was to investigate the association between HPV and BCC using polymerase chain reaction (PCR). Materials and Methods: HPV DNA detection was done for 42 paraffin-embedded tissue specimens of BCC and 42 normal skin samples around the lesions by PCR using GP5+/GP6+ primers. Results: HPV DNA was not found in any of the 42 samples of BCC, and only one normal skin sample around the lesions was positive for HPV DNA by PCR. Conclusion: In this study, no statistically significant difference was seen between the presence of HPV DNA in BCC and normal skin around the lesion, and HPV is not likely to have an important role in pathogenesis of BCC. PMID:26288402

  20. Development of Raman microspectroscopy for automated detection and imaging of basal cell carcinoma

    NASA Astrophysics Data System (ADS)

    Larraona-Puy, Marta; Ghita, Adrian; Zoladek, Alina; Perkins, William; Varma, Sandeep; Leach, Iain H.; Koloydenko, Alexey A.; Williams, Hywel; Notingher, Ioan

    2009-09-01

    We investigate the potential of Raman microspectroscopy (RMS) for automated evaluation of excised skin tissue during Mohs micrographic surgery (MMS). The main aim is to develop an automated method for imaging and diagnosis of basal cell carcinoma (BCC) regions. Selected Raman bands responsible for the largest spectral differences between BCC and normal skin regions and linear discriminant analysis (LDA) are used to build a multivariate supervised classification model. The model is based on 329 Raman spectra measured on skin tissue obtained from 20 patients. BCC is discriminated from healthy tissue with 90+/-9% sensitivity and 85+/-9% specificity in a 70% to 30% split cross-validation algorithm. This multivariate model is then applied on tissue sections from new patients to image tumor regions. The RMS images show excellent correlation with the gold standard of histopathology sections, BCC being detected in all positive sections. We demonstrate the potential of RMS as an automated objective method for tumor evaluation during MMS. The replacement of current histopathology during MMS by a ``generalization'' of the proposed technique may improve the feasibility and efficacy of MMS, leading to a wider use according to clinical need.

  1. The incidence of basal cell carcinoma in Croatia: an epidemiological study.

    PubMed

    Celić, Dijana; Lipozencić, Jasna; Jurakić Toncić, Ruzica; Ledić-Drvar, Daniela; Marasović, Dujomir; Puizina-Ivić, Neira; Cabrijan, Leo; Bradamante, Mirna

    2009-01-01

    The aim of the study was to investigate the basal cell carcinoma (BCC) incidence in Croatia in the 2003-2005 period. Data were collected from University Department of Dermatology and Venereology, Zagreb University Hospital Center and National Cancer Registry. The age-specific incidence rate and age-standardized incidence rate were calculated per 100,000 inhabitants according to the latest population census in Croatia from 2001. In the study period, there were 7,244 BCC cases (3,519 men and 3,725 women) in Croatia. The crude incidence rate for the Croatian population of 100,000 was 54.9 for men and 53.9 for women. The age-standardized incidence rate (adjusted for the world standard population) was 33.6 for men and 24.5 for women. The head and neck were almost exclusive localizations of BCC. The highest BCC incidence was recorded in Zadar County. The incidence of BCC was high in both littoral and inland counties of Croatia. Study results will serve as reference figures on studying the trend of BCC incidence in Croatia and Europe in the forthcoming years.

  2. The Importance of Frozen Section-Controlled Excision in Recurrent Basal Cell Carcinoma of the Eyelids

    PubMed Central

    Şahan, Berna; Çiftçi, Ferda; Özkan, Ferda; Öztürk, Vildan

    2016-01-01

    Objectives: To show the importance of frozen section-controlled excision to avoid the re-recurrence of recurrent basal cell carcinoma (BCC) of the eyelids. Materials and Methods: Thirty-five cases who underwent eyelid tumor excision in different centers and were admitted to our clinic with recurrent eyelid tumors. Recurrent tumors were resected by excision 1-2 mm from the tumor’s visible margin and sent to pathology for frozen section examination. Eyelid reconstructions with flap and graft were performed after confirming that the surgical margins were negative. Results: Twenty-one (60%) of our patients were male and 14 (40%) were female. Median age of our group was 63.4±14.2 years. Excision and sending the excised material for frozen section control was performed once for 11 patients, twice for 12 patients, 3 times for 8 patients and 4 times for 4 patients to confirm that the surgical margins were clean. All pathology samples were reported as BCC. All patients had eyelid reconstruction with flap and graft. Recurrence was detected in 2 patients (5.7%) during 1 to 8 years (mean 4.3 years) of follow-up and those patients were reoperated; no recurrence was detected in the remaining 33 patients (94.3%). Conclusion: Frozen section control can provide low re-recurrence rate in patients with recurrent BCC of the eyelids. PMID:28050325

  3. Ambient temperature and risk of first primary basal cell carcinoma: a nationwide United States cohort study

    PubMed Central

    Freedman, D. Michal; Kitahara, Cari M.; Linet, Martha S.; Alexander, Bruce H.; Neta, Gila; Little, Mark; Cahoon, Elizabeth K.

    2015-01-01

    The Earth's surface is warming and animal studies have shown higher temperatures promote ultraviolet radiation (UVR) skin carcinogenesis. There are, however, no population studies of long-term temperature exposure and basal cell carcinoma (BCC) risk. We linked average lifetime summer ambient temperatures (based on weather station data) and satellite-based UVR estimates to self-reported lifetime residences in the U.S. Radiologic Technologists' cohort. We assessed the relationship between time-dependent average lifetime summer ambient temperature (20-year lag) in quintiles and BCC in whites, using Cox proportional hazards regression. Risks were adjusted for time-dependent lagged average lifetime UVR and time outdoors, body mass index, eye color, and sex (baseline hazard stratified on birth cohort). During a median 19.4 years follow-up, we identified 3,556 BCC cases. There was no significant trend in risk between temperature and BCC. However, BCC risk was highest in the fourth quintile of temperature (Q4 vs. Q1; hazards ratio (HR)=1.18; 95% confidence interval (CI) = 1.06–1.31, p-trend =0.09). BCC risk was strongly related to average lifetime ambient UVR exposure (Q5 vs. Q1; HR = 1.54 (95% CI = 1.35–1.75, p-trend= <0.001)). Future studies of temperature and BCC risk should include a broad range of UVR and temperature values, along with improved indicators of exposure to temperatures and UVR. PMID:25996074

  4. Role of PTCH and p53 genes in early-onset basal cell carcinoma.

    PubMed

    Zhang, H; Ping, X L; Lee, P K; Wu, X L; Yao, Y J; Zhang, M J; Silvers, D N; Ratner, D; Malhotra, R; Peacocke, M; Tsou, H C

    2001-02-01

    Basal cell carcinoma (BCC) is the most common skin cancer in the Western world. Ultraviolet (UV) exposure, race, age, gender, and decreased DNA repair capacity are known risk factors for the development of BCC. Of these, UVB irradiation from sunlight is the most significant risk factor. The incidence of sporadic BCC increases in individuals older than age 55, with the greatest incidence reported in individuals who are older than 70, and is rare in individuals who are younger than 30. In this study, we analyzed 24 BCC samples from individuals who had BCC diagnosed by the age of 30. Fifteen single-stranded conformation polymorphism variants in the PTCH gene were identified in 13 BCC samples. Sequence analysis of these single-stranded conformation polymorphism variants revealed 13 single nucleotide changes, one AT insertion, and one 15-bp deletion. Most of these nucleotide changes (nine of 15) were predicted to result in truncated PTCH proteins. Fifteen p53 mutations were also found in 11 of the 24 BCC samples. Thirty-three percent (five of 15) and 60% (nine of 15) of the nucleotide changes in the PTCH and p53 genes, respectively, were UV-specific C-->T and CC-->TT nucleotide changes. Our data demonstrate that the p53 and PTCH genes are both implicated in the development of early-onset BCC. The identification of UV-specific nucleotide changes in both tumor suppressor genes suggests that UV exposure is an important risk factor in early onset of BCC.

  5. PTCH mutations in basal cell carcinomas from azathioprine-treated organ transplant recipients.

    PubMed

    Harwood, C A; Attard, N R; O'Donovan, P; Chambers, P; Perrett, C M; Proby, C M; McGregor, J M; Karran, P

    2008-10-21

    The immunosuppressant azathioprine is used to prevent graft rejection after organ transplantation. To investigate whether azathioprine-associated mutagenesis contributes to the high incidence of skin tumours in organ transplant recipients (OTRs), we analysed PTCH gene mutations in 60 basal cell carcinomas (BCC); 39 from OTRs receiving azathioprine and 21 from individuals never exposed to azathioprine. PTCH was mutated in 55% of all tumours, independent of azathioprine treatment. In both the azathioprine and non-azathioprine groups, transitions at dipyrimidine sequences, considered to indicate mutation by ultraviolet-B radiation, occurred frequently in tumours from chronically sun-exposed skin. In BCC from non-sun-exposed skin of azathioprine-treated patients, there was an over-representation of unusual G:C to A:T transitions at non-dipyrimidine sites. These were exclusive to the azathioprine-exposed group and all in the same TGTC sequence context at different positions within PTCH. Meta-analysis of 247 BCCs from published studies indicated that these mutations are rare in sporadic BCC and had never previously been reported in this specific sequence context. This study of post-transplant BCC provides the first indication that azathioprine exposure may be associated with PTCH mutations, particularly in tumours from non-sun-exposed skin.

  6. PTCH promoter methylation at low level in sporadic basal cell carcinoma analysed by three different approaches.

    PubMed

    Heitzer, Ellen; Bambach, Isabella; Dandachi, Nadia; Horn, Michael; Wolf, Peter

    2010-10-01

    Basal cell carcinoma (BCC) is the most common form of skin cancer. Mutations of the PTCH hallmark gene are detected in about 50-60% of BCCs, which raises the question whether other mechanisms such as promoter methylation can inactivate PTCH. Therefore, we performed methylation analysis of the PTCH promoter in a total of 56 BCCs. The sensitivity of three different methods, including direct bisulphite sequencing PCR, MethyLight and high-resolution melting (HRM), was applied and compared. We found that HRM analysis of DNA from fresh tissue [rather than formalin-fixed and paraffin-embedded tissue (FFPE)] was the most sensitive method to detect methylation. Low-level methylation of the PTCH promoter was detected in five out of 16 analysed BCCs (31%) on DNA from fresh tissue but only in two (13%) samples on short-time stored FFPE DNA from the very same tumors. In contrast, we were unable to detect methylation by HRM on long-time stored DNA in any of the remaining 40 BCC samples. Our data suggest that (i) HRM on DNA extracted from fresh tissue is the most sensitive method to detect methylation and (ii) methylation of the PTCH promoter may only play a minor role in BCC carcinogenesis.

  7. Advanced basal cell carcinoma, the hedgehog pathway, and treatment options – role of smoothened inhibitors

    PubMed Central

    Fecher, Leslie A; Sharfman, William H

    2015-01-01

    Cutaneous basal cell carcinoma (BCC) is the most common human cancer and its incidence is rising worldwide. Ultraviolet radiation exposure, including tanning bed use, as well as host factors play a role in its development. The majority of cases are treated and cured with local therapies including surgery. Yet, the health care costs of diagnosis and treatment of BCCs in the US is substantial. In the United States, the cost of nonmelanoma skin cancer care in the Medicare population is estimated to be US$426 million per year. While rare, locally advanced BCCs that can no longer be controlled with surgery and/or radiation, and metastatic BCCs do occur and can be associated with significant morbidity and mortality. Vismodegib (GDC-0449), a smoothened inhibitor targeted at the hedgehog pathway, is the first US Food and Drug Association (FDA)-approved agent in the treatment of locally advanced, unresectable, and metastatic BCCs. This class of agents appears to be changing the survival rates in advanced BCC patients, but appropriate patient selection and monitoring are important. Multidisciplinary assessments are essential for the optimal care and management of these patients. For some patients with locally advanced BCC, treatment with a hedgehog inhibitor may eliminate the need for an excessively disfiguring or morbid surgery. PMID:26604681

  8. Ambient temperature and risk of first primary basal cell carcinoma: A nationwide United States cohort study.

    PubMed

    Michal Freedman, D; Kitahara, Cari M; Linet, Martha S; Alexander, Bruce H; Neta, Gila; Little, Mark P; Cahoon, Elizabeth K

    2015-07-01

    The Earth's surface is warming and animal studies have shown higher temperatures promote ultraviolet radiation (UVR) skin carcinogenesis. There are, however, no population studies of long-term temperature exposure and basal cell carcinoma (BCC) risk. We linked average lifetime summer ambient temperatures (based on weather station data) and satellite-based UVR estimates to self-reported lifetime residences in the U.S. Radiologic Technologists' cohort. We assessed the relationship between time-dependent average lifetime summer ambient temperature (20-year lag) in quintiles and BCC in whites, using Cox proportional hazards regression. Risks were adjusted for time-dependent lagged average lifetime UVR and time outdoors, body mass index, eye color, and sex (baseline hazard stratified on birth cohort). During a median 19.4 years follow-up, we identified 3556 BCC cases. There was no significant trend in risk between temperature and BCC. However, BCC risk was highest in the fourth quintile of temperature (Q4 vs. Q1; hazards ratio (HR)=1.18; 95% confidence interval (CI)=1.06-1.31, p-trend=0.09). BCC risk was strongly related to average lifetime ambient UVR exposure (Q5 vs. Q1; HR=1.54 (95% CI=1.35-1.75, p-trend=<0.001)). Future studies of temperature and BCC risk should include a broad range of UVR and temperature values, along with improved indicators of exposure to temperatures and UVR.

  9. Combination Trimodality Therapy Using Vismodegib for Basal Cell Carcinoma of the Face.

    PubMed

    Block, Alec M; Alite, Fiori; Diaz, Aidnag Z; Borrowdale, Richard W; Clark, Joseph I; Choi, Mehee

    2015-01-01

    Background. For large basal cell carcinomas (BCCs) of the head and neck, definitive surgery often requires extensive resection and reconstruction that may result in prolonged recovery and limited cosmesis. Vismodegib, a small-molecule inhibitor of the hedgehog pathway, is approved for advanced and metastatic BCCs. We present a case of advanced BCC treated with combination of vismodegib, radiotherapy, and local excision resulting in excellent response and cosmesis. Case Presentation. A 64-year-old gentleman presented with a 5-year history of a 7 cm enlarging right cheek mass, with extensive vascularization, central ulceration, and skin, soft tissue, and buccal mucosa involvement. Biopsy revealed BCC, nodular type. Up-front surgical option involved a large resection and reconstruction. After multidisciplinary discussion, we recommended and he opted for combined modality of vismodegib, radiotherapy, and local excision. The patient tolerated vismodegib well and his right cheek lesion decreased significantly in size. He was then treated with radiotherapy followed by local excision that revealed only focal residual BCC. Currently, he is without evidence of disease and has excellent cosmesis. Conclusions. We report a case of locally advanced BCC treated with trimodality therapy with vismodegib, radiotherapy, and local excision, resulting in excellent outcome and facial cosmesis, without requiring extensive resection or reconstructive surgery.

  10. Periocular Basal Cell Carcinoma Predictors for Recurrence and Infiltration of the Orbit

    PubMed Central

    Furdova, Alena; Lukacko, Pavol

    2017-01-01

    Purpose: To present the proportion of patients with periocular basal cell carcinoma (BCC) who underwent orbital exenteration and to evaluate the significance of the risk factors. Design: Retrospective, comparative, interventional case series. Methods: Data of all patients with BCC between 2008 and 2014 were reviewed for patient demographics, previous treatment options, tumor localization, and histopathologic subtype. Results: In group of 256 patients, orbital exenteration underwent 7 patients (2.7%). For 2 patients (5.1%), orbital exenteration was the first procedure performed. In the exenterated group, the most common tumor site was the medial cantus and lower eyelid, whereas in the overall group, it was the lower eyelid (P = 0.011). The proportion of patients initially treated with histopathologic result of infiltration of 1 margin was significantly higher in patients undergoing exenteration (P = 0.282). During the 7-year period observership, the authors have seen 13 recurrences (5.08%). In patients with recurrent BCC after surgery, the authors applied adjuvant high dose rate 192Ir brachytherapy. Neoadjuvant therapy with Vismodegib was effective in patient with biorbital infiltration after 1 side exenteration. Conclusions: Orbital invasion may be clinically silent. Recurrence rate of BCC in our group 5% corresponds to date in the literature. The exenteration for BCC may be significantly higher when the lesion involves a medial canthal location and lower eyelid and initial surgery does not include margin-controlled excision. PMID:27906855

  11. Treatment of Pigmented Basal Cell Carcinoma with 3 mm Surgical Margin in Asians.

    PubMed

    Lin, Shang-Hung; Cheng, Yu-Wen; Yang, Yi-Chien; Ho, Ji-Chen; Lee, Chih-Hung

    2016-01-01

    Background. In Asians, most basal cell carcinomas (BCCs) are pigmented with clear borders. The consensus of 4 mm surgical margin for BCC largely depends on studies in nonpigmented BCCs in Caucasians. However, little is known about recurrences of pigmented BCCs with a narrower surgical margin. We aimed to investigate 5-year recurrence of BCCs, either pigmented or nonpigmented, in Taiwanese with 3 mm surgical margin. Materials and Methods. 143 patients with BCC (M/F = 66/77, average 64 years) were confirmed pathologically from 2002 to 2013. Based on the pathological margin (>1 mm, ≤1 mm, and involved), patients were categorized into the complete excision group (n = 77), histology with close proximity group (n = 43), and unclear surgical margin group (n = 23). Results. Among 143 cases, 105 were pigmented. With standard 3 mm excision, there were 7 recurrences, with 6 of them from nonpigmented BCC group. Logistic regression showed that pigmentation was associated with lower recurrence. Interestingly, 5-year recurrence of completely excised and histology with close proximity BCC (0/77 versus 1/43) was not different statistically. Conclusions. A 3 mm surgical margin is adequate for pigmented BCC. A "wait and see" approach rather than further wide excision is appropriate for BCC with <1 mm free margin.

  12. Diagnosis of basal cell carcinoma by two photon excited fluorescence combined with lifetime imaging

    NASA Astrophysics Data System (ADS)

    Fan, Shunping; Peng, Xiao; Liu, Lixin; Liu, Shaoxiong; Lu, Yuan; Qu, Junle

    2014-02-01

    Basal cell carcinoma (BCC) is the most common type of human skin cancer. The traditional diagnostic procedure of BCC is histological examination with haematoxylin and eosin staining of the tissue biopsy. In order to reduce complexity of the diagnosis procedure, a number of noninvasive optical methods have been applied in skin examination, for example, multiphoton tomography (MPT) and fluorescence lifetime imaging microscopy (FLIM). In this study, we explored two-photon optical tomography of human skin specimens using two-photon excited autofluorescence imaging and FLIM. There are a number of naturally endogenous fluorophores in skin sample, such as keratin, melanin, collagen, elastin, flavin and porphyrin. Confocal microscopy was used to obtain structures of the sample. Properties of epidermic and cancer cells were characterized by fluorescence emission spectra, as well as fluorescence lifetime imaging. Our results show that two-photon autofluorescence lifetime imaging can provide accurate optical biopsies with subcellular resolution and is potentially a quantitative optical diagnostic method in skin cancer diagnosis.

  13. Matrix metalloproteinases and E-cadherin immunoreactivity in different basal cell carcinoma histological types.

    PubMed

    Vanjaka-Rogošić, Lucija; Puizina-Ivić, Neira; Mirić, Lina; Rogošić, Veljko; Kuzmić-Prusac, Ivana; Babić, Mirna Saraga; Vuković, Dubravka; Mardešić, Snježana

    2014-06-01

    The immunohistochemical staining of matrix metalloproteinases (MMPs) and E-cadherin in tumor epithelial and stromal cells was analyzed in a group of solid, superficial spreading and cystic tumors and in a group of morpheaform and recurrent basal cell carcinomas (BCC) in order to determine whether any of these factors possibly contribute to tumor therapy resistance. Tumor tissues of 64 patients were obtained by complete excisional or curettage biopsy of BCC and these were immunohistochemically stained for MMP-1, MMP-2, MMP-9, MMP-13 and E-cadherin. In the morpheaform and recurrent BCC, MMP-9 expression significantly increased in the stroma, while E-cadherin expression was negative in epithelial cells. Odds ratio for development of morpheaform and recurrent BCC was 6.2 for positive MMP-1 immunostaining in epithelial tumor cells, 5.8 for positive MMP-9 immunostaining in tumor stroma, 3.2 for positive MMP-13 immunostaining in tumor stroma, and 4.5 for negative E-cadherin in epithelial tumor cells. Our results suggest that MMP-1 immunostaining in tumor cells, MMP-9 expression in stromal cells, and absence of E-cadherin expression are associated with morpheaform and recurrent BCC.

  14. Nanostructured lipid carrier in photodynamic therapy for the treatment of basal-cell carcinoma.

    PubMed

    Qidwai, Afreen; Khan, Saba; Md, Shadab; Fazil, Mohammad; Baboota, Sanjula; Narang, Jasjeet K; Ali, Javed

    2016-05-01

    Topical photodynamic therapy (PDT) is a promising alternative for malignant skin diseases such as basal-cell carcinoma (BCC), due to its simplicity, enhanced patient compliance, and localization of the residual photosensitivity to the site of application. However, insufficient photosensitizer penetration into the skin is the major issue of concern with topical PDT. Therefore, the aim of the present study was to enable penetration of photosensitizer to the different strata of the skin using a lipid nanocarrier system. We have attempted to develop a nanostructured lipid carrier (NLC) for the topical delivery of second-generation photosensitizer, 5-amino levulinic acid (5-ALA), whose hydrophilicity and charge characteristic limit its percutaneous absorption. The microemulsion technique was used for preparing 5-ALA-loaded NLC. The mean particle size, polydispersity index, and entrapment efficiency of the optimized NLC of 5-ALA were found to be 185.2 ± 1.20, 0.156 ± 0.02, and 76.8 ± 2.58%, respectively. The results of in vitro release and in vitro skin permeation studies showed controlled drug release and enhanced penetration into the skin, respectively. Confocal laser scanning microscopy and cell line studies respectively demonstrated that encapsulation of 5-ALA in NLC enhanced its ability to reach deeper skin layers and consequently, increased cytotoxicity.

  15. CD200-expressing human basal cell carcinoma cells initiate tumor growth.

    PubMed

    Colmont, Chantal S; Benketah, Antisar; Reed, Simon H; Hawk, Nga V; Telford, William G; Ohyama, Manabu; Udey, Mark C; Yee, Carole L; Vogel, Jonathan C; Patel, Girish K

    2013-01-22

    Smoothened antagonists directly target the genetic basis of human basal cell carcinoma (BCC), the most common of all cancers. These drugs inhibit BCC growth, but they are not curative. Although BCC cells are monomorphic, immunofluorescence microscopy reveals a complex hierarchical pattern of growth with inward differentiation along hair follicle lineages. Most BCC cells express the transcription factor KLF4 and are committed to terminal differentiation. A small CD200(+) CD45(-) BCC subpopulation that represents 1.63 ± 1.11% of all BCC cells resides in small clusters at the tumor periphery. By using reproducible in vivo xenograft growth assays, we determined that tumor initiating cell frequencies approximate one per 1.5 million unsorted BCC cells. The CD200(+) CD45(-) BCC subpopulation recreated BCC tumor growth in vivo with typical histological architecture and expression of sonic hedgehog-regulated genes. Reproducible in vivo BCC growth was achieved with as few as 10,000 CD200(+) CD45(-) cells, representing ~1,500-fold enrichment. CD200(-) CD45(-) BCC cells were unable to form tumors. These findings establish a platform to study the effects of Smoothened antagonists on BCC tumor initiating cell and also suggest that currently available anti-CD200 therapy be considered, either as monotherapy or an adjunct to Smoothened antagonists, in the treatment of inoperable BCC.

  16. Immunosuppressive Environment in Basal Cell Carcinoma: The Role of Regulatory T Cells.

    PubMed

    Omland, Silje H; Nielsen, Patricia S; Gjerdrum, Lise M R; Gniadecki, Robert

    2016-11-02

    Interaction between tumour survival tactics and anti-tumour immune response is a major determinant for cancer growth. Regulatory T cells (T-regs) contribute to tumour immune escape, but their role in basal cell carcinoma (BCC) is not understood. The fraction of T-regs among T cells was analysed by immunohistochemistry followed by automated image analysis in facial BCC, peritumoural skin and normal, buttock skin. Quantitative real-time PCR (qRT-PCR) was performed for FOXP3 and cytokines involved in T-reg attraction and T-cell activation. T-regs comprised 45% of CD4-cells surrounding BCC. FOXP3 was highly expressed in BCC, but absent in buttock skin. Unexpectedly, expression of FOXP3 was increased in peritumoural skin, with the FOXP3/CD3 fractions exceeding those of BCC (p?=?0.0065). Transforming growth factor (TGF)-? and T-reg chemokine expression was increased in BCC and peritumoural skin, but not in buttock skin, with expression levels correlating with FOXP3. T-regs are abundantly present both in BCC and in peritumoural skin, mediating an immunosuppressed microenvironment permissive for skin cancer.

  17. Sonidegib: mechanism of action, pharmacology, and clinical utility for advanced basal cell carcinomas

    PubMed Central

    Jain, Sachin; Song, Ruolan; Xie, Jingwu

    2017-01-01

    The Hedgehog (Hh) pathway is critical for cell differentiation, tissue polarity, and stem cell maintenance during embryonic development, but is silent in adult tissues under normal conditions. However, aberrant Hh signaling activation has been implicated in the development and promotion of certain types of cancer, including basal cell carcinoma (BCC), medulloblastoma, and gastrointestinal cancers. In 2015, the US Food and Drug Administration (FDA) approved sonidegib, a smoothened (SMO) antagonist, for treatment of advanced BCC (aBCC) after a successful Phase II clinical trial. Sonidegib, also named Odomzo, is the second Hh signaling inhibitor approved by the FDA to treat BCCs following approval of the first SMO antagonist vismodegib in 2012. What are the major features of sonidegib (mechanism of action; metabolic profiles, clinical efficacy, safety, and tolerability profiles)? Will the sonidegib experience help other clinical trials using Hh signaling inhibitors in the future? In this review, we will summarize current understanding of BCCs and Hh signaling. We will focus on sonidegib and its use in the clinic, and we will discuss ways to improve its clinical application in cancer therapeutics. PMID:28352196

  18. Merkel cell-poor trichoblastoma with basal cell carcinoma-like foci.

    PubMed

    Misago, Noriyuki; Satoh, Toshimi; Miura, Yoshihiro; Nagase, Kohtarou; Narisawa, Yutaka

    2007-06-01

    We reexamined 11 cases of trichoblastoma, and two cases of trichoblastoma with basal cell carcinoma (BCC)-like foci were found. In these two trichoblastomas with BCC-like foci, the BCC-like foci were often localized in peripheral or deep areas of lesions extending out of the fibrocytic stroma. Immunohistochemistry was performed in five conventional trichoblastomas and in two trichoblastomas with BCC-like foci, using antibodies against CK20 and CK15. No CK20-positive Merkel cells and no expression of CK15 were seen in any neoplastic aggregations of the two trichoblastomas with BCC-like foci. In contrast, increased numbers of Merkel cells and positive staining for CK15 were observed in all five trichoblastomas without BCC-like foci. The five trichoblastomas without BCC-like foci included two trichoblastomas with a popped out or shelled out appearance, which characteristically had a thick fibrous capsule surrounding the fibrotic stroma, demonstrating numerous Merkel cells in the aggregations. Some trichoblastomas may undergo mutations, resulting in the development of foci of BCC and in the loss of the expression of CK15 as well as the disappearance of Merkel cells.

  19. [Aproaches to immunotherapy in different immunophenotypes of cutaneous basal cell carcinoma].

    PubMed

    Petrunin, D D; Okovityĭ, S V; Kostalevskaia, A V; Suchkov, S V

    2012-01-01

    The combination of two immunomodulating agents (genferon derived from exogenous IFN-alpha2b and cycloferon, endogenous IFN inductor) was added to the complex therapy of 60 patients with different cutaneous basal cell carcinoma (CBCC) immunophenotypes. All patients underwent tumor resection, 1-3 days after surgery the patients received immunotropic therapy by focal cycloferon injections (2 ml of 12.5% solution) on days 1, 2, 4, 6, 8 and 10 post-operation with simultaneous genferon therapy via suppositoria (1 000 000 ME) twice a day for 10 days. The therapy was well-tolerated. Essential parameters of immune homeostasis were evaluated before and 3 months after immunotropic therapy. During further observation (for a mean period of 1.8 years) none of the patients displayed any signs of CBCC relapse. The immunological studies results give evidence for correction of immune disturbances characteristic for CBCC patients. This data confirm the effectiveness of immunotropic therapy for relapse prevention and immune disorders correction and allow recommending it for CBCC patients with high relapse risk.

  20. Nonsurgical treatment options for basal cell carcinoma - focus on advanced disease.

    PubMed

    Goldenberg, Gary; Hamid, Omid

    2013-12-01

    Basal cell carcinoma (BCC) is the most common cancer in the world. It is typically slow growing and usually effectively managed with surgery. However, BCCs in some patients are unsuitable for surgery or the patient may prefer a nonsurgical treatment. Radiotherapy is a nonsurgical option for the primary treatment of either low- or high-risk BCCs. It is associated with high cure rates, albeit somewhat lower than those observed with Mohs micrographic surgery for high-risk BCCs. Not all patients with BCCs are suitable for radiotherapy. Superficial therapies for BCC include topical imiquimod or 5- fluorouracil and photodynamic therapy (PDT). These therapies are generally associated with somewhat lower clearance rates and/or higher recurrence rates than surgery or radiotherapy, although they may be suitable in patients with low-risk BCCs when surgery or radiotherapy are impractical or less appropriate. An appealing feature of PDT is excellent cosmesis, but PDT is not currently approved by the Food and Drug Administration (FDA), and regimens are not well standardized. Vismodegib is a first-in-class hedgehog pathway inhibitor and recent addition to the armamentarium for the treatment of advanced BCC.

  1. Combination Trimodality Therapy Using Vismodegib for Basal Cell Carcinoma of the Face

    PubMed Central

    Block, Alec M.; Alite, Fiori; Diaz, Aidnag Z.; Borrowdale, Richard W.; Clark, Joseph I.; Choi, Mehee

    2015-01-01

    Background. For large basal cell carcinomas (BCCs) of the head and neck, definitive surgery often requires extensive resection and reconstruction that may result in prolonged recovery and limited cosmesis. Vismodegib, a small-molecule inhibitor of the hedgehog pathway, is approved for advanced and metastatic BCCs. We present a case of advanced BCC treated with combination of vismodegib, radiotherapy, and local excision resulting in excellent response and cosmesis. Case Presentation. A 64-year-old gentleman presented with a 5-year history of a 7 cm enlarging right cheek mass, with extensive vascularization, central ulceration, and skin, soft tissue, and buccal mucosa involvement. Biopsy revealed BCC, nodular type. Up-front surgical option involved a large resection and reconstruction. After multidisciplinary discussion, we recommended and he opted for combined modality of vismodegib, radiotherapy, and local excision. The patient tolerated vismodegib well and his right cheek lesion decreased significantly in size. He was then treated with radiotherapy followed by local excision that revealed only focal residual BCC. Currently, he is without evidence of disease and has excellent cosmesis. Conclusions. We report a case of locally advanced BCC treated with trimodality therapy with vismodegib, radiotherapy, and local excision, resulting in excellent outcome and facial cosmesis, without requiring extensive resection or reconstructive surgery. PMID:26504605

  2. Usefulness of Photodynamic Therapy as a Possible Therapeutic Alternative in the Treatment of Basal Cell Carcinoma

    PubMed Central

    Savoia, Paola; Deboli, Tommaso; Previgliano, Alberto; Broganelli, Paolo

    2015-01-01

    Basal cell carcinoma (BCC) is the most common cancer in individuals with fair skin type (I–II) and steadily increasing in incidence (70% of skin malignancy). It is locally invasive but metastasis is usually very rare, with an estimated incidence of 0.0028%–0.55%. Conventional therapy is surgery, especially for the H region of the face and infiltrative lesions; in case of inoperable tumors, radiotherapy is a valid option. Recently, topical photodynamic therapy (PDT) has become an effective treatment in the management of superficial and small nodular BCC. PDT is a minimally invasive procedure that involves the administration of a photo-sensibilizing agent followed by irradiation at a pre-defined wavelength; this determines the creation of reactive oxygen species that specifically destroy target cells. The only major side effect is pain, reported by some patients during the irradiation. The high cure rate and excellent cosmetic outcome requires considering this possibility for the management of patients with both sporadic and hereditary BCC. In this article, an extensive review of the recent literature was made, in order to clarify the role of PDT as a possible alternative therapeutic option in the treatment of BCC. PMID:26426005

  3. Challenges and new horizons in the management of advanced basal cell carcinoma: a UK perspective

    PubMed Central

    Lear, J T; Corner, C; Dziewulski, P; Fife, K; Ross, G L; Varma, S; Harwood, C A

    2014-01-01

    Basal cell carcinoma (BCC) is a common malignancy with a good prognosis in the majority of cases. However, some BCC patients develop a more advanced disease that poses significant management challenges. Such cases include locally advanced, recurrent or metastatic BCC, or tumours that occur in anatomical sites where surgical treatment would result in significant deformity. Until recently, treatment options for these patients have been limited, but increased understanding of the molecular basis of BCC has enabled potential therapies, such as hedgehog signalling pathway inhibitors, to be developed. A clear definition of advanced BCC as a distinct disease entity and formal management guidelines have not previously been published, presumably because of the rarity, heterogeneity and lack of treatment options available for the disease. Here we provide a UK perspective from a multidisciplinary group of experts involved in the treatment of complex cases of BCC, addressing the key challenges associated with the perceived definition and management of the disease. With new treatments on the horizon, we further propose a definition for advanced BCC that may be used as a guide for healthcare professionals involved in disease diagnosis and management. PMID:25211660

  4. Usefulness of confocal microscopy in distinguishing between basal cell carcinoma and intradermal melanocytic nevus on the face.

    PubMed

    Gamo, R; Floristan, U; Pampín, A; Caro, D; Pinedo, F; López-Estebaranz, J L

    2015-10-01

    The clinical distinction between basal cell carcinoma (BCC) and intradermal melanocytic nevus lesions on the face can be difficult, particularly in young patients or patients with multiple nevi. Dermoscopy is a useful tool for analyzing characteristic dermoscopic features of BCC, such as cartwheel structures, maple leaf-like areas, blue-gray nests and dots, and ulceration. It also reveals arborizing telangiectatic vessels and prominent curved vessels, which are typical of BCC, and comma vessels, which are typical of intradermal melanocytic nevi. It is, however, not always easy to distinguish between these 2 conditions, even when dermoscopy is used. We describe 2 facial lesions that posed a clinical and dermoscopic challenge in two 38-year-old patients; confocal microscopy showed separation between tumor nests and stroma and polarized nuclei, which are confocal microscopy features of basal cell carcinoma.

  5. Hedgehog signaling pathway: a novel target for cancer therapy: vismodegib, a promising therapeutic option in treatment of basal cell carcinomas.

    PubMed

    Abidi, Afroz

    2014-01-01

    The Hedgehog signaling pathway is one of the major regulators of cell growth and differentiation during embryogenesis and early development. It is mostly quiescent in adults but inappropriate mutation or deregulation of the pathway is involved in the development of cancers. Therefore; recently it has been recognized as a novel therapeutic target in cancers. Basal cell carcinomas (BCC) and medulloblastomas are the two most common cancers identified with mutations in components of the hedgehog pathway. The discovery of targeted Hedgehog pathway inhibitors has shown promising results in clinical trials, several of which are still undergoing clinical evaluation. Vismodegib (GDC-0449), an oral hedgehog signaling pathway inhibitor has reached the farthest in clinical development. Initial clinical trials in basal cell carcinoma and medulloblastoma have shown good efficacy and safety and hence were approved by U.S. FDA for use in advanced basal cell carcinomas. This review highlights the molecular basis and the current knowledge of hedgehog pathway activation in different types of human cancers as well as the present and future prospects of the novel drug vismodegib.

  6. Metastatic basal cell carcinoma with amplification of PD-L1: exceptional response to anti-PD1 therapy

    PubMed Central

    Ikeda, Sadakatsu; Goodman, Aaron M; Cohen, Philip R; Jensen, Taylor J; Ellison, Christopher K; Frampton, Garrett; Miller, Vincent; Patel, Sandip P; Kurzrock, Razelle

    2016-01-01

    Metastatic basal cell carcinomas are rare malignancies harbouring Hedgehog pathway alterations targetable by SMO antagonists (vismodegib/sonidegib). We describe, for the first time, the molecular genetics and response of a patient with Hedgehog inhibitor-resistant metastatic basal cell carcinoma who achieved rapid tumour regression (ongoing near complete remission at 4 months) with nivolumab (anti-PD1 antibody). He had multiple hallmarks of anti-PD1 responsiveness including high mutational burden (> 50 mutations per megabase; 19 functional alterations in tissue next-generation sequencing (NGS; 315 genes)) as well as PDL1/PDL2/JAK2 amplification (as determined by both tissue NGS and by analysis of plasma-derived cell-free DNA). The latter was performed using technology originally developed for the genome-wide detection of sub-chromosomal copy-number alterations (CNAs) in noninvasive prenatal testing and showed numerous CNAs including amplification of the 9p24.3-9p22.2 region containing PD-L1, PD-L2 and JAK2. Of interest, PD-L1, PD-L2 and JAK2 amplification is a characteristic of Hodgkin lymphoma, which is exquisitely sensitive to nivolumab. In conclusion, selected SMO antagonist-resistant metastatic basal cell carcinomas may respond to nivolumab based on underlying molecular genetic mechanisms that include PD-L1 amplification and high tumour mutational burden. PMID:27942391

  7. U.S. Food and Drug Administration approval: vismodegib for recurrent, locally advanced, or metastatic basal cell carcinoma.

    PubMed

    Axelson, Michael; Liu, Ke; Jiang, Xiaoping; He, Kun; Wang, Jian; Zhao, Hong; Kufrin, Dubravka; Palmby, Todd; Dong, Zedong; Russell, Anne Marie; Miksinski, Sarah; Keegan, Patricia; Pazdur, Richard

    2013-05-01

    The data and regulatory considerations leading to the U.S. Food and Drug Administration (FDA) January 30, 2012 approval of Erivedge (vismodegib) capsules for the treatment of patients with recurrent, locally advanced, or metastatic basal cell carcinoma (BCC) are described. The FDA's approval decision was based primarily on the results observed in a single-arm, parallel cohort, international trial of vismodegib, administered orally at 150 mg daily until disease progression, in patients with pathologically confirmed, recurrent, locally advanced basal cell carcinoma (laBCC) or metastatic basal cell carcinoma (mBCC). An independent review committee confirmed an overall response rate (ORR) of 30.3% [95% confidence interval (CI): 15.6-48.2] in 33 patients with mBCC and an ORR of 42.9% (95% CI: 30.5-56.0) in 63 patients with laBCC; median response durations were 7.6 months and 7.6 months for patients with mBCC and laBCC, respectively. The most common adverse reactions were muscle spasms, alopecia, dysgeusia, weight loss, fatigue, nausea, diarrhea, decreased appetite, constipation, cough, arthralgias, vomiting, headache, ageusia, insomnia, and upper respiratory tract infection. Animal toxicology studies confirmed that vismodegib is a potent teratogenic agent. Approval was based on durable objective tumor responses supported by knowledge of the pathologic role of Hedgehog signaling in BCC and acceptable toxicity in a population without effective alternative therapies.

  8. Invasive basal cell carcinoma in a xeroderma pigmentosum patient: facing secondary and tertiary aggressive recurrences.

    PubMed

    Lasso, José M; Yordanov, Yordan P; Pinilla, Carmen; Shef, Aylin

    2014-07-01

    Xeroderma pigmentosum (XP) is characterized by photohypersensitivity of sun-exposed tissues and several thousand-fold increased risk of developing malignant neoplasms of the skin and eyes. Inherited molecular defects in nucleotide excision repair genes cause the autosomal recessive condition XP. A 56-year-old woman with XP presented with an extensive multirecurrence basal cell carcinoma in the left naso-orbital region. At the time of the first visit, the patient had already received several interventions with local reconstructive techniques, a full course of radiotherapy, and bilateral neck dissection. A large tumor resection and free flap reconstruction were performed. Three years 9 months afterward, an aggressive recurrence occurred, and a second resection was needed. A new free flap was transferred, and microvascular anastomoses were done to the pedicle of the previously transferred flap. Nine months later, the patient returned with frontal bone tumoral lesions, and third microsurgical intervention was done. At that time, the reconstruction was practiced by a composite chimeric flap with a rib portion. Its pedicle was anastomosed to the one of the second free flaps. The objective of this article was to report the authors' experience concerning a unique case of XP requiring a complex reconstruction of the anterior skull base. Xeroderma pigmentosum patients need an early diagnosis and removal of cutaneous tumor lesions as some of them behave aggressively, especially those affecting the face. Free flaps are good solutions for reconstruction and should proceed from non-sun-exposed areas of the body. If reconstructed areas are highly radiated and/or skin tumors affect deep anatomical areas, complications are frequent.

  9. Common variants modify the age of onset for basal cell carcinomas in Gorlin syndrome.

    PubMed

    Yasar, Binnaz; Byers, Helen J; Smith, Miriam J; Lear, John; Oudit, Deemesh; Bholah, Zaynab; Roberts, Stephen A; Newman, William G; Evans, D Gareth

    2015-05-01

    Gorlin syndrome is an autosomal dominant disorder, characterized by multiple early-onset basal cell carcinomas (BCCs) and jaw keratocysts. Through association studies in cohorts of sporadic BCC, nine genetic variants have previously been identified to increase the risk of BCC. The nine SNPs were genotyped by Taqman allelic discrimination in 125 individuals with Gorlin syndrome. Kaplan-Meier survival curves and Cox proportional-Hazard regression analysis were applied to determine the association between genotypes and age of first BCC in individuals with Gorlin syndrome. The p.(Arg151Cys) variant in MC1R (rs1805007) was associated with an earlier median age of onset of BCC of 27 years (95% CI: 20-34) compared with 34 years (95% CI: 30-40) for wild-type individuals (hazard ratio (HR)=1.64, 95% CI: 1.04-2.58, P=0.034). The risk allele of the variant at the chromosome 5p15 locus encompassing TERT-CLPTM1L (rs401681) was also associated with an earlier median onset of BCC, 31 years (95% CI: 28-37) compared with 41 years (95% CI: 32-48, HR=1.44, 95% CI: 1.08-1.93, P=0.014). In individuals with a risk allele at either rs1805007 or rs401681 the median time to BCC was 31 years of age (95% CI: 28-34) compared with 44 years of age (95% CI: 38-53) in wild-type individuals (HR=2.48, 95% CI: 1.47-4.17, P=0.0002). Our findings may have implications for future personalized risk estimates and BCC screening strategies in individuals with Gorlin syndrome.

  10. Basal Cell Carcinoma of the Outer Nose: Overview on Surgical Techniques and Analysis of 312 Patients

    PubMed Central

    Wollina, Uwe; Bennewitz, Annett; Langner, Dana

    2014-01-01

    Background: Basal cell carcinoma of the nose is common, with a potential of local recurrence and high-risk features. Materials and Methods: We provide a review on anatomy of the nose, tumour surgery and defect closure on the nose. We analysed our own patients with nasal BCC of a 24 months period. Results: We identified 321 patients with nasal BCC. There was a predominance of female patients of 1.2 to 1. The mean age was 74.8 years. Slow Mohs technique was employed for all tumours until 3D tumour-free margins were achieved. That resulted on average in 1.8 ± 0.7 Mohs stages. The most common histologic types were solitary (n = 182), morpheic (79), and micronodular (20), Perineural infiltration was evident in 56 tumours. Primary closure after mobilisation of soft tissue was possible in 105 BCCs. Advancement flaps were used in 91 tumours, rotation flaps in 47, transposition flaps in 34 tumours, and combined procedures in 6 cases. In 36 patients full-thickness skin grafting was performed. In two patients healing by second intention was preferred. Partial flap loss was seen in four patients (1.4%). All of them had significant underlying pathologies. None of the tumours treated showed a relapse during the observation time. However, this is a limitation of the present study since follow-up was on average only 10 months. Conclusions: BCCs of the nose are common. Only 3D-controlled micrographic surgery (Mohs or slow Mohs) guarantee a high rate of complete tumour removal and a very low risk of recurrence. PMID:25538434

  11. Basal-Cell Carcinoma Incidence and Associated Risk Factors in US Women and Men

    PubMed Central

    Wu, Shaowei; Han, Jiali; Li, Wen-Qing; Li, Tricia; Qureshi, Abrar A.

    2013-01-01

    There is a paucity of data on basal-cell carcinoma (BCC) in the United States, since most national registries do not collect information on BCC. We evaluated BCC incidence trends and associated risk factors for BCC in 140,171 participants from a US female cohort, the Nurses' Health Study (1986–2006), and a US male cohort, the Health Professionals' Follow-up Study (1988–2006). Age-adjusted BCC incidence rates increased from 519 cases per 100,000 person-years to 1,019 cases per 100,000 person years for women and increased from 606 cases per 100,000 person-years to 1,488 cases per 100,000 person-years for men during the follow-up period. Cox proportional hazards analysis identified the following phenotypic risk factors for BCC in both cohorts: family history of melanoma, blond or red hair colors, higher number of extremity moles, higher susceptibility to sunburn as a child/adolescent, and higher lifetime number of severe/blistering sunburns. The multivariate-adjusted risk ratio for the highest quintile of cumulative midrange ultraviolet B flux exposure versus the lowest quintile was 3.18 (95% confidence interval: 2.70, 3.76) in women and 1.90 (95% confidence interval: 1.57, 2.29) in men. BCC incidence was generally higher in men than in women, and BCC risk was strongly associated with several phenotypic and exposure factors, including midrange ultraviolet B radiation, in our study populations. PMID:23828250

  12. Hedgehog signaling pathway and its targets for treatment in basal cell carcinoma

    PubMed Central

    Cucchi, Danilo; Occhione, Maria Anna; Gulino, Alberto; De Smaele, Enrico

    2012-01-01

    Basal cell carcinoma (BCC) of the skin is the most common type of cancer and accounts for up to 40% of all cancers in the US, with a growing incidence rate over recent decades in all developed countries. Surgery is curative for most patients, although it leaves unaesthetic scars, but those that develop locally advanced or metastatic BCC require different therapeutic approaches. Furthermore, patients with BCC present a high risk of developing additional tumors. The increasing economic burden and the morbidity of BCC render primary interest in the development of targeted treatments for this disease. Among the molecular signals involved in the development of BCC, the critical role of the morphogenetic Hedgehog (Hh) pathway has become evident. This pathway is found altered and activated in almost all BCCs, both sporadic and inherited. Given the centrality of the Hh pathway in the pathophysiology of BCC, the primary efforts to identify molecular targets for the topical or systemic treatment of this cancer have focused on the Hh components. Several Hh inhibitors have been so far identified – from the first identified natural cyclopamine to the recently Food and Drug Administration-approved synthetic vismodegib – most of which target the Hh receptor Smoothened (either its function or its translocation to the primary cilium). Other molecules await further characterization (bisamide compounds), while drugs currently approved for other diseases such as itraconazole (an antimicotic agent) and vitamin D3 have been tested on BCC with encouraging results. The outcomes of the numerous ongoing clinical trials are expected to expand the field in the very near future. Further research is needed to obtain drugs targeting downstream components of the Hh pathway (eg, Gli) or to exploit combinatorial therapies (eg, with phosphatidylinositol 3-kinase inhibitors or retinoids) in order to overcome potential drug resistance. PMID:27186130

  13. MC1R and PTCH gene polymorphism in French patients with basal cell carcinomas.

    PubMed

    Liboutet, Muriel; Portela, Marc; Delestaing, Gisèle; Vilmer, Catherine; Dupin, Nicolas; Gorin, Isabelle; Saiag, Philippe; Lebbé, Céleste; Kerob, Delphine; Dubertret, Louis; Grandchamp, Bernard; Basset-Seguin, Nicole; Soufir, Nadem

    2006-07-01

    In this study, we assessed the role of melanocortin 1 receptor (MC1R) variants and of two patched (PTCH) polymorphisms (c.3944C>T (P1315L), insertion 18 bp IVS1-83) as risk factors for basal cell carcinoma (BCC) in the French population. The population investigated comprised 126 BCC patients who were enrolled on the basis of specific criteria (multiple and/or familial BCC and/or onset before the age of 40 years and/or association with another tumor)--and 151 controls matched for ethnicity, age, and sex. MC1R variants appeared as a moderate risk factor for BCC (odds ratio (OR) for one and two variants, 2.17 [1.28-3.68] and 7.72 [3.42-17.38], respectively), independently of pigmentation characteristics (OR = 2.53 [1.34-4.8]). Interestingly, in addition to the predictable red hair color (RHC) alleles, two non-RHC alleles (V60L and V92M) were also closely associated with BCC risk (OR 3.21 [1.91-5.38] and 2.87 [1.5-5.48], respectively), which differs from the situation in the Celtic population. In addition, the PTCH c.3944C/C genotype was also associated with BCC risk (OR 1.94 [1.2-3.1]), especially in the subgroup of patients with multiple tumors (OR 2.16 [1.3-3.6]). Thus, our data show that MC1R and PTCH variants are associated with BCC risk in the French population. We further suggest that assessing MC1R and PTCH status could be useful, combined with the assessment of clinical risk factors, in identifying high-risk patients to be targeted for prevention or more rigorous surveillance.

  14. UV fingerprints predominate in the PTCH mutation spectra of basal cell carcinomas independent of clinical phenotype.

    PubMed

    Heitzer, Ellen; Lassacher, Anita; Quehenberger, Franz; Kerl, Helmut; Wolf, Peter

    2007-12-01

    Basal cell carcinoma (BCC) shows a wide interpatient variation in lesion accrual. To determine whether certain tumorigenic fingerprints and potentially predisposing patched (PTCH) tumor suppressor single-nucleotide polymorphisms (SNPs) are distributed differently among sporadic BCC patients, we compared the PTCH mutation spectra in early-onset BCC (first lesion at age < 35 years), regular BCC (first lesion at age > or = 35 years and < 10 lesions), and multiple BCC (> or = 10 lesions). The PTCH gene was mutated in 29 of 60 cases (48%). Most of the PTCH mutations bore the UV fingerprint (i.e., C --> T or tandem CC --> TT transitions at dipyrimidine sites). However, neither the proportion nor the spectra of exonic PTCH mutations differed significantly among the three groups. A large number of SNPs (IVS10+99C/T, IVS11-51G/C, 1665T/C, 1686C/T, IVS15+9G/C, IVS16-80G/C, IVS17+21G/A, and 3944C/T or its combinations) were also detected, but again their incidence did not differ significantly among the groups. Interestingly, expression of the IVS16-80G/C and the IVS17+21G/A genotype did not achieve the Hardy-Weinberg equilibrium in patients with regular and/or early-onset BCC. These data suggest that a (UV-) mutated PTCH gene is important for sporadic BCC formation independent of clinical phenotype and that the IVS16-80G/C and/or IVS17+21G/A SNP site might be important for tumorigenesis in certain BCC patients.

  15. Vismodegib for the treatment of basal cell carcinoma: results and implications of the ERIVANCE BCC trial.

    PubMed

    Dessinioti, Clio; Plaka, Michaela; Stratigos, Alexander J

    2014-05-01

    The need for effective treatment of patients with locally advanced or metastatic basal cell carcinoma (BCC), in conjunction with major advances in the elucidation of the molecular basis of this tumor has led to the advent of new targeted therapies - namely, hedgehog inhibitors. The rationale for their use in patients with advanced BCC is based on their inhibitory effect on the hedgehog pathway, which is aberrantly activated in BCCs due to mutations of its primary components, PTCH1 and SMO genes. Vismodegib (GDC-0449) is an orally bioavailable hedgehog pathway inhibitor that selectively inhibits SMO. The ERIVANCE BCC study is a Phase II, international, multicenter clinical trial evaluating the efficacy and safety of vismodegib 150 mg once daily in patients with locally advanced or metastatic BCC. Vismodegib has been approved for the treatment of adult patients with metastatic BCC, or with locally advanced BCC that has recurred following surgery or who are not candidates for surgery or radiation therapy. This article will outline the rationale, design and available results from the ERIVANCE BCC study and discuss the clinical implications of vismodegib in the management of patients with BCC. Challenges regarding vismodegib use include the recurrence of BCC after drug discontinuation, the development of acquired resistance, the dramatic efficacy in patients with Gorlin syndrome, and class-related drug toxicity. Ongoing clinical trials aim to explore the role of vismodegib in the neoadjuvant setting prior to surgery, the potential use of alternate dosing regimens in order to limit chronic adverse events, as well as the identification of patients with BCC that are more likely to respond to this targeted therapy based on genotypic and/or phenotypic characteristics.

  16. 18-FDG PET/CT assessment of basal cell carcinoma with vismodegib.

    PubMed

    Thacker, Curtis A; Weiss, Glen J; Tibes, Raoul; Blaydorn, Lisa; Downhour, Molly; White, Erica; Baldwin, Jason; Hoff, Daniel D; Korn, Ronald L

    2012-10-01

    The use of 18-fluorodeoxyglucose (FDG) positron emission tomography with computed tomography (PET/CT) in subjects with advanced basal cell carcinoma (BCC) has not been fully explored due to the rarity of disease presentation. This study evaluated PET/CTs from subjects with advanced BCC participating in a phase I dose-escalation clinical trial of vismodegib. Fourteen subjects with BCC were imaged with 18-FDG PET/CT for lesion identification and response categorizing (European Organisation for Research and Treatment for Cancer [EORTC] and PET response criteria in solid tumors [PERCIST] 1.0). Several parameters including metabolic activity of target lesions, site of disease presentation and spread, treatment response, and prognostic significance of metabolic activity following therapy were evaluated. All subjects exhibited at least one hypermetabolic lesion. Most subjects had only four organ systems involved at study enrollment: skin-muscle (93%), lung (57%), lymph nodes (29%), and bone (21%). SUVmax measured across all lesions decreased (median 33%, SD ± 45%) following therapy with metabolic activity normalizing or disappearing in 42% of lesions. No significant difference was observed between EORTC and PERCIST 1.0. Subjects that demonstrated at least a 33% reduction in SUVmax from baseline had a significantly longer progression-free survival (PFS) (median 17 months, 95% confidence interval [CI] ±4 months vs. 9 months, 95% CI ±5 months, P = 0.038) and overall survival (OS) (median 24 months, 95% CI ±4 months vs. 17 months, 95% CI ±13 months, P = 0.019). BCC lesions are hypermetabolic on 18-FDG PET/CT. A decrease in SUVmax was associated with improved PFS and OS. These results further support the incorporation of 18-FDG PET/CT scans in advanced BCC management.

  17. Smoothened (SMO) receptor mutations dictate resistance to vismodegib in basal cell carcinoma.

    PubMed

    Pricl, Sabrina; Cortelazzi, Barbara; Dal Col, Valentina; Marson, Domenico; Laurini, Erik; Fermeglia, Maurizio; Licitra, Lisa; Pilotti, Silvana; Bossi, Paolo; Perrone, Federica

    2015-02-01

    Basal cell carcinomas (BCCs) and a subset of medulloblastomas are characterized by loss-of-function mutations in the tumor suppressor gene, PTCH1. PTCH1 normally functions by repressing the activity of the Smoothened (SMO) receptor. Inactivating PTCH1 mutations result in constitutive Hedgehog pathway activity through uncontrolled SMO signaling. Targeting this pathway with vismodegib, a novel SMO inhibitor, results in impressive tumor regression in patients harboring genetic defects in this pathway. However, a secondary mutation in SMO has been reported in medulloblastoma patients following relapse on vismodegib to date. This mutation preserves pathway activity, but appears to confer resistance by interfering with drug binding. Here we report for the first time on the molecular mechanisms of resistance to vismodegib in two BCC cases. The first case, showing progression after 2 months of continuous vismodegib (primary resistance), exhibited the new SMO G497W mutation. The second case, showing a complete clinical response after 5 months of treatment and a subsequent progression after 11 months on vismodegib (secondary resistance), exhibited a PTCH1 nonsense mutation in both the pre- and the post-treatment specimens, and the SMO D473Y mutation in the post-treatment specimens only. In silico analysis demonstrated that SMO(G497W) undergoes a conformational rearrangement resulting in a partial obstruction of the protein drug entry site, whereas the SMO D473Y mutation induces a direct effect on the binding site geometry leading to a total disruption of a stabilizing hydrogen bond network. Thus, the G497W and D473Y SMO mutations may represent two different mechanisms leading to primary and secondary resistance to vismodegib, respectively.

  18. Multistep carcinogenesis in the formation of basal cell carcinoma of the skin

    SciTech Connect

    Gailani, M.; Leffell, D.; Ziegler, A.

    1994-09-01

    Basal cell carcinoma of the skin (BCC) is the most common cancer in humans, a slow growing tumor whose incidence strongly correlates with exposure to UV light. Although the molecular basis of BCC formation is not well understood, loss of heterozygosity (LOH) for markers on chromosome 9q in 70% of BCCs suggests that inactivation of a tumor suppressor on 9q22 is an important early step. UV induced mutations in the p53 gene have also been found in over 50% of sporadic BCCs. We analyzed 18 sporadic BCCs for allelic loss on chromosome 9 and point mutations in the p53 gene and attempted to correlate genetic alteration with pathological subtype and relative UV light exposure. Eight of eighteen tumors (45%) showed LOH on chromosome 9 as well as point mutation of the p53 gene, three of eighteen tumors (17%) showed mutation of the p53 gene without LOH on chromosome 9, five of eighteen tumors (27%) showed LOH for chromosome 9 without evidence of mutation in the p53 gene, and two of eighteen tumors (11%) showed neither LOH on chromosome 9 nor mutation in the p53 gene. Tumor pathology showed no obvious correlation between mutation and tumor aggressiveness. However, one tumor of a unique, aggressive growth subtype had no genetic alteration suggesting a different genetic mechanism in this particular subgroup. 38% of tumors from areas of greatest sun-exposure showed both mutations. The data suggests a strong correlation between inactivation of a tumor suppressor gene on chromosome 9 and mutation in the p53 gene though the sequence of events cannot be determined. Because carcinogenesis is a multistep process and genetic injury from UV light is only one factor, further correlation with degree of tumor differentiation may clarify the genetic process in BCCs.

  19. Differential pharmacology and clinical utility of sonidegib in advanced basal cell carcinoma

    PubMed Central

    Wahid, Mohd; Jawed, Arshad; Dar, Sajad Ahmad; Mandal, Raju K; Haque, Shafiul

    2017-01-01

    Patients suffering from advanced basal cell carcinoma (BCC) have very limited treatment options. Sonidegib selectively inhibits the growth of Hedgehog pathway-dependent tumors and can treat locally advanced BCC patients who are not candidates for surgery or radiation therapy. The BOLT clinical trials were conducted to evaluate the efficacy/potency of sonidegib in the treatment of advanced BCC or metastatic BCC. The patients were randomized in 1:2 ratios to receive 200 or 800 mg oral sonidegib daily, stratified by disease, histological subtype and geographical region. The primary efficacy analyses showed that 18 patients in the 200 mg group and 35 patients in the 800 mg group show an objective response (Central Review Committee) that corresponds to 43% (95% confidence interval [CI]: 28–59) and 38% (95% CI: 28–48) in their respective categories. Disease control was found in 93% (39 patients) and 80% (74 patients) of the patients administered 200 and 800 mg sonidegib, respectively. The adverse events were assessed by the Central Review Committee as well as the investigator review team as per the guidelines of National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. The most frequently found adverse events reported in BOLT trials were muscle spasms, alopecia, dysgeusia (taste disturbance), nausea, elevated blood creatine kinase and fatigue. Comparatively, the patients administered 200 mg sonidegib showed fewer adverse events than those in the 800 mg sonidegib category. Thus, the benefit of using the 200 mg dose of sonidegib outweighs the associated risks and it can be inferred that it would be judicious to choose doses of lesser strength. PMID:28182134

  20. Efficacy and safety of electronic brachytherapy for superficial and nodular basal cell carcinoma

    PubMed Central

    Pons-Llanas, Olga; Candela-Juan, Cristian; Celada-Alvarez, Francisco Javier; de Unamuno-Bustos, Blanca; Llavador-Ros, Margarita; Ballesta-Cuñat, Antonio; Barker, Christopher A.; Tormo-Mico, Alejandro; Botella-Estrada, Rafael; Perez-Calatayud, Jose

    2015-01-01

    Purpose Surface electronic brachytherapy (EBT) is an alternative radiotherapy solution to external beam electron radiotherapy and high-dose-rate radionuclide-based brachytherapy. In fact, it is also an alternative solution to surgery for a subgroup of patients. The objective of this work is to confirm the clinical efficacy, toxicity and cosmesis of a new EBT system, namely Esteya® in the treatment of nodular and superficial basal cell carcinoma (BCC). Material and methods This is a prospective single-center, non-randomized pilot study to assess the efficacy and safety of EBT in nodular and superficial BCC using the Esteya® system. The study was conducted from June 2014 to February 2015. The follow up time was 6 months for all cases. Results Twenty patients with 23 lesions were included. A complete response was documented in all lesions (100%). A low level of toxicity was observed after the 4th fraction in all cases. Erythema was the most frequent adverse event. Cosmesis was excellent, with more than 60% of cases without skin alteration and with subtle changes in the rest. Conclusions Electronic brachytherapy with Esteya® appears to be an effective, simple, safe, and comfortable treatment for nodular and superficial BCC associated with excellent cosmesis. It could be a good choice for elderly patients, patients with contraindications for surgery (due to comorbidities or anticoagulant drugs) or patients where surgery would result in a more disfiguring outcome. A longer follow-up and more studies are needed to confirm these preliminary results. PMID:26207112

  1. Efficacy of low-dose mTHPC-PDT for the treatment of basal cell carcinomas

    NASA Astrophysics Data System (ADS)

    Betz, Christian S.; Rauschning, Winrich; Stranadko, Evgueni P.; Riabov, Mikhail V.; Albrecht, Volker; Nifantiev, Nikolay E.; Hopper, Colin

    2009-06-01

    Objectives: Basal cell carcinomas (BCCs) are the most common skin cancers, and incidence rates are still rising. Photodynamic Therapy (PDT) with mTHPC (Foscan®) has shown to be a promising alternative to other treatments with good cosmetic results. This study was performed to determine optimal treatment parameters for this indication. Methods: 117 patients with a total of 460 BCCs received mTHPC-PDT. The treatment parameters were varied as follows: Foscan® dose 0.03 - 0.15 mg/kg, drug-light interval (DLI) 1 - 96 hours, total energy density 20 - 120 J/cm2. The clinical outcomes were assessed 8 weeks after PDT following WHO guidelines. Results: The rate of complete remissions (CR) was 96.7% and the general cosmetic outcome rated very good. In the largest subgroup (n=80) with low-dose mTHPC (0.05 mg/kg mTHPC; 48 hours DLI; 50 J/cm2 total energy density), a CR rate of 100% was accomplished. Minor changes of the parameters (0.04 mg/kg mTHPC or 24 hours DLI) yielded similar results. Side effects were encountered in 52 out of 133 PDT sessions. They were more common in patients who had received high drug doses (0.06 - 0.15 mg/kg) and comprised pain and phototoxic reactions. 3 patients developed severe sunburns with subsequent scarring at the injection site following sunlight exposure 2-3 weeks after mTHPC administration. Conclusions: The data suggests that low-dose mTHPC-PDT is an effective treatment option for BCCs. If sensibly applied, it is well tolerated and provides mostly excellent cosmetic results. The evaluation of long term results is still to be undertaken.

  2. Clinical Benefit Assessment of Vismodegib Therapy in Patients With Advanced Basal Cell Carcinoma

    PubMed Central

    Basset-Seguin, Nicole; Caro, Ivor; Yue, Huibin; Schadendorf, Dirk

    2014-01-01

    Purpose. Vismodegib was approved for the treatment of advanced basal cell carcinoma (aBCC) based on the pivotal ERIVANCE BCC study. The primary endpoint (objective response rate [ORR]) was assessed 9 months after the last patient was enrolled. To confirm the clinical benefit of vismodegib, an additional analysis was performed 12 months after the primary analysis. Materials and Methods. ERIVANCE BCC was a multicenter, nonrandomized, two-cohort study of 104 patients with histologically confirmed aBCC. Patients received 150 mg oral vismodegib daily until disease progression, intolerable toxicity, or withdrawal. An independent review panel comprising three expert clinicians reviewed patient photographs individually and as a consensus panel to evaluate baseline disease severity and clinical benefit after vismodegib treatment in 71 patients with locally advanced BCC (laBCC). Results. Sixty-three patients were efficacy evaluable; baseline and postprogression photographs for 61 were available for review. Baseline disease severity was judged as 5 or 4 (very severe or moderately severe) in 71.4%. Clinical benefit was observed in 76.2% (significant: 65.1%; some: 11.1%). Interpanelist agreement (maximum difference ≤1 point among panelists’ scores in 65.1% and 87.3% of patients for clinical benefit and baseline disease severity, respectively) and correlation between individual and panel reviews were strong. Clinical benefit scores showed good concordance with the protocol-specified ORR obtained by an independent review facility and with investigator-assessed response. Conclusion. Clinical benefit assessed by independent review based on expert clinical judgment provides strong evidence that treatment with vismodegib results in clinically meaningful and durable responses in patients with laBCC. PMID:25001266

  3. Human Papillomaviruses, p16INK4a and Akt expression in basal cell carcinoma

    PubMed Central

    2011-01-01

    Background The pathogenic role of beta-HPVs in non melanoma skin cancer (NMSC), is not still completely understood, and literature data indicate that they might be at least cofactors in the development of certain cutaneous squamous cell carcinomas. However, only few reports contain data on basal cell carcinoma (BCC). The HPVs interact with many cellular proteins altering their function or the expression levels, like the p16INK4a and Akt. Our study aimed to determine the presence of different beta -HPV types and the expression of p16INK4a and Akt in BCC, the commonest NMSC, in the normal appearing perilesional skin and in forehead swab of 37 immunocompetent patients. Methods The expression of p16INK4a and Akt, by immunohistochemistry, and the HPV DNA, by nested PCR, were investigated in each sample. Results No correspondence of HPV types between BCC and swab samples was found, whereas a correspondence between perilesional skin and BCC was ascertained in the 16,7% of the patients. In BCC, 16 different types of beta HPV were found and the most frequent types were HPV107 (15,4%), HPV100 (11,5%) and HPV15 (11,5%) all belonging to the beta HPV species 2. Immunohistochemistry detected significant p16INK4a expression in almost all tumor samples (94,3%) with the highest percentages (> 30%) of positive cells detected in 8 cases. A statistically significant (p = 0,012) increase of beta HPV presence was detected in p16INK4a strongly positive samples, in particular of species 2. pAkt expression was detected in all tumor samples with only 2 cases showing rare positive cells, whereas Akt2 expression was found in 14 out of 35 BCC (40%); in particular in HPV positive samples over-expressing p16INK4a. Conclusions Our data show that p16INK4a and pAkt are over-expressed in BCC and that the high expression of p16INK4a and of Akt2 isoform is often associated with the presence of beta-HPV species 2 (i.e. HPV 15). The association of these viruses with the up-regulation of p16INK4a and Akt

  4. Topical 5% 5-fluorouracil in the treatment of multifocal basal cell carcinoma of the face: A novel chemotherapeutic approach.

    PubMed

    Naik, Mayuresh P; Mehta, Anuj; Abrol, Sangeeta; Kumar, Sandeep; Gupta, Vishnu S

    2016-12-01

    To determine the safety and efficacy of topical 5-fluorouracil (5-FU) 5% ointment in treatment of non-syndromic multifocal basal cell carcinoma. A 55-year-old male patient, with 8 hours of daily sun exposure, having histologically proven and radiologically non-syndromic, multifocal basal cell carcinoma with involvement of 6 sites on the face, was treated with topical 5-FU 5% ointment twice daily over all sites except the site involving lid margin to prevent corneal toxicity. Left lid lesion underwent wide surgical excision with 5-mm clear margins and reconstruction with nasal septal mucoperichondrium and local skin mobilization. Pharmacologic effects first appeared at 4 weeks and by 8 weeks, the lesions had scabbed and had fallen off with no induration but residual mild perilesional erythema. Patient had post-op histopathological clear margins and recovered uneventfully. No recurrence in 6 months. A topical 5-FU 5% ointment represents a paradigm shift in the treatment of BCC from invasive and disfiguring options (surgery and chemoradiotherapy) to cheap, convenient, effective, non-invasive, non-disfiguring topical chemotherapy. Topical 5% 5-FU is a safe and effective modality of treatment of superficial spreading multifocal basal carcinoma, especially lesions larger than 10 mm, where margins cannot be identified clearly and recurrent lesions.

  5. Combined reflectance confocal microscopy-optical coherence tomography for delineation of basal cell carcinoma margins: an ex vivo study

    PubMed Central

    Iftimia, Nicusor; Peterson, Gary; Chang, Ernest W.; Maguluri, Gopi; Fox, William; Rajadhyaksha, Milind

    2016-01-01

    Abstract. We present a combined reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) approach, integrated within a single optical layout, for diagnosis of basal cell carcinomas (BCCs) and delineation of margins. While RCM imaging detects BCC presence (diagnoses) and its lateral spreading (margins) with measured resolution of ∼1  μm, OCT imaging delineates BCC depth spreading (margins) with resolution of ∼7  μm. When delineating margins in 20 specimens of superficial and nodular BCCs, depth could be reliably determined down to ∼600  μm, and agreement with histology was within about ±50  μm. PMID:26780224

  6. Emergence of chemoresistance in a metastatic basal cell carcinoma patient after complete response to hedgehog pathway inhibitor vismodegib (GDC-0449).

    PubMed

    Meani, Rowena E; Lim, Shueh-Wen; Chang, Anne Lynn S; Kelly, John W

    2014-08-01

    Vismodegib (GDC-0449, Genentech, USA), a small molecule inhibitor of the Hedgehog signalling pathway, has potent anti-tumour activity in advanced basal cell carcinoma (BCC). We report a case of a 67-year-old Australian man with metastatic BCC including pulmonary disease with malignant effusion who showed a dramatic complete response to vismodegib but subsequently experienced a recurrence of pulmonary disease, indicative of chemoresistance to vismodegib. This case is the first to illustrate chemoresistance in a patient with metastatic BCC, and demonstrates the need for closely monitoring metastatic BCC patients even after an apparently complete response.

  7. Combined reflectance confocal microscopy-optical coherence tomography for delineation of basal cell carcinoma margins: an ex vivo study

    NASA Astrophysics Data System (ADS)

    Iftimia, Nicusor; Peterson, Gary; Chang, Ernest W.; Maguluri, Gopi; Fox, William; Rajadhyaksha, Milind

    2016-01-01

    We present a combined reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) approach, integrated within a single optical layout, for diagnosis of basal cell carcinomas (BCCs) and delineation of margins. While RCM imaging detects BCC presence (diagnoses) and its lateral spreading (margins) with measured resolution of ˜1 μm, OCT imaging delineates BCC depth spreading (margins) with resolution of ˜7 μm. When delineating margins in 20 specimens of superficial and nodular BCCs, depth could be reliably determined down to ˜600 μm, and agreement with histology was within about ±50 μm.

  8. Reflectance confocal microscopy and dermoscopy for in vivo, non-invasive skin imaging of superficial basal cell carcinoma

    PubMed Central

    GHITA, MIHAELA A.; CARUNTU, CONSTANTIN; ROSCA, ADRIAN E.; KALESHI, HARILLAQ; CARUNTU, ANA; MORARU, LILIANA; DOCEA, ANCA OANA; ZURAC, SABINA; BODA, DANIEL; NEAGU, MONICA; SPANDIDOS, DEMETRIOS A.; TSATSAKIS, ARISTIDIS M.

    2016-01-01

    Superficial basal cell carcinoma (sBCC) is the second most frequent histological type of basal cell carcinoma (BCC), usually requiring a skin biopsy to confirm the diagnosis. It usually appears on the upper trunk and shoulders as erythematous and squamous lesions. Although it has a slow growth and seldom metastasizes, early diagnosis and management are of crucial importance in preventing local invasion and subsequent disfigurement. Dermoscopy is nowadays an indispensable tool for the dermatologist when evaluating skin tumors. Reflectance confocal microscopy (RCM) is a novel imaging technique that allows the non-invasive, in vivo quasi-microscopic morphological and dynamic assessment of superficial skin tumors. Moreover, it offers the advantage of performing infinite repeatable determinations to monitor disease progression and non-surgical treatment for sBCC. Herein, we present three lesions of sBCC evaluated using in vivo and non-invasive imaging techniques, emphasizing the usefulness of combining RCM with dermoscopy for increasing the diagnostic accuracy of sBCC. PMID:27123056

  9. Expression of Ulex europaeus agglutinin I lectin-binding sites in squamous cell carcinomas and their absence in basal cell carcinomas. Indicator of tumor type and differentiation.

    PubMed

    Heng, M C; Fallon-Friedlander, S; Bennett, R

    1992-06-01

    Lectins bind tightly to carbohydrate moieties on cell surfaces. Alterations in lectin binding have been reported to accompany epidermal cell differentiation, marking alterations in membrane sugars during this process. The presence of UEA I (Ulex europaeus agglutinin I) L-fucose-specific lectin-binding sites has been used as a marker for terminally differentiated (committed) keratinocytes. In this article, we report the presence of UEA-I-binding sites on squamous keratinocytes of well-differentiated squamous cell carcinomas, with patchy loss of UEA I positivity on poorly differentiated cells of squamous cell carcinomas, suggesting a possible use for this technique in the rapid assessment of less differentiated areas within the squamous cell tumor. The absence of UEA-I-binding sites on basal cell carcinomas may be related to an inability of cells comprising this tumor to convert the L-D-pyranosyl moiety on basal cells to the L-fucose moiety, resulting in an inability of basal cell carcinoma cell to undergo terminal differentiation into a committed keratinocyte.

  10. Elevated YAP and its downstream targets CCN1 and CCN2 in basal cell carcinoma: impact on keratinocyte proliferation and stromal cell activation.

    PubMed

    Quan, Taihao; Xu, Yiru; Qin, Zhaoping; Robichaud, Patrick; Betcher, Stephanie; Calderone, Ken; He, Tianyuan; Johnson, Timothy M; Voorhees, John J; Fisher, Gary J

    2014-04-01

    Yes-associated protein (YAP) is a transcriptional co-activator of hippo signaling pathway, which plays an important role in organ size control and tumorigenesis. Here we report that YAP and its downstream transcriptional targets CCN1 and CCN2 are markedly elevated in keratinocytes in human skin basal cell carcinoma tumor islands. In human keratinocytes, knockdown of YAP significantly reduced expression of CCN1 and CCN2, and repressed proliferation and survival. This inhibition of proliferation and survival was rescued by restoration of CCN1 expression, but not by CCN2 expression. In basal cell carcinoma stroma, CCN2-regulated genes type I collagen, fibronectin, and α-smooth muscle actin were highly expressed. Furthermore, atomic force microscopy revealed increased tissue stiffness in basal cell carcinoma stroma compared to normal dermis. These data provide evidence that up-regulation of YAP in basal cell carcinoma impacts both aberrant keratinocyte proliferation, via CCN1, and tumor stroma cell activation and stroma remodeling, via CCN2. Targeting YAP and/or CCN1 and CCN2 may provide clinical benefit in basal cell carcinoma.

  11. Initial basal cell carcinomas diagnosed in the National Campaign for Skin Cancer Prevention are smaller than those identified by the conventional medical referral system*

    PubMed Central

    Wakiyama, Thweicyka Pinheiro; França, Maria Laura Marconi; Carvalho, Larissa Pierri; Marques, Mariangela Esther Alencar; Miot, Hélio Amante; Schmitt, Juliano Vilaverde

    2017-01-01

    BACKGROUND Basal cell carcinoma is the malignant tumor most often diagnosed in the National Campaign for Skin Cancer Prevention (NCSCP). Little is known about the profile of these lesions compared to the profile of lesions diagnosed by conventional routes of public dermatological care. OBJECTIVE To identify if basal cell carcinomas identified in prevention campaigns and referred to surgery are smaller than those routinely removed in a same medical institution. METHODS Cross-sectional study including tumors routed from 2011-2014 campaigns and 84 anatomopathological reports of outpatients. RESULTS The campaigns identified 223 individuals with suspicious lesions among 2,531 examinations (9%), with 116 basal cell carcinomas removed. Anatomopathological examinations revealed that the primary lesions identified in the national campaigns were smaller than those referred to surgery by the conventional routes of public health care (28 [13-50] x 38 [20-113] mm2, p <0.01). On the other hand, after a mean follow-up of 15.6 ± 10.3 months, 31% of cases identified in campaigns showed new basal cell carcinoma lesions. STUDY LIMITATIONS Retrospective study and inaccuracies in the measurements of the lesions. CONCLUSIONS The NCSCP promotes an earlier treatment of basal cell carcinomas compared to patients referred to surgery by the conventional routes of public health care, which can result in lower morbidity rates and better prognosis. PMID:28225952

  12. Merkel cell polyomavirus infection in both components of a combined Merkel cell carcinoma and basal cell carcinoma with ductal differentiation; each component had a similar but different novel Merkel cell polyomavirus large T antigen truncating mutation.

    PubMed

    Iwasaki, Takeshi; Kodama, Hajime; Matsushita, Michiko; Kuroda, Naoto; Yamasaki, Yoshikazu; Murakami, Ichiro; Yamamoto, Osamu; Hayashi, Kazuhiko

    2013-03-01

    Merkel cell polyomavirus infects up to 80% of patients with Merkel cell carcinoma. Combined Merkel cell carcinoma and cutaneous tumors occur occasionally. Previous reports have suggested that Merkel cell polyomavirus is absent from combined Merkel cell carcinoma and squamous cell carcinomas. This is the first report that Merkel cell polyomavirus infected in both lesions of a combined Merkel cell carcinoma and basal cell carcinoma. A 92-year-old Japanese man presented with a right thigh small subcutaneous mass. Histologic examination revealed a combined tumor with Merkel cell carcinoma and basal cell carcinoma with ductal differentiation. Both tumors and intermingled Merkel cells in basal cell carcinoma expressed Merkel cell polyomavirus large T antigen, and 17 and 240 copies of Merkel cell polyomavirus/cell were detected in the microdissected Merkel cell carcinoma and basal cell carcinoma specimens, respectively. Mutation analysis of Merkel cell polyomavirus large T antigen revealed a novel truncating mutation in Merkel cell carcinoma and a similar but different mutation in the basal cell carcinoma. These results suggest that each was infected by a different Merkel cell polyomavirus subclone derived from a single Merkel cell polyomavirus.

  13. Sonidegib for the treatment of advanced basal cell carcinoma: a comprehensive review of sonidegib and the BOLT trial with 12-month update.

    PubMed

    Chen, Leon; Silapunt, Sirunya; Migden, Michael R

    2016-09-01

    The Hedgehog inhibitors are promising alternative for patients with advanced basal cell carcinoma that are not amenable to radiotherapy or surgery. Sonidegib, also known as LDE225, is an orally available SMO antagonist that was recently approved by the US FDA for the treatment of patients with locally advanced basal cell carcinoma. This article will provide an overview of the pharmacology and pharmacokinetics of sonidegib and in-depth analysis of the BOLT trial with additional data from the 12-month update. The present challenges associated with Hedgehog inhibitors will also be discussed.

  14. Diagnosing basal cell carcinoma in vivo by near-infrared Raman spectroscopy: a Principal Components Analysis discrimination algorithm

    NASA Astrophysics Data System (ADS)

    Silveira, Landulfo, Jr.; Silveira, Fabrício L.; Bodanese, Benito; Pacheco, Marcos Tadeu T.; Zângaro, Renato A.

    2012-02-01

    This work demonstrated the discrimination among basal cell carcinoma (BCC) and normal human skin in vivo using near-infrared Raman spectroscopy. Spectra were obtained in the suspected lesion prior resectional surgery. After tissue withdrawn, biopsy fragments were submitted to histopathology. Spectra were also obtained in the adjacent, clinically normal skin. Raman spectra were measured using a Raman spectrometer (830 nm) with a fiber Raman probe. By comparing the mean spectra of BCC with the normal skin, it has been found important differences in the 800-1000 cm-1 and 1250-1350 cm-1 (vibrations of C-C and amide III, respectively, from lipids and proteins). A discrimination algorithm based on Principal Components Analysis and Mahalanobis distance (PCA/MD) could discriminate the spectra of both tissues with high sensitivity and specificity.

  15. Overexpression of the human homologue of Drosophila patched (PTCH) in skin tumours: specificity for basal cell carcinoma.

    PubMed

    Nagano, T; Bito, T; Kallassy, M; Nakazawa, H; Ichihashi, M; Ueda, M

    1999-02-01

    The human homologue of the Drosophila segment polarity gene patched (PTCH) has been identified as the gene for the naevoid basal cell carcinoma (BCC) syndrome and has also been shown to be mutated in sporadic BCC. In order to elucidate the specificity of the PTCH abnormality in BCC, we examined normal skin and 12 BCC and 24 other types of tumour from Japanese patients for expression of the PTCH transcript by competitive reverse transcription-polymerase chain reaction, as mutational inactivation of PTCH leads to overexpression of the mutant transcript owing to failure of a negative feedback mechanism. We found a high level of PTCH expression in all 12 BCCs, while 23 of the other tumours and four specimens of normal skin showed no or weak expression of the gene, with the exception of one specimen from a patient with Bowen's disease which had high expression. These results indicate that the PTCH abnormality plays a critical role in the pathogenesis of BCC.

  16. Basal cell carcinoma of the nipple in male patients with gastric cancer recurrence: report of a case.

    PubMed

    Takeno, Shinsuke; Kikuchi, Nobuyuki; Miura, Takashi; Anami, Kentaro; Takahashi, Yoshiaki; Hashimoto, Takafumi; Moroga, Toshihiko; Akizuki, Shin-ichiro; Kamei, Mirei; Suehiro, Shuji; Yamashita, Shin-ichi; Kawahara, Katsunobu

    2014-01-01

    Although basal cell carcinoma (BCC) is the most common dermatological malignancy arising from sun exposed skin, BCC of the nipple is extremely rare. To our knowledge only 34 cases have been reported. We report a 78-year-old man who was undergoing chemotherapy for liver metastasis of gastric cancer 1 year after surgery. The chief complaint was exudation and oozing from the nipple. A mass lesion was palpable and detected on mammography and enhanced computed tomography, and atypical cells were detected on cytological examination. Simple resection was performed because histopathological diagnosis of an intraoperative frozen section revealed BCC. Final pathological diagnosis was also BCC. The authors report this case and review the previous reports, and discuss the clinicopathologic characteristics and adequate treatment for this disease.

  17. Surface-Enhanced Raman Spectroscopy Study of 4-ATP on Gold Nanoparticles for Basal Cell Carcinoma Fingerprint Detection

    NASA Astrophysics Data System (ADS)

    Quynh, Luu Manh; Nam, Nguyen Hoang; Kong, K.; Nhung, Nguyen Thi; Notingher, I.; Henini, M.; Luong, Nguyen Hoang

    2016-05-01

    The surface-enhanced Raman signals of 4-aminothiophenol (4-ATP) attached to the surface of colloidal gold nanoparticles with size distribution of 2 to 5 nm were used as a labeling agent to detect basal cell carcinoma (BCC) of the skin. The enhanced Raman band at 1075 cm-1 corresponding to the C-S stretching vibration in 4-ATP was observed during attachment to the surface of the gold nanoparticles. The frequency and intensity of this band did not change when the colloids were conjugated with BerEP4 antibody, which specifically binds to BCC. We show the feasibility of imaging BCC by surface-enhanced Raman spectroscopy, scanning the 1075 cm-1 band to detect the distribution of 4-ATP-coated gold nanoparticles attached to skin tissue ex vivo.

  18. Vismodegib Therapy for Basal Cell Carcinoma in an 8-Year-Old Chinese Boy with Xeroderma Pigmentosum.

    PubMed

    Fife, Douglas; Laitinen, Marko A; Myers, David J; Landsteiner, Pamela B

    2017-03-01

    Vismodegib is an oral inhibitor of the Hedgehog signaling pathway and has been used to treat basal cell carcinoma (BCC) in adults. This article reports clearance of a nodular BCC of the nasal tip in an 8-year-old boy with xeroderma pigmentosum (XP). BCC can pose therapeutic challenges when located in areas that are not amenable to traditional therapies such as Mohs micrographic surgery or topical agents. Vismodegib was used at a dose of 150 mg/day to treat the boy's BCC. After 4 months of therapy, we achieved complete clinical clearance. During 21 months of follow-up, the patient's nose remained clinically clear of tumor. Vismodegib was successfully used to treat a child with XP and nodular BCC. Our goal in using vismodegib was tumor regression while avoiding cosmetic and functional disfigurement. Vismodegib was effective in clinically clearing the tumor, and the patient has shown no signs of recurrence. Further studies are warranted.

  19. Treatment of margin positive basal cell carcinoma with vismodegib: case report and consideration of treatment options and their implications.

    PubMed

    Bayers, Stephanie; Kapp, Daniel L; Beer, Kenneth R; Slavin, Benjamin

    2013-10-01

    Historically, basal cell carcinomas (BCCs) that are neither surgically resectable nor candidates for radiation therapy have had few treatment options. The hedgehog pathway inhibitor, vismodegib, represents a new opportunity for the treatment of such patients. Vismodegib has approval from the United States Food and Drug Administration for treatment of metastatic BCC, locally advanced BCC recurring after surgery, and BCC that is not treatable via surgery or radiation. We present the case of a patient with a BCC infiltrating the spinal column that was neither possible to fully remove surgically nor a candidate for primary treatment with radiation. Treatment with vismodegib followed by adjuvant radiation therapy resulted in complete disease clearance. Vismodegib represents a promising treatment option for patients with surgically non-resectable BCCs that are not candidates for radiation therapy. Mechanism of action, benefits, and adverse events of vismodegib are reviewed, along with a brief discussion on newer options in the hedgehog inhibitor class.

  20. Confocal microscopy to guide erbium:yttrium aluminum garnet laser ablation of basal cell carcinoma: an ex vivo feasibility study.

    PubMed

    Sierra, Heidy; Larson, Bjorg A; Chen, Chih-Shan Jason; Rajadhyaksha, Milind

    2013-09-01

    For the removal of superficial and nodular basal cell carcinomas (BCCs), laser ablation provides certain advantages relative to other treatment modalities. However, efficacy and reliability tend to be variable because tissue is vaporized such that none is available for subsequent histopathological examination for residual BCC (and to confirm complete removal of tumor). Intra-operative reflectance confocal microscopy (RCM) may provide a means to detect residual tumor directly on the patient and guide ablation. However, optimization of ablation parameters will be necessary to control collateral thermal damage and preserve sufficient viability in the underlying layer of tissue, so as to subsequently allow labeling of nuclear morphology with a contrast agent and imaging of residual BCC. We report the results of a preliminary study of two key parameters (fluence, number of passes) vis-à-vis the feasibility of labeling and RCM imaging in human skin ex vivo, following ablation with an erbium:yttrium aluminum garnet laser.

  1. Electronic brachytherapy for superficial and nodular basal cell carcinoma: a report of two prospective pilot trials using different doses

    PubMed Central

    Pons-Llanas, Olga; Candela-Juan, Cristian; Celada-Álvarez, Francisco Javier; Barker, Christopher A.; Tormo-Micó, Alejandro; Pérez-Calatayud, Jose; Botella-Estrada, Rafael

    2016-01-01

    Purpose Basal cell carcinoma (BCC) is a very common cancer in the Caucasian population. Treatment aims to eradicate the tumor with the lowest possible functional and aesthetic impact. Electronic brachytherapy (EBT) is a treatment technique currently emerging. This study aims to show the outcomes of two consecutive prospective pilot clinical trials using different radiation doses of EBT with Esteya® EB system for the treatment of superficial and nodular basal cell carcinoma. Material and methods Two prospective, single-center, non-randomized, pilot studies were conducted. Twenty patients were treated in each study with different doses. The first group (1) was treated with 36.6 Gy in 6 fractions of 6.1 Gy, and the second group (2) with 42 Gy in 6 fractions of 7 Gy. Cure rate, acute toxicity, and late toxicity related to cosmesis were analyzed in the two treatment groups. Results In group 1, a complete response in 90% of cases was observed at the first year of follow-up, whereas in group 2, the complete response was 95%. The differences with reference to acute toxicity and the cosmetic results between the two treatment groups were not statistically significant. Conclusions Our initial experience with Esteya® EB system to treat superficial and nodular BCC shows that a dose of 36.6 Gy and 42 Gy delivered in 6 fraction of 7 Gy achieves a 90% and 95% clinical cure rate at 1 year, respectively. Both groups had a tolerable toxicity and a very good cosmesis. The role of EBT in the treatment of BCC is still to be defined. It will probably become an established option for selected patients in the near future. PMID:26985197

  2. Expression of gelatinase A and TIMP-2 mRNAs in desmoplastic fibroblasts in both mammary carcinomas and basal cell carcinomas of the skin.

    PubMed Central

    Poulsom, R; Hanby, A M; Pignatelli, M; Jeffery, R E; Longcroft, J M; Rogers, L; Stamp, G W

    1993-01-01

    AIMS--To compare the localisation of mRNAs for the basement membrane degrading enzyme gelatinase A (72 kilodalton type IV collagenase) and its inhibitor TIMP-2 in carcinomas of the breast and basal cell carcinomas of the skin which have little or no ability to metastasize. METHODS--In situ hybridisation was performed on formalin fixed, paraffin wax embedded blocks using 35S-labelled riboprobes on 16 mammary carcinomas, three fibroadenomas, and a benign phyllodes tumour, and on 15 basal cell carcinomas of the skin (BCC). RESULTS--Labelling for both mRNAs was detectable in 14 of 16 mammary carcinomas and in 13 of 15 BCC, most often over organising desmoplastic fibroblasts in the stroma around invasive epithelial aggregates. Some sparse labelling was seen over malignant epithelial cells in six of the mammary carcinomas but not in the BCC. Some expression of gelatinase A mRNA was also seen in fibroblasts of breast lobules adjacent to the mammary carcinomas and around engulfed adnexal elements in the BCC, but not in unaffected breast tissues, fibroadenomas, the phyllodes tumour or unaffected skin. CONCLUSIONS--Maximal expression of gelatinase A and TIMP-2 mRNAs occurs in malignant neoplasms as part of the host response to the presence of established neoplastic cells rather than as an initial response to invasion. The degree to which this is present suggests this may be a highly relevant mechanism modulating tumour differentiation, growth and progression, possibly entailing uptake via specific receptors on the tumour cell surface. Images PMID:8391548

  3. Discrimination between basal cell carcinoma and hair follicles in skin tissue sections by Raman micro-spectroscopy

    NASA Astrophysics Data System (ADS)

    Larraona-Puy, M.; Ghita, A.; Zoladek, A.; Perkins, W.; Varma, S.; Leach, I. H.; Koloydenko, A. A.; Williams, H.; Notingher, I.

    2011-05-01

    Skin cancer is the most common human malignancy and basal cell carcinoma (BCC) represents approximately 80% of the non-melanoma cases. Current methods of treatment require histopathological evaluation of the tissues by qualified personnel. However, this method is subjective and in some cases BCC can be confused with other structures in healthy skin, including hair follicles. In this preliminary study, we investigated the potential of Raman micro-spectroscopy (RMS) to discriminate between hair follicles and BCC in skin tissue sections excised during Mohs micrographic surgery (MMS). Imaging and diagnosis of skin sections was automatically generated using ' a priori'-built spectral model based on LDA. This model had 90 ± 9% sensitivity and 85 ± 9% specificity for discrimination of BCC from dermis and epidermis. The model used selected Raman bands corresponding to the largest spectral differences between the Raman spectra of BCC and the normal skin regions, associated mainly with nucleic acids and collagen type I. Raman spectra corresponding to the epidermis regions of the hair follicles were found to be closer to those of healthy epidermis rather than BCC. Comparison between Raman spectral images and the gold standard haematoxylin and eosin (H&E) histopathology diagnosis showed good agreement. Some hair follicle regions were misclassified as BCC; regions corresponded mainly to the outermost layer of hair follicle (basal cells) which are expected to have higher nucleic acid concentration. This preliminary study shows the ability of RMS to distinguish between BCC and other tissue structures associated to healthy skin which can be confused with BCC due to their similar morphology.

  4. Imiquimod 5% cream for the treatment of large nodular basal cell carcinoma at the medial canthal area

    PubMed Central

    Karabulut, Gamze Ozturk; Kaynak, Pelin; Ozturker, Can; Fazil, Korhan; Ocak, Osman Bulut; Taskapılı, Muhittin

    2017-01-01

    Context (Background): Imiquimod (IMQ) 5% cream is an immunomodulatory and antitumorigenic agent, which was used as a topical treatment regimen, who had periocular basal cell carcinoma (BCC). Aim: This study aims to present three cases with large BCC at the medial canthal area treated with IMQ 5% cream. Materials and Methods: IMQ 5% cream was used in three patients with ages 45, 49, and 73 who preferred medical treatment over surgery. Following incisional biopsy IMQ cream was used once a day, 5 times a week and the patients were followed up weekly during 12 week treatment period and monthly after the clearance of the lesion. Results: Erythema and erosion on the surface of the lesion, injection of conjunctiva, burning and itching sensation, epiphora and punctate keratitis were seen in all patients during the treatment period. The ophthalmic side effects could be managed by topical lubricating eye drops and the inflammatory reactions resolved within 1 month after cessation of therapy. The patients were followed up for at least 3 years without tumor recurrence and the biopsies taken from the suspected area were found to be tumor free. Conclusion: Surgical excision of carcinoma of the eyelid at medial canthal area can be difficult without causing damage to the lacrimal system and reconstruction of the defect may need grafts or flaps. IMQ may provide an alternative therapy to surgery in certain cases. PMID:28300740

  5. Cellular and biological evaluation and diagnostic immunohistochemistry of cytokeratin 15/19 expression in distinguishing cutaneous basal cell carcinoma.

    PubMed

    Ziari, Katayoun; Behdad, Behnoosh; Mohammadshahi, Ali; Pirasteh, Hamid Reza; Sharifi, Mohammad Davood; Dadpay, Masoomeh

    2015-05-01

    Recent studies have investigated the expression of proliferative markers, but little is known about the expression of cytokeratin 15 and 19 in different histological subtypes of basal cell carcinoma (BCC). We conducted cellular, biological, clinicopathological and immunohistochemical analysis on the manifestations of 8 BCC by hematoxylin and eosin stain (H&E) staining and immunohistochemistry and reviewed relevant literature. Microscopically, the tumor cells were multiple remarkable foci of epidermolytic hyperkeratosis with large pleomorphic nuclei and scant cytoplasm together with peripheral palisading and forming solid nests. Furthermore, the most tumors were composed of highly cellular areas with a homogenous population of round, ovoid and spindle cells, hyperchromatic nuclei, high cellular pleomorphism, high mitotic index and various morphologic patterns. Moreover, the tumors displayed an invasive growth, with positive expression of Cytokeratin 19 (CK19) and negative expression of CK15. Our study revealed that the expression of CK19 was associated with progression and invasion in cases with BCC and immunohistochemistry is indispensable in distinguishing this tumor from other types of cutaneous carcinoma. To our best knowledge, it may be a considerable biomarker to assess invasiveness of cutaneous-surface BCC and to guide clinical management of such tumors.

  6. Predictors of basal cell carcinoma in high-risk patients in the VATTC (VA Topical Tretinoin Chemoprevention) trial.

    PubMed

    Dyer, Robert K; Weinstock, Martin A; Cohen, Tobias S D; Rizzo, Amilcar E; Bingham, Stephen F

    2012-11-01

    Basal cell carcinoma (BCC) is the most common cancer in the United States today, and patients who have had one are likely to have multiple carcinomas over time. Predictors of new BCCs on the face and ears among those at very high risk have not been studied in detail. We sought to do so prospectively in the context of a 6-year trial. We found that the number of BCCs in the prior 5 years was the most important predictor. Age, sun sensitivity, occupational sun exposure before the age of 30 years (but not afterward), lower educational level, history of eczema, the use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and more sunscreen use in the week, but not the 6 months, before enrollment were also independent predictors, but sunburns, baseline sun exposure, and other sun-protective measures, other skin cancers, and actinic keratoses were not. None of the eczema patients had a history of topical calcineurin use. The cumulative risk of BCC was 55% at 5 years. These findings document the key risk factors in this very high-risk population, suggesting that the history of eczema may increase the risk in those at high risk and that early sun exposure is important even in this group, and underscoring the need for chemopreventive strategies.

  7. Characterization and Management of Hedgehog Pathway Inhibitor-Related Adverse Events in Patients With Advanced Basal Cell Carcinoma

    PubMed Central

    Dréno, Brigitte; Ascierto, Paolo Antonio; Dummer, Reinhard; Basset-Seguin, Nicole; Fife, Kate; Ernst, Scott; Licitra, Lisa; Neves, Rogerio I.; Peris, Ketty; Puig, Susana; Sokolof, Jonas; Sekulic, Aleksandar; Hauschild, Axel; Kunstfeld, Rainer

    2016-01-01

    Abnormal activation of hedgehog pathway signaling is a key driver in the pathogenesis of basal cell carcinoma (BCC). Vismodegib, a first-in-class small-molecule inhibitor of hedgehog pathway signaling, is approved by regulatory authorities for the treatment of adults who have metastatic BCC or locally advanced BCC that has recurred after surgery, or who are not candidates for surgery and who are not candidates for radiation. A second inhibitor, sonidegib, was also recently approved for the same patient group with locally advanced BCC. Adverse events (AEs) commonly observed in hedgehog pathway inhibitor (HPI)-treated patients include muscle spasms, ageusia/dysgeusia, alopecia, weight loss, and asthenia (fatigue). These AEs are thought to be mechanistically related to inhibition of the hedgehog pathway in normal tissue. Although the severity of the majority of AEs associated with HPIs is grade 1–2, the long-term nature of these AEs can lead to decreased quality of life, treatment interruption, and in some cases discontinuation, all of which might affect clinical outcome. The incidence, clinical presentation, putative mechanisms, and management strategies for AEs related to HPIs in advanced BCC are described. These observations represent the first step toward the development of mechanism-based preventive and management strategies. Knowledge of these AEs will allow health care professionals to provide appropriate counseling and supportive care interventions, all of which will contribute to improved quality of life and optimal benefit from therapy. Implications for Practice: The hedgehog pathway inhibitors (HPIs) vismodegib and sonidegib represent a therapeutic breakthrough for patients with advanced basal cell carcinoma. However, the nature of the low-grade adverse events (AEs) commonly observed in HPI-treated patients, including muscle spasms, ageusia/dysgeusia, alopecia, weight loss, and fatigue, can impact clinical outcomes as a result of decreased quality of life

  8. Arborizing vessels in a targetoid hemosiderotic hemangioma: mistaken dermoscopic diagnosis of basal cell carcinoma

    PubMed Central

    Enei, María L.; Paschoal, Francisco M.; Valdes, Rodrigo

    2017-01-01

    Targetoid hemosiderotic hemangioma (THH) or hobnail hemangioma (HH) is a benign vascular lesion that presents with the classical clinical presentation of a ring-shaped tumor having a targetoid appearance, with a central purple-brown papule surrounded by a thin pale area and an ecchymotic ring on the outside. Dermoscopic features and patterns of HH have been documented and have proven to be sufficient to establish a clinical diagnosis in many cases. We present a facial lesion in which both the clinical presentation and dermoscopy were atypical. The presence of arborizing vessels in the dermoscopic pattern, never before described for this lesion, led us to the diagnosis of basocellular carcinoma (BCC). We also report the changes in this pattern experienced over 12 months of progression and their correlation with the histopathologic findings. PMID:28243494

  9. Laser-induced fluorescence made simple: implications for the diagnosis and follow-up monitoring of basal cell carcinoma.

    PubMed

    Drakaki, Eleni; Dessinioti, Clio; Stratigos, Alexander J; Salavastru, Carmen; Antoniou, Christina

    2014-03-01

    Noninvasive treatments are increasingly being used for the management of basal cell carcinoma (BCC), the predominant type of nonmelanoma skin cancer, making the development of noninvasive diagnostic technologies highly relevant for clinical practice. Laser-induced fluorescence (LIF) spectroscopy emerges as an attractive diagnostic technique for the diagnosis and demarcation of BCC due to its noninvasiveness, high sensitivity, real-time measurements, and user-friendly methodology. LIF relies on the principle of differential fluorescence emission between abnormal and normal skin tissues (ex vivo and in vivo) in response to excitation by a specific wavelength of light. Fluorescence originates either from endogenous fluorophores (autofluorescence) or from exogenously administered fluorophores (photosensitizers). The measured optical properties and fluorophore contributions of normal skin and BCC are significantly different from each other and correlate well with tissue histology. Photodynamic diagnosis (PDD) is based on the visualization of a fluorophore, with the ability to accumulate in tumor tissue, by the use of fluorescence imaging. PDD may be used for detecting subclinical disease, determining surgical margins, and following-up patients for residual tumor or BCC relapse. In this review, we will present the basic principles of LIF and discuss its uses for the diagnosis, management, and follow-up of BCC.

  10. Robust demarcation of basal cell carcinoma by dependent component analysis-based segmentation of multi-spectral fluorescence images.

    PubMed

    Kopriva, Ivica; Persin, Antun; Puizina-Ivić, Neira; Mirić, Lina

    2010-07-02

    This study was designed to demonstrate robust performance of the novel dependent component analysis (DCA)-based approach to demarcation of the basal cell carcinoma (BCC) through unsupervised decomposition of the red-green-blue (RGB) fluorescent image of the BCC. Robustness to intensity fluctuation is due to the scale invariance property of DCA algorithms, which exploit spectral and spatial diversities between the BCC and the surrounding tissue. Used filtering-based DCA approach represents an extension of the independent component analysis (ICA) and is necessary in order to account for statistical dependence that is induced by spectral similarity between the BCC and surrounding tissue. This generates weak edges what represents a challenge for other segmentation methods as well. By comparative performance analysis with state-of-the-art image segmentation methods such as active contours (level set), K-means clustering, non-negative matrix factorization, ICA and ratio imaging we experimentally demonstrate good performance of DCA-based BCC demarcation in two demanding scenarios where intensity of the fluorescent image has been varied almost two orders of magnitude.

  11. Diagnosis of basal cell carcinoma by infrared spectroscopy of whole blood samples applying soft independent modeling class analogy.

    PubMed

    Khanmohammadi, Mohammadreza; Nasiri, Razieh; Ghasemi, Keyvan; Samani, Simin; Bagheri Garmarudi, Amir

    2007-12-01

    Attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy was applied to discriminate the blood samples obtained from healthy people and those with basal cell carcinoma, demonstrating high accuracy while soft independent modeling class analogy (SIMCA) chemometric technique is benefited. It was aimed to classify the normal case and cancer case blood samples through the use of ATR-FTIR spectroscopy as a rapid method while the sample preparation is so easy in comparison with the common pathologic methods. A total of 72 blood samples, including 32 cancer and 40 normal cases, were analyzed in 1,800-900 cm(-1) spectral region. Results showed 97.6% of accuracy being compared with the current clinical methods. Research results were exemplified with comparable data of other classification methods such as principal component analysis (PCA) and Cluster analysis. The residual errors in prediction (REP) of calibration model for normal and cancerous groups in SIMCA method were 0.00362 and 0.00343, respectively.

  12. Mutations of the p53 and PTCH gene in basal cell carcinomas: UV mutation signature and strand bias.

    PubMed

    Kim, Mi-Yeon; Park, Hyun Jeong; Baek, Seung-Cheol; Byun, Dae Gyoo; Houh, Dong

    2002-05-01

    Mutations of p53 and PTCH gene, two candidate tumor suppressor genes for basal cell carcinoma (BCC), were screened in 15 cases of sporadic BCCs that developed in sun-exposed skin region in a Korean population. p53 and PTCH mutations were detected at a frequency of 33 and 40%, respectively, and the mutations were predominantly UV-signature transition, C-->T transitions at dipyrimidine sites and CC-->TT tandem mutations. In both genes, the most common mutations were missense mutations resulting in amino acid substitution, which is different than the results from Caucasian BCCs where mutations are frequently predicted to make truncated or absent proteins. All mutations, except for one, occurred on the nontranscribed strand where is little efficient removal of UV-induced pyrimidine dimers relative to the transcribed strand. Loss of heterozygocity (LOH) of 9q22 for PTCH loci was found in eight of 15 informative cases of BCCs (53%), but none of the cases were informative for LOH of 17p13 for p53 loci. Not only do our data indicate the key role played by p53 and PTCH in the development of BCCs, these findings also suggest that UVB may significantly contribute to BCC tumorigenesis. Moreover, molecular epidemiology composed of incidence of p53 and PTCH mutations, difference in the type of mutation and repair bias of UV-induced DNA lesions might affect the distinct features of BCCs between different racial population.

  13. Human patched (PTCH) mRNA is overexpressed consistently in tumor cells of both familial and sporadic basal cell carcinoma.

    PubMed

    Undén, A B; Zaphiropoulos, P G; Bruce, K; Toftgård, R; Ståhle-Bäckdahl, M

    1997-06-15

    Recently, a human homologue of the Drosophila patched gene, PTCH, was identified as a putative tumor suppressor mutated in both hereditary and sporadic basal cell carcinomas. Because PTCH controls its own transcription, inactivating mutations in PTCH may lead to overexpression of mutant PTCH mRNA due to loss of autoregulation. The present study is aimed at evaluating whether deregulation of PTCH mRNA expression is a general feature of BCCs of varying histological growth pattern and malignant potential. Irrespective of histological subtype, PTCH mRNA was overexpressed consistently as determined by in situ hybridization in all of the sporadic (n = 16) and hereditary (n = 20) tumors examined. PTCH expression was found in all of the tumor cells but appeared stronger in the peripheral palisading cells. PTCH mRNA was not detected in adjacent nontumor epidermal cells or in other parts of the epidermis. In the majority of tumors (20 of 36), nuclear immunostaining for p53 was found in scattered cells, whereas seven tumors completely lacked p53 immunoreactivity. Our finding of an up-regulation of PTCH mRNA levels in all of the BCCs analyzed indicates that deregulation of the PTCH signaling pathway constitutes an early rate-limiting event in BCC development.

  14. Patched (ptch)-associated preferential expression of smoothened (smoh) in human basal cell carcinoma of the skin.

    PubMed

    Kallassy, M; Toftgård, R; Ueda, M; Nakazawa, K; Vorechovský, I; Yamasaki, H; Nakazawa, H

    1997-11-01

    The discovery of specific overexpression of a gatekeeper gene, ptch, in basal cell carcinoma (BCC) led to a hypothesis that the human homologue of patched (PTCH) normally functions as a negative regulator of the signaling pathway that is initiated by hedgehogs (HHs) and activated by the human homologue of smoothened (SMOH); however, no evidence for the involvement of smoh and hhs has been provided. Here, we show novel evidence that smoh is also preferentially overexpressed in BCC, together with ptch (P < 0.002), and that Sonic hh was expressed in only some BCCs. Our data, therefore, indicate that such overexpression of smoh may be associated with overexpression or mutation of PTCH and that this overexpression subsequently stimulates the PTCH/SMOH signaling pathway. In an investigation of a possible regulation of ptch and smoh, we demonstrated that expression of exogenous p21WAF1 in immortalized keratinocytes down-regulates both ptch and smoh and that the down-regulation is accompanied by growth arrest, which suggests the involvement of p21WAF1 in regulation of the PTCH/SMOH signaling pathway.

  15. Preliminary results of comparative study for subsequent photodynamic therapy versus secondary excision after primary excision for treating basal cell carcinoma.

    PubMed

    Bu, Wenbo; Zhang, Mengli; Zhang, Qian; Yuan, Chunyu; Chen, Xu; Fang, Fang

    2016-11-22

    Some basal cell carcinomas (BCCs) are indistinguishable from nevi based on clinical manifestations. Therefore, it is often difficult for the excision margins of the initial surgical treatment to achieve radical removal of the malignancy. This study was a comparative analysis of the clinical results of aminolevulinic acid (ALA)-photodynamic therapy (PDT) or secondary surgery after the primary excision. In total, 20 patients with preoperative clinical diagnoses of nevi underwent in situ resection. The postoperative pathological diagnoses confirmed all cases were BCC. Ten patients received PDT twice after the primary excision, and 10 cases received extended resection after the primary excision. Patients were followed up for 8 months at least, and the 2 groups did not show statistically significant differences in the recurrence rate, while the PDT group had better results in terms of economic burden, healing period, and cosmetic satisfaction than the group with secondary surgery. Our study demonstrates that ALA-PDT can sever as a considerable remedial treatment for the BCC patients who have not accepted radical resection due to primary clinical misdiagnosis.

  16. A recurrent germline BAP1 mutation and extension of the BAP1 tumor predisposition spectrum to include basal cell carcinoma.

    PubMed

    Wadt, K A W; Aoude, L G; Johansson, P; Solinas, A; Pritchard, A; Crainic, O; Andersen, M T; Kiilgaard, J F; Heegaard, S; Sunde, L; Federspiel, B; Madore, J; Thompson, J F; McCarthy, S W; Goodwin, A; Tsao, H; Jönsson, G; Busam, K; Gupta, R; Trent, J M; Gerdes, A-M; Brown, K M; Scolyer, R A; Hayward, N K

    2015-09-01

    We report four previously undescribed families with germline BRCA1-associated protein-1 gene (BAP1) mutations and expand the clinical phenotype of this tumor syndrome. The tumor spectrum in these families is predominantly uveal malignant melanoma (UMM), cutaneous malignant melanoma (CMM) and mesothelioma, as previously reported for germline BAP1 mutations. However, mutation carriers from three new families, and one previously reported family, developed basal cell carcinoma (BCC), thus suggesting inclusion of BCC in the phenotypic spectrum of the BAP1 tumor syndrome. This notion is supported by the finding of loss of BAP1 protein expression by immunochemistry in two BCCs from individuals with germline BAP1 mutations and no loss of BAP1 staining in 53 of sporadic BCCs consistent with somatic mutations and loss of heterozygosity of the gene in the BCCs occurring in mutation carriers. Lastly, we identify the first reported recurrent mutation in BAP1 (p.R60X), which occurred in three families from two different continents. In two of the families, the mutation was inherited from a common founder but it arose independently in the third family.

  17. Vismodegib, itraconazole and sonidegib as hedgehog pathway inhibitors and their relative competencies in the treatment of basal cell carcinomas.

    PubMed

    Wahid, Mohd; Jawed, Arshad; Mandal, Raju K; Dar, Sajad A; Khan, Saif; Akhter, Naseem; Haque, Shafiul

    2016-02-01

    The advent of more sophisticated studies published has clarified the understating of the root cause of various skin cancers or basal cell carcinomas (BCCs). The remarkable role is played by the comprehensive work done on unraveling the mechanism controlling the function of hedgehog (Hh) pathway. The defective Hh pathway has been found as the major cause for BCCs as activated Hh signaling within primary cilia plays a key role in the pathogenesis of BCCs. The BCC accounts for up to 40% of all cancers in the US, with growing incidences in other countries as well. Thus, it is considered to be utmost important by the researchers all over the world developing drugs for the treatment of skin cancers targeting Hh pathway. Fewer drugs like vismodegib, itraconazole and sonidegib have shown promising results inhibiting the awry function of Hh pathway resulting in treatment of different forms of skin cancers. These drugs have shown positive results but failed to prove their potential as expected. Vismodegib and sonidegib are better but fail in case of resistant tumors. This review article describes the mechanism of actions of these Hh pathway inhibitors and provides the rationale for their effectiveness/non-effectiveness for the treatment of metastatic or locally advanced BCC.

  18. In vivo detection of basal cell carcinoma: comparison of a reflectance confocal microscope and a multiphoton tomograph.

    PubMed

    Ulrich, Martina; Klemp, Marisa; Darvin, Maxim E; König, Karsten; Lademann, Jürgen; Meinke, Martina C

    2013-06-01

    The standard diagnostic procedure for basal cell carcinoma (BCC) is invasive tissue biopsy with time-consuming histological examination. To reduce the number of biopsies, noninvasive optical methods have been developed providing high-resolution skin examination. We present direct comparison of a reflectance confocal microscope (RLSM) and a multiphoton tomograph (MPT) for BCC diagnosis. Both systems are applied to nine patients prior to surgery, and the results are analyzed, including histological results. Both systems prove suitable for detecting typical characteristics of BCC in various stages. The RLSM allows large horizontal overview images to be obtained, enabling the investigator to find the regions of interest quickly, e.g., BCC nests. Elongated cells and palisading structures are easily recognized using both methods. Due to the higher resolution, changes in nucleus diameter or cytoplasm could be visualized with the MPT. Therefore, the nucleus diameter, nucleus/cytoplasm ratio, and cell density are estimated for normal and BCC cells using the MPT. The nucleus of elongated BCC cells is significantly longer than other measured normal skin cells, whereas the cell density and nucleus/cytoplasm ratio of BCC cannot be significantly distinguished from granular cells.

  19. Efficacy of fluorescence diagnosis-guided Mohs micrographic surgery for pigmented vs non-pigmented basal cell carcinoma.

    PubMed

    Jeon, Su-Young; Kim, Ki-Ho; Song, Ki-Hoon

    2014-09-01

    Pigmented basal cell carcinoma (PBCC) occurs more frequently in Asian population. The efficacy of fluorescence diagnosis (FD) for PBCCs treated with Mohs micrographic surgery has not yet been determined. This study enrolled 255 patients with 258 biopsy-proven BCC lesions: 199 PBCCs (77.1%) and 59 non-PBCCs (22.9%). We compared the clinicopathological and surgical features of the PBCCs and non-PBCCs. Each group was divided into 2 sub-groups, those assessed and not assessed by FD, to retrospectively analyse surgical features. Aggressive histological subtypes were less prevalent in PBCCs than in non-PBCCs. PBCCs required significantly fewer stages of Mohs excision, with significantly smaller surgical margins and surgical depth, than non-PBCCs. FD did not confer any benefits on PBCCs during Mohs micrographic surgery. However, non-PBCCs assessed by FD required significantly fewer Mohs stages, with significantly smaller surgical margins, than lesions not assessed by FD. These findings suggest that FD should be performed before Mohs micrographic surgery to delineate the margins of non-PBCCs in Asians.

  20. In vivo detection of basal cell carcinoma: comparison of a reflectance confocal microscope and a multiphoton tomograph

    NASA Astrophysics Data System (ADS)

    Ulrich, Martina; Klemp, Marisa; Darvin, Maxim E.; König, Karsten; Lademann, Jürgen; Meinke, Martina C.

    2013-06-01

    The standard diagnostic procedure for basal cell carcinoma (BCC) is invasive tissue biopsy with time-consuming histological examination. To reduce the number of biopsies, noninvasive optical methods have been developed providing high-resolution skin examination. We present direct comparison of a reflectance confocal microscope (RLSM) and a multiphoton tomograph (MPT) for BCC diagnosis. Both systems are applied to nine patients prior to surgery, and the results are analyzed, including histological results. Both systems prove suitable for detecting typical characteristics of BCC in various stages. The RLSM allows large horizontal overview images to be obtained, enabling the investigator to find the regions of interest quickly, e.g., BCC nests. Elongated cells and palisading structures are easily recognized using both methods. Due to the higher resolution, changes in nucleus diameter or cytoplasm could be visualized with the MPT. Therefore, the nucleus diameter, nucleus/cytoplasm ratio, and cell density are estimated for normal and BCC cells using the MPT. The nucleus of elongated BCC cells is significantly longer than other measured normal skin cells, whereas the cell density and nucleus/cytoplasm ratio of BCC cannot be significantly distinguished from granular cells.

  1. Discriminating model for diagnosis of basal cell carcinoma and melanoma in vitro based on the Raman spectra of selected biochemicals

    NASA Astrophysics Data System (ADS)

    Silveira, Landulfo; Silveira, Fabrício Luiz; Bodanese, Benito; Zângaro, Renato Amaro; Pacheco, Marcos Tadeu T.

    2012-07-01

    Raman spectroscopy has been employed to identify differences in the biochemical constitution of malignant [basal cell carcinoma (BCC) and melanoma (MEL)] cells compared to normal skin tissues, with the goal of skin cancer diagnosis. We collected Raman spectra from compounds such as proteins, lipids, and nucleic acids, which are expected to be represented in human skin spectra, and developed a linear least-squares fitting model to estimate the contributions of these compounds to the tissue spectra. We used a set of 145 spectra from biopsy fragments of normal (30 spectra), BCC (96 spectra), and MEL (19 spectra) skin tissues, collected using a near-infrared Raman spectrometer (830 nm, 50 to 200 mW, and 20 s exposure time) coupled to a Raman probe. We applied the best-fitting model to the spectra of biochemicals and tissues, hypothesizing that the relative spectral contribution of each compound to the tissue Raman spectrum changes according to the disease. We verified that actin, collagen, elastin, and triolein were the most important biochemicals representing the spectral features of skin tissues. A classification model applied to the relative contribution of collagen III, elastin, and melanin using Euclidean distance as a discriminator could differentiate normal from BCC and MEL.

  2. Diallyl trisulfide induces apoptosis of human basal cell carcinoma cells via endoplasmic reticulum stress and the mitochondrial pathway.

    PubMed

    Wang, Hsiao-Chi; Hsieh, Shu-Chen; Yang, Jen-Hung; Lin, Shuw-Yuan; Sheen, Lee-Yan

    2012-01-01

    Diallyl trisulfide (DATS), an active component of garlic oil, has attracted much attention because of its anticancer effect on several types of cancers. However, the mechanism of DATS-induced apoptosis of basal cell carcinoma (BCC) is not fully understood. In the present study, we revealed that DATS-mediated dose-dependent induction of apoptosis in BCC cells was associated with intracellular reactive oxygen species accumulation and disrupted mitochondrial membrane potential. Western analysis demonstrated concordant expression of molecules involved in mitochondrial apoptosis, including DATS-associated increases in phospho-p53, proapoptotic Bax, and decreases in antiapoptotic Bcl-2 and Bcl-xl in BCC cells. Moreover, DATS induced the release of cytochrome c, apoptosis-inducing factor, and HtrA2/Omi into the cytoplasm, and activated factors downstream of caspase-dependent and caspase-independent apoptosis, including nuclear translocation of apoptotic-inducing factor and endonuclease G and the caspase cascade. These results were confirmed by pretreatment with the antioxidant N-acetyl-L-cysteine and the caspase inhibitor (z-VAD-fmk), the latter of which did not completely enhance the viability of DATS-treated BBC cells. Exposure to DATS additionally induced endogenous endoplasmic reticulum stress markers and intracellular Ca2⁺ mobilization, upregulation of Bip/GRP78 and CHOP/GADD153, and activation of caspase-4. Our findings suggest that DATS exerts chemopreventive potential via ER stress and the mitochondrial pathway in BCC cells.

  3. Multiphoton laser tomography and fluorescence lifetime imaging of basal cell carcinoma: morphologic features for non-invasive diagnostics.

    PubMed

    Seidenari, Stefania; Arginelli, Federica; Dunsby, Christopher; French, Paul; König, Karsten; Magnoni, Cristina; Manfredini, Marco; Talbot, Clifford; Ponti, Giovanni

    2012-11-01

    Multiphoton laser tomography (MPT) combined with fluorescence lifetime imaging (FLIM) is a non-invasive imaging technique, which gives access to the cellular and extracellular morphology of the skin. The aim of our study was to assess the sensitivity and specificity of MPT/FLIM descriptors for basal cell carcinoma (BCC), to improve BCC diagnosis and the identification of tumor margins. In the preliminary study, FLIM images referring to 35 BCCs and 35 healthy skin samples were evaluated for the identification of morphologic descriptors characteristic of BCC. In the main study, the selected parameters were blindly evaluated on a test set comprising 63 BCCs, 63 healthy skin samples and 66 skin lesions. Moreover, FLIM values inside a region of interest were calculated on 98 healthy skin and 98 BCC samples. In the preliminary study, three epidermal descriptors and 7 BCC descriptors were identified. The specificity of the diagnostic criteria versus 'other lesions' was extremely high, indicating that the presence of at least one BCC descriptor makes the diagnosis of 'other lesion' extremely unlikely. FLIM values referring to BCC cells significantly differed from those of healthy skin. In this study, we identified morphological and numerical descriptors enabling the differentiation of BCC from other skin disorders and its distinction from healthy skin in ex vivo samples. In future, MPT/FLIM may be applied to skin lesions to provide direct clinical guidance before biopsy and histological examination and for the identification of tumor margins allowing a complete surgical removal.

  4. GLI activation by atypical protein kinase C ι/λ regulates the growth of basal cell carcinomas.

    PubMed

    Atwood, Scott X; Li, Mischa; Lee, Alex; Tang, Jean Y; Oro, Anthony E

    2013-02-28

    Growth of basal cell carcinomas (BCCs) requires high levels of hedgehog (HH) signalling through the transcription factor GLI. Although inhibitors of membrane protein smoothened (SMO) effectively suppress HH signalling, early tumour resistance illustrates the need for additional downstream targets for therapy. Here we identify atypical protein kinase C ι/λ (aPKC-ι/λ) as a novel GLI regulator in mammals. aPKC-ι/λ and its polarity signalling partners co-localize at the centrosome and form a complex with missing-in-metastasis (MIM), a scaffolding protein that potentiates HH signalling. Genetic or pharmacological loss of aPKC-ι/λ function blocks HH signalling and proliferation of BCC cells. Prkci is a HH target gene that forms a positive feedback loop with GLI and exists at increased levels in BCCs. Genome-wide transcriptional profiling shows that aPKC-ι/λ and SMO control the expression of similar genes in tumour cells. aPKC-ι/λ functions downstream of SMO to phosphorylate and activate GLI1, resulting in maximal DNA binding and transcriptional activation. Activated aPKC-ι/λ is upregulated in SMO-inhibitor-resistant tumours and targeting aPKC-ι/λ suppresses signalling and growth of resistant BCC cell lines. These results demonstrate that aPKC-ι/λ is critical for HH-dependent processes and implicates aPKC-ι/λ as a new, tumour-selective therapeutic target for the treatment of SMO-inhibitor-resistant cancers.

  5. Discriminating model for diagnosis of basal cell carcinoma and melanoma in vitro based on the Raman spectra of selected biochemicals.

    PubMed

    Silveira, Landulfo; Silveira, Fabrício Luiz; Bodanese, Benito; Zângaro, Renato Amaro; Pacheco, Marcos Tadeu T

    2012-07-01

    Raman spectroscopy has been employed to identify differences in the biochemical constitution of malignant [basal cell carcinoma (BCC) and melanoma (MEL)] cells compared to normal skin tissues, with the goal of skin cancer diagnosis. We collected Raman spectra from compounds such as proteins, lipids, and nucleic acids, which are expected to be represented in human skin spectra, and developed a linear least-squares fitting model to estimate the contributions of these compounds to the tissue spectra. We used a set of 145 spectra from biopsy fragments of normal (30 spectra), BCC (96 spectra), and MEL (19 spectra) skin tissues, collected using a near-infrared Raman spectrometer (830 nm, 50 to 200 mW, and 20 s exposure time) coupled to a Raman probe. We applied the best-fitting model to the spectra of biochemicals and tissues, hypothesizing that the relative spectral contribution of each compound to the tissue Raman spectrum changes according to the disease. We verified that actin, collagen, elastin, and triolein were the most important biochemicals representing the spectral features of skin tissues. A classification model applied to the relative contribution of collagen III, elastin, and melanin using Euclidean distance as a discriminator could differentiate normal from BCC and MEL.

  6. Nonlinear spectral imaging of human normal skin, basal cell carcinoma and squamous cell carcinoma based on two-photon excited fluorescence and second-harmonic generation

    NASA Astrophysics Data System (ADS)

    Xiong, S. Y.; Yang, J. G.; Zhuang, J.

    2011-10-01

    In this work, we use nonlinear spectral imaging based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) for analyzing the morphology of collagen and elastin and their biochemical variations in basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and normal skin tissue. It was found in this work that there existed apparent differences among BCC, SCC and normal skin in terms of their thickness of the keratin and epithelial layers, their size of elastic fibers, as well as their distribution and spectral characteristics of collagen. These differences can potentially be used to distinguish BCC and SCC from normal skin, and to discriminate between BCC and SCC, as well as to evaluate treatment responses.

  7. Topical thymidine dinucleotide treatment reduces development of ultraviolet-induced basal cell carcinoma in Ptch-1+/- mice.

    PubMed

    Arad, Simin; Zattra, Edoardo; Hebert, Jennifer; Epstein, Ervin H; Goukassian, David A; Gilchrest, Barbara A

    2008-05-01

    Treatment with thymidine dinucleotide (pTT) has well documented DNA-protective effects and reduces development of squamous cell carcinoma in UV-irradiated mice. The preventive effect of pTT on basal cell carcinoma (BCC) was evaluated in UV-irradiated Ptch-1(+/-) mice, a model of the human disease Gorlin syndrome. Topical pTT treatment significantly reduced the number and size (P < 0.001) of BCCs in murine skin after 7 months of chronic irradiation. Skin biopsies collected 24 hours after the final UV exposure showed that pTT reduced the number of nuclei positive for cyclobutane pyrimidine dimers by 40% (P < 0.0002) and for 8-hydroxy-2'-deoxyguanosine by 61% (P < 0.01 compared with vehicle control). Immunostaining with an antibody specific for mutated p53 revealed 63% fewer positive patches in BCCs of pTT-treated mice compared with controls (P < 0.01), and the number of Ki-67-positive cells was decreased by 56% (P < 0.01) in pTT-treated tumor-free epidermis and by 76% (P < 0.001) in BCC tumor nests (P < 0.001). Terminal dUTP nick-end labeling staining revealed a 213% increase (P < 0.04) in the number of apoptotic cells in BCCs of pTT-treated mice. Cox-2 immunostaining was decreased by 80% in tumor-free epidermis of pTT-treated mice compared with controls (P < 0.01). We conclude that topical pTT treatment during a prolonged period of intermittent UV exposure decreases the number and size of UV-induced BCCs through several anti-cancer mechanisms.

  8. Hair follicle disruption facilitates pathogenesis to UVB-induced cutaneous inflammation and basal cell carcinoma development in Ptch(+/-) mice.

    PubMed

    Xu, Jianmin; Weng, Zhiping; Arumugam, Aadithya; Tang, Xiuwei; Chaudhary, Sandeep C; Li, Changzhao; Christiano, Angela M; Elmets, Craig A; Bickers, David R; Athar, Mohammad

    2014-05-01

    Hairless mice carrying homozygous mutations in hairless gene manifest rudimentary hair follicles (HFs), epidermal cysts, hairless phenotype, and enhanced susceptibility to squamous cell carcinomas. However, their susceptibility to basal cell carcinomas (BCCs), a neoplasm considered originated from HF-localized stem cells, is unknown. To demonstrate the role of HFs in BCC development, we bred Ptch(+/-)/C57BL6 with SKH-1 hairless mice, followed by brother-sister cross to get F2 homozygous mutant (hairless) or wild-type (haired) mice. UVB-induced inflammation was less pronounced in shaved haired than in hairless mice. In hairless mice, inflammatory infiltrate was found around the rudimentary HFs and epidermal cysts. Expression of epidermal IL1f6, S100a8, vitamin D receptor, repetin, and major histocompatibility complex II, biomarkers depicting susceptibility to cutaneous inflammation, was also higher. In these animals, HF disruption altered susceptibility to UVB-induced BCCs. Tumor onset in hairless mice was 10 weeks earlier than in haired littermates. The incidence of BCCs was significantly higher in hairless than in haired animals; however, the magnitude of sonic hedgehog signaling did not differ significantly. Overall, 100% of hairless mice developed >12 tumors per mouse after 32 weeks of UVB therapy, whereas haired mice developed fewer than three tumors per mouse after 44 weeks of long-term UVB irradiation. Tumors in hairless mice were more aggressive than in haired littermates and manifested decreased E-cadherin and enhanced mesenchymal proteins. These data provide novel evidence that disruption of HFs in Ptch(+/-) mice enhances cutaneous susceptibility to inflammation and BCCs.

  9. Endoscopic findings using narrow-band imaging to distinguish between basal cell hyperplasia and carcinoma of the pharynx.

    PubMed

    Yagishita, Atsushi; Fujii, Satoshi; Yano, Tomonori; Kaneko, Kazuhiro

    2014-07-01

    Narrow-band imaging (NBI) has been reported to be useful for detecting superficial-type esophageal or head and neck squamous cell carcinoma (SCC), and in the present study we have used NBI to detect non-carcinomatous lesions, such as basal cell hyperplasia (BCH) accompanied by microvascular irregularities; these non-carcinomatous lesions were pathologically discriminated from squamous cell carcinoma of the pharynx. The aim of the present study was to clarify the endoscopic characteristics of BCH that contribute to the discrimination of superficial-type head and neck SCC (HNSCC). We examined the key endoscopic findings capable of distinguishing BCH from SCC using 26 BCH and 37 superficial-type SCC of the pharynx that had been pathologically diagnosed at our institution between January 2008 and July 2012. The clinicopathological factors were also compared. The size of the BCH lesions was significantly smaller (P < 0.001), and their intervascular transparency was more clearly observed (P < 0.001). Intra-epithelial papillary capillary loop (IPCL) shapes were less variable and monotonous (P < 0.001), and the distribution of the IPCL was more regular with an interval comparable to that of SCC (P < 0.001), although no significant differences in the sharpness of the lesion border, dilatation of IPCL and tortuosity of the IPCL were seen between the BCH and SCC lesions. This study revealed that BCH was an independent entity in terms of not only pathological findings, but also endoscopic findings observed using NBI, such as the regular distribution of IPCL and the preserved intervascular transparency.

  10. Survival after squamous cell and basal cell carcinoma of the skin: A retrospective cohort analysis.

    PubMed

    Rees, Judy R; Zens, M Scot; Celaya, Maria O; Riddle, Bruce L; Karagas, Margaret R; Peacock, Janet L

    2015-08-15

    A retrospective cohort analysis of survival after keratinocyte cancer (KC) was conducted using data from a large, population-based case-control study of KC in New Hampshire. The original study collected detailed information during personal interviews between 1993 and 2002 from individuals with squamous (SCC) and basal (BCC) cell carcinoma, and controls identified through the Department of Transportation, frequency-matched on age and sex. Participants without a history of non-skin cancer at enrolment were followed as a retrospective cohort to assess survival after either SCC or BCC, or a reference date for controls. Through 2009, cancers were identified from the New Hampshire State Cancer Registry and self-report; death information was obtained from state death certificate files and the National Death Index. There were significant differences in survival between those with SCC, BCC and controls (p = 0.040), with significantly greater risk of mortality after SCC compared to controls (adjusted hazard ratio [HR] 1.25; 95% confidence interval 1.01-1.54). Mortality after BCC was not significantly altered (HR 0.96; 95% CI 0.77-1.19). The excess mortality after SCC persisted after adjustment for numerous personal risk factors including time-varying non-skin cancer occurrence, age, sex and smoking. Survival from the date of the intervening cancer, however, did not vary (HR for SCC 0.98; 95% CI 0.70-1.38). Mortality also remained elevated when individuals with subsequent melanoma were excluded (HR for SCC 1.30; 95% CI 1.05-1.61). Increased mortality after SCC cannot be explained by the occurrence of intervening cancers, but may reflect a more general predisposition to life threatening illness that merits further investigation.

  11. Giant Basal Cell Carcinomas Arising on the Bilateral Forearms of a Patient: A Case Report and Review of Nonsurgical Treatment Options

    PubMed Central

    Shangraw, Sarah; Stone, Rivka C.; Cho-Vega, Jeong Hee; Kirsner, Robert S.

    2016-01-01

    Giant basal cell carcinomas (GBCCs) are large basal cell carcinomas (BCCs; <5 cm) with a greater propensity to invade and metastasize than standard BCCs. The presence of 2 GBCCs in a single individual is rare. We present the case of a 71-year-old Caucasian male with bilateral GBCCs on the dorsal forearms, measuring 130 cm2 and 24 cm2, respectively, that developed over a 21-year period. Over this period, the patient treated the tumors with herbal remedies. Histologic evaluation showed a conventional nodular BCC for both tumors. Computed tomography and magnetic resonance imaging revealed a T4N0M0 stage for the larger lesion. Surgical excision and grafting and reconstruction were offered, but he declined. This case highlights a shared belief in holistic treatments and rejection of Western medical interventions that are common among many patients with GBCC. Studies reporting nonsurgical treatments for GBCCs, including radiotherapy, vismodegib, topical imiquimod, and acitretin are reviewed. PMID:28101025

  12. Adult interfollicular tumour-initiating cells are reprogrammed into an embryonic hair follicle progenitor-like fate during basal cell carcinoma initiation.

    PubMed

    Youssef, Khalil Kass; Lapouge, Gaëlle; Bouvrée, Karine; Rorive, Sandrine; Brohée, Sylvain; Appelstein, Ornella; Larsimont, Jean-Christophe; Sukumaran, Vijayakumar; Van de Sande, Bram; Pucci, Doriana; Dekoninck, Sophie; Berthe, Jean-Valery; Aerts, Stein; Salmon, Isabelle; del Marmol, Véronique; Blanpain, Cédric

    2012-12-01

    Basal cell carcinoma, the most frequent human skin cancer, arises from activating hedgehog (HH) pathway mutations; however, little is known about the temporal changes that occur in tumour-initiating cells from the first oncogenic hit to the development of invasive cancer. Using an inducible mouse model enabling the expression of a constitutively active Smoothened mutant (SmoM2) in the adult epidermis, we carried out transcriptional profiling of SmoM2-expressing cells at different times during cancer initiation. We found that tumour-initiating cells are massively reprogrammed into a fate resembling that of embryonic hair follicle progenitors (EHFPs). Wnt/ β-catenin signalling was very rapidly activated following SmoM2 expression in adult epidermis and coincided with the expression of EHFP markers. Deletion of β-catenin in adult SmoM2-expressing cells prevents EHFP reprogramming and tumour initiation. Finally, human basal cell carcinomas also express genes of the Wnt signalling and EHFP signatures.

  13. Diagnosis of Basal Cell Carcinoma by Reflectance Confocal Microscopy: Study Design and Protocol of a Randomized Controlled Multicenter Trial

    PubMed Central

    Alkemade, Hans A.C; Maessen-Visch, Birgitte; Hendriks, Jan C.M; van Erp, Piet E.J; Adang, Eddy M.M; Gerritsen, Marie-Jeanne P

    2016-01-01

    Background Skin cancer, including basal cell carcinoma (BCC), has become a major health care problem. The limitations of a punch biopsy (at present the gold standard) as diagnostic method together with the increasing incidence of skin cancer point out the need for more accurate, cost-effective, and patient friendly diagnostic tools. In vivo reflectance confocal microscopy (RCM) is a noninvasive imaging technique that has great potential for skin cancer diagnosis. Objective To investigate whether in vivo RCM can correctly identify the subtype of BCC and to determine the cost-effectiveness of RCM compared with punch biopsy (usual care). Study design: Randomized controlled multicenter trial. Methods On the basis of 80% power and an alpha of 0.05, 329 patients with lesions clinically suspicious for BCC will be included in this study. Patients will be randomized for RCM or for a punch biopsy (usual care). When a BCC is diagnosed, surgical excision will follow and a follow-up visit will be planned 3 months later. Several questionnaires will be filled in (EQ-5D, EQ-5D VAS, iMTA PCQ, and TSQM-9). We will perform statistical analysis, cost-effectiveness, and patient outcome analysis after data collection. Results This research started in January 2016 and is ethically approved. We expect to finish this study at the end of 2018. Conclusions In this study, we will investigate whether RCM is at least as good in identifying BCC subtypes as conventional pathological investigation of skin biopsies. Anticipating that RCM is found to be a cost-effective alternative, it saves on direct medical consumption like labor of the pathologist and other medical personnel as well as materials related to treatment failure with at least equal effectiveness. Trial Registration Clinicaltrials.gov NCT02623101; https://clinicaltrials.gov/ct2/show/NCT02623101 (Archived by WebCite at http://www.webcitation.org/6id54WQa2) PMID:27363577

  14. Evasion of p53 and G2/M checkpoints are characteristic of Hh-driven basal cell carcinoma.

    PubMed

    Li, Z J; Mack, S C; Mak, T H; Angers, S; Taylor, M D; Hui, C-C

    2014-05-15

    Basal cell carcinoma (BCC), the most common type of cancer, is characterized by aberrant Hedgehog (Hh) pathway activity. Mutations in pathway components, such as PATCHED1 (PTCH1), are commonly found in BCC. While the tumor suppressor role of PTCH1 in BCC is well established, how Hh pathway activation disrupts normal skin homeostasis to promote BCC formationremains poorly understood. Like Ptc1, Sufu is a major negative regulator of the Hh pathway. Previously, we showed that inactivation of Sufu in the skin does not result in BCC formation. Why loss of Ptc1, but not Sufu, in the epidermis induces BCC formation is unclear. In this report, we utilized gene expression profiling to identify biological pathways and processes that distinguish Sufu from Ptc1 mutants, and discovered a novel role for Sufu in cell cycle regulation. We demonstrated that the Hh pathway activation inSufu and Ptc1 mutant skin is associated with abnormal cell cycle entry, ectopic expression of D-type cyclins and increasedDNA damage. However, despite the presence of DNA damage, p53 stabilization was impaired in the mutant skin. Alternative mechanism to halt genomic instability is the activation of G2/M cell cycle checkpoint, which can occur independent of p53. We found that while Ptc1 mutant cells continue to cycle, which would favor genomic instability, loss of Sufu results in G2/M cell cycle arrest.This finding may explain why inactivation of Sufu is not sufficient to drive BCC formation. Taken together, these studies revealed a unique role for Sufu in G2/M phase progression, and uncovered the molecular and cellular features associated with Hh-driven BCC.

  15. BASAL CELL CARCINOMA OF THE HEAD-AND-NECK REGION: A SINGLE CENTER ANALYSIS OF 1,750 TUMORS.

    PubMed

    Tourli, I; Langner, D; Haroske, G; Tchernev, G; Lotti, T; Wollina, U

    2016-01-01

    Basal cell carcinoma (BCC) is the most common malignancy in humans with a pre-dominance for the sun-exposed head-and-neck region. Its incidence is rising world-wide. Early detection and appropriate treatment ensures an excellent prognosis. We analyzed patients with BCC of the head-and-neck region treated at our Department from January 2008 to December 2012 with a follow-up between 2 to 6 years. Data were collected retrospectively. During a 4-year period, 1,750 BCC lesions of head-and-neck region were excised from 1,380 patients. Distribution of gender among the patients was nearly even. Mean age of patients was 74.3±11.4 years. Solid histological subtype dominated the series. Most tumors were removed surgically by delayed MOHS technique (77.0%). The recurrence rate of BCC was 1.6%. The highest recurrence rate of 15.5% was seen in cases of morphea-like BCC compared to 3.9% among solid BCC. The recurrence rate among R0 resected tumors was 0.24% compared to 19.8% among R1-resections (Pearson's Chi-square 56.000). The majority of recurrences occurred within the first 5 year-interval (64%). Multivariate analysis of risk factors for recurrences demonstrated an Odd's ratio for recurrences of 54.89 (95% confidence interval, 21.16, 142.37) in case of R1-resection status. Gender had a minor influence with a slight benefit toward males versus females (Odd's ratio 0.51; 95% confidence interval, 0.28, 0.92). The age of the patients had no impact on recurrence rate. Although there is relatively low mortality attributable to BCC, the morbidity and cost of treatment are significant. Surgical excision remains the mainstay of treatment. For head-and-neck BCC, delayed MOHS surgery offers significantly lower recurrence in both primary BCC and recurrent (secondary) BCC.

  16. Integrating pathway analysis and genetics of gene expression for genome-wide association study of basal cell carcinoma.

    PubMed

    Zhang, Mingfeng; Liang, Liming; Morar, Nilesh; Dixon, Anna L; Lathrop, G Mark; Ding, Jun; Moffatt, Miriam F; Cookson, William O C; Kraft, Peter; Qureshi, Abrar A; Han, Jiali

    2012-04-01

    Genome-wide association studies (GWASs) have primarily focused on marginal effects for individual markers and have incorporated external functional information only after identifying robust statistical associations. We applied a new approach combining the genetics of gene expression and functional classification of genes to the GWAS of basal cell carcinoma (BCC) to identify potential biological pathways associated with BCC. We first identified 322,324 expression-associated single-nucleotide polymorphisms (eSNPs) from two existing GWASs of global gene expression in lymphoblastoid cell lines (n = 955), and evaluated the association of these functionally annotated SNPs with BCC among 2,045 BCC cases and 6,013 controls in Caucasians. We then grouped them into 99 KEGG pathways for pathway analysis and identified two pathways associated with BCC with p value <0.05 and false discovery rate (FDR) <0.5: the autoimmune thyroid disease pathway (mainly HLA class I and II antigens, p < 0.001, FDR = 0.24) and Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway (p = 0.02, FDR = 0.49). Seventy-nine (25.7%) out of 307 significant eSNPs in the JAK-STAT pathway were associated with BCC risk (p < 0.05) in an independent replication set of 278 BCC cases and 1,262 controls. In addition, the association of JAK-STAT signaling pathway was marginally validated using 16,691 eSNPs identified from 110 normal skin samples (p = 0.08). Based on the evidence of biological functions of the JAK-STAT pathway on oncogenesis, it is plausible that this pathway is involved in BCC pathogenesis.

  17. Family History of Skin Cancer is Associated with Early-Onset Basal Cell Carcinoma Independent of MC1R Genotype

    PubMed Central

    Berlin, Nicholas L.; Cartmel, Brenda; Leffell, David J.; Bale, Allen E.; Mayne, Susan T.; Ferrucci, Leah M.

    2015-01-01

    Background As a marker of genetic susceptibility and shared lifestyle characteristics, family history of cancer is often used to evaluate an individual’s risk for developing a particular malignancy. With comprehensive data on pigment characteristics, lifestyle factors, and melanocortin-1 receptor (MC1R) gene sequence, we sought to clarify the role of family history of skin cancer in early-onset basal cell carcinoma (BCC). Materials and Methods Early onset BCC cases (n=376) and controls with benign skin conditions (n=383) under age 40 were identified through Yale Dermatopathology. Self-report data on family history of skin cancer (melanoma and non-melanoma skin cancer), including age of onset in relatives, was available from a structured interview. Participants also provided saliva samples for sequencing of MC1R. Results A family history of skin cancer was associated with an increased risk of early-onset BCC (OR 2.49, 95% CI 1.80–3.45). In multivariate models, family history remained a strong risk factor for early-onset BCC after adjustment for pigment characteristics, UV exposure, and MC1R genotype (OR 2.41, 95% CI 1.74–3.35). Conclusions Risk for BCC varied based upon the type and age of onset of skin cancer among affected relatives; individuals with a first-degree relative diagnosed with skin cancer prior to age 50 were at highest risk for BCC (OR 4.79, 95% CI 2.90–7.90). Even after taking into account potential confounding effects of MC1R genotype and various lifestyle factors that close relatives may share, family history of skin cancer remained strongly associated with early-onset BCC. PMID:26381319

  18. Indoor tanning and the MC1R genotype: risk prediction for basal cell carcinoma risk in young people.

    PubMed

    Molinaro, Annette M; Ferrucci, Leah M; Cartmel, Brenda; Loftfield, Erikka; Leffell, David J; Bale, Allen E; Mayne, Susan T

    2015-06-01

    Basal cell carcinoma (BCC) incidence is increasing, particularly in young people, and can be associated with significant morbidity and treatment costs. To identify young individuals at risk of BCC, we assessed existing melanoma or overall skin cancer risk prediction models and built a novel risk prediction model, with a focus on indoor tanning and the melanocortin 1 receptor gene, MC1R. We evaluated logistic regression models among 759 non-Hispanic whites from a case-control study of patients seen between 2006 and 2010 in New Haven, Connecticut. In our data, the adjusted area under the receiver operating characteristic curve (AUC) for a model by Han et al. (Int J Cancer. 2006;119(8):1976-1984) with 7 MC1R variants was 0.72 (95% confidence interval (CI): 0.66, 0.78), while that by Smith et al. (J Clin Oncol. 2012;30(15 suppl):8574) with MC1R and indoor tanning had an AUC of 0.69 (95% CI: 0.63, 0.75). Our base model had greater predictive ability than existing models and was significantly improved when we added ever-indoor tanning, burns from indoor tanning, and MC1R (AUC = 0.77, 95% CI: 0.74, 0.81). Our early-onset BCC risk prediction model incorporating MC1R and indoor tanning extends the work of other skin cancer risk prediction models, emphasizes the value of both genotype and indoor tanning in skin cancer risk prediction in young people, and should be validated with an independent cohort.

  19. Immunohistochemical markers of advanced basal cell carcinoma: CD56 is associated with a lack of response to vismodegib.

    PubMed

    Castillo, Jean-Marie; Knol, Anne-Chantal; Nguyen, Jean-Michel; Khammari, Amir; Saint-Jean, Mélanie; Dreno, Brigitte

    2016-10-01

    Vismodegib is an effective treatment for advanced basal cell carcinoma (BCC), but primary resistance to vismodegib remains to be elucidated. Alternative approaches are warranted to help selecting patients most likely to be responsive to treatment. The identification of immunohistochemical markers may support this perspective, as well as better understanding of resistance mechanisms. To determine the level of expression of CD56, PDGF-R, CD117, MMP9, TIMP3, and CXCR4 in advanced BCC, and explore whether expression levels are associated with non-response to vismodegib. A cross-sectional study was conducted. Immunohistochemical markers were selected based on their roles in tumour proliferation and/or migration in skin tumours. Tissue samples included pretreatment advanced BCC samples from patients treated with vismodegib, with an available response after six months of treatment. Regression optimised models were used to build hypotheses regarding a possible association between expression levels and non-response to vismodegib, which was then tested by logistic regression. Twenty-three patients were included. The percentage of samples expressing markers ranged from 43.5% (CD117) to 91.3% (CXCR4). CD56 expression was significantly associated with an increased risk of non-response to vismodegib (OR = 5.5; CI 95%: 3.4-29.8; p = 0.0488); a similar association was suggested for CXCR4 (p = 0.066), but not identified for other markers. These results provide a better understanding of the expression of immunohistochemical markers in advanced BCC. Further detailed analysis of CD56 expression may provide insights into guiding further investigation of the correlation between this marker and non-response to vismodegib.

  20. Inorganic Arsenic and Basal Cell Carcinoma in Areas of Hungary, Romania, and Slovakia: A Case–Control Study

    PubMed Central

    Leonardi, Giovanni; Vahter, Marie; Clemens, Felicity; Goessler, Walter; Gurzau, Eugen; Hemminki, Kari; Hough, Rupert; Koppova, Kvetoslava; Kumar, Rajiv; Rudnai, Peter; Surdu, Simona

    2012-01-01

    Background: Inorganic arsenic (iAs) is a potent carcinogen, but there is a lack of information about cancer risk for concentrations < 100 μg/L in drinking water. Objectives: We aimed to quantify skin cancer relative risks in relation to iAs exposure < 100 μg/L and the modifying effects of iAs metabolism. Methods: The Arsenic Health Risk Assessment and Molecular Epidemiology (ASHRAM) study, a case–control study, was conducted in areas of Hungary, Romania, and Slovakia with reported presence of iAs in groundwater. Consecutively diagnosed cases of basal cell carcinoma (BCC) of the skin were histologically confirmed; controls were general surgery, orthopedic, and trauma patients who were frequency matched to cases by age, sex, and area of residence. Exposure indices were constructed based on information on iAs intake over the lifetime of participants. iAs metabolism status was classified based on urinary concentrations of methylarsonic acid (MA) and dimethylarsinic acid (DMA). Associations were estimated by multivariable logistic regression. Results: A total of 529 cases with BCC and 540 controls were recruited for the study. BCC was positively associated with three indices of iAs exposure: peak daily iAs dose rate, cumulative iAs dose, and lifetime average water iAs concentration. The adjusted odds ratio per 10-μg/L increase in average lifetime water iAs concentration was 1.18 (95% confidence interval: 1.08, 1.28). The estimated effect of iAs on cancer was stronger in participants with urinary markers indicating incomplete metabolism of iAs: higher percentage of MA in urine or a lower percentage of DMA. Conclusion: We found a positive association between BCC and exposure to iAs through drinking water with concentrations < 100 μg/L. PMID:22436128

  1. Arecoline decreases interleukin-6 production and induces apoptosis and cell cycle arrest in human basal cell carcinoma cells.

    PubMed

    Huang, Li-Wen; Hsieh, Bau-Shan; Cheng, Hsiao-Ling; Hu, Yu-Chen; Chang, Wen-Tsan; Chang, Kee-Lung

    2012-01-15

    Arecoline, the most abundant areca alkaloid, has been reported to decrease interleukin-6 (IL-6) levels in epithelial cancer cells. Since IL-6 overexpression contributes to the tumorigenic potency of basal cell carcinoma (BCC), this study was designed to investigate whether arecoline altered IL-6 expression and its downstream regulation of apoptosis and the cell cycle in cultured BCC-1/KMC cells. BCC-1/KMC cells and a human keratinocyte cell line, HaCaT, were treated with arecoline at concentrations ranging from 10 to 100μg/ml, then IL-6 production and expression of apoptosis- and cell cycle progress-related factors were examined. After 24h exposure, arecoline inhibited BCC-1/KMC cell growth and decreased IL-6 production in terms of mRNA expression and protein secretion, but had no effect on HaCaT cells. Analysis of DNA fragmentation and chromatin condensation showed that arecoline induced apoptosis of BCC-1/KMC cells in a dose-dependent manner, activated caspase-3, and decreased expression of the anti-apoptotic protein Bcl-2. In addition, arecoline induced progressive and sustained accumulation of BCC-1/KMC cells in G2/M phase as a result of reducing checkpoint Cdc2 activity by decreasing Cdc25C phosphatase levels and increasing p53 levels. Furthermore, subcutaneous injection of arecoline led to decreased BCC-1/KMC tumor growth in BALB/c mice by inducing apoptosis. This study demonstrates that arecoline has potential for preventing BCC tumorigenesis by reducing levels of the tumor cell survival factor IL-6, increasing levels of the tumor suppressor factor p53, and eliciting cell cycle arrest, followed by apoptosis.

  2. Effects of Combined Treatment With Arsenic Trioxide and Itraconazole in Patients With Refractory Metastatic Basal Cell Carcinoma

    PubMed Central

    Ally, Mina S.; Ransohoff, Katherine; Sarin, Kavita; Atwood, Scott X.; Rezaee, Melika; Bailey-Healy, Irene; Kim, Jynho; Beachy, Philip A.; Chang, Anne Lynn S.; Oro, Anthony; Tang, Jean Y.; Colevas, A. Dimitrios

    2016-01-01

    IMPORTANCE Tumor resistance is an emerging problem for Smoothened (SMO) inhibitor–treated metastatic basal cell carcinoma (BCC). Arsenic trioxide and itraconazole antagonize the hedgehog (HH) pathway at sites distinct from those treated by SMO inhibitors. OBJECTIVE To determine whether administration of intravenous arsenic trioxide and oral itraconazole in patients with metastatic BCC is associated with a reduction in GLI1 messenger RNA expression in tumor and/or normal skin biopsy samples. DESIGN, SETTING, AND PARTICIPANTS Five men with metastatic BCC who experienced relapse after SMO inhibitor treatment underwent intravenous arsenic trioxide treatment for 5 days, every 28 days, and oral itraconazole treatment on days 6 to 28. Data were collected from April 10 to November 14, 2013. Follow-up was completed on October 3, 2015, and data were analyzed from June 5 to October 6, 2015. MAIN OUTCOMES AND MEASURES The primary outcome was the change in messenger RNA levels of the GLI family zinc finger 1 (GLI1) gene (HH-pathway target gene) in biopsy specimens of normal skin or BCC before and after treatment. Secondary objectives were evaluation of tumor response and tolerability. RESULTS Of the 5 patients (mean [SD] age, 52 [9] years; age range, 43-62 years), 3 completed 3 cycles of treatment and 2 discontinued treatment early owing to disease progression or adverse events. Adverse effects included grade 2 transaminitis and grade 4 leukopenia with a grade 3 infection. Overall, arsenic trioxide and itraconazole reduced GLI1 messenger RNA levels by 75% from baseline (P < .001). The best overall response after 3 treatment cycles was stable disease in 3 patients. CONCLUSIONS AND RELEVANCE Targeting the HH pathway with sequential arsenic trioxide and itraconazole treatment is a feasible treatment for metastatic BCC. Although some patients experienced stable disease for 3 months, none had tumor shrinkage, which may be owing to transient GLI1 suppression with sequential dosing

  3. A novel imaging approach to periocular basal cell carcinoma: in vivo optical coherence tomography and histological correlates

    PubMed Central

    Pelosini, L; Smith, H B; Schofield, J B; Meeckings, A; Dithal, A; Khandwala, M

    2015-01-01

    Purpose Optical coherence tomography (OCT) is a non-invasive imaging method widely used in ophthalmology. Recent developments have produced OCT devices for imaging the skin. The purpose of this study was to investigate Fourier Domain OCT morphological features of periocular basal cell carcinoma (BCC) in correlation with conventional histopathology. Methods Consecutive patients with periocular nodular BCC were prospectively examined with VivoSight OCT (Michelson Ltd) prior to surgical excision. OCT slice mode images were analysed using criteria defined for conventional and HD-OCT; the images were correlated to haematoxylin and eosin stained histology sections. Results A total of 15 patients with periocular BCC were recruited. Three categories of BCC morphological features were identified from slice mode OCT images: 1) Epidermal changes included epidermal thinning (15/15; 100%), ulceration and crusting (5/15, 33.3%) and decreased density of hair follicles (8/15; 53.3%); 2) Intralesional features included hyporeflective nodules (15/15; 100%), hyper-reflective edges (15/15; 100%) and hyporeflective central necrosis (3/15; 20%) 3) Perilesional features included hyporeflective borders (11/15; 73%), hypereflective margins (15/15; 100%) and dilated blood vessels (5/15; 33%). Conclusions This study demonstrated that Fourier Domain OCT imaging offers additional information in the identification of morphological features of nodular BCC compared to conventional OCT diagnostic criteria. VivoSight produced fast, non-invasive imaging of skin lesions in the periocular region and high correlation with histology. Further studies are necessary to investigate OCT features of different histological subtypes of BCC. PMID:26088676

  4. The invisible basal cell carcinoma: how reflectance confocal microscopy improves the diagnostic accuracy of clinically unclear facial macules and papules.

    PubMed

    Ruini, C; Hartmann, D; Saral, S; Krammer, S; Ruzicka, T; von Braunmühl, T

    2016-11-01

    Difficult to diagnose and early non-melanoma skin cancer lesions are frequently seen in daily clinical practice. Besides precancerous lesions such as actinic keratosis, basal cell carcinomas (BCCs) score the highest frequency in skin tumors. While infiltrative and nodular BCCs require a surgical treatment with a significant impact on the patients' quality of life, early and superficial BCCs might benefit from numerous conservative treatments, such as topical immune-modulators or photodynamic therapy. Dermoscopy has shown a high sensitivity and specificity in the diagnosis of early BCCs, and non-invasive imaging techniques like reflectance confocal microscopy (RCM) have proven to be helpful. The aim of our study was to investigate the importance of RCM in the diagnosis of BCCs with indistinct clinical and dermoscopic features. We retrospectively examined 27 histologically proven BCCs in which diagnosis was not possible based on naked eye examination; we separately reviewed clinical, dermoscopic, and confocal microscopy features and evaluated the lesions meeting the common diagnostic criteria for BCCs, and our diagnostic confidence. All lesions were clinically unclear, with no characteristic features suggestive for BCC; dermoscopy showed in most cases unspecific teleangiectasias (74 %) and micro-erosions (52 %). Confocal microscopy revealed in most of the cases the presence of specific criteria: peripheral palisading of the nuclei (89 %), clefting (70 %), stromal reaction (70 %), dark silhouettes (70 %), inflammatory particles (70 %), and tumor islands (67 %). In the absence of significant diagnostic clinical signs and with unclear dermoscopic features, specific confocal patterns were present in most of the lesions and enabled a correct diagnosis. In the absence of significant clinical features of BCC and in the case of uncertain dermoscopy, striking confocal features are detectable and easy to recognize in most cases. Confocal microscopy can therefore be

  5. P16INK4a Immunostaining but Lack of Human Papilloma Virus Type 16 in Cutaneous Squamous Cell Carcinoma and Basal Cell Carcinoma: a Report from West Iran.

    PubMed

    Ramezani, Mazaher; Abdali, Elham; Khazaei, Sedigheh; Vaisi-Raygani, Asad; Sadeghi, Masoud

    2016-01-01

    The tumor suppressor p16 is a biomarker for transforming human papilloma virus (HPV) infections that can lead to contradictory results in skin carcinomas. The aim of this study was to evaluate p16 expression and HPV-16 infection in the cutaneous basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). This case-control study was performed on paraffin blocks of BCCs and SCCs and normal skin (53, 36, and 44 cases, respectively), between 2006 to 2015. Initial sections for groups were stained with hematoxylin and eosin (H and E). Immunohistochemistry was performed for p16 expression and human papilloma virus type 16 (HPV-16) infection. Normal group was skin of mammoplasty specimens and normal skin tissue in the periphery of tumors. The mean age at diagnosis was 42.1, 61.7 and 71.4 years for normal, BCC and SCC groups, respectively. P16 positivity was more in SCC and BCC groups compared to normal group (P<0.05) and HPV was negative in all patients in three groups. Also, the mean age at diagnosis and P16-positivity were higher for the SCC group than the BCC group (P<0.005). In conclusion, in non-melanoma skin cancers (SCC and BCC), p16-positivity can be a prognostic factor but there is no correlation between HPV-16 and p16 in these tumors.

  6. SOX10-positive salivary gland tumors: a growing list, including mammary analogue secretory carcinoma of the salivary gland, sialoblastoma, low-grade salivary duct carcinoma, basal cell adenoma/adenocarcinoma, and a subgroup of mucoepidermoid carcinoma.

    PubMed

    Hsieh, Min-Shu; Lee, Yi-Hsuan; Chang, Yih-Leong

    2016-10-01

    Transcription factor SRY-related HMG-box 10 (SOX10) is an important marker for melanocytic, schwannian, myoepithelial, and some salivary gland tumors. The aim of this study was to investigate SOX10 expression more thoroughly in the salivary gland neoplasms, including mammary analogue secretory carcinoma and hyalinizing clear cell carcinoma harboring specific genetic rearrangements. A new rabbit monoclonal anti-SOX10 antibody (clone EP268) was used to examine SOX10 expression in 14 different types of salivary gland tumors. We found that acinic cell carcinoma (AciCC), adenoid cystic carcinoma, mammary analogue secretory carcinoma (MASC), epithelial-myoepithelial carcinoma, low-grade salivary duct carcinoma, sialoblastoma, basal cell adenocarcinoma, basal cell adenoma, and pleomorphic adenoma were SOX10 positive. Salivary duct carcinoma, lymphoepithelial carcinoma, hyalinizing clear cell carcinoma, and oncocytoma were SOX10 negative. Earlier, mucoepidermoid carcinoma (MEC) was considered a SOX10-negative tumor. This study identified a subgroup of SOX10-positive MEC cases with characteristic polygonal epithelial cells, pale-to-eosinophilic cytoplasm, and colloid-like dense eosinophilic material. Our data show SOX10 expression can be observed in salivary gland tumors with either one of the 4 cell types: acinic cells, cuboidal ductal cells with low-grade cytologic features, basaloid cells, and myoepithelial cells. In this article we thoroughly evaluated SOX10 expression in salivary gland tumors. SOX10 is useful in the differential diagnosis between myoepithelial carcinoma with clear cell features and hyalinizing clear cell carcinoma. It can also be used to discriminate low-grade salivary duct carcinoma from high-grade ones. Pathologists should be cautious with the interpretation of SOX10 positivity in salivary gland tumors, and correlation with histologic feature is mandatory.

  7. Alcohol consumption and risk of cutaneous basal cell carcinoma in women and men: 3 prospective cohort studies12

    PubMed Central

    Wu, Shaowei; Li, Wen-Qing; Qureshi, Abrar A; Cho, Eunyoung

    2015-01-01

    Background: Alcohol consumption has been associated with an increased prevalence of sunburn, which is an established skin cancer risk factor. Objective: We investigated whether alcohol consumption is associated with risk of cutaneous basal cell carcinoma (BCC). Design: We conducted a prospective analysis on alcohol consumption and risk of BCC on the basis of data from 167,765 women in the NHS (Nurses’ Health Study) (1984–2010) and NHS II (1991–2011) and 43,697 men in the Health Professionals Follow-Up Study (1986–2010). Alcohol intake was repeatedly assessed every 2–4 y over the follow-up period. HRs and 95% CIs for BCC in association with alcohol intake were computed with the use of Cox proportional hazards models with adjustment for sun exposure and other skin cancer risk factors. Results: A total of 28,951 incident BCC cases were documented over 3.74 million person-years of follow-up. Increased alcohol intake was associated with increased BCC risk in both women and men (both P-trend < 0.0001). Pooled multivariable-adjusted HRs over increasing cumulative averaged alcohol intake categories were 1.00 (reference) for nondrinkers, 1.13 (95% CI: 1.06, 1.20) for 0.1–9.9 g/d, 1.24 (95% CI: 1.14, 1.35) for 10.0–19.9 g/d, 1.27 (95% CI: 1.20, 1.35) for 20.0–29.9 g/d, and 1.22 (95% CI: 1.15, 1.30) for ≥30.0 g/d (P-trend < 0.0001, P-heterogeneity by study = 0.10 ). The association remained consistent when we used alcohol intakes over different latency periods (0–4, 4–8, 8–12, and 12–16 y) as exposures and over categories of sun exposure–related factors. In the individual alcoholic beverages, white wine and liquor were positively associated with BCC risk. Conclusion: Alcohol consumption is associated with increased risk of cutaneous BCC in both women and men. PMID:26423390

  8. Immunohistochemical analysis of TIMP-3 and MMP-9 in actinic keratosis, squamous cell carcinoma of the skin, and basal cell carcinoma.

    PubMed

    Poswar, Fabiano O; Fraga, Carlos A C; Farias, Lucyana C; Feltenberger, John D; Cruz, Vitória P D; Santos, Sérgio H S; Silveira, Christine M; de Paula, Alfredo M B; Guimarães, André L S

    2013-11-01

    The expression of metalloproteinases and their inhibitors has been related to different invasive and metastatic potentials in cancer. This study aims to investigate the immunohistochemical expression of TIMP-3 and MMP-9 in samples of basal cell carcinoma (BCC), squamous cell carcinoma of the skin (SCC), and actinic keratosis (AK). Immunohistochemistry was performed to evaluate the expression of TIMP-3 and MMP-9 in samples of BCC (n=22), SCC (n=10), and AK (n=15). Ten fields of both tumor parenchyma and tumor stroma were photographed and counted in image software. The ratio of positive cells to total cells was used to quantify the staining. A higher expression of MMP-9 was found in tumor stroma of SCC compared to BCC and AK. No significant differences in TIMP-3 expression were observed among the groups. Considering the well-described differences between these neoplasms, these results provide additional evidence of the role of MMP-9 in tumor invasiveness of keratinocyte-derived tumors.

  9. Protein expression of MMP-2 and MT1-MMP in actinic keratosis, squamous cell carcinoma of the skin, and basal cell carcinoma.

    PubMed

    de Oliveira Poswar, Fabiano; de Carvalho Fraga, Carlos Alberto; Gomes, Emisael Stênio Batista; Farias, Lucyana Conceição; Souza, Linton Wallis Figueiredo; Santos, Sérgio Henrique Souza; Gomez, Ricardo Santiago; de-Paula, Alfredo Maurício Batista; Guimarães, André Luiz Sena

    2015-02-01

    Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are 2 skin neoplasms with distinct potentials to invasion and metastasis. Actinic keratosis (AK) is a precursor lesion of SCC. Immunohistochemistry was performed to evaluate the expression of MMP-2 and MT1-MMP in samples of BCC (n = 29), SCC (n = 12), and AK (n = 13). The ratio of positive cells to total cells was used to quantify the staining. Statistical significance was considered under the level P < .05. We found a higher expression of MMP-2 in tumor stroma and parenchyma of SCC as compared to BCC. The expression of this protein was also similar between SCC and its precursor actinic keratosis, and it was higher in the stroma of high-risk BCC when compared to low-risk BCC. MT1-MMP, which is an activator of MMP-2, was similarly expressed in all groups. Our results suggest that MMP-2 expression may contribute to the distinct invasive patterns seen in SCC and BCC.

  10. Quantification of PpIX concentration in basal cell carcinoma and squamous cell carcinoma models using spatial frequency domain imaging

    PubMed Central

    Sunar, Ulas; Rohrbach, Daniel J.; Morgan, Janet; Zeitouni, Natalie; Henderson, Barbara W.

    2013-01-01

    5-aminolaevulinic acid photodynamic therapy (ALA-PDT) is an attractive treatment option for nonmelanoma skin tumors, especially for multiple lesions and large areas. The efficacy of ALA-PDT is highly dependent on the photosensitizer (PS) concentration present in the tumor. Thus it is desirable to quantify PS concentration and distribution, preferably noninvasively to determine potential outcome. Here we quantified protoporphyrin IX (PpIX) distribution induced by topical and intra-tumoral (it) administration of the prodrug ALA in basal and squamous cell carcinoma murine models by using spatial frequency domain imaging (SFDI). The in vivo measurements were validated by analysis of the ex vivo extraction of PpIX. The study demonstrates the feasibility of non-invasive quantification of PpIX distributions in skin tumors. PMID:23577288

  11. Basal cell nevus syndrome - close-up of palm (image)

    MedlinePlus

    ... skeletal abnormalities. Skin manifestations include pits in the palms and soles, and numerous basal cell carcinomas. This ... close-up of the pits found in the palm of an individual with basal cell nevus syndrome.

  12. Diagnostic value of CD10 and Bcl2 expression in distinguishing cutaneous basal cell carcinoma from squamous cell carcinoma and seborrheic keratosis.

    PubMed

    Gaballah, Mohammad A; Ahmed, Rehab-Allah

    2015-12-01

    The distinction between cutaneous basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and seborrheic keratosis (SK), which are common entities in clinical practice, can be difficult clinically and histologically. CD10 and Bcl2 antigens are important factors in tumor growth, survival and spread. The aim of the present study is to define the frequency of CD10 and Bcl2 expression in such cutaneous tumors and its relation to the clinicopathological characteristics as well as their possible diagnostic utility. CD10 and Bcl2 immunohistochemistry was performed on 30 BCC, 20 SCC and 15 SK. 93.3% of SK cases and 53.3% of BCC cases showed significant expression of CD10 in tumor cells when compared either with each other or with SCC cases (100% negative). Stromal CD10 expression was positive in 50% of BCC cases and 75% of SCC cases. Stromal CD10 expression was significantly higher in high risk BCC and BCC with infiltrating deep margins; furthermore, it showed a significant positive correlation with grade of SCC. A significant inverse correlation between CD10 expression in stromal and tumor cells of BCC was present. Bcl2 was significantly expressed in 93.3% of SK cases and 80% of BCC cases when compared with SCC cases (100% negative). It was found that for distinguishing BCC from SK, only CD10 expression in tumor cells provided a high diagnostic value with positive likelihood ratio (PLR) was 7.00. In addition, CD10 and Bcl2 expression in tumor cells could give convincing diagnostic value to distinguish SCC from SK (PLR=15.00 for each marker). Moreover, for differentiating BCC from SCC, only Bcl2 in the tumor cells could provide a high diagnostic value (PLR=5.5). In conclusion, CD10 and Bcl2 can help in differentiating cutaneous BCC from SK and SCC. The overexpression of CD10 in the stromal cells of SCC and some variants of BCC suggests the invasive properties of such tumors.

  13. Basal Cell Carcinoma on the Pubic Area: Report of a Case and Review of 19 Korean Cases of BCC from Non-sun-exposed Areas.

    PubMed

    Park, Jin; Cho, Yong-Sun; Song, Ki-Hun; Lee, Jong-Sun; Yun, Seok-Kweon; Kim, Han-Uk

    2011-08-01

    Basal cell carcinoma (BCC) is one of the most commonly diagnosed malignant skin tumors and develops characteristically on sun-exposed areas, such as the head and neck. Ultraviolet light exposure is an important etiologic factor in BCCs, and BCCs arising from non-sun- exposed areas are, therefore, very rare. In particular, the axilla, nipple, the genital and perianal areas are not likely to be exposed to ultraviolet light; thus, if BCC develops in these areas, other predisposing factors should be considered. Herein, we report a case of BCC arising on the pubic area in a 70-year-old man. We also performed a survey of the literature and discussed the 19 cases of BCC from non-sun-exposed areas reported to date in Korea.

  14. Basal Cell Carcinoma on the Pubic Area: Report of a Case and Review of 19 Korean Cases of BCC from Non-sun-exposed Areas

    PubMed Central

    Park, Jin; Cho, Yong-Sun; Song, Ki-Hun; Lee, Jong-Sun; Kim, Han-Uk

    2011-01-01

    Basal cell carcinoma (BCC) is one of the most commonly diagnosed malignant skin tumors and develops characteristically on sun-exposed areas, such as the head and neck. Ultraviolet light exposure is an important etiologic factor in BCCs, and BCCs arising from non-sun- exposed areas are, therefore, very rare. In particular, the axilla, nipple, the genital and perianal areas are not likely to be exposed to ultraviolet light; thus, if BCC develops in these areas, other predisposing factors should be considered. Herein, we report a case of BCC arising on the pubic area in a 70-year-old man. We also performed a survey of the literature and discussed the 19 cases of BCC from non-sun-exposed areas reported to date in Korea. PMID:21909220

  15. Classification of basal cell carcinoma in human skin using machine learning and quantitative features captured by polarization sensitive optical coherence tomography

    PubMed Central

    Marvdashti, Tahereh; Duan, Lian; Aasi, Sumaira Z.; Tang, Jean Y.; Ellerbee Bowden, Audrey K.

    2016-01-01

    We report the first fully automated detection of basal cell carcinoma (BCC), the most commonly occurring type of skin cancer, in human skin using polarization-sensitive optical coherence tomography (PS-OCT). Our proposed automated procedure entails building a machine-learning based classifier by extracting image features from the two complementary image contrasts offered by PS-OCT, intensity and phase retardation (PR), and selecting a subset of features that yields a classifier with the highest accuracy. Our classifier achieved 95.4% sensitivity and specificity, validated by leave-one-patient-out cross validation (LOPOCV), in detecting BCC in human skin samples collected from 42 patients. Moreover, we show the superiority of our classifier over the best possible classifier based on features extracted from intensity-only data, which demonstrates the significance of PR data in detecting BCC. PMID:27699133

  16. Principle component analysis and linear discriminant analysis of multi-spectral autofluorescence imaging data for differentiating basal cell carcinoma and healthy skin

    NASA Astrophysics Data System (ADS)

    Chernomyrdin, Nikita V.; Zaytsev, Kirill I.; Lesnichaya, Anastasiya D.; Kudrin, Konstantin G.; Cherkasova, Olga P.; Kurlov, Vladimir N.; Shikunova, Irina A.; Perchik, Alexei V.; Yurchenko, Stanislav O.; Reshetov, Igor V.

    2016-09-01

    In present paper, an ability to differentiate basal cell carcinoma (BCC) and healthy skin by combining multi-spectral autofluorescence imaging, principle component analysis (PCA), and linear discriminant analysis (LDA) has been demonstrated. For this purpose, the experimental setup, which includes excitation and detection branches, has been assembled. The excitation branch utilizes a mercury arc lamp equipped with a 365-nm narrow-linewidth excitation filter, a beam homogenizer, and a mechanical chopper. The detection branch employs a set of bandpass filters with the central wavelength of spectral transparency of λ = 400, 450, 500, and 550 nm, and a digital camera. The setup has been used to study three samples of freshly excised BCC. PCA and LDA have been implemented to analyze the data of multi-spectral fluorescence imaging. Observed results of this pilot study highlight the advantages of proposed imaging technique for skin cancer diagnosis.

  17. Lichenoid reaction as a potential immune response marker of intratreatment histological response during successful vismodegib treatment for a giant basal cell carcinoma.

    PubMed

    Fosko, Scott W; Chu, Melinda B; Mattox, Adam R; Richart, John M; Burkemper, Nicole M; Slutsky, Jordan B

    2015-01-01

    We report an 83 year-old patient with a 13 × 7.5 cm(2) basal cell carcinoma (BCC) successfully treated with the combination of vismodegib and minimal surgery. On Day 109, a 0.9 cm papule suspicious for residual BCC was seen centrally within a large pink atrophic plaque. This lesion was excised; pathology confirmed BCC with negative surgical margins. Simultaneously, suspecting noncontiguous histologic response, we performed 21 biopsies at the periphery of the pretreatment tumor location. Seventeen (17/21, 81%) revealed lichenoid dermatitis. No tumor was seen on any. We believe the lichenoid dermatitis observed is a novel finding for two reasons. First, it may be considered a marker of a positive intratreatment response. This may help guide clinicians on the optimal treatment duration of vismodegib to maximize efficacy and mitigate side effects. Second, we think it suggests an additional mechanism of vismodegib action, possibly via local immune effects. Further investigations are warranted.

  18. Twist1 in tumor cells and α-smooth muscle actin in stromal cells are possible biomarkers for metastatic giant basal cell carcinoma.

    PubMed

    Motegi, Sei-ichiro; Yamada, Kazuya; Ishikawa, Osamu

    2013-08-01

    We previously reported a case of giant basal cell carcinoma (BCC) in a 75-year-old Japanese man, who subsequently developed a pulmonary metastasis. With regard to the pathogenesis of metastasis of BCC, recently, it has been reported that high levels of expression of Twist1 and N-cadherin in primary and metastatic tumor cells, suggesting that Twist1 expression and an epithelial-mesenchymal transition (EMT) of tumor cells are important for the promotion of tumor invasion and subsequent metastasis. In this report, we identified the expressions of Twist1 in tumor cells and α-smooth muscle actin (α-SMA) in stromal cells in the primary and metastatic sites of giant BCC. These results suggest that Twist1-induced EMT of tumor cells might have been associated with distant organ metastasis in our case, and the presence of α-SMA-positive myofibroblasts surrounding a BCC nest can be one of hallmarks of the aggressiveness of BCC.

  19. The Use of Noninvasive Optical Coherence Tomography to Monitor the Treatment Progress of Vismodegib and Imiquimod 5% Cream in a Transplant Patient with Advanced Basal Cell Carcinoma of the Nose

    PubMed Central

    Markowitz, Orit; Schwartz, Michelle

    2016-01-01

    Immunosuppressed transplant recipients have increased risk for the development of basal cell carcinoma skin cancers. While oral vismodegib therapy has been successful in treating locally advanced basal cell tumors, few studies document its use and efficacy in organ transplant patients. In this immunocompromised population, topical imiquimod 5% cream has been shown to be an effective and well-tolerated option for superficial and nodular basal cell carcinomas. To the authors’ knowledge, no data documents the use of optical coherence tomography, a noninvasive imaging technique, to monitor progress of such combined therapies on in vivo skin. The authors report the successful treatment of an extensive basal cell carcinoma on the nose of an immunosuppressed 54-year-old Caucasian man with a history of kidney and pancreas transplantations. By combining continuous noninvasive lesion monitoring with vismodegib 150mg/d therapy and adjuvant imiquimod 5% topical cream, the patient showed complete disease clearance on clinical, optical coherence tomography, and histological evaluation. This report supports the feasibility and efficacy of nonsurgical treatment of basal cell lesions in complicated transplant patients and the need for individualized treatment plans. A noninvasive follow-up tool, especially during nonsurgical therapy, is of critical value to ensure the best possible treatment outcome for the patient. PMID:27672417

  20. The multicentre south European study 'Helios'. II: Different sun exposure patterns in the aetiology of basal cell and squamous cell carcinomas of the skin.

    PubMed Central

    Rosso, S.; Zanetti, R.; Martinez, C.; Tormo, M. J.; Schraub, S.; Sancho-Garnier, H.; Franceschi, S.; Gafà, L.; Perea, E.; Navarro, C.; Laurent, R.; Schrameck, C.; Talamini, R.; Tumino, R.; Wechsler, J.

    1996-01-01

    The role of sun exposure in development of basal cell and squamous cell carcinomas among different populations from south Europe was investigated. Between 1989 and 1993 we interviewed incident cases and a random population sample of controls from five centres where a cancer registry was operating, whereas we selected a sample of hospital-based cases and controls from the other three centres. We gathered information on life-long exposure to sunlight during different activities. Results are analysed for 1549 basal cell carcinoma (BCC) cases and 228 squamous cell carcinoma (SCC) cases compared with 1795 controls. We observed a statistically significant increase of risk of SCC with increasing sun exposure beyond a threshold of 70,000 cumulated hours of exposure in a lifetime. Sun exposures during work and holidays were, however, inversely correlated. Odds ratios (ORs) of SCC were up to eight or nine times the reference for the highest exposures (200,000 cumulated hours or more). BCC exhibited a 2-fold increase of risk for lower exposure (8000-10,000 cumulated hours in a lifetime) with a plateau and a slight decrease of risk for the highest exposures (100,000 cumulated hours or more). Outdoor work showed a significantly increased risk of SCC (OR 1.6 for more than 54,000 cumulated hours of exposure in a lifetime), whereas recreational activities such as sun exposure during holidays at the beach (OR 1.6 for more than 2600 cumulated hours of exposure in a lifetime) or during water sports (OR 1.6 for more than 2600 cumulated hours of exposure in a lifetime) were associated with an increased risk of BCC. Risk patterns were different in poor or good tanners with a significant risk trend for good tanners, whereas poor tanners were on a plateau of increased risk at any level of exposure. Solar radiation is associated with a risk of BCC even for relatively short periods of exposure such as during holidays and sports, whereas SCC develops later if exposure continues. The skin

  1. Differentiating Early Stage Cystic Keratoacanthoma, Nodular Basal Cell Carcinoma, and Excoriated Acne Vulgaris by Clinical Exam, Dermoscopy, and Optical Coherence Tomography: A Report of 3 Cases.

    PubMed

    Markowitz, Orit; Utz, Sarah

    2015-04-01

    Making accurate diagnoses when certain lesions are in a relatively young stage can prove challenging, as their "textbook descriptions" are often not fully apparent, and may in fact be markedly different. The authors present three interesting cases of early lesions that were clinically difficult to differentiate from one another: a cystic variation of a keratoacanthoma squamous cell carcinoma, a basal cell carcinoma, and an excoriated facial acne vulgaris. The subtle clinical nuances found in each of these cases demonstrated the importance of a careful clinical evaluation; however, this was not sufficient for adequate assessment of whether or not to biopsy. With early lesions such as these, the use of the noninvasive imaging modalities of dermoscopy and optical coherence tomography becomes critical in order to avoid unnecessary biopsy. The discussion of the clinically and dermoscopically challenging features is both instructive and enlightening. Oftentimes, "textbook descriptions" of lesions focus on the description of an already mature stage of growth, despite the fact that we continue to strive toward earlier detection of potential malignancies. With this in mind, the features found with optical coherence tomography proved essential to the elucidation of these difficult lesions. These three interesting cases illustrated the challenges encountered when dealing with early lesions specifically. The authors bring to light features in each of these cases that are often not thought of as being the "typical" presentation in each lesion category and demonstrate the clinical utility of noninvasive devices in difficult-to-diagnose cases such as these.

  2. Differentiating Early Stage Cystic Keratoacanthoma, Nodular Basal Cell Carcinoma, and Excoriated Acne Vulgaris by Clinical Exam, Dermoscopy, and Optical Coherence Tomography: A Report of 3 Cases

    PubMed Central

    Utz, Sarah

    2015-01-01

    Making accurate diagnoses when certain lesions are in a relatively young stage can prove challenging, as their “textbook descriptions” are often not fully apparent, and may in fact be markedly different. The authors present three interesting cases of early lesions that were clinically difficult to differentiate from one another: a cystic variation of a keratoacanthoma squamous cell carcinoma, a basal cell carcinoma, and an excoriated facial acne vulgaris. The subtle clinical nuances found in each of these cases demonstrated the importance of a careful clinical evaluation; however, this was not sufficient for adequate assessment of whether or not to biopsy. With early lesions such as these, the use of the noninvasive imaging modalities of dermoscopy and optical coherence tomography becomes critical in order to avoid unnecessary biopsy. The discussion of the clinically and dermoscopically challenging features is both instructive and enlightening. Oftentimes, “textbook descriptions” of lesions focus on the description of an already mature stage of growth, despite the fact that we continue to strive toward earlier detection of potential malignancies. With this in mind, the features found with optical coherence tomography proved essential to the elucidation of these difficult lesions. These three interesting cases illustrated the challenges encountered when dealing with early lesions specifically. The authors bring to light features in each of these cases that are often not thought of as being the “typical” presentation in each lesion category and demonstrate the clinical utility of noninvasive devices in difficult-to-diagnose cases such as these. PMID:26060518

  3. Analysis of incomplete excisions of basal-cell carcinomas after breadloaf microscopy compared with 3D-microscopy: a prospective randomized and blinded study.

    PubMed

    Boehringer, Alexandra; Adam, Patrick; Schnabl, Saskia; Häfner, Hans-Martin; Breuninger, Helmut

    2015-08-01

    Basal-cell carcinomas may show irregular, asymmetric subclinical growth. This study analyzed the efficacy of 'breadloaf' microscopy (serial sectioning) and three-dimensional (3D) microscopy in detecting positive tumor margins. Two hundred eighty-three (283) tumors (51.2%) were put into the breadloaf microscopy group; 270 tumors (48.8%) into the 3D microscopy group. The position of any detected tumor outgrowths was identified in clock face fashion. The time required for cutting and embedding the specimens and the examination of the microscopic slides was measured. Patient/tumor characteristics and surgical margins did not differ significantly. Tumor outgrowths at the excision margin were found in 62 of 283 cases (21.9%) in the breadloaf microscopy group and in 115 of 270 cases (42.6%) in the 3D microscopy group, constituting a highly significant difference (p < 0.001). This difference held true with incomplete excision of fibrosing (infiltrative/sclerosing/morpheaform) tumors [32.9% in the breadloaf microscopy group and 57.5% in the 3D microscopy group (p = 0.003)] and also with solid (nodular) tumors [16.1 and 34.2%, respectively (p < 0.001)]. The mean overall examination time required showed no important difference. In summary, for detection of tumor outgrowths, 3D microscopy has almost twice the sensitivity of breadloaf microscopy, particularly in the situation of aggressive/infiltrative carcinomas.

  4. Localization of telomerase hTERT protein in frozen sections of basal cell carcinomas (BCC) and tumor margin tissues.

    PubMed

    Fabricius, Eva-Maria; Kruse-Boitschenko, Ute; Khoury, Reem; Wildner, Gustav-Paul; Raguse, Jan-Dirk; Klein, Martin; Hoffmeister, Bodo

    2009-12-01

    In previous studies we demonstrated telomerase activity in frozen tissues from BCC and their tumor-free margins by the PCR ELISA. In this study we examined in the same frozen sections immunohistochemical presence of hTERT in the nucleus. After fixation in acetone and methanol followed by steaming we used for visualization the antigen-antibody reactions by APAAP. This was the best method of preparation of the frozen sections in our preliminary hTERT-study with squamous cell carcinomas. This study was supplemented with antibodies against Ki-67, nucleolin, common leucocyte antigen CD45 and mutated p53. The immunoreactive scores were determined and included the comparison with telomerase activity. The investigation of hTERT expression was performed in the tissues of 41 patients with BCC and control tissues of 14 patients without tumor. Eleven commercial antibodies were used for a nuclear staining of hTERT expression. With the anti-hTERT antibodies we looked for both satisfactory distribution and intensity of immunohistochemical labeling in the carcinomas and in the squamous epithelia of the tumor centers, of the tumor-free margins and of the control tissues. The hTERT expression in the BCC was distributed heterogeneously. The score values established by the anti-hTERT antibodies used were variably or significantly increased. In the stroma they tended to be negative, so we disregarded stroma hTERT. Proof of hTERT did not differ uniformly from telomerase activity. We compared the high with the lower median hTERT values in the Kaplan-Meier curve. Patients with lower hTERT scores in the center or tumor margin as shown by some of the antibodies suffered relapse earlier. Finally, we compared the hTERT expression in BCC tissues with the hTERT scores in HNSCC tissues from our previous study. Only one anti-hTERT antibody (our Ab 7) yielded significantly higher scores in BCC than in HNSCC.

  5. In vivo assessment of optical properties of basal cell carcinoma and differentiation of BCC subtypes by high-definition optical coherence tomography

    PubMed Central

    Boone, Marc; Suppa, Mariano; Miyamoto, Makiko; Marneffe, Alice; Jemec, Gregor; Del Marmol, Veronique

    2016-01-01

    High-definition optical coherence tomography (HD-OCT) features of basal cell carcinoma (BCC) have recently been defined. We assessed in vivo optical properties (IV-OP) of BCC, by HD-OCT. Moreover their critical values for BCC subtype differentiation were determined. The technique of semi-log plot whereby an exponential function becomes linear has been implemented on HD-OCT signals. The relative attenuation factor (µraf) at different skin layers could be assessed.. IV-OP of superficial BCC with high diagnostic accuracy (DA) and high negative predictive values (NPV) were (i) decreased µraf in lower part of epidermis and (ii) increased epidermal thickness (E-T). IV-OP of nodular BCC with good to high DA and NPV were (i) less negative µraf in papillary dermis compared to normal adjacent skin and (ii) significantly decreased E-T and papillary dermal thickness (PD-T). In infiltrative BCC (i) high µraf in reticular dermis compared to normal adjacent skin and (ii) presence of peaks and falls in reticular dermis had good DA and high NPV. HD-OCT seems to enable the combination of in vivo morphological analysis of cellular and 3-D micro-architectural structures with IV-OP analysis of BCC. This permits BCC sub-differentiation with higher accuracy than in vivo HD-OCT analysis of morphology alone. PMID:27375943

  6. Use of Drawing Lithography-Fabricated Polyglycolic Acid Microneedles for Transdermal Delivery of Itraconazole to a Human Basal Cell Carcinoma Model Regenerated on Mice

    NASA Astrophysics Data System (ADS)

    Zhang, Jennifer; Wang, Yan; Jin, Jane Y.; Degan, Simone; Hall, Russell P.; Boehm, Ryan D.; Jaipan, Panupong; Narayan, Roger J.

    2016-04-01

    Itraconazole is a triazole agent that is routinely used for treatment of nail infections and other fungal infections. Recent studies indicate that itraconazole can also inhibit the growth of basal cell carcinoma (BCC) through suppression of the Sonic Hedgehog (SHH) signaling pathway. In this study, polyglycolic acid microneedle arrays and stainless steel microneedle arrays were used for transdermal delivery of itraconazole to a human BCC model which was regenerated on mice. One-by-four arrays of 642- μm-long polyglycolic acid microneedles with sharp tips were prepared using injection molding and drawing lithography. Arrays of 85 stainless steel 800- μm-tall microneedles attached to syringes were obtained for comparison purposes. Skin grafts containing devitalized split-thickness human dermis that had been seeded with human keratinocytes transduced to express human SHH protein were sutured to the skin of immunodeficient mice. Mice with this human BCC model were treated daily for 2 weeks with itraconazole dissolved in 60% dimethylsulfoxane and 40% polyethylene glycol-400 solution; transdermal administration of the itraconazole solution was facilitated by either four 1 × 4 polyglycolic acid microneedle arrays or stainless steel microneedle arrays. The epidermal tissues treated with polyglycolic acid microneedles or stainless steel microneedles were markedly thinner than that of the control (untreated) graft tissue. These preliminary results indicate that microneedles may be used to facilitate transdermal delivery of itraconazole for localized treatment of BCC.

  7. –2518 A/G MCP-1 but not –403 G/A RANTES gene polymorphism is associated with enhanced risk of basal cell carcinoma

    PubMed Central

    Zabłotna, Monika; Szczerkowska-Dobosz, Aneta; Ruckemann-Dziurdzińska, Katarzyna; Sokolowska-Wojdylo, Malgorzata; Nowicki, Roman

    2016-01-01

    Introduction Polymorphic variants of MCP-1 and RANTES genes and their protein serum levels have been implicated in the increased risk and severity of several malignancies. However, the subject has not been explored in basal cell carcinoma (BCC) patients so far. Aim To investigate the association between monocyte chemoattractant protein 1 (MCP-1) (–2518 A/G) and RANTES (–403 G/A) polymorphism and risk and clinical course of BCC. Material and methods The study group consisted of 150 unrelated patients with BCC and 140 healthy, unrelated, age- and sex-matched volunteers. The polymorphisms were analysed using the amplification refractory mutation system polymerase chain reaction method (ARMS-PCR) and single specific primer-polymerase chain reaction (SSP-PCR). Serum cytokine levels were measured with ELISA. Results The presence of the MCP-1 –2518 GG genotype was statistically more frequent in BCC patients and it increased the risk of BCC (OR = 2.63, p = 0.003). Genotype –330 GG was statistically more common in patients with less advanced tumours (OR = 2.8, p = 0.017). Monocyte chemoattractant protein 1 serum level was statistically higher with GG genotype. In the BCC group MCP-1 serum levels were decreased. Neither polymorphic variants of RANTES nor the chemokine serum concentration differed significantly between the study groups. Conclusions These findings suggest that –2518 A/G MCP-1 polymorphism may be involved in BCC pathogenesis. PMID:27881944

  8. Is There a Relationship between the Stratum Corneum Thickness and That of the Viable Parts of Tumour Cells in Basal Cell Carcinoma?

    PubMed Central

    Foss, Olav A.; Mjønes, Patricia; Fismen, Silje; Christensen, Eidi

    2016-01-01

    Basal cell carcinoma (BCC) is an invasive epithelial skin tumour. The thickness of the outermost epidermal layer of the skin, the stratum corneum (SC), influences drug uptake and penetration into tumour and may thereby affect the response of BCC to topical treatment. The aim was to investigate a possible relationship between the thickness of the SC and that of the viable part of BCC. Histopathological evaluations of the corresponding SC and viable tumour thickness measurements of individual BCCs of different subtypes were explored. A total of 53 BCCs from 46 patients were studied. The median tumour thickness was 1.7 mm (0.8–3.0 mm), with a significant difference between subtypes (p < 0.001). The SC had a median thickness of 0.3 mm (0.2–0.4 mm), with no difference between tumour subtypes (p = 0.415). Additionally, no significant association between the thickness of the SC and that of the viable part of the tumour was demonstrated (p = 0.381). In conclusion our results indicate that SC thickness is relatively constant in BCC. PMID:26942011

  9. In vivo assessment of optical properties of basal cell carcinoma and differentiation of BCC subtypes by high-definition optical coherence tomography.

    PubMed

    Boone, Marc; Suppa, Mariano; Miyamoto, Makiko; Marneffe, Alice; Jemec, Gregor; Del Marmol, Veronique

    2016-06-01

    High-definition optical coherence tomography (HD-OCT) features of basal cell carcinoma (BCC) have recently been defined. We assessed in vivo optical properties (IV-OP) of BCC, by HD-OCT. Moreover their critical values for BCC subtype differentiation were determined. The technique of semi-log plot whereby an exponential function becomes linear has been implemented on HD-OCT signals. The relative attenuation factor (µraf ) at different skin layers could be assessed.. IV-OP of superficial BCC with high diagnostic accuracy (DA) and high negative predictive values (NPV) were (i) decreased µraf in lower part of epidermis and (ii) increased epidermal thickness (E-T). IV-OP of nodular BCC with good to high DA and NPV were (i) less negative µraf in papillary dermis compared to normal adjacent skin and (ii) significantly decreased E-T and papillary dermal thickness (PD-T). In infiltrative BCC (i) high µraf in reticular dermis compared to normal adjacent skin and (ii) presence of peaks and falls in reticular dermis had good DA and high NPV. HD-OCT seems to enable the combination of in vivo morphological analysis of cellular and 3-D micro-architectural structures with IV-OP analysis of BCC. This permits BCC sub-differentiation with higher accuracy than in vivo HD-OCT analysis of morphology alone.

  10. Tumor stroma-derived Wnt5a induces differentiation of basal cell carcinoma of Ptch-mutant mice via CaMKII.

    PubMed

    Nitzki, Frauke; Zibat, Arne; König, Simone; Wijgerde, Mark; Rosenberger, Albert; Brembeck, Felix H; Carstens, Per-Ole; Frommhold, Anke; Uhmann, Anja; Klingler, Stefan; Reifenberger, Julia; Pukrop, Tobias; Aberger, Fritz; Schulz-Schaeffer, Walter; Hahn, Heidi

    2010-04-01

    Basal cell carcinoma (BCC) is the most common skin tumor in humans. Although BCCs rarely metastasize, they can cause significant morbidity due to local aggressiveness. Approximately 20% of BCCs show signs of spontaneous regression. The understanding of molecular events mediating spontaneous regression has the potential to reduce morbidity of BCC and, potentially, other tumors, if translated into tumor therapies. We show that BCCs induced in conditional Ptch(flox/flox)ERT2(+/-) knockout mice regress with time and show a more differentiated phenotype. Differentiation is accompanied by Wnt5a expression in the tumor stroma, which is first detectable at the fully developed tumor stage. Coculture experiments revealed that Wnt5a is upregulated in tumor-adjacent macrophages by soluble signals derived from BCC cells. In turn, Wnt5a induces the expression of the differentiation marker K10 in tumor cells, which is mediated by Wnt/Ca(2+) signaling in a CaMKII-dependent manner. These data support a role of stromal Wnt5a in BCC differentiation and regression, which may have important implications for development of new treatment strategies for this tumor. Taken together, our results establish BCC as an easily accessible model of tumor regression. The regression of BCC despite sustained Hedgehog signaling activity seems to be mediated by tumor-stromal interactions via Wnt5a signaling.

  11. A case-control study of MC1R variants in Greek patients with basal cell carcinoma: increased risk independently of pigmentary characteristics.

    PubMed

    Dessinioti, Clio; Sypsa, Vana; Kypreou, Katerina; Dimisianos, Gerasimos; Kodela, Elisavet; Nikolaou, Vasiliki; Antoniou, Christina; Stratigos, Alexander J

    2015-06-01

    Melanocortin 1 receptor (MC1R) gene variants are a major contributor to pigmentation characteristics and the modulation of sporadic basal cell carcinoma (BCC) risk. This is a hospital-based, case-control study to investigate the association of MC1R variants and pigmentary characteristics with the risk of BCC development in a Southern European population in Greece. In total, 141 patients with BCC and 166 controls were studied. Increased BCC risk was found for the presence of 2 or more MC1R variants (OR:3.07, 95% CI:1.13-8.34), or 2 or more variants of which at least 1 was major function (OR:7.15, 95% CI:1.37-5.52), after adjustment for the 'red hair colour' (RHC) phenotype. Increased BCC risk persisted in the presence of 2 or more MC1R variants (OR:4.15, 95% CI:1.35-12.72), after adjustment for potential confounding factors including skin color (P:0.237) and atypical nevi (OR:9.57, 95% CI:2.19-41.81, P:0.003). MC1R genotype is a risk factor for the development of BCC in Greek patients independently of pigmentary characteristics, and the combination of MC1R variants may modulate this risk.

  12. Systematic review of vismodegib toxicity profile in the treatment of advanced basal cell carcinomas compared to other systemic therapies in dermatology.

    PubMed

    Juhasz, Margit L W; Marmur, Ellen S

    2014-06-01

    Vismodegib is a first-in-class, hedgehog-signal inhibitor that is FDA-approved for use with advanced basal cell carcinomas (BCCs) that cannot be removed by either surgical resection or treated with radiation. Release of the drug was fast-tracked because of need for this type of drug, and its overall efficacy in clinical trial by producing either regression or even resolution of advanced BCCs. Compared to placebo, patients using vismodegib have arrested BCC progression, reduced size of BCC, and decreased recurrence of BCC. Unfortunately, vismodegib has notable adverse effects (especially those of alopecia, gastrointestinal, muscle spasms, and dysguesia) that make dermatologists reluctant to prescribe the drug and patients unwilling to undergo therapy. In this article, we tackle this dilemma by comparing the toxicity profile of vismodegib to the adverse effect profiles of other dermatologic chemotherapeutics, immunomodulators, retinoids, and biologics. Considering that many of these drugs carry their own risks and those drugs used to treat advanced melanoma have similar toxicity profiles to that of vismodegib, we hope dermatologists and patients alike will be more willing to try vismodegib as a treatment option for advanced BCCs in the future.

  13. Monte Carlo modeling of in vivo protoporphyrin IX fluorescence and singlet oxygen production during photodynamic therapy for patients presenting with superficial basal cell carcinomas

    NASA Astrophysics Data System (ADS)

    Valentine, Ronan M.; Brown, C. Tom A.; Moseley, Harry; Ibbotson, Sally; Wood, Kenny

    2011-04-01

    We present protoporphyrin IX (PpIX) fluorescence measurements acquired from patients presenting with superficial basal cell carcinoma during photodynamic therapy (PDT) treatment, facilitating in vivo photobleaching to be monitored. Monte Carlo (MC) simulations, taking into account photobleaching, are performed on a three-dimensional cube grid, which represents the treatment geometry. Consequently, it is possible to determine the spatial and temporal changes to the origin of collected fluorescence and generated singlet oxygen. From our clinical results, an in vivo photobleaching dose constant, β of 5-aminolaevulinic acid-induced PpIX fluorescence is found to be 14 +/- 1 J/cm2. Results from our MC simulations suggest that an increase from our typical administered treatment light dose of 75-150 J/cm2 could increase the effective PDT treatment initially achieved at a depth of 2.7-3.3 mm in the tumor, respectively. Moreover, this increase reduces the surface PpIX fluorescence from 0.00012 to 0.000003 of the maximum value recorded before treatment. The recommendation of administrating a larger light dose, which advocates an increase in the treatment time after surface PpIX fluorescence has diminished, remains valid for different sets of optical properties and therefore should have a beneficial outcome on the total treatment effect.

  14. Motion tracking to enable pre-surgical margin mapping in basal cell carcinoma using optical imaging modalities: initial feasibility study using optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Duffy, M.; Richardson, T. J.; Craythorne, E.; Mallipeddi, R.; Coleman, A. J.

    2014-02-01

    A system has been developed to assess the feasibility of using motion tracking to enable pre-surgical margin mapping of basal cell carcinoma (BCC) in the clinic using optical coherence tomography (OCT). This system consists of a commercial OCT imaging system (the VivoSight 1500, MDL Ltd., Orpington, UK), which has been adapted to incorporate a webcam and a single-sensor electromagnetic positional tracking module (the Flock of Birds, Ascension Technology Corp, Vermont, USA). A supporting software interface has also been developed which allows positional data to be captured and projected onto a 2D dermoscopic image in real-time. Initial results using a stationary test phantom are encouraging, with maximum errors in the projected map in the order of 1-2mm. Initial clinical results were poor due to motion artefact, despite attempts to stabilise the patient. However, the authors present several suggested modifications that are expected to reduce the effects of motion artefact and improve the overall accuracy and clinical usability of the system.

  15. Sunlight-induced basal cell carcinoma tumor cells and ultraviolet-B-irradiated psoriatic plaques express Fas ligand (CD95L).

    PubMed Central

    Gutierrez-Steil, C; Wrone-Smith, T; Sun, X; Krueger, J G; Coven, T; Nickoloff, B J

    1998-01-01

    The skin is constantly exposed to sunlight and frequently develops sun-induced skin cancers such as basal cell carcinoma (BCC). These epidermal-derived tumors escape local immune surveillance and infiltrate the dermis, requiring surgical removal. We report here that in contrast to keratinocytes in normal skin (n = 4), BCC tumor cells (n = 6) strongly and diffusely express Fas ligand (CD95L), but not Fas antigen (CD95). This CD95L expression in vivo by BCC tumor cells is associated with peritumoral T lymphocytes that are undergoing apoptosis. Moreover, CD95L can be induced on normal cultured keratinocytes after exposure to ultraviolet-B light (UV-B) irradiation. This induction of CD95L was confirmed at the mRNA and protein levels using multipassaged human keratinocytes and a keratinocyte cell line. Keratinocytes induced to express CD95L acquired the functional capacity to kill a CD95-positive lymphocyte cell line. Whereas hyperplastic keratinocytes in untreated psoriatic plaques do not express CD95L on their plasma membrane, after UV-B treatment there is strong and diffuse keratinocyte CD95L expression that coincided in a temporal fashion with depletion of intraepidermal T cells in all five patients studied. Our data suggest a novel molecular pathway by which UV light can contribute to the ability of a skin cancer to escape from immune attack by cytotoxic T lymphocytes, and a previously unrecognized therapeutic mechanism of action for UV-B light in psoriasis via keratinocyte CD95L expression. Such immunological events involving CD95L provide new insight and opportunity for novel treatment approaches not only for cutaneous neoplasms but also for various T cell-mediated dermatoses such as psoriasis. PMID:9421463

  16. Lack of selectivity of protoporphyrin IX fluorescence for basal cell carcinoma after topical application of 5-aminolevulinic acid: implications for photodynamic treatment.

    PubMed

    Martin, A; Tope, W D; Grevelink, J M; Starr, J C; Fewkes, J L; Flotte, T J; Deutsch, T F; Anderson, R R

    1995-01-01

    Clinical trials of topical ALA in photodynamic therapy (PDT) of basal cell carcinoma (BCC) show significant recurrence rates. Exogenous 5-aminolevulinic acid (ALA) is converted by intracellular enzymes to photoactive protoporphyrin IX (PpIX) in human tissues. PpIX generates cytotoxic singlet oxygen when irradiated with visible light in the 400-640 nm range. To evaluate variability and heterogeneity in PpIX production by tumors in such trials, and to assess the usefulness of PpIX for marking skin tumors, we measured PpIX fluorescence distribution in BCC after topical application of 20% ALA cream. ALA cream was applied under occlusion for periods ranging from 3 to 18 h (average 6.9 h, SD 4 h) to 16 BCCs. ALA conversion to PpIX in the BCCs was assessed by in vivo photography, ex vivo video fluorescence imaging, and fluorescence microscopy. External macroscopic PpIX fluorescence, as assessed by in vivo and ex vivo imaging, correlated with the clinical presence of BCC. Examination by a digital imaging fluorescence microscope revealed inter- and intratumor fluorescence variability and heterogeneity. PpIX fluorescence corresponding to full tomor thickness was found in six superficial and four nodular tumors, and partial-thickness fluorescence was observed in five nodular tumors, but no PpIX fluorescence was observed in some areas of superficial, nodular and infiltrating tumors. In a significant number of nodular and infiltrating BCCs, topical ALA appeared to provide little or no PpIX in deep tumor lobules. In addition, no selectivity for tumor tissue versus normal epidermis was seen. The grossly brighter external PpIX fluorescence over tumors may be due, therefore, to enhanced penetration through tumor-reactive stratum corneum and to the tumor thickness.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Silibinin and its 2,3-dehydro-derivative inhibit basal cell carcinoma growth via suppression of mitogenic signaling and transcription factors activation.

    PubMed

    Tilley, Cynthia; Deep, Gagan; Agarwal, Chapla; Wempe, Michael F; Biedermann, David; Valentová, Kateřina; Kren, Vladimir; Agarwal, Rajesh

    2016-01-01

    Basal cell carcinoma (BCC) is the most common cancer worldwide, and its current treatment options are insufficient and toxic. Surprisingly, unlike several other malignancies, chemopreventive efforts against BCC are almost lacking. Silibinin, a natural agent from milk thistle seeds, has shown strong efficacy against several cancers including ultraviolet radiation-induced skin (squamous) cancer; however, its potential activity against BCC is not yet examined. Herein, for the first time, we report the efficacy of silibinin and its oxidation product 2,3-dehydrosilibinin (DHS) against BCC both in vitro and in vivo using ASZ (p53 mutated) and BSZ (p53 deleted) cell lines derived from murine BCC tumors. Both silibinin and DHS significantly inhibited cell growth and clonogenicity while inducing apoptosis in a dose- and time-dependent manner, with DHS showing higher activity at lower concentrations. Both agents also inhibited the mitogenic signaling by reducing EGFR, ERK1/2, Akt, and STAT3 phosphorylation and suppressed the activation of transcription factors NF-κB and AP-1. More importantly, in an ectopic allograft model, oral administration of silibinin and DHS (200 mg/kg body weight) strongly inhibited the ASZ tumor growth by 44% and 71% (P < 0.05), respectively, and decreased the expression of proliferation biomarkers (PCNA and cyclin D1) as well as NF-κB p50 and c-Fos in the tumor tissues. Taken together, these results provide the first evidence for the efficacy and usefulness of silibinin and its derivative DHS against BCC, and suggest the need for additional studies with these agents in pre-clinical and clinical BCC chemoprevention and therapy models.

  18. Soluble Lutheran/basal cell adhesion molecule is detectable in plasma of hepatocellular carcinoma patients and modulates cellular interaction with laminin-511 in vitro.

    PubMed

    Kikkawa, Yamato; Miwa, Takahiro; Tanimizu, Naoki; Kadoya, Yuichi; Ogawa, Takaho; Katagiri, Fumihiko; Hozumi, Kentaro; Nomizu, Motoyoshi; Mizuguchi, Toru; Hirata, Koichi; Mitaka, Toshihiro

    2014-10-15

    Lutheran (Lu), an immunoglobulin superfamily transmembrane receptor, is also known as basal cell adhesion molecule (B-CAM). Lu/B-CAM is a specific receptor for laminin α5, a subunit of laminin-511 (LM-511) that is a major component of basement membranes in various tissues. Our previous study showed that Lu/B-CAM was cleaved by MT1-MMP and released from cell surfaces. In this study we examined the soluble Lu/B-CAM in culture media and in plasma of mice bearing HuH-7 hepatocellular carcinoma (HCC) cells and patients with HCC. Two HCC cell lines, HepG2 and HuH-7, released Lu/B-CAM into the culture media. Although Lu/B-CAM was cleaved by MT1-MMP in HuH-7 cells, HepG2 cells released Lu/B-CAM in a MMP-independent manner. The concentration of Lu/B-CAM released into mouse plasma correlated with tumor size. Moreover the soluble Lu/B-CAM in plasma of HCC patients was significantly decreased after resection of the tumor. Immunohistochemical studies showed that although the expression of Lu/B-CAM was observed in most HCCs, MT1-MMP was not always expressed in tumor tissues, suggesting that a part of Lu/B-CAM in plasma of HCC patients was also released in a MMP-independent manner. In vitro studies showed that the soluble Lu/B-CAM released from HCC cells bound to LM-511. Moreover the soluble Lu/B-CAM influenced cell migration on LM-511. These results suggest that soluble Lu/B-CAM serves as not only a novel marker for HCC but also a modulator in tumor progression.

  19. Genetic Variation in Arsenic (+3 Oxidation State) Methyltransferase (AS3MT), Arsenic Metabolism and Risk of Basal Cell Carcinoma in a European Population

    PubMed Central

    Engström, Karin S; Vahter, Marie; Fletcher, Tony; Leonardi, Giovanni; Goessler, Walter; Gurzau, Eugen; Koppova, Kvetoslava; Rudnai, Peter; Kumar, Rajiv; Broberg, Karin

    2015-01-01

    Exposure to inorganic arsenic increases the risk of basal cell carcinoma (BCC). Arsenic metabolism is a susceptibility factor for arsenic toxicity, and specific haplotypes in arsenic (+3 oxidation state) methyltransferase (AS3MT) have been associated with increased urinary fractions of the most toxic arsenic metabolite, methylarsonic acid (MMA). The aim of this study is to elucidate the association of AS3MT haplotypes with arsenic metabolism and the risk of BCC. Four AS3MT polymorphisms were genotyped in BCC cases (N = 529) and controls (N = 533) from Eastern Europe with low to moderate arsenic exposure (lifetime average drinking water concentration: 1.3 µg/L, range 0.01–167 µg/L). Urinary metabolites [inorganic arsenic (iAs), MMA, dimethylarsinic acid (DMA)] were analyzed by HPLC-ICPMS. Five AS3MT haplotypes (based on rs3740400 A/C, rs3740393 G/C, rs11191439 T/C and rs1046778 T/C) had frequencies >5%. Individuals with the CCTC haplotype had lower %iAs (P = 0.032) and %MMA (P = 0.020) in urine, and higher %DMA (P = 0.033); individuals with the CGCT haplotype had higher %MMA (P < 0.001) and lower %DMA (P < 0.001). All haplotypes showed increased risk of BCC with increasing arsenic exposure through drinking water (ORs 1.1–1.4, P values from <0.001 to 0.082), except for the CCTC haplotype (OR 1.0, CI 0.9–1.2, P value 0.85). The results suggest that carriage of AS3MT haplotypes associated with less-efficient arsenic methylation, or lack of AS3MT haplotypes associated with a more-efficient arsenic methylation, results in higher risk of arsenic-related BCC. The fact that AS3MT haplotype status modified arsenic metabolism, and in turn the arsenic-related BCC risk, supports a causal relationship between low-level arsenic exposure and BCC. Environ. Mol. Mutagen. 56:60–69, 2015. © 2014 The Authors. Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society PMID:25156000

  20. Is There Truly No Benefit with Sunscreen Use and Basal Cell Carcinoma? A Critical Review of the Literature and the Application of New Sunscreen Labeling Rules to Real-World Sunscreen Practices

    PubMed Central

    Chesnut, Cameron; Kim, Jenny

    2012-01-01

    Basal cell carcinoma (BCC) is the most common human malignancy. Both epidemiological and direct evidence have established ultraviolet (UV) exposure from the sun as the most important risk factor for BCC development. There has only been one randomized and controlled study to examine sunscreen's role in the prevention of BCC, and no significant protective benefit was found. This study did not address four important concepts: sunscreen abuse, sunscreen misuse, sunscreen formulation, and cumulative UV exposure. Thus, the results of this study are difficult to interpret and extrapolate with real-world sunscreen practices. PMID:22649734

  1. Photodynamic Therapy Followed by Mohs Micrographic Surgery Compared to Mohs Micrographic Surgery Alone for the Treatment of Basal Cell Carcinoma: Results of a Pilot Single-Blinded Randomised Controlled Trial

    PubMed Central

    Al-Niaimi, Firas; Sheth, Nisith; Kurwa, Habib A; Mallipeddi, Raj

    2015-01-01

    Introduction: Basal cell carcinoma is a common cutaneous malignant tumour. Surgical excision is the “gold standard” treatment for most subtypes, with Mohs micrographic surgery (MMS) offering the highest cure rate. Other treatment modalities used include photodynamic therapy (PDT). Background: We aimed to study the efficacy of combining MMS with PDT to see whether this would reduce the number of stages and final defect size when compared with MMS alone. Materials and Methods: Our study was a single-centre, single-blinded, randomised and controlled pilot study involving a total of 19 patients. Nine patients were randomised to pre-treatment with PDT followed by MMS of whom two withdrew; the remaining 10 patients were randomised to the MMS alone. Follow-up visits were arranged at 3 and 6 months post-surgery. Results: In the PDT arm, five out of the seven treated patients (71%) had their initial tumour size decreased following PDT treatment prior to MMS. The average number of stages in the PDT arm was 1.85, compared to 2.5 in the MMS arm. The average number of sections in the PDT arm was 4.2, in comparison to 5.2 in the MMS arm. Conclusion: Our pilot study showed a promising but limited role for PDT as an adjunct in MMS in the treatment of selected cases of basal cell carcinomas. Larger trials, preferably multi-centred are required to further examine the role of this combination therapy. PMID:26157307

  2. Basal cell nevus syndrome or Gorlin syndrome.

    PubMed

    Thalakoti, Srikanth; Geller, Thomas

    2015-01-01

    Basal cell nevus syndrome (BCNS) or Gorlin syndrome is a rare neurocutaneous syndrome sometimes known as the fifth phacomatosis, inherited in autosomal dominant fashion with complete penetrance and variable expressivity. Gorlin syndrome is characterized by development of multiple basal cell carcinomas (BCCs), jaw cysts, palmar or plantar pits, calcification of falx cerebri, various developmental skeletal abnormalities such as bifid rib, hemi- or bifid vertebra and predisposition to the development of various tumors. BCNS is caused by a mutation in the PTCH1 gene localized to 9q22.3. Its estimated prevalence varies between 1/55600 and 1/256000 with an equal male to female ratio. The medulloblastoma variant seen in Gorlin syndrome patients is of the desmoplastic type, characteristically presenting during the first 3 years of life. Therefore, children with desmoplastic medulloblastoma should be carefully screened for other features of BCNS. Radiation therapy for desmoplastic medulloblastoma should be avoided in BCNS patients as it may induce development of invasive BCCs and other tumors in the skin area exposed to radiation. This syndrome is a multisystem disorder so involvement of multiple specialists with a multimodal approach to detect and treat various manifestations at early stages will reduce the long-term sequelae and severity of the condition. Life expectancy is not significantly altered but morbidity from complications and cosmetic scarring can be substantial.

  3. Real-life practice study of the clinical outcome and cost-effectiveness of photodynamic therapy using methyl aminolevulinate (MAL-PDT) in the management of actinic keratosis and basal cell carcinoma.

    PubMed

    Annemans, Lieven; Caekelbergh, Karin; Roelandts, Rik; Boonen, Hugo; Leys, Christoph; Nikkels, Arjen F; van Den Haute, V; van Quickenborne, L; Verhaeghe, Evelien; Leroy, Bernard

    2008-01-01

    Clinical trials have shown that photodynamic therapy using methyl aminolevulinate (MAL-PDT) is an effective treatment for actinic keratosis (AK), and nodular and superficial basal cell carcinoma (nBCC and sBCC) unsuitable for other available therapies. Economic evaluation models have shown that it is a cost effective intervention as well. The objectives of this prospective, observational, one arm study were (i) to verify in a real-life practice study the results obtained in previous clinical trials with MAL-PDT in the treatment of AK, nBCC and sBCC; (ii) to calculate the real-life cost of treatment and validate predictions from an economic evaluation model. Patients with AK and/or BCC were selected according to Belgian reimbursement criteria for treatment with MAL-PDT. Clinical response, cosmetic outcome and tolerability were assessed. MAL-PDT cost was calculated and compared to published model cost data. Data were collected from 247 patients (117 AK, 130 BCC). A complete clinical response was obtained for 83% of AK (85/102) and BCC (97/116) patients. A good or excellent cosmetic outcome was obtained for 95% of AK patients and 93% of BCC patients. Tolerability was good: only 2 patients withdrew for adverse events. Clinical results were similar to previous studies. Total cost of care per patient was euro 381 for AK, euro 318 for nBCC, and euro 298 for sBCC. Total cost per lesion was euro 58 for AK (identical to model prediction), euro 316 for nBCC and euro 178 for sBCC (both within 20% of model prediction). The clinical results of MAL-PDT in this real-life practice study confirm those demonstrated in previous clinical trials. Costs calculated from this study confirm predicted cost-effectiveness in the original model for MAL-PDT in the management of AK and BCC.

  4. PTCH polymorphism is associated with the rate of increase in basal cell carcinoma numbers during follow-up: preliminary data on the influence of an exon 12-exon 23 haplotype.

    PubMed

    Strange, Richard C; El-Genidy, Noha; Ramachandran, Sudarshan; Lovatt, Tracy J; Fryer, Anthony A; Smith, Andrew G; Lear, John T; Ichii-Jones, Fumiyo; Jones, Peter W; Hoban, Paul R

    2004-01-01

    After first presentation with a basal cell carcinoma (BCC), patients demonstrate interindividual diversity in the rate of development of further BCCs (number/year of follow-up). The mechanism for this variation is unknown. In this study, we evaluated whether PTCH variants mediate this phenomenon. We used negative binomial regression analysis to identify associations between BCC numbers/year and host characteristics, parameters of exposure to ultraviolet radiation (UVR), and PTCH exon 12(1686) C/T, intron 15(2560+9) G/C, and exon 23(3944) C/T genotypes and haplotypes in 279 BCC cases who presented with an initial tumor on the head/neck. PTCH genotypes were not significantly associated with BCCs/year, although cases with two copies of the C1686-C3944 haplotype developed significantly fewer BCCs/year than those without this haplotype (rate ratio = 0.44; 95% CI = 0.27-0.71). Cases with one copy of T1686-T3944 developed more BCCs/year (rate ratio = 2.46; 95% CI = 1.27-3.97) than those without the haplotype. We found no significant associations between BCCs/year and the other PTCH haplotypes studied. We reexamined the association of C1686-C3944 with BCCs/year in a model that included UVR exposure parameters (sunburning in childhood, sunbathing score, intermittency of exposure between 40 and 60 years of age, exposure in hours/year) and skin type, gender, and age at first presentation. The association between C1686-C3944 and BCCs/year remained significant (rate ratio = 0.44; 95% CI = 0.26-0.73 for two copies of the haplotype). The data show that allelic variation in PTCH contributes to the rate of development of BCC.

  5. Nanoelectroablation therapy for murine basal cell carcinoma

    SciTech Connect

    Nuccitelli, Richard; Tran, Kevin; Athos, Brian; Kreis, Mark; Nuccitelli, Pamela; Chang, Kris S.; Epstein, Ervin H.; Tang, Jean Y.

    2012-08-03

    Highlights: Black-Right-Pointing-Pointer Nanoelectroablation is a new, non-thermal therapy that triggers apoptosis in tumors. Black-Right-Pointing-Pointer Low energy, ultrashort, high voltage pulses ablate the tumor with little or no scar. Black-Right-Pointing-Pointer Nanoelectroablation eliminates 99.8% of the BCC but may leave a few remnants behind. Black-Right-Pointing-Pointer Pilot clinical trials on human BCCs are ongoing and leave no remnants in most cases. -- Abstract: When skin tumors are exposed to non-thermal, low energy, nanosecond pulsed electric fields (nsPEF), apoptosis is initiated both in vitro and in vivo. This nanoelectroablation therapy has already been proven effective in treating subdermal murine allograft tumors. We wanted to determine if this therapy would be equally effective in the treatment of autochthonous BCC tumors in Ptch1{sup +/-}K14-Cre-ER p53 fl/fl mice. These tumors are similar to human BCCs in histology and in response to drug therapy . We have treated 27 BCCs across 8 mice with either 300 pulses of 300 ns duration or 2700 pulses of 100 ns duration, all at 30 kV/cm and 5-7 pulses per second. Every nsPEF-treated BCC began to shrink within a day after treatment and their initial mean volume of 36 {+-} 5 (SEM) mm{sup 3} shrunk by 76 {+-} 3% over the ensuing two weeks. After four weeks, they were 99.8% ablated if the size of the treatment electrode matched the tumor size. If the tumor was larger than the 4 mm wide electrode, multiple treatments were needed for complete ablation. Treated tumors were harvested for histological analysis at various times after treatment and exhibited apoptosis markers. Specifically, pyknosis of nuclei was evident as soon as 2 days after nsPEF treatment, and DNA fragmentation as detected via TUNEL staining was also evident post treatment. Nanoelectroablation is effective in triggering apoptosis and remission of radiation-induced BCCs with a single 6 min-long treatment of 2700 pulses.

  6. Basal cell adenoma of the parotid gland. Case report and review of the literature.

    PubMed

    González-García, Raúl; Nam-Cha, Syong H; Muñoz-Guerra, Mario F; Gamallo-Amat, C

    2006-03-01

    Basal cell adenoma of the salivary glands is an uncommon type of monomorphous adenoma. Its most frequent location is the parotid gland. It usually appears as a firm and mobile slow-growing mass. Histologically, isomorphic cells in nests and interlaced trabecules with a prominent basal membrane are observed. It is also characterized by the presence of a slack and hyaline stroma and the absence of myxoid or condroid stroma. In contrast to pleomorphic adenoma, it tends to be multiple and its recurrence rate after surgical excision is high. Due to prognostic implications, differential diagnosis with basal cell adenocarcinoma, adenoid cystic carcinoma and basaloid squamous cell carcinoma is mandatory. We describe a case of basal cell adenoma of the parotid gland. We also review the literature and discuss the diagnosis and management of this rare entity.

  7. Basal cell-specific and hyperproliferation-related keratins in human breast cancer.

    PubMed Central

    Wetzels, R. H.; Kuijpers, H. J.; Lane, E. B.; Leigh, I. M.; Troyanovsky, S. M.; Holland, R.; van Haelst, U. J.; Ramaekers, F. C.

    1991-01-01

    In normal breast tissue and in noninvasive breast carcinomas, various keratin-14 antibodies were reactive predominantly with the basal/myoepithelial cell layer, although mainly in terminal and larger ducts luminal cells sometimes also were stained. A similar reaction pattern was found with an antibody directed against keratin 17, although this antibody was more often found negative than keratin 14 in the pre-existing myoepithelial cells in intraductal carcinomas. Furthermore antibodies reactive with hyperproliferation-related keratins 6 and 16 were used. One of these (LL025) was completely negative in normal breast tissue and noninvasive breast carcinomas. However 10% of the invasive carcinomas were diffusely or focally positive with this latter antibody, while in 18 of 115 cases of invasive breast carcinomas studied, a basal cell phenotype was detected. A relatively high concordance was found between the carcinomas immunostaining with the basal cell and the hyperproliferation-related keratins, but not between these markers and the proliferation marker Ki-67. This supports the conclusion that basal cells in breast cancer may show extensive proliferation, and that absence of Ki-67 staining does not mean that (tumor) cells are not proliferating. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:1705754

  8. Dermatocosmetologic aspects of treatment of basal-cell skin cancer

    NASA Astrophysics Data System (ADS)

    Geinitz, A. V.; Stranadko, Ye. F.; Yusupova, Zh. M.; Tkachenko, S. B.

    2005-08-01

    The obtained clinical findings demonstrate excellent results after surgical MSC treatment with the application of modem laser surgical technologies. All the operated patients were under oncologist"s control during 1.5-2.5 years. In 6 cases we observed topical recurrences which needed a repeated intervention. Thus, our experience of applying LPh for surgical treatment of basal-cell carcinomas of the head and neck dem- onstrate that in the analysed cases it is more reasonable to use two models of laser devices different in their physical parameters. These devices are used at different surgical stages so as to provide a precise effect in laser tumour va- porization within the borders of the healthy tissue, to make better vascular coagulation and laser smoothing of wound surface. Immediate, direct and long-term results of modern surgical lasers" application for treating skin BSC almost in all cases give good and excellent cosmetic effect after such intenventions.

  9. Lichen planopilaris after imiquimod 5% cream for multiple BCC in basal cell naevus syndrome.

    PubMed

    Drummond, Alessandra; Pichler, Janine; Argenziano, Giuseppe; Zalaudek, Iris; Longo, Caterina; Lallas, Aimilios; Piana, Simonetta; Moscarella, Elvira

    2015-11-01

    Basal cell naevus syndrome is an inherited autosomal dominant genetic disorder characterised by multiple basal cell carcinomas (BCC), skeletal, neurological and opthalmological abnormalities. The treatment of choice of the often multiple and large BCC consists of a combined approach including surgery, liquid nitrogen and other topical treatment modalities. Imiquimod 5% cream is an immune-response-modifying drug with antiviral and anti-tumour activity. Recent reports have associated the immune-stimulant properties of imiquimod with the exacerbation of several autoimmune skin diseases, such as eczema, psoriasis, vitiligo and lichenoid dermatitis. Here we report a patient with basal cell naevus syndrome who developed a lichen planopilaris on the same site of the scalp, which had been previously treated with two cycles of imiquimod for multiple BCC.

  10. Bax/bcl-2: cellular modulator of apoptosis in feline skin and basal cell tumours.

    PubMed

    Madewell, B R; Gandour-Edwards, R; Edwards, B F; Matthews, K R; Griffey, S M

    2001-01-01

    Bcl-2 and bax are two members of the BCL-2 gene family that play a prominent role in the regulation of apoptosis. Bax and bcl-2 expression were examined immunohistochemically in normal (healthy) feline skin and in 24 benign feline cutaneous basal cell tumours. The tumours were also examined for cellular proliferation by measurement of reactivity for the proliferation marker Ki-67, and for apoptosis by in-situ labelling for fragmented DNA. Bcl-2 was detected in normal basal epithelium and in 23 of 24 basal cell tumours. Bax was detected in both basal and suprabasal epithelium, but in only seven of 24 tumours. For tumours that expressed both bax and bcl-2, the bax:bcl-2 ratio was low. Neither bax nor bcl-2 expression was detected in 14 feline cutaneous squamous cell carcinomas. Basal cell tumours showed modest cellular proliferation (median, 17.5% Ki-67- reactive cells), but few (less than 1%) apoptotic cells. The slow, indolent growth of feline cutaneous basal cells in these benign skin tumours may be a response, at least in part, to opposing regulatory expressions of bcl-2 and bax.

  11. Linear and whorled nevoid hypermelanosis: dermatoscopic features.

    PubMed

    Ertam, Ilgen; Turk, Bengu Gerceker; Urkmez, Asli; Kazandi, Alican; Ozdemir, Fezal

    2009-02-01

    Linear and whorled nevoid hypermelanosis (LWNH) is a pigmentation disorder characterized by macular hyperpigmentation following the lines of Blaschko. Dermatoscopy can be used in the differential diagnosis of this pigmentation disorder. To our knowledge, the dermatoscopic features of pigmented lesions in LWNH have not been described previously. Here, a case of LWNH is discussed together with its dermatoscopic findings. An 11-year-old girl presented to our department with hyperpigmentation along the lines of Blaschko over the entire body. The mental status of the patient was normal and no associated anomaly was detected in the physical examination or genetic analysis. Dermatologic examination revealed a whorled-like configuration of hyperpigmented macules on the neck, trunk, and buttocks, and a linear configuration of hyperpigmented macules, some of which were arranged in a parallel linear fashion on the extremities along the lines of Blaschko. Histopathologic examination confirmed the diagnosis. Dermatoscopic examination revealed linear or circular arrangement of streak-like pigmentations arranged in a parallel manner. This is the first known reported case of LWNH that describes its dermatoscopic findings. Dermatoscopy may be used to facilitate the differential diagnosis of melanotic lesions of this pigmentation disorder.

  12. Multiple nevoid hypertrichosis as an isolated developmental defect.

    PubMed

    Sotiriadis, Dimitrios; Patsatsi, Aikaterini; Lazaridou, Elizabeth; Sotiriou, Eleni; Devliotou-Panagiotidou, Despina

    2009-01-01

    A 3-year-old girl presented with longer hair on the left side of her scalp, coarse hair of abnormal length on her extremities, and a tuft of hair in the lumbosacral region, with all hair distributed on normally pigmented skin. Neither similar or relevant family history nor associated extracutaneous abnormalities was detected after a thorough examination. Clinical diagnosis of patchy nevoid hypetrichosis was confirmed by histology. Nevoid hypertrichosis is a rare hair growth disorder that usually presents at or soon after birth. It is characterized by patches of hypertrichosis distributed in a segmental pattern. It may be accompanied by mental, ocular, or myoskeletal abnormalities. Cases of nevoid hypertrichosis with multiple patches presenting as a solitary developmental defect have been rarely described in the literature.

  13. Bilateral Lymphatic Spread of Metastatic Basal Cell Carcinoma

    PubMed Central

    Sleightholm, Richard L.; Willcockson, James R.; Watley, Duncan C.; Durden, Frederick L.

    2016-01-01

    Summary: Herein, we report a case of a patient with an abnormal skin lesion that remained unchecked by medical professionals for approximately 20 years. Upon physical examination in the emergency department for a fractured hip, an infiltrative mass was incidentally discovered. The neoplasm was noted to have progressed from an eraser-sized mass to a 3.5-cm invasive lesion. Initial surgical intervention was believed to have been successful in removal, as margins were clear with the exception of 1 indeterminate segment. However, subsequent 1-year follow-up revealed recurrence of the disease with bilateral axillary node and deep muscle involvement. This prompted a more extensive surgical approach complemented with radiation therapy. The patient had remained disease-free for a year. PMID:28293526

  14. Learning semantic histopathological representation for basal cell carcinoma classification

    NASA Astrophysics Data System (ADS)

    Gutiérrez, Ricardo; Rueda, Andrea; Romero, Eduardo

    2013-03-01

    Diagnosis of a histopathology glass slide is a complex process that involves accurate recognition of several structures, their function in the tissue and their relation with other structures. The way in which the pathologist represents the image content and the relations between those objects yields a better and accurate diagnoses. Therefore, an appropriate semantic representation of the image content will be useful in several analysis tasks such as cancer classification, tissue retrieval and histopahological image analysis, among others. Nevertheless, to automatically recognize those structures and extract their inner semantic meaning are still very challenging tasks. In this paper we introduce a new semantic representation that allows to describe histopathological concepts suitable for classification. The approach herein identify local concepts using a dictionary learning approach, i.e., the algorithm learns the most representative atoms from a set of random sampled patches, and then models the spatial relations among them by counting the co-occurrence between atoms, while penalizing the spatial distance. The proposed approach was compared with a bag-of-features representation in a tissue classification task. For this purpose, 240 histological microscopical fields of view, 24 per tissue class, were collected. Those images fed a Support Vector Machine classifier per class, using 120 images as train set and the remaining ones for testing, maintaining the same proportion of each concept in the train and test sets. The obtained classification results, averaged from 100 random partitions of training and test sets, shows that our approach is more sensitive in average than the bag-of-features representation in almost 6%.

  15. Unilateral nevoid acanthosis nigricans: Uncommon variant of a common disease

    PubMed Central

    Das, Anupam; Bhattacharya, Sabari; Kumar, Piyush; Gayen, Tirthankar; Roy, Kunal; Das, Nilay K.; Gharami, Ramesh C.

    2014-01-01

    Acanthosis nigricans (AN) is a fairly common dermatosis characterized by hyperpigmented velvety plaques, having a predilection for the intertriginous areas. We herein present a case of unilateral nevoid acanthosis nigricans over the left lateral chest, in an adult male. The rarity of documentation of this entity in the world literature prompted us to report the case. PMID:25506563

  16. Morphologic changes in basal cells during repair of tracheal epithelium.

    PubMed Central

    Wang, C. Z.; Evans, M. J.; Cox, R. A.; Burke, A. S.; Zhu, Q.; Herndon, D. N.; Barrow, R. E.

    1992-01-01

    Basal cells are differentiated with respect to junctional adhesion mechanisms and play a role in attachment of columnar epithelium to the basal lamina. Although much is known about nonciliated and ciliated cell differentiation during the repair process after injury, little is known about the basal cell. We studied the morphology of basal cells and quantitated junctional adhesion structures during repair of tracheal epithelium exposed to toxic cotton smoke. Ten adult ewes were given a smoke injury to a portion of the upper cervical trachea and were killed at 4, 6, 8, 10, and 18 days after injury for morphometric studies. At 4 days, there was a stratified reparative epithelium over the basal lamina, which was two to four cells in depth. The basal cells were identified by their hemidesmosome (HD) attachment to the basal lamina. Basal cells were about 69% larger than controls and flattened rather than columnar. The amount of HD attachment was 192% greater than controls. In contrast, volume density of cytokeratin filaments had decreased about 47%. Basal cells had returned to normal numbers and size and a columnar shape by day 18. The amount of desmosome (D) and HD attachment and volume density of cytokeratins had also reached control levels by day 18. These data indicate that morphology of basal cells changes during the initial stages of reparative regeneration but returns to normal by 18 days. Morphologic changes appear to reflect changes in size of the cell associated with cell division rather than differentiation of recently divided basal cells. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:1381564

  17. Cutaneous basal cell carcinosarcomas: evidence of clonality and recurrent chromosomal losses.

    PubMed

    Harms, Paul W; Fullen, Douglas R; Patel, Rajiv M; Chang, Dannie; Shalin, Sara C; Ma, Linglei; Wood, Benjamin; Beer, Trevor W; Siddiqui, Javed; Carskadon, Shannon; Wang, Min; Palanisamy, Nallasivam; Fisher, Gary J; Andea, Aleodor

    2015-05-01

    Cutaneous carcinosarcomas are heterogeneous group of tumors composed of malignant epithelial and mesenchymal components. Although mutation analyses have identified clonal changes between these morphologically disparate components in some subtypes of cutaneous carcinosarcoma, few cases have been analyzed thus far. To our knowledge, copy number variations (CNVs) and copy-neutral loss of heterozygosity (CN-LOH) have not been investigated in cutaneous carcinosarcomas. We analyzed 4 carcinosarcomas with basal cell carcinoma and osteosarcomatous components for CNVs/CN-LOH by comparative genomic hybridization/single-nucleotide polymorphism array, TP53 hot spot mutations by polymerase chain reaction and Sanger sequencing, and TP53 genomic rearrangements by fluorescence in situ hybridization. All tumors displayed multiple CNV/CN-LOH events (median, 7.5 per tumor). Three of 4 tumors displayed similar CNV/CN-LOH patterns between the epithelial and mesenchymal components within each tumor, supporting a common clonal origin. Recurrent changes included allelic loss at 9p21 (CDKN2A), 9q (PTCH1), and 17p (TP53). Allelic losses of chromosome 16 including CDH1 (E-cadherin) were present in 2 tumors and were restricted to the sarcomatous component. TP53 mutation analysis revealed an R248L mutation in both epithelial and mesenchymal components of 1 tumor. No TP53 rearrangements were identified. Our findings indicate that basal cell carcinosarcomas harbor CNV/CN-LOH changes similar to conventional basal cell carcinoma, with additional changes including recurrent 9p21 losses and a relatively high burden of copy number changes. In addition, most cutaneous carcinosarcomas show evidence of clonality between epithelial and mesenchymal components.

  18. Familial papular epidermal nevus with "skyline" basal cell layer.

    PubMed

    Brena, Michela; Besagni, Francesca; Boneschi, Vinicio; Tadini, Gianluca

    2014-01-01

    Papular epidermal nevus with "skyline" basal cell layer (PENS), a novel keratinocytic nevus, has recently been described as a mosaic condition with varying presentations. We herein describe typical PENS lesions, which usually occur sporadically, affecting two members of the same family. The concept of paradominant inheritance is proposed to explain the paradox of occasional transmission of normally sporadically occurring traits.

  19. Cell cycle of globose basal cells in rat olfactory epithelium.

    PubMed

    Huard, J M; Schwob, J E

    1995-05-01

    The olfactory epithelium of adult mammals has the unique property of generating olfactory sensory neurons throughout life. Cells of the basal compartment, which include horizontal and globose basal cells, are responsible for the ongoing process of neurogenesis in this system. We report here that the globose basal cells in olfactory epithelium of rats, as in mice, are the predominant type of proliferating cell, and account for 97.6% of the actively dividing cells in the basal compartment of the normal epithelium. Globose basal cells have not been fully characterized in terms of their proliferative properties, and the dynamic aspects of neurogenesis are not well understood. As a consequence, it is uncertain whether cell kinetic properties are under any regulation that could affect the rate of neurogenesis. To address this gap in our knowledge, we have determined the duration of both the synthesis phase (S-phase) and the full cell cycle of globose basal cells in adult rats. The duration of the S-phase was found to be 9 hr in experiments utilizing sequential injections of either IdU followed by BrdU or 3H-thy followed by BrdU. The duration of the cell cycle was determined by varying the time interval between the injections of 3H-thy and BrdU and tracking the set of cells that exit S shortly after the first injection. With this paradigm, the interval required for these cells to traverse G2, M, G1, and a second S-phase, is equivalent to the duration of one mitotic cycle and equals 17 hr. These observations serve as the foundation to assess whether the cell cycle duration is subject to regulation in response to experimental injury, and whether such regulation is partly responsible for changes in the rate of neurogenesis in such settings.

  20. Adamantinoma-like Ewing sarcoma mimicking basal cell adenocarcinoma of the parotid gland: a case report and review of the literature.

    PubMed

    Lezcano, Cecilia; Clarke, Martha R; Zhang, Lei; Antonescu, Cristina R; Seethala, Raja R

    2015-06-01

    Adamantinoma-like Ewing sarcoma (AES) is a rare variant of the Ewing family of tumors that resembles classic adamantinoma of bone. AES shows epithelial differentiation and a more complex immunohistochemical expression profile with keratin and basal marker immunoreactivity and can resemble a variety of carcinomas. We report an unusual case of an AES of the parotid gland that mimicked a basal cell adenocarcinoma. Like basal cell adenocarcinoma, this AES showed a nested basaloid proliferation with peripheral palisading in tumor nests with 'basaloid' epithelial differentiation as highlighted by cytokeratin AE1/3 and p40 positivity. However, unlike most basal cell adenocarcinomas, this tumor demonstrated high grade morphology, showed no true ductal or myoepithelial component, and also showed a tendency towards neuroectodermal phenotype with focal rosette formation, CD99 and weak synaptophysin immunoreactivity. EWSR1 and FLI1 fluorescence in situ hybridization confirmed the presence of a translocation supporting the diagnosis of AES. This is the first case of AES presenting as a primary parotid mass highlighting the potential to be mistaken for primary salivary gland carcinomas, which in addition to basal cell adenocarcinoma include other basaloid tumors such as adenoid cystic carcinoma.

  1. Mycosis fungoides mimicking nevoid hyperkeratosis of the nipple and areola in an adolescent.

    PubMed

    Yalçın, Başak; Gür, Güneş; Tabanlıoğlu-Onan, Duru; Ekici, Özlem

    2014-01-01

    Mycosis fungoides is one of the great imitators in dermatology; it can mimic many dermatoses. Nevoid hyperkeratosis of the nipple and areola is a rare idiopathic disease with typical clinical features of verrucous thickening and brownish discoloration of the nipple, areola or both. Here, a 16-year-old male patient with mycosis fungoides mimicking nevoid hyperkeratosis of the nipple and areola has been reported. To our knowledge, this is the first atypical MF patient to have presented with a NHNA-like lesion. Although the clinical appearance of nevoid hyperkeratosis of the nipple and areola is highly characteristic for diagnosis, histopathological examination is recommended, especially in cases with atypical features such as unexpected age, male gender and unilateral location.

  2. Lack of correlation between basal cell survival and gross response in irradiated swine skin

    SciTech Connect

    Shymko, R.M.; Hauser, D.L.; Archambeau, J.O.

    1984-07-01

    The relationship between basal cell survival and gross response in irradiated swine skin was tested by comparing dose survival curves derived from time-dose isoeffect data with curves obtained directly from basal cell counts in histological sections. Assuming equal effect per exposure and constant cell survival at isoeffect, best-fitting single-hit multi-target and liner-quadratic response curves were determined for time-dose schedules resulting in non-healing of 50% of irradiated fields. Basal cell survivals for single doses of 970, 1649, 2231, and 2619 rad were estimated 1) by counting regenerating islands and 2) by monitoring total basal cell counts through time. The dose survival curve derived from the isoeffect data was steeper than the curve obtained from direct basal cell counts. Furthermore, the direct basal cell survival curve extrapolates to less than 100% at zero dose, indicating the presence of a resistant basal cell subpopulation. The data show that the isoeffect in this case is not strongly coupled to basal cell survival.

  3. Isolated Rat Epididymal Basal Cells Share Common Properties with Adult Stem Cells1

    PubMed Central

    Mandon, Marion; Hermo, Louis; Cyr, Daniel G.

    2015-01-01

    There is little information on the function of epididymal basal cells. These cells secrete prostaglandins, can metabolize radical oxygen species, and have apical projections that are components of the blood-epididymis barrier. The objective of this study was to develop a reproducible protocol to isolate rat epididymal basal cells and to characterize their function by gene expression profiling. Integrin-alpha6 was used to isolate a highly purified population of basal cells. Microarray analysis indicated that expression levels of 552 genes were enriched in basal cells relative to other cell types. Among these genes, 45 were expressed at levels of 5-fold or greater. These highly expressed genes coded for proteins implicated in cell adhesion, cytoskeletal function, ion transport, cellular signaling, and epidermal function, and included proteases and antiproteases, signal transduction, and transcription factors. Several highly expressed genes have been reported in adult stem cells, suggesting that basal cells may represent an epididymal stem cell population. A basal cell culture was established that showed that these basal cells can differentiate in vitro from keratin (KRT) 5-positive cells to cells that express KRT8 and connexin 26, a marker of columnar cells. These data provide novel information on epididymal basal cell gene expression and suggest that these cells can act as adult stem cells. PMID:26400399

  4. Basal cell adenoma of nasal septum: report of a case and review of literature.

    PubMed

    Wang, Qinying; Chen, Haihong; Wang, Shenqing

    2015-01-01

    Basal cell adenoma is an uncommon benign salivary gland neoplasm, presenting isomorphic basaloid cells with a prominent basal cell layer. Basal cell adenoma arising from the nasal septum is exceptionally rare. Reports on positron emission tomography with 2-deoxy-2-fluorine-18-fluoro-D-glucose (18FDG-PET) imaging for basal cell adenoma are limited. Here, we present the case of a 49-year-old man who had the symptoms of intermittent repeated bleeding from the left nose for half a year. 18FDG-PET scanning showed increased accumulation of 18FDG with its characteristic benign pathology has a potential to malignancy. After removal of the mass, the patient became symptom free. Pathology showed basal cell adenoma. The evidence of active and growing cells was present in the specimen.

  5. Epidermal growth factor receptor activity is necessary for mouse basal cell proliferation

    PubMed Central

    Brechbuhl, Heather M.; Li, Bilan; Smith, Russell W.

    2014-01-01

    ERB family receptors (EGFR, ERB-B2, ERB-B3, and ERB-B4) regulate epithelial cell function in many tissue types. In the human airway epithelium, changes in ERB receptor expression are associated with epithelial repair defects. However, the specific role(s) played by ERB receptors in repair have not been determined. We aimed to determine whether ERB receptors regulate proliferation of the tracheobronchial progenitor, the basal cell. Receptor tyrosine kinase arrays were used to evaluate ERB activity in normal and naphthalene (NA)-injured mouse trachea and in air-liquid interface cultures. Roles for epidermal growth factor (EGF), EGFR, and ERB-B2 in basal cell proliferation were evaluated in vitro. NA injury and transgenic expression of an EGFR-dominant negative (DN) receptor were used to evaluate roles for EGFR signaling in vivo. EGFR and ERB-B2 were active in normal and NA-injured trachea and were the only active ERB receptors detected in proliferating basal cells in vitro. EGF was necessary for basal cell proliferation in vitro. The EGFR inhibitor, AG1478, decreased proliferation by 99, and the Erb-B2 inhibitor, AG825, decreased proliferation by ∼66%. In vivo, EGFR-DN expression in basal cells significantly decreased basal cell proliferation after NA injury. EGF and EGFR are necessary for basal cell proliferation. The EGFR/EGFR homo- and the EGFR/ERB-B2 heterodimer account for ∼34 and 66%, respectively, of basal cell proliferation in vitro. Active EGFR is necessary for basal cell proliferation after NA injury. We conclude that EGFR activation is necessary for mouse basal cell proliferation and normal epithelial repair. PMID:25217659

  6. Are the basal cells of the mammalian epididymis still an enigma?

    PubMed

    Arrighi, S

    2014-10-01

    Basal cells are present in the columnar pseudostratified epithelium covering the epididymis of all mammalian species, which regulates the microenvironment where the functionally incompetent germ cells produced by the testis are matured and stored. Striking novelties have come from investigations on epididymal basal cells in the past 30-40 years. In addition to an earlier hypothesised scavenger role for basal cells, linked to their proven extratubular origin and the expression of macrophage antigens, basal cells have been shown to be involved in cell-cell cross-talk, as well as functioning as luminal sensors to regulate the activity of principal and clear cells. Involvement of basal cells in the regulation of electrolyte and water transport by principal cells was hypothesised. This control is suggested to be mediated by the local formation of prostaglandins. Members of the aquaporin (AQP) and/or aquaglyceroporin family (AQP3, AQP7 and AQP8) are also specifically expressed in the rat epididymal basal cells. Transport of glycerol and glycerylphosphorylcholine from the epithelium of the epididymis to the lumen in relation to sperm maturation may be mediated by AQP. Most probably basal cells collaborate to the building up of the blood-epididymis barrier through cell adhesion molecules, implying an involvement in immune control exerted towards sperm cells, which are foreigners in the environment in which they were produced.

  7. Molecular basis of basal cell carcinogenesis in the atomic-bomb survivor population: p53 and PTCH gene alterations.

    PubMed

    Mizuno, Terumi; Tokuoka, Shoji; Kishikawa, Masao; Nakashima, Eiji; Mabuchi, Kiyohiko; Iwamoto, Keisuke S

    2006-11-01

    Epidemiological studies suggest that UV exposure from sunlight is the major etiology for skin cancers, both melanocytic and non-melanocytic. However, the radiation-related risk for skin cancer among atomic bomb survivors of Hiroshima and Nagasaki is primarily derived from the excess risk of basal cell carcinoma (BCC), with no demonstrable excess in squamous cell carcinoma or melanoma. The BCCs in this cohort are therefore unusual in being potentially attributable to two types of radiation-UV and ionizing (IR). BCCs have been associated with PTCH and/or p53 tumor suppressor gene alterations. To investigate the roles of these genes in relation to IR and UV exposures, we analyzed both genes in BCC samples from atomic bomb survivors. We examined 47 tumors, of which 70% had non-silent base-substitution p53 mutations independent of IR or UV exposure. However, the distribution of mutation type depends on UV and/or IR exposure. For example, C-to-T transitions at CpG sites adjacent to pyrimidine-pyrimidine (PyPy) sequences were more prevalent in tumors from UV-exposed than UV-shielded body areas and CpG-mutations at non-PyPy sequences were more prevalent in tumors from UV-shielded body areas with high-IR (>or=1 Gy) than low-IR (<0.2 Gy) exposure. And notably, although p53 deletion-frequencies demonstrated no IR-dose associations, deletions at the PTCH locus were more frequent (79% versus 44%) in tumors with high-IR than low-IR exposure. Moreover, 60% of high-IR tumors harbored both p53 and PTCH abnormalities compared with 23% of low-IR tumors. Therefore, alteration of both genes is likely to play a role in radiation-induced basal cell carcinogenesis.

  8. Transepithelial projections from basal cells are luminal sensors in pseudostratified epithelia

    PubMed Central

    Shum, Winnie Wai Chi; Silva, Nicolas Da; McKee, Mary; Smith, Peter J.S.; Brown, Dennis; Breton, Sylvie

    2008-01-01

    Basal cells are by definition located on the basolateral side of several epithelia, and they have never been observed reaching the lumen. Using high-resolution 3D confocal imaging, we report that basal cells extend long and slender cytoplasmic projections that not only reach towards the lumen but can cross the tight junction barrier in some epithelia of the male reproductive and respiratory tracts. In this way, the basal cell plasma membrane is exposed to the luminal environment. In the epididymis, in which luminal acidification is crucial for sperm maturation and storage, these projections contain the angiotensin II type 2 receptor (AGTR2). Activation of AGTR2 by luminal angiotensin II, increases proton secretion by adjacent clear cells, which are devoid of AGTR2. We propose a new paradigm in which basal cells scan and sense the luminal environment of pseudostratified epithelia, and modulate epithelial function by a mechanism involving cross-talk with other epithelial cells. PMID:19070580

  9. α7 Nicotinic Acetylcholine Receptor Regulates Airway Epithelium Differentiation by Controlling Basal Cell Proliferation

    PubMed Central

    Maouche, Kamel; Polette, Myriam; Jolly, Thomas; Medjber, Kahina; Cloëz-Tayarani, Isabelle; Changeux, Jean-Pierre; Burlet, Henriette; Terryn, Christine; Coraux, Christelle; Zahm, Jean-Marie; Birembaut, Philippe; Tournier, Jean-Marie

    2009-01-01

    Airway epithelial basal cells are known to be critical for regenerating injured epithelium and maintaining tissue homeostasis. Recent evidence suggests that the α7 nicotinic acetylcholine receptor (nAChR), which is highly permeable to Ca2+, is involved in lung morphogenesis. Here, we have investigated the potential role of the α7 nAChR in the regulation of airway epithelial basal cell proliferation and the differentiation of the human airway epithelium. In vivo during fetal development and in vitro during the regeneration of the human airway epithelium, α7 nAChR expression coincides with epithelium differentiation. Inactivating α7 nAChR function in vitro increases cell proliferation during the initial steps of the epithelium regeneration, leading to epithelial alterations such as basal cell hyperplasia and squamous metaplasia, remodeling observed in many bronchopulmonary diseases. The regeneration of the airway epithelium after injury in α7−/− mice is delayed and characterized by a transient hyperplasia of basal cells. Moreover, 1-year-old α7−/− mice more frequently present basal cells hyperplasia. Modulating nAChR function or expression shows that only α7 nAChR, as opposed to heteropentameric αxβy nAChRs, controls the proliferation of human airway epithelial basal cells. These findings suggest that α7 nAChR is a key regulator of the plasticity of the human airway epithelium by controlling basal cell proliferation and differentiation pathway and is involved in airway remodeling during bronchopulmonary diseases. PMID:19808646

  10. Expression of basal cell marker revealed by RAM11 antibody during epithelial regeneration in rabbits.

    PubMed

    Lis, Grzegorz J; Jasek, Ewa; Litwin, Jan A; Gajda, Mariusz; Zarzecka, Joanna; Cichocki, Tadeusz

    2010-01-01

    RAM11 is a mouse monoclonal anti-rabbit macrophage antibody recognizing connective tissue and vascular macrophages. Our previous report showed that RAM11 reacted with basal cells of stratified squamous epithelia of rabbit skin, oral mucosa and esophagus. The aim of the present study was to follow the appearance of RAM11 immunoreactivity in basal cells of regenerating oral epithelium in rabbits. No RAM11 immunostaining was observed in the regenerating epithelium examined on days 1 and 3 of wound healing. A weak immunofluorescence first appeared on day 7 in single basal cells and 32% of RAM11- positive basal cells were observed on day 14. These findings indicate that expression of the antigen recognized by RAM11 antibody is a transient event in the differentiation of oral keratinocytes which not always occurs during epithelial repair, although it is a constant feature of epithelial turnover in mature epithelium. Therefore this antigen can be regarded as basal cell marker only in mature stratified squamous epithelia.

  11. [Changes in proliferation and differentiation of basal cells during wound healing of rabbit corneal epithelial abrasions].

    PubMed

    Yamada, M; Mashima, Y

    1995-01-01

    Changes in the mitotic rate and epithelial keratin expression of corneal epithelial basal cells following corneal abrasion (7.0 mm in diameter) in rabbits were studied immunohistochemically using antiproliferating cell nuclear antigen (PCNA) monoclonal antibody and anti-epithelial keratin 1 (AE1). In the non-wounded control, the mitotic rate (PCNA positive cells in the basal cell layer) was approximately 4%, and only the superficial cells were stained by AE1 monoclonal antibody. One day after wounding, migrating epithelial cells at the leading edge, which reacted to AE1, showed low mitotic activity. At days 3 and 7, the mitotic rates of basal cells of regenerating epithelium were 3 times higher than that of controls. These basal cells displayed intensive staining with AE1, while the epithelium over the unwounded cornea exhibited a normal pattern limited to superficial cells. By 14 days after injury, the mitotic rate returned to normal and all epithelial cells expressed a normal AE1 staining pattern. Theses results suggest that regeneration of corneal epithelial basal cells involves changes in keratin expression, which might correlate with changes in the mitotic rate.

  12. Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer.

    PubMed

    Zhang, Dingxiao; Park, Daechan; Zhong, Yi; Lu, Yue; Rycaj, Kiera; Gong, Shuai; Chen, Xin; Liu, Xin; Chao, Hsueh-Ping; Whitney, Pamela; Calhoun-Davis, Tammy; Takata, Yoko; Shen, Jianjun; Iyer, Vishwanath R; Tang, Dean G

    2016-02-29

    The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here we describe a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. Through molecular and biological characterizations, we show that the differential gene-expression profiles account for their distinct functional properties. Strikingly, basal cells preferentially express gene categories associated with stem cells, neurogenesis and ribosomal RNA (rRNA) biogenesis. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene-expression profile is enriched in advanced, anaplastic, castration-resistant and metastatic prostate cancers. Therefore, we link the cell-type-specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features.

  13. Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer

    PubMed Central

    Zhang, Dingxiao; Park, Daechan; Zhong, Yi; Lu, Yue; Rycaj, Kiera; Gong, Shuai; Chen, Xin; Liu, Xin; Chao, Hsueh-Ping; Whitney, Pamela; Calhoun-Davis, Tammy; Takata, Yoko; Shen, Jianjun; Iyer, Vishwanath R.; Tang, Dean G.

    2016-01-01

    The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here we describe a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. Through molecular and biological characterizations, we show that the differential gene-expression profiles account for their distinct functional properties. Strikingly, basal cells preferentially express gene categories associated with stem cells, neurogenesis and ribosomal RNA (rRNA) biogenesis. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene-expression profile is enriched in advanced, anaplastic, castration-resistant and metastatic prostate cancers. Therefore, we link the cell-type-specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features. PMID:26924072

  14. Endogenous synchronous fluorescence spectroscopy (SFS) of basal cell carcinoma-initial study

    NASA Astrophysics Data System (ADS)

    Borisova, E.; Zhelyazkova, Al.; Keremedchiev, M.; Penkov, N.; Semyachkina-Glushkovskaya, O.; Avramov, L.

    2016-01-01

    The human skin is a complex, multilayered and inhomogeneous organ with spatially varying optical properties. Analysis of cutaneous fluorescence spectra could be a very complicated task; therefore researchers apply complex mathematical tools for data evaluation, or try to find some specific approaches, that would simplify the spectral analysis. Synchronous fluorescence spectroscopy (SFS) allows improving the spectral resolution, which could be useful for the biological tissue fluorescence characterization and could increase the tumour detection diagnostic accuracy.

  15. Carinal resection, left pneumonectomy, and right lung anastomosis for adenocystic basal cell carcinoma (cylindroma)

    PubMed Central

    Thompson, Douglas T.; Doyle, Jorge A.; Roncoroni, Aquiles J.

    1969-01-01

    The surgical approach to, and resection of, a cylindroma of the left main bronchus involving the trachea and right main bronchus is described. The literature on bronchial adenoma and cylindroma is reviewed, both the pathogenesis and surgery being discussed. A plea for a more aggressive approach is made. Images PMID:4310817

  16. A supervised visual model for finding regions of interest in basal cell carcinoma images

    PubMed Central

    2011-01-01

    This paper introduces a supervised learning method for finding diagnostic regions of interest in histopathological images. The method is based on the cognitive process of visual selection of relevant regions that arises during a pathologist's image examination. The proposed strategy emulates the interaction of the visual cortex areas V1, V2 and V4, being the V1 cortex responsible for assigning local levels of relevance to visual inputs while the V2 cortex gathers together these small regions according to some weights modulated by the V4 cortex, which stores some learned rules. This novel strategy can be considered as a complex mix of "bottom-up" and "top-down" mechanisms, integrated by calculating a unique index inside each region. The method was evaluated on a set of 338 images in which an expert pathologist had drawn the Regions of Interest. The proposed method outperforms two state-of-the-art methods devised to determine Regions of Interest (RoIs) in natural images. The quality gain with respect to an adaptated Itti's model which found RoIs was 3.6 dB in average, while with respect to the Achanta's proposal was 4.9 dB. PMID:21447178

  17. Ezh2 represses the basal cell lineage during lung endoderm development.

    PubMed

    Snitow, Melinda E; Li, Shanru; Morley, Michael P; Rathi, Komal; Lu, Min Min; Kadzik, Rachel S; Stewart, Kathleen M; Morrisey, Edward E

    2015-01-01

    The development of the lung epithelium is regulated in a stepwise fashion to generate numerous differentiated and stem cell lineages in the adult lung. How these different lineages are generated in a spatially and temporally restricted fashion remains poorly understood, although epigenetic regulation probably plays an important role. We show that the Polycomb repressive complex 2 component Ezh2 is highly expressed in early lung development but is gradually downregulated by late gestation. Deletion of Ezh2 in early lung endoderm progenitors leads to the ectopic and premature appearance of Trp63+ basal cells that extend the entire length of the airway. Loss of Ezh2 also leads to reduced secretory cell differentiation. In their place, morphologically similar cells develop that express a subset of basal cell genes, including keratin 5, but no longer express high levels of either Trp63 or of standard secretory cell markers. This suggests that Ezh2 regulates the phenotypic switch between basal cells and secretory cells. Together, these findings show that Ezh2 restricts the basal cell lineage during normal lung endoderm development to allow the proper patterning of epithelial lineages during lung formation.

  18. Basal Cell Adenoma of Palate, a Rare Occurrence with Review of Literature

    PubMed Central

    Yadav, Achla Bharti; Narwal, Anjali; Devi, Anju; Kumar, Sanjay; Yadav, Sumit Kumar

    2015-01-01

    Basal cell adenoma is an uncommon benign epithelial neoplasm of salivary gland which derives its name from the basaloid appearance of tumor cells and accounting for 1-2 % of all salivary gland epithelial tumors. This tumor usually arises in the major salivary glands, with the parotid being the most frequent site of occurrence, followed by the upper lip; while it is very rare in the minor salivary glands. Microscopically, it is composed of isomorphic cells similar to basal cells with nuclear palisading. We report a case of BCA presenting as an asymptomatic swelling over the right side of palate of 55-year-old female patient. A follow-up of 1 year revealed no recurrence. This report emphasizes the rare site of occurrence of this tumor and briefly reviews the literature. PMID:26535412

  19. AKT1 Activation is Obligatory for Spontaneous BCC Tumor Growth in a Murine Model that Mimics Some Features of Basal Cell Nevus Syndrome.

    PubMed

    Kim, Arianna L; Back, Jung Ho; Zhu, Yucui; Tang, Xiuwei; Yardley, Nathan P; Kim, Katherine J; Athar, Mohammad; Bickers, David R

    2016-10-01

    Patients with basal cell nevus syndrome (BCNS), also known as Gorlin syndrome, develop numerous basal cell carcinomas (BCC) due to germline mutations in the tumor suppressor PTCH1 and aberrant activation of Hedgehog (Hh) signaling. Therapies targeted at components of the Hh pathway, including the smoothened (SMO) inhibitor vismodegib, can ablate these tumors clinically, but tumors recur upon drug discontinuation. Using SKH1-Ptch1(+/-) as a model that closely mimics the spontaneous and accelerated growth pattern of BCCs in patients with BCNS, we show that AKT1, a serine/threonine protein kinase, is intrinsically activated in keratinocytes derived from the skin of newborn Ptch1(+/-) mice in the absence of carcinogenic stimuli. Introducing Akt1 haplodeficiency in Ptch1(+/-) mice (Akt1(+/-) Ptch1(+/-)) significantly abrogated BCC growth. Similarly, pharmacological inhibition of AKT with perifosine, an alkyl phospholipid AKT inhibitor, diminished the growth of spontaneous and UV-induced BCCs. Our data demonstrate an obligatory role for AKT1 in BCC growth, and targeting AKT may help reduce BCC tumor burden in BCNS patients. Cancer Prev Res; 9(10); 794-802. ©2016 AACR.

  20. Papular epidermal nevus with "skyline" basal cell layer (PENS) with extracutaneous findings.

    PubMed

    Rodríguez-Díaz, Eloy; Gonzalvo, Pablo; Colmenero, Isabel; Requena, Luis; Hernández-Martín, Angela; Torrelo, Antonio

    2013-01-01

    Papular epidermal nevus with "skyline" basal cell layer (PENS), a variant of epidermal nevus, was recently described in otherwise normal children. We describe herein a patient with multiple, typical PENS lesions associated with peculiar facies, bilateral Achilles tendon shortening, and mild psychomotor delay. The association of PENS with extracutaneous manifestations suggests the possibility of a new type of epidermal nevus syndrome, for which we propose the term PENS syndrome.

  1. Repression of Igf1 expression by Ezh2 prevents basal cell differentiation in the developing lung

    PubMed Central

    Galvis, Laura A.; Holik, Aliaksei Z.; Short, Kieran M.; Pasquet, Julie; Lun, Aaron T. L.; Blewitt, Marnie E.; Smyth, Ian M.; Ritchie, Matthew E.; Asselin-Labat, Marie-Liesse

    2015-01-01

    Epigenetic mechanisms involved in the establishment of lung epithelial cell lineage identities during development are largely unknown. Here, we explored the role of the histone methyltransferase Ezh2 during lung lineage determination. Loss of Ezh2 in the lung epithelium leads to defective lung formation and perinatal mortality. We show that Ezh2 is crucial for airway lineage specification and alveolarization. Using optical projection tomography imaging, we found that branching morphogenesis is affected in Ezh2 conditional knockout mice and the remaining bronchioles are abnormal, lacking terminally differentiated secretory club cells. Remarkably, RNA-seq analysis revealed the upregulation of basal genes in Ezh2-deficient epithelium. Three-dimensional imaging for keratin 5 further showed the unexpected presence of a layer of basal cells from the proximal airways to the distal bronchioles in E16.5 embryos. ChIP-seq analysis indicated the presence of Ezh2-mediated repressive marks on the genomic loci of some but not all basal genes, suggesting an indirect mechanism of action of Ezh2. We found that loss of Ezh2 de-represses insulin-like growth factor 1 (Igf1) expression and that modulation of IGF1 signaling ex vivo in wild-type lungs could induce basal cell differentiation. Altogether, our work reveals an unexpected role for Ezh2 in controlling basal cell fate determination in the embryonic lung endoderm, mediated in part by repression of Igf1 expression. PMID:25790853

  2. Gorlin syndrome.

    PubMed

    Devi, Basanti; Behera, Binodini; Patro, Sibasish; Pattnaik, Subhransu S; Puhan, Manas R

    2013-05-01

    Gorlin Syndrome, a rare genodermatosis, otherwise known as Nevoid basal cell carcinoma syndrome (NBCCS) is a multisystem disease affecting skin, nervous system, eyes, endocrine glands, and bones. It is characterized by multiple basal cell carcinomas, palmoplantar pits, jaw cysts, and bony deformities like kyphoscoliosis and frontal bossing. We would like to report a case of Gorlin syndrome with classical features, as this is a rare genodermatosis.

  3. Congenital Mirror Movements in Gorlin Syndrome: A Case Report With DTI and Functional MRI Features.

    PubMed

    Sag, Erdal; Gocmen, Rahsan; Yildiz, F Gokcem; Ozturk, Zeynelabidin; Temucin, Cagri; Teksam, Ozlem; Utine, Eda

    2016-03-01

    Congenital mirror movements are rare conditions that define the inability to perform unimanual movements. Gorlin syndrome, also known as nevoid basal cell carcinoma syndrome, is a genetic disorder with multiple nevi predisposing to basal cell carcinoma, odontogenic keratocysts, and skeletal malformations. Herein we report on an adolescent patient with Gorlin syndrome and coexisting congenital mirror movements. To our knowledge, this is the first patient in the literature who has both of these very rare conditions.

  4. Gorlin-goltz syndrome: a rare case.

    PubMed

    Ganguly, Satyaki; Jaykar, Kranti C; Kumar, Rajesh; Jha, Abhijeet Kumar; Banerjee, P K

    2015-01-01

    Gorlin-Goltz syndrome or nevoid basal cell carcinoma syndrome is characterized by multiple basocellular epitheliomas, keratocysts in the jaws, bifid ribs, palmar and/or plantar pits and ectopic calcifications of the falx cerebri. We describe a case of Gorlin-Goltz syndrome illustrating the importance of a thorough examination including the examination of palms and soles and detailed investigations in a patient having lesions suggestive of basal cell carcinoma and multiple naevi.

  5. Heterogeneity of basal keratinocytes: nonrandom distribution of thymidine-labeled basal cells in confluent cultures is not a technical artifact

    SciTech Connect

    Milstone, L.M.; LaVigne, J.F.

    1985-06-01

    Basal surface autoradiography of (/sup 3/H)dThd-labeled, confluent, keratinocyte cultures reveals that proliferating cells have a nonrandom, patterned distribution. Unlabeled cells, likewise, appear nonrandomly in clusters. The authors show here that failure to detect DNA synthesis in some basal cells in culture is not an artifact caused either by physical separation of the labeled nuclei from the radiographic emulsion or by a diffusion barrier that would prevent (/sup 3/H)dThd from reaching basal cells.

  6. Primary cilia in the basal cells of equine epididymis: a serendipitous finding.

    PubMed

    Arrighi, Silvana

    2013-04-01

    Occurrence of a solitary cilium was an unexpected discovery while studying the ultrastructure of epididymal epithelium in equidae. Primary cilia were detected in epididymal basal cells of all individuals of the equines studied - horses, donkey and mules - independently from age and tract of the duct, emerging from the basal cell surface and insinuating into the intercellular spaces. More rarely solitary cilia occurred also at the luminal surface of the principal cells. The ciliary apparatus was constituted by a structurally typical basal body continuous with the finger-like ciliary shaft extending from the cell surface, and an adjacent centriole oriented at right angles to the basal body. The cilium was structured as the typical primary, non-motile cilia found in many mammalian cells, having a 9+0 microtubular pattern. The basal diplosome was randomly associated with other cellular organelles including the Golgi complex, the endoplasmic reticulum, the microfilament network, the plasma membrane, vesicles and pits. Primary ciliogenesis is a new and unexpected finding in the epididymal epithelium. A monitoring role of luminal factors and extracellular liquids might be attributed to this organelle, likely acting as chemical receptor of the luminal environment, thus modulating the epithelial function by a cell-to-cell crosstalk involving the entire epithelium.

  7. BMP-driven NRF2 activation in esophageal basal cell differentiation and eosinophilic esophagitis

    PubMed Central

    Jiang, Ming; Ku, Wei-Yao; Zhou, Zhongren; Dellon, Evan S.; Falk, Gary W.; Nakagawa, Hiroshi; Wang, Mei-Lun; Liu, Kuancan; Wang, Jun; Katzka, David A.; Peters, Jeffrey H.; Lan, Xiaopeng; Que, Jianwen

    2015-01-01

    Tissue homeostasis requires balanced self-renewal and differentiation of stem/progenitor cells, especially in tissues that are constantly replenished like the esophagus. Disruption of this balance is associated with pathological conditions, including eosinophilic esophagitis (EoE), in which basal progenitor cells become hyperplastic upon proinflammatory stimulation. However, how basal cells respond to the inflammatory environment at the molecular level remains undetermined. We previously reported that the bone morphogenetic protein (BMP) signaling pathway is critical for epithelial morphogenesis in the embryonic esophagus. Here, we address how this pathway regulates tissue homeostasis and EoE development in the adult esophagus. BMP signaling was specifically activated in differentiated squamous epithelium, but not in basal progenitor cells, which express the BMP antagonist follistatin. Previous reports indicate that increased BMP activity promotes Barrett’s intestinal differentiation; however, in mice, basal progenitor cell–specific expression of constitutively active BMP promoted squamous differentiation. Moreover, BMP activation increased intracellular ROS levels, initiating an NRF2-mediated oxidative response during basal progenitor cell differentiation. In both a mouse EoE model and human biopsies, reduced squamous differentiation was associated with high levels of follistatin and disrupted BMP/NRF2 pathways. We therefore propose a model in which normal squamous differentiation of basal progenitor cells is mediated by BMP-driven NRF2 activation and basal cell hyperplasia is promoted by disruption of BMP signaling in EoE. PMID:25774506

  8. The significance of galectin-3 as a new basal cell marker in prostate cancer

    PubMed Central

    Wang, Y; Balan, V; Gao, X; Reddy, P G; Kho, D; Tait, L; Raz, A

    2013-01-01

    Prostate cancer may originate from distinct cell types, resulting in the heterogeneity of this disease. Galectin-3 (Gal-3) and androgen receptor (AR) have been reported to play important roles in the progression of prostate cancer, and their heterogeneous expressions might be associated with different cancer subtypes. Our study found that in various prostate cancer cell lines Gal-3 expression was always opposite to AR expression and other luminal cell markers but consistent with basal cell markers including glutathione S-transferase-π and Bcl-2. This expression pattern was confirmed in human prostate cancer tissues. Our results also showed that prostate cancer cells positive with basal cell markers were more aggressive. Downregulation of Gal-3 expression resulted in increased apoptotic potential and decreased metastasis potential of prostate cancer cells. Our findings demonstrate for the first time that Gal-3 may serve as a new marker for basal characteristics of prostate cancer epithelium. This study helps us to better understand the heterogeneity of prostate cancer. The clinical significance of this study lies in the application of Gal-3 to distinguish prostate cancer subtypes and improve treatment efficacy with designed personalized therapy. PMID:23907467

  9. Clonal Dynamics Reveal Two Distinct Populations of Basal Cells in Slow-Turnover Airway Epithelium

    PubMed Central

    Watson, Julie K.; Rulands, Steffen; Wilkinson, Adam C.; Wuidart, Aline; Ousset, Marielle; Van Keymeulen, Alexandra; Göttgens, Berthold; Blanpain, Cédric; Simons, Benjamin D.; Rawlins, Emma L.

    2015-01-01

    Summary Epithelial lineages have been studied at cellular resolution in multiple organs that turn over rapidly. However, many epithelia, including those of the lung, liver, pancreas, and prostate, turn over slowly and may be regulated differently. We investigated the mouse tracheal epithelial lineage at homeostasis by using long-term clonal analysis and mathematical modeling. This pseudostratified epithelium contains basal cells and secretory and multiciliated luminal cells. Our analysis revealed that basal cells are heterogeneous, comprising approximately equal numbers of multipotent stem cells and committed precursors, which persist in the basal layer for 11 days before differentiating to luminal fate. We confirmed the molecular and functional differences within the basal population by using single-cell qRT-PCR and further lineage labeling. Additionally, we show that self-renewal of short-lived secretory cells is a feature of homeostasis. We have thus revealed early luminal commitment of cells that are morphologically indistinguishable from stem cells. PMID:26119728

  10. Syndrome in question: Gorlin-Goltz syndrome*

    PubMed Central

    Ribeiro, Pauline Lyrio; de Souza Filho, João Basílio; de Abreu, Karina Demoner; Brezinscki, Marisa Simon; Pignaton, Christine Chambo

    2016-01-01

    The Nevoid Basal Cell Carcinoma Syndrome (NBCCS) is an uncommon disorder caused by a mutation in Patched, tumor suppressor gene. It is mainly characterized by numerous early onset basal cell carcinomas, odontogenic cysts of jaw and skeletal abnormalities. Due to the wide clinical spectrum, treatment and management of its modalities are not standardized and should be individualized and monitored by a multidisciplinary team. We report a typical case in a 30-year-old man with multiple basal cell carcinomas, keratotic pits of palmar creases and bifid ribs, with a history of several corrective surgeries for keratocystic odontogenic tumors, among other lesions characteristic of the syndrome. PMID:27579759

  11. Surgical management of Gorlin syndrome: a 4-decade experience using local excision technique.

    PubMed

    Griner, Devan; Sutphin, Daniel; Sargent, Larry A

    2015-04-01

    Basal cell nevus syndrome (aka Gorlin syndrome, Gorlin-Goltz syndrome, nevoid basal cell carcinoma syndrome, and fifth phacomatosis) is a rare but well-described autosomal dominant condition with variable penetrance. We present a female patient who has been successfully treated using local surgical excision and diligent skin surveillance for more than 4 decades, demonstrating that simple local incision is an efficacious and reasonable surgical alternative that may circumvent the specialization and expense of Mohs technique.

  12. Targeting EGFR and sonic hedgehog pathways for locally advanced eyelid and periocular carcinomas

    PubMed Central

    Yin, Vivian T; Merritt, Helen; Esmaeli, Bita

    2014-01-01

    For patients with metastatic or locally advanced eyelid and periocular carcinoma not amenable to surgical excision, targeted therapies have shown efficacy with better tolerability compared to cytotoxic chemotherapy. Overexpression of epithelial growth factor receptor was found in squamous cell carcinomas. Vismodegib targets the mutation in the hedgehog pathway identified in basal cell carcinoma and basal cell nevus syndrome. Targeted therapies provide a novel and potentially effective treatment alternative for patients with eyelid carcinoma not amendable for surgery, including those with metastatic, locally advanced disease, advanced age, and significant comorbidities. High cost, need for long-term treatment, and toxicity are relative limitations. PMID:25232546

  13. Isolating subpopulations of human epidermal basal cells based on polyclonal serum against trypsin-resistant CSPG4 epitopes.

    PubMed

    Gunnarsson, Anders Patrik; Christensen, Rikke; Praetorius, Jeppe; Jensen, Uffe Birk

    2017-01-15

    Chondroitin sulfate proteoglycan 4 (CSPG4) is highly expressed by human epidermal keratinocytes located at the tip of the dermal papilla where keratinocytes show characteristics of stem cells. However, since available antibodies to CSPG4 are directed against trypsin-sensitive epitopes we have been unable to study these keratinocytes isolated directly from skin samples by flow cytometry. By choosing epitopes of CSPG4 relatively close to the cell membrane we were able to generate a polyclonal antibody that successfully detects CSPG4 on keratinocytes after trypsinization. Although CSPG4-positive basal cells express higher levels of Itgβ1 the colony-forming efficiency is slightly lower than CSPG4-negative basal cells. Sorting the directly isolated keratinocytes based on Itgβ1 did not reveal differences in colony-forming efficiency between keratinocytes expressing high or low levels of Itgβ1. However, after the first passage Itgβ1 could be used to predict colony-forming efficiency whether the culture was established from CSPG4-positive or CSPG4-negative basal cell keratinocytes. Although we were unable to detect differences in the colony-forming assay, global gene expression profiling showed that CSPG4-positive basal cell keratinocytes are distinct from CSPG4-negative basal cell keratinocytes. Our study demonstrates that it is possible to generate antibodies against trypsin-resistant epitopes of CSPG4. Our study also documents a marked change in behaviour upon cell culturing and challenges the way we assess for stemness within the human epidermal basal layer.

  14. The use of vismodegib to shrink keratocystic odontogenic tumors in basal cell nevus syndrome patients

    PubMed Central

    Ally, Mina S.; Tang, Jean Y.; Joseph, Timmy; Thompson, Bobbye; Lindgren, Joselyn; Raphael, Maria Acosta; Ulerio, Grace; Chanana, Anita M.; Mackay-Wiggan, Julian M.; Bickers, David R.; Epstein, Ervin H

    2014-01-01

    Importance Keratocystic odontogenic tumors of the jaw (KCOTs) affect more than 65% of patients with basal cell nevus syndrome (BCNS). Surgery frequently causes facial disfigurement and is not always curative. Most BCNS-related and some sporadic KCOTs have malignant activation of the Hedgehog (HH) signaling pathway. Observations We examined the effect of vismodegib (an oral HH-pathway inhibitor) on KCOT size in BCNS patients enrolled in a clinical trial testing vismodegib for BCC prevention (NCT00957229), using pre and post-treatment MRIs. Four men and 2 women had pretreatment KCOTs, mean longest diameter 2.0cm (range: 0.7–3.3cm), occurring primarily in the mandible. Subjects were treated with vismodegib (150mg/day) for a mean 18 months (SD: 4.8, range: 11–24). Four subjects experienced a size reduction and 2 had no change. Vismodegib reduced the mean longest diameter of KCOTs in all subjects by 1.0cm (95% CI: 0.03, 1.94, p= 0.02) or 50% from baseline. We observed no enlargement of existing KCOTs or new KCOT development. Conclusions and relevance Vismodegib shrinks some KCOTs in BCNS patients and may offer an alternative to surgical therapy. These effects were maintained for at least 9 months after drug cessation in 1 patient. Further studies assessing long-term efficacy and optimal maintenance regimens should be performed. PMID:24623282

  15. Basal cell induced differentiation of noncancerous prostate epithelial cells (RWPE-1) by glycitein.

    PubMed

    Clubbs, Elizabeth A; Bomser, Joshua A

    2009-01-01

    Increased consumption of soy and soy isoflavones is associated with a reduced risk for prostate cancer (PCa). PCa progression is characterized, in part, by a loss of luminal/basal epithelial differentiation; however, the effects of soy isoflavones on cellular differentiation in the prostate are unknown. The present study examined the effects of the soy isoflavone glycitein on cellular differentiation in prostate epithelial cells (RWPE-1, WPE1-NB14, and RWPE-2). Glycitein significantly inhibited RWPE-1 cellular proliferation at concentrations ranging from 0.4 to 50 microM. Expression of the luminal epithelial cell marker cytokeratin 18 was not affected by glycitein treatment in the WPE1-NB14 and RWPE-2 cell lines. However, expression of cytokeratin 18 and prostate specific antigen (PSA) was decreased in the RWPE-1 cell line in response to glycitein treatment, whereas the expression of the basal epithelial cell markers p63 and cytokeratin 5 remained unchanged. These data suggest that glycitein may induce basal cell differentiation in the RWPE-1 cell line.

  16. AmotL2 disrupts apical-basal cell polarity and promotes tumour invasion.

    PubMed

    Mojallal, Mahdi; Zheng, Yujuan; Hultin, Sara; Audebert, Stéphane; van Harn, Tanja; Johnsson, Per; Lenander, Claes; Fritz, Nicolas; Mieth, Christin; Corcoran, Martin; Lembo, Frédérique; Hallström, Marja; Hartman, Johan; Mazure, Nathalie M; Weide, Thomas; Grandér, Dan; Borg, Jean-Paul; Uhlén, Per; Holmgren, Lars

    2014-08-01

    The establishment and maintenance of apical-basal cell polarity is essential for the functionality of glandular epithelia. Cell polarity is often lost in advanced tumours correlating with acquisition of invasive and malignant properties. Despite extensive knowledge regarding the formation and maintenance of polarity, the mechanisms that deregulate polarity in metastasizing cells remain to be fully characterized. Here we show that AmotL2 expression correlates with loss of tissue architecture in tumours from human breast and colon cancer patients. We further show that hypoxic stress results in activation of c-Fos-dependent expression of AmotL2 leading to loss of polarity. c-Fos/hypoxia-induced p60 AmotL2 interacts with the Crb3 and Par3 polarity complexes retaining them in large vesicles and preventing them from reaching the apical membrane. The resulting loss of polarity potentiates the response to invasive cues in vitro and in vivo in mice. These data provide a molecular mechanism how hypoxic stress deregulates cell polarity during tumour progression.

  17. Differential regulation of the Hippo pathway by adherens junctions and apical-basal cell polarity modules.

    PubMed

    Yang, Chih-Chao; Graves, Hillary K; Moya, Ivan M; Tao, Chunyao; Hamaratoglu, Fisun; Gladden, Andrew B; Halder, Georg

    2015-02-10

    Adherens junctions (AJs) and cell polarity complexes are key players in the establishment and maintenance of apical-basal cell polarity. Loss of AJs or basolateral polarity components promotes tumor formation and metastasis. Recent studies in vertebrate models show that loss of AJs or loss of the basolateral component Scribble (Scrib) cause deregulation of the Hippo tumor suppressor pathway and hyperactivation of its downstream effectors Yes-associated protein (YAP) and Transcriptional coactivator with PDZ-binding motif (TAZ). However, whether AJs and Scrib act through the same or independent mechanisms to regulate Hippo pathway activity is not known. Here, we dissect how disruption of AJs or loss of basolateral components affect the activity of the Drosophila YAP homolog Yorkie (Yki) during imaginal disc development. Surprisingly, disruption of AJs and loss of basolateral proteins produced very different effects on Yki activity. Yki activity was cell-autonomously decreased but non-cell-autonomously elevated in tissues where the AJ components E-cadherin (E-cad) or α-catenin (α-cat) were knocked down. In contrast, scrib knockdown caused a predominantly cell-autonomous activation of Yki. Moreover, disruption of AJs or basolateral proteins had different effects on cell polarity and tissue size. Simultaneous knockdown of α-cat and scrib induced both cell-autonomous and non-cell-autonomous Yki activity. In mammalian cells, knockdown of E-cad or α-cat caused nuclear accumulation and activation of YAP without overt effects on Scrib localization and vice versa. Therefore, our results indicate the existence of multiple, genetically separable inputs from AJs and cell polarity complexes into Yki/YAP regulation.

  18. Global Expression Profiling of Globose Basal Cells and Neurogenic Progression Within the Olfactory Epithelium

    PubMed Central

    Krolewski, Richard C.; Packard, Adam; Schwob, James E.

    2013-01-01

    Ongoing, lifelong neurogenesis maintains the neuronal population of the olfactory epithelium in the face of piecemeal neuronal turnover and restores it following wholesale loss. The molecular phenotypes corresponding to different stages along the progression from multipotent globose basal cell (GBC) progenitor to differentiated olfactory sensory neuron are poorly characterized. We used the transgenic expression of enhanced green fluorescent protein (eGFP) and cell surface markers to FACS-isolate ΔSox2-eGFP(+) GBCs, Neurog1-eGFP(+) GBCs and immature neurons, and ΔOMP-eGFP(+) mature neurons from normal adult mice. In addition, the latter two populations were also collected 3 weeks after olfactory bulb ablation, a lesion that results in persistently elevated neurogenesis. Global profiling of mRNA from the populations indicates that all stages of neurogenesis share a cohort of >2,100 genes that are upregulated compared to sustentacular cells. A further cohort of >1,200 genes are specifically upregulated in GBCs as compared to sustentacular cells and differentiated neurons. The increased rate of neurogenesis caused by olfactory bulbectomy had little effect on the transcriptional profile of the Neurog1-eGFP(+) population. In contrast, the abbreviated lifespan of ΔOMP-eGFP(+) neurons born in the absence of the bulb correlated with substantial differences in gene expression as compared to the mature neurons of the normal epithelium. Detailed examination of the specific genes upregulated in the different progenitor populations revealed that the chromatin modifying complex proteins LSD1 and coREST were expressed sequentially in upstream ΔSox2-eGFP(+) GBCs and Neurog1-eGFP(+) GBCs/immature neurons. The expression patterns of these proteins are dynamically regulated after activation of the epithelium by methyl bromide lesion. PMID:22847514

  19. Metastatic Basosquamous Carcinoma: Report of Two Cases and Clinicopathological Considerations.

    PubMed

    Bucci, Tommaso; Santoro, Angela; Pannone, Giuseppe; Rodriguez, Javier; Fior, Andrea; Nocini, Pier Francesco

    2016-12-01

    Basosquamous carcinoma is a rare cutaneous tumor considered by some authors as an aggressive type of basal cell carcinoma having a propensity for local recurrence and a potential risk for regional and distant metastatic spread. Herein we present 2 cases of basosquamous carcinoma of head and neck region, with metastatic spread to parotid gland (case 1) and to cervical nodes (case 2). Both patients had recurrence 2 years after initial treatment of the primary lesion (first patient: surgery; second patient: radiotherapy) and at the same time developed regional metastases. We conclude that basosquamous carcinoma must be considered as an aggressive variant of basal cell carcinoma having a great propensity to metastasize even at an early tumor stage. The clinical features, the morphologic aspects, and the treatment of this rare entity are discussed in this article.

  20. Computer vision approach to morphometric feature analysis of basal cell nuclei for evaluating malignant potentiality of oral submucous fibrosis.

    PubMed

    Muthu Rama Krishnan, M; Pal, Mousumi; Paul, Ranjan Rashmi; Chakraborty, Chandan; Chatterjee, Jyotirmoy; Ray, Ajoy K

    2012-06-01

    This research work presents a quantitative approach for analysis of histomorphometric features of the basal cell nuclei in respect to their size, shape and intensity of staining, from surface epithelium of Oral Submucous Fibrosis showing dysplasia (OSFD) to that of the Normal Oral Mucosa (NOM). For all biological activity, the basal cells of the surface epithelium form the proliferative compartment and therefore their morphometric changes will spell the intricate biological behavior pertaining to normal cellular functions as well as in premalignant and malignant status. In view of this, the changes in shape, size and intensity of staining of the nuclei in the basal cell layer of the NOM and OSFD have been studied. Geometric, Zernike moments and Fourier descriptor (FD) based as well as intensity based features are extracted for histomorphometric pattern analysis of the nuclei. All these features are statistically analyzed along with 3D visualization in order to discriminate the groups. Results showed increase in the dimensions (area and perimeter), shape parameters and decreasing mean nuclei intensity of the nuclei in OSFD in respect to NOM. Further, the selected features are fed to the Bayesian classifier to discriminate normal and OSFD. The morphometric and intensity features provide a good sensitivity of 100%, specificity of 98.53% and positive predicative accuracy of 97.35%. This comparative quantitative characterization of basal cell nuclei will be of immense help for oral onco-pathologists, researchers and clinicians to assess the biological behavior of OSFD, specially relating to their premalignant and malignant potentiality. As a future direction more extensive study involving more number of disease subjects is observed.

  1. Sonic hedgehog-expressing basal cells are general post-mitotic precursors of functional taste receptor cells

    PubMed Central

    Miura, Hirohito; Scott, Jennifer K.; Harada, Shuitsu; Barlow, Linda A.

    2014-01-01

    Background Taste buds contain ~60 elongate cells and several basal cells. Elongate cells comprise three functional taste cell types: I - glial cells, II - bitter/sweet/umami receptor cells, and III - sour detectors. Although taste cells are continuously renewed, lineage relationships among cell types are ill-defined. Basal cells have been proposed as taste bud stem cells, a subset of which express Sonic hedgehog (Shh). However, Shh+ basal cells turnover rapidly suggesting that Shh+ cells are precursors of some or all taste cell types. Results To fate map Shh-expressing cells, mice carrying ShhCreERT2 and a high (CAG-CAT-EGFP) or low (R26RLacZ) efficiency reporter allele were given tamoxifen to activate Cre in Shh+ cells. Using R26RLacZ, lineage-labeled cells occur singly within buds, supporting a post-mitotic state for Shh+ cells. Using either reporter, we show that Shh+ cells differentiate into all three taste cell types, in proportions reflecting cell type ratios in taste buds (I > II > III). Conclusions Shh+ cells are not stem cells, but are post-mitotic, immediate precursors of taste cells. Shh+ cells differentiate into each of the three taste cell types, and the choice of a specific taste cell fate is regulated to maintain the proper ratio within buds. PMID:24590958

  2. NtDRP is necessary for accurate zygotic division orientation and differentiation of basal cell lineage toward suspensor formation.

    PubMed

    Zhao, Jing; Xin, Haiping; Cao, Lingyan; Huang, Xiaorong; Shi, Ce; Zhao, Peng; Fu, Ying; Sun, Meng-Xiang

    2016-11-01

    Plant embryogenesis begins with an asymmetric division of the zygote, producing apical and basal cells with distinct cell fates. The asymmetric zygote division is thought to be critical for embryo pattern formation; however, the molecular mechanisms regulating this process, especially maintaining the accurate position and proper orientation of cell division plane, remain poorly understood. Here, we report that a dynamin-related protein in Nicotiana tabacum, NtDRP, plays a critical role in maintaining orientation of zygotic division plane. Down-regulation of NtDRP caused zygotic cell division to occur in different, incorrect orientations and resulted in disruption of suspensor formation, and even development of twin embryos. The basal cell lineage totally integrated with the apical cell lineage into an embryo-like structure, suggesting that NtDRP is essential to accurate zygotic division orientation and differentiation of basal cell lineage toward suspensor formation. We also reveal that NtDRP plays its role by modulating microtubule spatial organization and spindle orientation during early embryogenesis. Thus, we revealed that NtDRP is involved in orientation of the asymmetric zygotic division and differentiation of distinct suspensor and embryo domains, as well as subsequent embryo pattern formation.

  3. Airway basal cells of healthy smokers express an embryonic stem cell signature relevant to lung cancer.

    PubMed

    Shaykhiev, Renat; Wang, Rui; Zwick, Rachel K; Hackett, Neil R; Leung, Roland; Moore, Malcolm A S; Sima, Camelia S; Chao, Ion Wa; Downey, Robert J; Strulovici-Barel, Yael; Salit, Jacqueline; Crystal, Ronald G

    2013-09-01

    Activation of the human embryonic stem cell (hESC) signature genes has been observed in various epithelial cancers. In this study, we found that the hESC signature is selectively induced in the airway basal stem/progenitor cell population of healthy smokers (BC-S), with a pattern similar to that activated in all major types of human lung cancer. We further identified a subset of 6 BC-S hESC genes, whose coherent overexpression in lung adenocarcinoma (AdCa) was associated with reduced lung function, poorer differentiation grade, more advanced tumor stage, remarkably shorter survival, and higher frequency of TP53 mutations. BC-S shared with hESC and a considerable subset of lung carcinomas a common TP53 inactivation molecular pattern which strongly correlated with the BC-S hESC gene expression. These data provide transcriptome-based evidence that smoking-induced reprogramming of airway BC toward the hESC-like phenotype might represent a common early molecular event in the development of aggressive lung carcinomas in humans.

  4. Papular Epidermal Nevus with “Skyline” Basal Cell Layer Syndrome – Natural Course: Case Report and Literature Review

    PubMed Central

    Zahn, Carole Anouk; Itin, Peter

    2017-01-01

    Papular epidermal nevus with “skyline” basal cell layer (PENS) is a very rare type of keratinocytic nevus and is associated with extracutaneous findings such as neurological symptoms in about 50% of the cases. Therefore, it is also referred to as PENS syndrome. Clinically visible hyperkeratotic papules and plaques already appear at birth or shortly thereafter, while neurological symptoms such as epilepsy and mental retardation manifest themselves during childhood. Genetics suggests gonadal mosaicism as a possible cause for the disease. Another hypothesis is that genetic mutation can occur in a mendelian trait or through a paradominant inheritance. PMID:28203156

  5. Transcription factor p63 controls the reserve status but not the stemness of horizontal basal cells in the olfactory epithelium

    PubMed Central

    Schnittke, Nikolai; Herrick, Daniel B.; Lin, Brian; Peterson, Jesse; Coleman, Julie H.; Packard, Adam I.; Jang, Woochan; Schwob, James E.

    2015-01-01

    Adult tissue stem cells can serve two broad functions: to participate actively in the maintenance and regeneration of a tissue or to wait in reserve and participate only when activated from a dormant state. The adult olfactory epithelium, a site for ongoing, life-long, robust neurogenesis, contains both of these functional stem cell types. Globose basal cells (GBCs) act as the active stem cell population and can give rise to all the differentiated cells found in the normal tissue. Horizontal basal cells (HBCs) act as reserve stem cells and remain dormant unless activated by tissue injury. Here we show that HBC activation following injury by the olfactotoxic gas methyl bromide is coincident with the down-regulation of protein 63 (p63) but anticipates HBC proliferation. Gain- and loss-of-function studies show that this down-regulation of p63 is necessary and sufficient for HBC activation. Moreover, activated HBCs give rise to GBCs that persist for months and continue to act as bona fide stem cells by participating in tissue maintenance and regeneration over the long term. Our analysis provides mechanistic insight into the dynamics between tissue stem cell subtypes and demonstrates that p63 regulates the reserve state but not the stem cell status of HBCs. PMID:26305958

  6. Gorlin-Goltz syndrome: A series of three cases.

    PubMed

    Patankar, Amod P; Kshirsagar, Rajesh A; Dugal, Arun; Mishra, Akshay; Ram, Hari

    2014-01-01

    The Gorlin-Goltz syndrome (GGS) is also known as nevoid basal cell carcinoma syndrome. It is characterized by multiple keratocystic odontogenic tumors (KCOTs) in the jaw, multiple basal cell nevi carcinomas and skeletal abnormities. The syndrome may be diagnosed early by a dentist during the routine radiographic exams in the first decade of life, since the KCOTs are usually one of the first manifestations of the syndrome. This article reports the series of 3 cases, emphasizing its clinical and radiographic manifestations of GGS.

  7. Radiotherapy in Gorlin Syndrome: Can It Be Safe and Effective in Adult Patients?

    PubMed

    Baker, Sarah; Joseph, Kurian; Tai, Patricia

    2016-01-01

    Gorlin syndrome, also known as nevoid basal cell carcinoma syndrome, is a rare autosomal dominant disorder with multiple manifestations including early onset of cutaneous basal cell carcinomas (BCCs). Radiotherapy has traditionally been contraindicated due to reports of BCC induction. We describe here a patient treated successfully with radiotherapy with no tumour induction at 57 months of follow-up. A comprehensive literature review of radiotherapy outcomes in patients with Gorlin syndrome suggests radiotherapy may be a feasible treatment option for adult patients with treatment refractory lesions or surgical contraindication.

  8. [Gorlin syndrome: photodynamic therapy, as a useful adjunct to surgery].

    PubMed

    Huguier, V; Wierzbicka-Hainaut, E; Fray, J; Guillet, G; Dagrégorio, G

    2012-04-01

    Gorlin syndrome, also called nevoid basal cell carcinoma syndrome, is well known by dermatologists. Since its onset, 10 years ago, photodynamic therapy has found new applications and is now currently used to cure single or multiple basal cell carcinomas, with good results and without residual scars. We recall some of the basic principles of this technique, as well as its indications in Gorlin syndrome, which we illustrate with one case. Plastic surgeons must consider this relatively new technique, developed by dermatologists, as a useful adjunct to surgery in the management of Gorlin syndrome.

  9. Macrophage-specific RAM11 monoclonal antibody cross-reacts with basal cells of stratified squamous epithelia.

    PubMed

    Lis, Grzegorz J; Litwin, Jan A; Furgal-Borzych, Alicja; Zarzecka, Joanna; Cichocki, Tadeusz

    2007-01-01

    RAM11 is a mouse monoclonal anti-rabbit macrophage antibody recognizing connective tissue and vascular (atheromatous tissue) macrophages. This study demonstrates a cross-reaction of RAM11 with an unknown antigen in rabbit normal epithelial cells. Formalin-fixed, paraffin sections of the New Zealand White rabbit normal skin, oral mucosa, esophagus, small intestine and lung were immunostained with RAM11 antibody followed by goat anti-mouse Cy-3-conjugated antiglobulin. RAM11-positive immunofluorescence was observed in basal layer cells of stratified squamous epithelia (skin, oral mucosa, esophagus). No RAM11 immunostaining was found in any cells of simple (intestinal, bronchial) epithelia. These findings show that basal cells of stratified squamous keratinized and non-keratinized epithelia of the rabbit express an antigenic epitope which is common with that of macrophage antigen recognized by RAM11 monoclonal antibody.

  10. Basosquamous carcinoma with systemic metastasis in a miniature Pinscher.

    PubMed

    Shin, Sang-Kyung; Kim, Tae-Wang; Youm, So-Young; Kim, Gonhyung; Na, Ki-Jeong; Chang, Dongwoo; Ahn, Byeongwoo

    2011-11-01

    Basosquamous carcinoma (BSCC) is a rare malignancy, primarily composed of basal cells with foci of squamous differentiation. It is considered to be histologically an intermediate type between basal cell carcinoma and squamous cell carcinoma, and is known to have aggressive behaviors. BSCC occurred in a 17-year-old female minipin with a history of surgical excision for a mammary tumor. The right upper hindlimb was severely enlarged to 8 x 5 cm. Cross-section showed a homogenous white to yellow-white mass compressing the surrounding muscular tissues. The tumor metastasized also to the lungs, heart, abdominal cavity, liver and salivary gland. Microscopically, basaloid cells were crowded into solid nests or lobules separated by well-developed fibrous tissues with occasional keratinizations. Since there was no skin lesions, the tumor is assumed to be originated from the formerly present tumor in mammary gland. To our literature review, this case is the first BSCC with systemic metastasis in a dog.

  11. Basosquamous carcinoma: appearance and reality

    PubMed Central

    Anand, Rakesh L.; Collins, Damian; Chapman, Anna

    2017-01-01

    Basosquamous carcinoma (BsC) is a controversial entity and both a diagnostic and therapeutic challenge. BsC has mixed histopathological characteristics of both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). BCC and SCC display characteristic histopathology and behaviour; on the other hand, BsC is a rare tumour, which has variable morphology and displays less predictable behaviour. An early diagnosis of BsC is important due to the particularly aggressive nature of the tumour, the increased likelihood of recurrence and the potential for metastasis. Here, we present a case of BsC presenting as an extensive ulcer on the back. The case highlights the aggressive nature of the tumour and variation in appearance. It is important for all clinicians to be aware of this diagnosis so that the urgency of adequate biopsy in specialist clinics is not underestimated. PMID:28058108

  12. The effect of androgen and estrogen on secretory epithelial cells and basal cells of the rat ventral prostate after long-term castration.

    PubMed

    Kawamura, H; Kimura, M; Ichihara, I

    1993-12-01

    After long-term castration, rats were injected with cotton seed oil, testosterone- and estradiol-17 beta-cypionate (CS, TC and EC). The height of the epithelial cells of the ventral prostates from the castrated rats increased after TC and EC-injection. The secretory and basal cells formed two layers of epithelium, an inner layer near the lumen with pale nuclei and another layer with dark nuclei. These two layers could result from a reduction of secretory epithelial cells. Castration decreased the ratio of secretory cells to basal cells (S/B). TC-injection increased the ratio of S/B because of the secretory epithelial cell growth. Longer dark cells may be transient cells, appearing during the differentiation of basal cells into secretory epithelial cells. A sheet branching off from the basal lamina was observed. Androgen may stimulate the synthesis of the lamina, but whether it induces the synthesis or turnover of the basal lamina has not been established. EC increased the ventral prostatic weight and secretory epithelial cell height and induced the appearance of crystalline granules. Increase in S/B ratio may result from an increase in the secretory epithelial cells, but not from basal cell multiplication due to squamous metaplasia. The ratio is significantly correlated to the weight of the ventral prostate, but not to the secretory epithelial cell height. Its value could indicate the multiplication of secretory epithelial cells, differentiation of basal cells into epithelial cells, or both. It is probable that basal cells do not change in number, but control the size of the rat ventral prostate in response to the hormone level.

  13. HPV type 16 in conjunctival and junctional papilloma, dysplasia, and squamous cell carcinoma.

    PubMed Central

    Saegusa, M; Takano, Y; Hashimura, M; Okayasu, I; Shiga, J

    1995-01-01

    AIMS--To clarify the role of human papillomavirus (HPV) infection in the development of papilloma, dysplasia, squamous cell carcinoma, and basal cell epithelioma arising from the eyelids, including the tunica conjunctiva palpebrum (conjunctiva), its junction to epidemis of eyelid skin (junction), and eyelid skin. METHODS--Sixteen cases of papilloma, four of dysplasia, four of squamous cell carcinoma, and 12 of basal cell epithelioma were examined using formalin fixed and paraffin embedded samples. Detection of HPV-DNA was performed by PCR-RFLP and in situ hybridisation (ISH) methods. RESULTS--HPV-16 was detected in 12/16 papillomas (75%), 2/4 dysplasias (50%), and 1/4 squamous cell carcinomas (25%) but in none of the basal cell epitheliomas. No other HPV subtypes were found. ISH assay showed positive signals in only two cases of dysplasia and squamous cell carcinoma. The mean age of HPV-16 positive dysplasia and squamous cell carcinoma cases (81.7 years) was significantly higher than that of HPV-16 positive papilloma cases (p < 0.01). CONCLUSIONS--Based on the presence of HPV-16 in both benign and malignant lesions and the age distribution, it seems likely that HPV-16 alone may be incapable of causing development of conjunctival and junctional dysplasia and squamous cell carcinoma, and that any correlation between the papilloma-squamous cell carcinoma sequence and HPV infection may be due to rare events. Images PMID:8567996

  14. Epoc-1: a POU-domain gene expressed in murine epidermal basal cells and thymic stromal cells.

    PubMed

    Yukawa, K; Yasui, T; Yamamoto, A; Shiku, H; Kishimoto, T; Kikutani, H

    1993-11-15

    POU-domain transcription factors are known as developmental regulators which control organ development and cell phenotypes. In order to clarify the roles of POU-domain transcription factors in cell differentiation, we cloned a novel POU family gene, Epoc-1, from a murine thymus cDNA library. The amino acid (aa) sequence of the POU-specific domain of Epoc-1 is almost identical to those of Oct-1 and Oct-2. However, within the POU-homeodomain, 13 out of 60 aa differ between Epoc-1 and Oct-2. Recombinant Epoc-1 products were found to bind specifically to the octamer sequence. Epoc-1 was found to be expressed in skin, thymus, stomach and testis. In situ hybridization experiments and RNase protection assays indicated that Epoc-1 is expressed in the epidermal basal cells of the skin, which contain stem cells unipotent for keratinocyte differentiation and in thymic stromal elements. These results suggest that Epoc-1 might be one of the developmental regulators which controls epidermal development and thymic organogenesis.

  15. Expression of p75(NGFR), a Proliferative and Basal Cell Marker, in the Buccal Mucosa Epithelium during Re-epithelialization.

    PubMed

    Ishii, Akihiro; Muramatsu, Takashi; Lee, Jong-Min; Higa, Kazunari; Shinozaki, Naoshi; Jung, Han-Sung; Shibahara, Takahiko

    2014-08-29

    We investigated the expression of p75(NGFR), a proliferative and basal cell marker, in the mouse buccal mucosa epithelium during wound healing in order to elucidate the role of epithelial stem cells. Epithelial defects were generated in the epithelium of the buccal mucosa of 6-week-old mice using CO2 laser irradiation. BrdU was immediately administered to mice following laser irradiation. They were then sacrificed after 1, 3, 7, and 14 days. Paraffin sections were prepared and the irradiated areas were analyzed using immunohistochemistry with anti-p75(NGFR), BrdU, PCNA, and CK14 antibodies. During re-epithelialization, PCNA (-)/p75(NGFR) (+) cells extended to the wound, which then closed, whereas PCNA (+)/p75(NGFR) (+) cells were not observed at the edge of the wound. In addition, p75(NGFR) (-)/CK14 (+), which reflected the presence of post-mitotic differentiating cells, was observed in the supra-basal layers of the extended epithelium. BrdU (+)/p75(NGFR) (+), which reflected the presence of epithelial stem cells, was detected sparsely in buccal basal epithelial cells after healing, and disappeared after 7 days. These results suggest that p75(NGFR) (+) keratinocytes are localized in the basal layer, which contains oral epithelial stem cells, and retain the ability to proliferate in order to regenerate the buccal mucosal epithelium.

  16. The Ptch1DL mouse: a new model to study lambdoid craniosynostosis and basal cell nevus syndrome associated skeletal defects

    PubMed Central

    Feng, Weiguo; Choi, Irene; Clouthier, David E.; Niswander, Lee; Williams, Trevor

    2013-01-01

    Mouse models provide valuable opportunities for probing the underlying pathology of human birth defects. Employing an ENU-based screen for recessive mutations affecting craniofacial anatomy we isolated a mouse strain, Dogface-like (DL), with abnormal skull and snout morphology. Examination of the skull indicated that these mice developed craniosynostosis of the lambdoid suture. Further analysis revealed skeletal defects related to the pathology of basal cell nevus syndrome (BCNS) including defects in development of the limbs, scapula, ribcage, secondary palate, cranial base, and cranial vault. In humans, BCNS is often associated with mutations in the Hedgehog receptor PTCH1 and genetic mapping in DL identified a point mutation at a splice donor site in Ptch1. Using genetic complementation analysis we determined that DL is a hypomorphic allele of Ptch1, leading to increased Hedgehog signaling. Two aberrant transcripts are generated by the mutated Ptch1DL gene, which would be predicted to reduce significantly the levels of functional Patched1 protein. This new Ptch1 allele broadens the mouse genetic reagents available to study the Hedgehog pathway and provides a valuable means to study the underlying skeletal abnormalities in BCNS. In addition, these results strengthen the connection between elevated Hedgehog signaling and craniosynostosis. PMID:23897749

  17. Basal cell skin cancer

    MedlinePlus

    ... occur on skin that is regularly exposed to sunlight or other ultraviolet radiation. This type of skin ... skin cancer is to reduce your exposure to sunlight . Always use sunscreen: Apply sunscreen with sun protection ...

  18. Brachytherapy in Lip Carcinoma: Long-Term Results

    SciTech Connect

    Guibert, Mireille; David, Isabelle; Vergez, Sebastien; Rives, Michel; Filleron, Thomas; Bonnet, Jacques; Delannes, Martine

    2011-12-01

    Purpose: The aim of this study was to evaluate the effectiveness of low-dose-rate brachytherapy for local control and relapse-free survival in squamous cell and basal cell carcinomas of the lips. We compared two groups: one with tumors on the skin and the other with tumors on the lip. Patients and methods: All patients had been treated at Claudius Regaud Cancer Centre from 1990 to 2008 for squamous cell or basal cell carcinoma. Low-dose-rate brachytherapy was performed with iridium 192 wires according to the Paris system rules. On average, the dose delivered was 65 Gy. Results: 172 consecutive patients were included in our study; 69 had skin carcinoma (squamous cell or basal cell), and 92 had squamous cell mucosal carcinoma. The average follow-up time was 5.4 years. In the skin cancer group, there were five local recurrences and one lymph node recurrence. In the mucosal cancer group, there were ten local recurrences and five lymph node recurrences. The 8-year relapse-free survival for the entire population was 80%. The 8-year relapse-free survival was 85% for skin carcinoma 75% for mucosal carcinoma, with no significant difference between groups. The functional results were satisfactory for 99% of patients, and the cosmetic results were satisfactory for 92%. Maximal toxicity observed was Grade 2. Conclusions: Low-dose-rate brachytherapy can be used to treat lip carcinomas at Stages T1 and T2 as the only treatment with excellent results for local control and relapse-free survival. The benefits of brachytherapy are also cosmetic and functional, with 91% of patients having no side effects.

  19. Multiple keratocysts of the mandible in association with Gorlin-Goltz syndrome: A rare case report.

    PubMed

    Kulkarni, Gayithri Harish; Khaji, Shahanavaj I; Metkari, Suryakant; Kulkarni, Harish S; Kulkarni, Reshma

    2014-07-01

    Nevoid basal cell carcinoma syndrome is a syndrome with wide variety of manifestations ranging from oral lesions to skeletal deformities. It calls for due responsibility of maxillofacial surgeon to diagnose the syndrome because very often they are the first health professionals to see the patient for the treatment of keratocystic odontogenic tumor. Keratocystic odontogenic tumor has been the topic of numerous investigators, is known for its potentially aggressive behavior, significant rate of recurrences. KCOT often occurs as a solitary lesion, in some instances multiple keratocysts may occur in association with a syndrome called Gorlin-Goltz syndrome (nevoid BCC, jaw cyst bifid rib basal cell nevus syndrome). Here, we present a case of multiple keratocysts in the mandible in association with skeletal, ocular, cutaneous anomalies in the given clinical scenario, which has profound relevance in the clinical dental practice.

  20. Gastric leiomyoma in a child with Gorlin-Goltz syndrome: First pediatric case.

    PubMed

    Virgone, Calogero; Decker, Emily; Mitton, Sally G; Mansour, Sahar; Giuliani, Stefano

    2016-04-01

    Gorlin-Goltz syndrome (GGS), also known as nevoid basal cell carcinoma syndrome (MIM 109 400), is a rare genetic condition with a prevalence between 1/56 000 and 1/256 000. Clinical presentation is usually characterized by multiple basal cell carcinomas, odontogenic jaw keratocysts, palmar or plantar pitting and skeletal anomalies. It is furthermore associated with the development of various tumors beside basal cell carcinoma, among which medulloblastoma is the most frequent. Increased incidence of other mesenchymal neoplasms, however, is also well known: recently the first adult case of gastric leiomyoma in GGS was reported, and the inclusion of "fibromas and leiomyomas of other organs" in the minor criteria for the diagnosis was suggested. We report the first case of a pediatric patient with GGS who also developed a gastric leiomyoma: the present case illustrates the need for this change to the diagnostic criteria to encompass the highly variable presentations and phenotype in GGS.

  1. Secretory and basal cells of the epithelium of the tubular glands in the male Mullerian gland of the caecilian Uraeotyphlus narayani (Amphibia: Gymnophiona).

    PubMed

    George, Jancy M; Smita, Matthew; Kadalmani, Balamuthu; Girija, Ramankutty; Oommen, Oommen V; Akbarsha, Mohammad A

    2004-12-01

    Caecilians are exceptional among the vertebrates in that males retain the Mullerian duct as a functional glandular structure. The Mullerian gland on each side is formed from a large number of tubular glands connecting to a central duct, which either connects to the urogenital duct or opens directly into the cloaca. The Mullerian gland is believed to secrete a substance to be added to the sperm during ejaculation. Thus, the Mullerian gland could function as a male accessory reproductive gland. Recently, we described the male Mullerian gland of Uraeotyphlus narayani using light and transmission electron microscopy (TEM) and histochemistry. The present TEM study reports that the secretory cells of both the tubular and basal portions of the tubular glands of the male Mullerian gland of this caecilian produce secretion granules in the same manner as do other glandular epithelial cells. The secretion granules are released in the form of structured granules into the lumen of the tubular glands, and such granules are traceable to the lumen of the central duct of the Mullerian gland. This is comparable to the situation prevailing in the epididymal epithelium of several reptiles. In the secretory cells of the basal portion of the tubular glands, mitochondria are intimately associated with fabrication of the secretion granules. The structural and functional organization of the epithelium of the basal portion of the tubular glands is complicated by the presence of basal cells. This study suggests the origin of the basal cells from peritubular tissue leukocytes. The study also indicates a role for the basal cells in acquiring secretion granules from the neighboring secretory cells and processing them into lipofuscin material in the context of regression of the Mullerian gland during the period of reproductive quiescence. In these respects the basal cells match those in the epithelial lining of the epididymis of amniotes.

  2. Vismodegib induces significant clinical response in locally advanced trichoblastic carcinoma.

    PubMed

    Lepesant, P; Crinquette, M; Alkeraye, S; Mirabel, X; Dziwniel, V; Cribier, B; Mortier, L

    2015-10-01

    Patients with advanced basal cell carcinoma due to local extension or metastatic disease were previously at a therapeutic impasse. Targeted inhibition of the sonic hedgehog pathway by vismodegib represents a new therapeutic strategy. Adnexal carcinomas are rare malignant skin tumours derived from epithelial annexes. Conventional treatment of adnexal tumours is based on surgical excision. Although the radiosensitivity of adnexal carcinomas has not been established, radiotherapy could be offered alone or in combination in locally advanced or inoperable disease. Chemotherapy represents a therapeutic option in the treatment of metastatic adnexal tumours. Currently there is no effective treatment for these tumours when they become metastatic or unresectable, and treatment is palliative. Sunitinib represents a new therapeutic strategy, with efficiency described in the literature for a small number of patients. However, its efficacy is partial, and its tolerance is not always good. We report a patient with trichoblastic carcinoma, initially diagnosed as basal cell carcinoma, treated effectively with vismodegib. The remarkable response we have observed in this patient suggests an encouraging therapeutic role of vismodegib in trichoblastic carcinoma that should be evaluated in a carefully designed trial.

  3. Identification of genetic loci for basal cell nevus syndrome and inflammatory bowel disease in a single large pedigree.

    PubMed

    Panhuysen, Carolien I; Karban, Amir; Knodle Manning, Alisa; Bayless, Theodore M; Duerr, Richard H; Bailey-Wilson, Joan E; Epstein, Ervin H; Brant, Steven R

    2006-08-01

    Basal Cell Nevus Syndrome (BCNS) is an autosomal dominant disease. PTCH1 gene mutations have been found responsible in many but not all pedigrees. Inflammatory Bowel Disease (IBD) is a complex genetic disorder, disproportionate in Ashkenazim, and characterized by chronic intestinal inflammation. We revisited a large Ashkenazim pedigree, first reported in 1968, with multiple diagnoses of BCNS and IBD, and with a common genetic cause for both disorders proposed. We expanded the pedigree to four generations and performed a genome-wide linkage study for BCNS and IBD traits. Twelve members with BCNS, seven with IBD, five with both diagnoses and eight unaffected were genotyped. Both non-parametric (GENEHUNTER 2.1) and parametric (FASTLINK) linkage analyses were performed and a validation through simulation was performed. BCNS linked to chromosome 9q22 (D9S1120) just proximal to the PTCH1 gene (NPL=3.26, P=0.003; parametric two-point LOD=2.4, parametric multipoint LOD=3.7). Novel IBD linkage evidence was observed at chromosome 1p13 (D1S420, NPL 3.92, P=0.0047; parametric two-point LOD=1.9). Linkage evidence was also observed to previously reported IBD loci on 4q, (D4S2623, NPL 3.02, P=0.012; parametric two-point LOD=2.15), 10q23 (D10S1225 near DLG5, NPL 3.33, P=0.0085; parametric two-point LOD=1.3), 12 overlapping the IBD2 locus (D12S313, NPL 2.6, P=0.018; parametric two-point LOD=1.52), and 7q (D7S510 and D7S3046, NPL 4.06, P=0.0035; parametric two-point LOD=2.18). In this pedigree affected by both BCNS and IBD, the two traits and their respective candidate genetic loci segregate independently; BCNS maps to the PTCH1 gene and IBD maps to several candidate regions, mostly overlapping previously observed IBD loci.

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

    PubMed Central

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

    2017-01-01

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

  5. Activation of the basal cell carcinoma pathway in a patient with CNS HGNET-BCOR diagnosis: consequences for personalized targeted therapy

    PubMed Central

    Russo, Alexandra; Kron, Bettina; Malki, Khalifa El; Lehmann, Nadine; Wingerter, Arthur; Neu, Marie A.; Gerhold-Ay, Aslihan; Wagner, Wolfgang; Sommer, Clemens; Pietsch, Torsten; Seidmann, Larissa; Faber, Jörg

    2016-01-01

    High grade neuroepithelial tumor of the central nervous system with BCOR alteration (CNS HGNET-BCOR) is a recently described new tumor entity with a dismal prognosis. The objective of this study was to identify and validate pathways deregulated in CNS HGNET-BCOR as basis for targeted therapy approaches. We characterized the BCOR alteration in a pediatric patient with CNS HGNET-BCOR diagnosis by Sanger sequencing and demonstrated an elevated BCOR expression by qRT-PCR and western blot. By whole transcriptome sequencing and Ingenuity Pathway Analysis, we identified the activation of the Sonic Hedgehog (SHH) and of the WNT signaling pathway in two different regions of the primary tumor and of one inoculation metastasis compared to normal brain. We validated the activation of the SHH and of the WNT pathway by qRT-PCR analysis of GLI1 and AXIN2 respectively. GLI1 and AXIN2 were upregulated in the primary tumor and in two inoculation metastases compared to normal brain. Mutational analysis of SMO, PTCH1 and SUFU, three key components of the SHH pathway, revealed a Single Nucleotide Polymorphism (SNP) in PTCH1 (rs357564). We tested the effect of the GLI-inhibitor arsenic trioxide (ATO) on a short-term cell culture isolated from the metastasis. ATO was able to reduce the viability of the cells with an IC50 of 1.3 μM. In summary, these results provide functional evidence of altered BCOR expression and homogeneous coactivation of both the SHH and WNT signaling pathways, building the basis for potential novel therapeutic approaches for patients with a CNS HGNET-BCOR diagnosis. PMID:27825128

  6. Giant metastatic Merkel cell carcinoma.

    PubMed

    Bognet, Rachel; Thompson, Christina; Campanelli, Carmen

    2013-01-01

    A 68-year-old man presented with a rapidly growing, asymptomatic mass on his left mid-back for the past 3 months. The patient's medical history revealed an intentional 60-pound weight loss over the previous 2 years along with smoking approximately 1 pack of cigarettes per day. On physical examination, a fungating, 11-cm red tumor with palpable broader underlying extension (23 cm total) was present on the left mid-back with distinct red dermal nodules in a dermatomal distribution. In close proximity were two ulcerated nodules, proven histologically to be basal cell carcinomas. In the left groin was massive, fixed lymphadenopathy. A punch biopsy of the tumor was performed, which showed a dense infiltrate of small, round hyperchromatic blue cells that stained positive for CD 56 and pancytokeratin in a perinuclear dot pattern. Tumor cells were negative for CK20, TTF, CK7, and LCA.

  7. Involvement of PTCH gene in various noninflammatory cysts.

    PubMed

    Levanat, S; Pavelić, B; Crnić, I; Oresković, S; Manojlović, S

    2000-01-01

    Constitutional hemizygous inactivation of PTCH, the Shh signaling pathway gene that moderates the signal, manifests itself as nevoid basal cell carcinoma syndrome or Gorlin syndrome, a condition variably characterized by a number of developmental disorders and malformations, and by predisposition to some malignancies, basal cell carcinoma in particular. Loss of heterozygosity for the PTCH region was found several years ago in the epithelial lining of odontogenic keratocysts, the cyst type with highly increased incidence in nevoid basal cell carcinoma syndrome. This finding confirmed the expectations that the gene responsible for the syndrome would have a decisive role in the genesis of these cysts even when they are not syndrome related. Suggestive temporal distribution of Shh signaling, recently observed during tooth development, lead us to investigate PTCH association with dentigerous cysts, the other major noninflammatory cyst of odontogenic origin. We report here that PTCH appears to be inactivated in dentigerous cysts, suggesting that it is responsible for their genesis as well. More generally, if our similar observations of incomplete heterozygosity in this region for dermoid cysts can be interpreted as loss of heterozygosity, PTCH alterations may prove to be a necessary, and perhaps the initiating event, in formation and growth of various noninflammatory cysts. This would be consistent with our view that local PTCH inactivation can, under favorable circumstances, lead to persistent though not by itself truly aggressive cell proliferation.

  8. Powerful neodymium laser radiation for the treatment of facial carcinoma: 5 year follow-up data.

    PubMed

    Moskalik, Konstantin; Kozlow, Alexander; Demin, Eugeny; Boiko, Ernest

    2010-01-01

    A retrospective non-comparative follow-up study was performed to evaluate the curative efficacy of powerful neodymium laser radiation (λ = 1,060 nm) for the treatment of 2,837 patients with 3,001 histologically confirmed facial skin carcinoma lesions of stages T1-2N0M0: 2,743 primary basal cell carcinomas (BCC), 172 recurrent limited basal cell carcinomas (RLBCC), and 86 primary squamous cells carcinomas (SCC). All patients were followed-up from 5 to 11 years (mean: 8.2 years; median: 7.0 years) after treatment. The overall recurrence rate (RR) after treatment with laser radiation of facial carcinomas was 2.5% of all irradiated tumours (mean: 13.4 months; median: 11.0 months). Patients with BCC treated by radiation with the pulsed Neodymium (Nd) laser developed RR in 2.2% of cases and patients treated with the Nd:YAG laser had RR of 3.1%. Recurrences following treatment for RLBCC, and those of SCC, after irradiation with the Nd laser appeared in 4.1% and 4.6% of patients, respectively. Neodymium laser radiation is a safe and effective means of treating facial carcinomas of stages T1-2N0M0 with good cosmetic results.

  9. Gorlin-Goltz Syndrome: A Rare Case Report of a 11-Year-Old Child.

    PubMed

    Tandon, Sandeep; Chauhan, Yashwant; Sharma, Meenakshi; Jain, Manish

    2016-01-01

    Gorlin-Goltz Syndrome, also known as nevoid basal cell carcinoma syndrome (NBCCS), is an autosomal dominant trait caused due to mutations in the patched tumor suppressor gene (PTCH) gene found on the long arm of chromosome 9. The syndrome is characterized by the presence of odontogenic keratocysts (OKCs), basal cell carcinomas, and skeletal malformations. Early diagnosis of the syndrome can be done by pedodontist as OKC is one of the early manifestations of the syndrome. Early diagnosis and treatment is important for long-term prognosis of the syndrome by reducing the severity of cutaneous carcinomas and deformities due to jaw cyst. The present case describes an 11-year-old patient with some typical features of NBCCS, which were diagnosed through its oral and maxillofacial manifestations. This case emphasizes the importance of pedodontist in early recognition of the syndrome.

  10. Endocrine mucin-producing sweat gland carcinoma of the eyelid.

    PubMed

    Collinson, Anne C; Sun, Michelle T; James, Craig; Huilgol, Shyamala C; Selva, Dinesh

    2015-12-01

    An elderly woman was incidentally noted to have a nodular mass on the upper eyelid, whilst under investigation for cataracts. Punch biopsy of this presumed basal cell carcinoma revealed it to be endocrine mucin-producing sweat gland carcinoma (EMPSGC). The tumour extended to the deep dermal layer and comprised solid nests with foci of cystic and papillary change, and additional cytoplasmic and focal extracellular mucin deposits. Immunohistochemistry confirmed epithelial lineage and neuroendocrine differentiation, and adjacent tissue invasion. The tumour was excised completely with Mohs micrographic surgery with no recurrence after 8 months. EMPSGC is a low-grade sweat gland carcinoma with variable neuroendocrine differentiation, a solid, papillary, or cystic growth pattern, and a predilection for the eyelid of elderly women [Am J Surg Pathol 29:1330-1339, 2005]. There have been 54 previously documented cases of EMPSCG. We report an additional case and review the literature.

  11. Carcinoma of the hand: a 20-year experience

    SciTech Connect

    Bean, D.J.; Rees, R.S.; O'Leary, J.P.; Lynch, J.B.

    1984-08-01

    The authors reviewed their 20-year experience with cutaneous carcinoma of the hand and identified 70 cases (basal cell 23%, squamous cell 77%). The documented risk factors included solar radiation, trauma, and irradiation. Lesions were treated surgically with amputation, excision, skin graft, or flap closure, and nonsurgically with cryosurgery, curettage, 5-fluorouracil, or irradiation. The recurrence was lower with surgical treatment (3%) than with nonsurgical (33%). Regional lymphadenectomy was required in four patients for metastatic squamous cell carcinoma. Recurrence was greater (9%) and metastasis more common (38%) in patients with Marjolin's type of secondary squamous cell carcinoma than with solar-induced lesions. Cause is an important factor in outcome and should be considered in initial treatment and long-term management.

  12. Carcinoma of the hand: a 20-year experience

    SciTech Connect

    Bean, D.J.; Rees, R.S.; O'Leary, J.P.; Lynch, J.B.

    1984-08-01

    We reviewed our 20-year experience with cutaneous carcinoma of the hand and identified 70 cases (basal cell 23%, squamous cell 77%). The documented risk factors included solar radiation, trauma, and irradiation. Lesions were treated surgically with amputation, excision, skin graft, or flap closure, and nonsurgically with cryosurgery, curettage, 5-fluorouracil, or irradiation. The recurrence was lower with surgical treatment (3%) than with nonsurgical (33%). Regional lymphadenectomy was required in four patients for metastatic squamous cell carcinoma. Recurrence was greater (9%) and metastasis more common (38%) in patients with Marjolin's type of secondary squamous cell carcinoma than with solar-induced lesions. Cause is an important factor in outcome and should be considered in initial treatment and long-term management.

  13. Research Techniques Made Simple: Noninvasive Imaging Technologies for the Delineation of Basal Cell Carcinomas.

    PubMed

    Que, Syril Keena T

    2016-04-01

    In this article we discuss the development of noninvasive imaging modalities to help delineate tumor margins of basal cell carcinomas in the setting of Mohs micrographic surgery. A review of the available literature reveals that dermoscopy can help delineate basal cell carcinomas before surgical removal but that it has no benefit over clinical inspection in reducing the number of Mohs stages. In contrast, fluorescence confocal microscopy has a sensitivity of 88-96% and specificity of 89-99% for the detection of basal cell carcinomas and can potentially serve as a rapid means for tumor evaluation on ex vivo specimens. Optical coherence tomography has shown some success in the presurgical evaluation of tumor margins in vivo, before surgical excision. With ongoing developments in device portability, speed of image retrieval, and image resolution, these technologies are likely to gain traction in cutaneous oncology research and practice. It is therefore important for dermatology clinicians and researchers to understand the mechanisms, principal uses, advantages, and limitations of each device.

  14. The Lutheran/Basal Cell Adhesion Molecule Promotes Tumor Cell Migration by Modulating Integrin-mediated Cell Attachment to Laminin-511 Protein*

    PubMed Central

    Kikkawa, Yamato; Ogawa, Takaho; Sudo, Ryo; Yamada, Yuji; Katagiri, Fumihiko; Hozumi, Kentaro; Nomizu, Motoyoshi; Miner, Jeffrey H.

    2013-01-01

    Cell-matrix interactions are critical for tumor cell migration. Lutheran (Lu), also known as basal cell adhesion molecule (B-CAM), competes with integrins for binding to laminin α5, a subunit of LM-511, a major component of basement membranes. Here we show that the preferential binding of Lu/B-CAM to laminin α5 promotes tumor cell migration. The attachment of Lu/B-CAM transfectants to LM-511 was slightly weaker than that of control cells, and this was because Lu/B-CAM disturbed integrin binding to laminin α5. Lu/B-CAM induced a spindle cell shape with pseudopods and promoted cell migration on LM-511. In addition, blocking with an anti-Lu/B-CAM antibody led to a flat cell shape and inhibited migration on LM-511, similar to the effects of an activating integrin β1 antibody. We conclude that tumor cell migration on LM-511 requires that Lu/B-CAM competitively modulates cell attachment through integrins. We suggest that this competitive interaction is involved in a balance between static and migratory cell behaviors. PMID:24036115

  15. Hydroxycarbamide decreases sickle reticulocyte adhesion to resting endothelium by inhibiting endothelial lutheran/basal cell adhesion molecule (Lu/BCAM) through phosphodiesterase 4A activation.

    PubMed

    Chaar, Vicky; Laurance, Sandrine; Lapoumeroulie, Claudine; Cochet, Sylvie; De Grandis, Maria; Colin, Yves; Elion, Jacques; Le Van Kim, Caroline; El Nemer, Wassim

    2014-04-18

    Vaso-occlusive crises are the main acute complication in sickle cell disease. They are initiated by abnormal adhesion of circulating blood cells to vascular endothelium of the microcirculation. Several interactions involving an intricate network of adhesion molecules have been described between sickle red blood cells and the endothelial vascular wall. We have shown previously that young sickle reticulocytes adhere to resting endothelial cells through the interaction of α4β1 integrin with endothelial Lutheran/basal cell adhesion molecule (Lu/BCAM). In the present work, we investigated the functional impact of endothelial exposure to hydroxycarbamide (HC) on this interaction using transformed human bone marrow endothelial cells and primary human pulmonary microvascular endothelial cells. Adhesion of sickle reticulocytes to HC-treated endothelial cells was decreased despite the HC-derived increase of Lu/BCAM expression. This was associated with decreased phosphorylation of Lu/BCAM and up-regulation of the cAMP-specific phosphodiesterase 4A expression. Our study reveals a novel mechanism for HC in endothelial cells where it could modulate the function of membrane proteins through the regulation of phosphodiesterase expression and cAMP-dependent signaling pathways.

  16. An oral clinical approach to Gorlin-Goltz syndrome.

    PubMed

    Abreu, Lucas Guimaraes; Paiva, Saul Martins; Pretti, Henrique; Bastos Lages, Elizabeth Maria; Castro, Wagner Henriques

    2015-01-01

    Gorlin-Goltz syndrome is a rare hereditary disease that can have negative effects on one's quality of life. The main clinical features are multiple nevoid basal cell carcinomas, odontogenic keratocysts, congenital skeletal abnormalities, calcification of the falx cerebri, facial dysmorphism, and skin depressions (pits) on the palms and soles. Diagnosis is based on major and minor clinical and radiological criteria and can be confirmed by DNA analysis. This article describes the case of a child with Gorlin-Goltz syndrome and outlines the clinical manifestations of the disease.

  17. Gorlin-goltz syndrome.

    PubMed

    Mehta, Dn; Raval, N; Patadiya, H; Tarsariya, V

    2014-03-01

    The Gorlin-Goltz syndrome (GGS) (the nevoid basal cell carcinoma syndrome) is a rare autosomal dominant syndrome caused due to mutations in the patched gene found on chromosome arm 9 q. It shows high penetrance and variable expressivity; is characterized by basal cell carcinomas, odontogenic keratocysts, palmar and/or plantar pits and ectopic calcifications of the falx cerebri. Until date, very few cases of GGS have been reported in India. Early diagnosis and treatment as well as genetic counseling are essential for this syndrome. A rare case report of a patient with characteristic features of GGS diagnosed at a rural dental college of Gujarat, India is presented here. This case report draws attention of the valuable role of dentist in diagnosis and early management of this syndrome.

  18. Gorlin-Goltz Syndrome

    PubMed Central

    Mehta, DN; Raval, N; Patadiya, H; Tarsariya, V

    2014-01-01

    The Gorlin-Goltz syndrome (GGS) (the nevoid basal cell carcinoma syndrome) is a rare autosomal dominant syndrome caused due to mutations in the patched gene found on chromosome arm 9 q. It shows high penetrance and variable expressivity; is characterized by basal cell carcinomas, odontogenic keratocysts, palmar and/or plantar pits and ectopic calcifications of the falx cerebri. Until date, very few cases of GGS have been reported in India. Early diagnosis and treatment as well as genetic counseling are essential for this syndrome. A rare case report of a patient with characteristic features of GGS diagnosed at a rural dental college of Gujarat, India is presented here. This case report draws attention of the valuable role of dentist in diagnosis and early management of this syndrome. PMID:24761254

  19. Gorlin syndrome and bilateral ovarian fibroma

    PubMed Central

    Pirschner, Fernanda; Bastos, Pollyana Marçal; Contarato, George Luiz; Bimbato, Anna Carolina Bon Lima; Filho, Antônio Chambô

    2012-01-01

    INTRODUCTION Gorlin syndrome (GS), also known as nevoid basal cell carcinoma syndrome (NBCCS), is a rare hereditary, autosomal dominant disease that affects various systems. Its prevalence is estimated at 1/57,000 to 1/256,000 of the population. It is characterized by basal cell carcinomas, multiple odontogenic keratocysts, skeletal abnormalities and ovarian fibroma, among other disorders. PRESENTATION OF CASE To report the case of a young patient with Gorlin syndrome and bilateral ovarian fibroma. DISCUSSION A 20-year old patient with Gorlin syndrome presented with facial asymmetry, broad nasal root, dental abnormalities, micrognathism, convergent strabismus, multiple pigmented lesions on the trunk and face, pectus excavatum, kyphoscoliosis and a palpable mass in the abdomen occupying the entire pelvic region. CONCLUSION Gorlin–Goltz syndrome is a hereditary pathology that includes numerous clinical manifestations. Diagnosis is clinical and genetic confirmation is unnecessary. PMID:22771908

  20. Rippled Pattern Extraocular Sebaceous Carcinoma: A Rare Case Report with Brief Review of Literature

    PubMed Central

    K., Amita; S., Vijayshankar; S.N., Shobha

    2013-01-01

    Sebaceous carcinoma (SC) is a highly aggressive malignant adnexal tumor of sebaceous gland origin, accounting for less than 1% of cutaneous. Extraocular sebaceous carcinomas are more aggressive than their ocular counterpart with a predilection for the skin of head and neck, trunk, salivary glands and extremities in decreasing order of frequency. Rippled effect literally means “gradually spreading effect”. In histopathology it describes the unique arrangement of tumor cells in palisading pattern. The tumors in which rippled effect has been reported include adnexal tumors like trichoblastoma, trichomatricoma, trichoblastoma with sebaceous differentiation, trichoblastoma with apocrine differentiation, sebaceoma, basal cell carcinoma, fibrohistiocytic tumors, mesenchymal tumors and melanocytic tumors. We report the first case of extra ocular sebaceous carcinoma with rippled effect with emphasis on the fact that differentiation from other tumors demonstrating rippled effect is important in view of different treatment protocols. PMID:24298500

  1. CD99 Is Strongly Expressed in Basal Cells of the Normal Adult Epidermis and Some Subpopulations of Appendages: Comparison with Developing Fetal Skin

    PubMed Central

    Choi, Gawon; Roh, Jin; Park, Chan-Sik

    2016-01-01

    Background CD99 is a cell surface transmembrane glycoprotein expressed in various tissues. CD99 is differentially expressed between subpopulations of each tissue and is highly expressed in certain hematopoietic and precursor cells. However, there has been no comprehensive study of CD99 expression in normal skin. We evaluated CD99 expression in normal human skin and developing fetal skin. Methods Seventy-five adult skin samples containing normal skin and eight fetal skin samples of different gestational ages were collected. CD99 immunohistochemical staining was performed to evaluate expression pattern in adult and fetal skin samples. CD99 and CD34 expression were compared by double immunofluorescence. Results In normal adult skin, CD99 was strongly expressed in the membrane of epidermal basal keratinocytes, hair follicle bulges and outer root sheaths, and inner secretory cells of eccrine sweat glands. In fetal skin, CD99 was not expressed on the periderm at 16 weeks of gestation but was expressed in basal cells of fetal skin at around 19 weeks of gestation. CD99 expression became comparable to that of the adult skin after 20 weeks of gestation. CD99 and CD34 were co-expressed in hair follicle outer root sheaths, as seen by double immunofluorescence study. Conclusions This is the first study examining CD99 expression pattern in normal adult and fetal skin. CD99 tends to be expressed in the basal/precursor cells of epidermis and in hair follicles. These results provide a basis for future investigation on functions of CD99 in the skin and provide a novel potential target for the treatment of dermatologic lesions. PMID:27498544

  2. Re-epithelialization resulted from prostate basal cells in canine prostatic urethra may represent the ideal healing method after two-micron laser resection of the prostate.

    PubMed

    Cao, Ying; Luo, Guang-Heng; Luo, Lei; Yang, Xiu-Shu; Hu, Jian-Xin; Shi, Hua; Huang, Ping; Sun, Zhao-Lin; Xia, Shu-Jie

    2015-01-01

    The purpose of this study is to characterize the re-epithelialization of wound healing in canine prostatic urethra and to evaluate the effect of this re-epithelialization way after two-micron laser resection of the prostate (TmLRP). TmLRP and partial bladder neck mucosa were performed in 15 healthy adult male crossbred canines. Wound specimens were harvested at 3 days, and 1, 2, 3, and 4 weeks after operation, respectively. The histopathologic characteristics were observed by hematoxylin and eosin staining. The expression of cytokeratin 14 (CK14), CK5, CK18, synaptophysin (Syn), chromogranin A (CgA), uroplakin, transforming growth factor-β1 (TGF-β1 ), and TGF-β type II receptor in prostatic urethra wound were examined by immunohistochemistry and real-time polymerase chain reaction, respectively. Van Gieson staining was performed to determine the expression of collagen fibers in prostatic urethra and bladder neck would. The results showed that the re-epithelialization of the prostatic urethra resulted from the mobilization of proliferating epithelial cells from residual prostate tissue under the wound. The proliferating cells expressed CK14, CK5, but not CK18, Syn, and CgA and re-epithelialize expressed uroplakin since 3 weeks. There were enhanced TGF-β1 and TGF-β type II receptor expression in proliferating cells and regenerated cells, which correlated with specific phases of re-epithelialization. Compared with the re-epithelialization of the bladder neck, re-epithelialization of canine prostatic urethra was faster, and the expression of collagen fibers was relatively low. In conclusion, re-epithelialization in canine prostatic urethra resulted from prostate basal cells after TmLRP and this re-epithelialization way may represent the ideal healing method from anatomic repair to functional recovery after injury.

  3. Tri-modal confocal margin screening for the presence of residual squamous cell carcinoma in Mohs surgical excisions

    NASA Astrophysics Data System (ADS)

    Bar, Anna; Snavely, Nicholas; Chen, Nathaniel; Jacques, Steven; Gareau, Daniel S.

    2012-03-01

    Screening cancer in excision margins may be done with confocal microscopy to save time and cost over the gold standard histopathology (H&E). However, diagnostic accuracy requires sufficient contrast. Reflectance mode enables detection of large (>500um) nodular tumors. Enhanced nuclear contrast with acridine orange fluorescence mode additionally enables detection of tiny (<50um) basal cell carcinomas. Here, we present a novel combination of three modes to detect squamous cell carcinoma (SCC). Accurate screening of SCC requires eosin fluorescence, reflectance and acridine orange fluorescence to enable contrast for cytoplasm, collagen and nuclei respectively. Combining these signals replicates H&E for rapid clinical translation.

  4. Multimodal confocal mosaicing microscopy: an emphasis on squamous cell carcinoma

    NASA Astrophysics Data System (ADS)

    Chen, Nathaniel W.; Sensibaugh, Jordan; Ardeshiri, Ardaland; Blanchard, Adam; Jacques, Steven; Gareau, Daniel

    2010-02-01

    Our previous study reported a sensitivity of 96.6% and a specificity of 89.2% in rapidly detecting Basal Cell Carcinomas (BCCs) when nuclei were stained with acridine orange. Squamous Cell Carcinomas (SCCs) and infiltrative BCCs remain difficult to detect. More complete screening can be achieved utilizing both acridine orange for nuclei staining and eosin for cytoplasmic contrast, using two lasers to excite the two stains independently. Nuclear fluorescence is achieved by staining with acridine orange (0.5mM, 60 s), and cytoplasmic fluorescence is achieved by staining with eosin working solution (30 s). This work shows good morphological contrast of SCC and infiltrative BCC with eosin, acridine orange, and reflectance, and presents a means for rapid SCC and infiltrative BCC detection in fresh skin excisions using multimodal confocal microscopy. In addition, digital staining is shown to effectively simulate hematoxylin and eosin (H&E) histology with confocal mosaics.

  5. Sarcomatoid carcinoma arising in the congenital pigmented nevus after treatment with carbon dioxide snow freezing method.

    PubMed

    Nakajima, Rina; Komine, Mayumi; Miyamoto, Yukiko; Fusumae, Takayuki; Fujita, Yurika; Maekawa, Takeo; Murata, Satoru; Fukushima, Noriyoshi; Ohtsuki, Mamitaro

    2015-11-01

    We report a case of sarcomatoid carcinoma of the skin in a 63-year-old man who was treated with the carbon dioxide snow freezing method for a huge congenital pigmented nevus that extended from the right upper extremity to the right trunk during childhood. He had an exophytic red tumor on the nevus in the right upper extremity that grew slowly for 4 years and rapidly recently. Histological and immunohistochemical studies revealed both epithelial and mesenchymal malignancy in the same tumor. The epithelial component was composed of basaloid cells forming multiple nests with peripheral palisading, positive for keratins and BerEP4, implying basal cell carcinoma. The mesenchymal component was composed of spindle-shaped cells negative for keratins and positive for vimentin, suggesting sarcoma. This is, to our knowledge, the first report of sarcomatoid carcinoma arising in the primary pigmented nevus that had been treated by the carbon dioxide snow freezing method.

  6. Hepatocellular carcinoma.

    PubMed

    Macdonald, G A

    1999-05-01

    Hepatitis C infection is associated with the development of hepatocellular carcinoma, and progress has been made in a number of areas. Transgenic mice lines expressing the hepatitis C core protein develop hepatic steatosis, adenomas, and hepatocellular carcinomas, with no significant hepatitis or fibrosis. This implies that hepatitis C can lead directly to malignant transformation. A new lesion, irregular regeneration, has been described in chronic hepatitis C infection and is associated with a 15-fold increase in the relative risk of developing hepatocellular carcinoma. A minority of patients with hepatitis C-related hepatocellular carcinoma have intense lymphocytic infiltration of the cancer, a feature associated with a better prognosis. Several studies have confirmed the association between large cell dysplasia and hepatocellular carcinoma. However, large cell dysplasia may not be a premalignant lesion and instead may be a marker for premalignant alterations elsewhere in the liver. Oral contraceptives previously have been linked to an increased risk of hepatocellular carcinoma. A large multicenter European case-control study has shown minimal increased risk of hepatocellular carcinoma with use of steroidal contraception. Tamoxifen had shown promise in the management of advanced hepatocellular carcinoma. However, a randomized placebo-controlled study of 477 patients with hepatocellular carcinoma found no benefit from tamoxifen. In a preliminary study, however, octreotide has shown improved survival and quality of life in patients with advanced hepatocellular carcinoma. Finally, interferon treatment continues to be linked to a reduced risk of hepatocellular carcinoma in patients with hepatitis C. These studies generally are not randomized, and a randomized prospective study is required to address this issue.

  7. The prognostic significance of β-catenin, cyclin D1 and PIN1 in minor salivary gland carcinoma: β-catenin predicts overall survival.

    PubMed

    Schneider, Sven; Thurnher, Dietmar; Seemann, Rudolf; Brunner, Markus; Kadletz, Lorenz; Ghanim, Bahil; Aumayr, Klaus; Heiduschka, Gregor; Lill, Claudia

    2016-05-01

    Minor salivary gland carcinoma is a rare and heterogeneous type of cancer. Molecular prognostic and predictive markers are sparse. The aim of this study was to identify new prognostic and predictive markers in minor salivary gland carcinoma. 50 tissue samples of carcinomas of the minor salivary glands (adenoid cystic carcinoma n = 23, mucoepidermoid carcinoma n = 12, adenocarcinoma n = 10, carcinoma ex pleomorphic adenoma n = 2, salivary duct carcinoma n = 1, clear cell carcinoma n = 1, basal cell carcinoma n = 1) were immunohistochemically stained for β-catenin, cyclin D1 and PIN1. Expression patterns were analyzed and correlated to clinical outcome of 37 patients with complete clinical data. High expression of membranous β-catenin was linked to significantly better overall survival in patients with adenoid cystic carcinoma (log rank test, χ (2) = 13.3, p = .00397, Bonferroni corrected p = .024). PIN1 and cyclin D1 did not show any significant correlation to patients' clinical outcome. Expression of β-catenin in adenoid cystic carcinoma of the minor salivary glands significantly correlates with better overall survival. Hence, evaluation of β-catenin might serve as a clinical prognostic marker.

  8. Metallothionein immunolocalization in actinic skin nonmelanoma carcinomas.

    PubMed

    Borges Júnior, Paulo C; Ribeiro, Rosy I M A; Cardoso, Sérgio V; Berbet, Alceu L C; Rocha, Ademir; Espindola, Foued S; Loyola, Adriano M

    2007-06-01

    Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most frequent skin cancer. Its pathogeny is linked to genotoxic effects of actinic radiation exposure, especially to ultraviolet wavelength. Metallothionein (MT) is a low-molecular weight protein with high affinity for heavy metal. Its intracellular function has been related to heavy metals and free-radical detoxification, although many studies linked MT to protective action against actinic mutagenesis. In other way, overexpression in malignant tumors has been related to worse prognosis. We aimed to evaluate MT immunohistochemical expression in skin cancer associated to actinic radiation. Twenty-six BCC cases, 20 SCC, and 6 normal skin fragments were investigated. Immunohistochemical assay were performed by streptavidin-biotin-peroxidase technique with standard monoclonal antibody (E9). In normal skin, immunostaining was observed in basal layer of the epithelium. In the epithelium adjacent to tumors, suprabasal layer was also intensely labeled. Mean MT immunostaining indices were 18.5+21.2% for BCC and 69.1+14.4% for SCC. This difference was statistically significant. Higher MT expression in SCC as compared with BCC suggests association with tumoral aggressiveness.

  9. Childhood Carcinoma.

    PubMed

    Vargas, Sara O

    2010-09-01

    Carcinoma in children differs from that occurring in adults. It is far rarer and represents only a small fraction of all pediatric cancer diagnoses. Pediatric sarcomas were among the first tumors in which recurrent chromosomal aberrations were discovered. Once defined, these recurrent aberrations, many of them translocations, became incorporated into the pathologist's diagnostic armamentarium. In the past several years, defining chromosomal rearrangements have been identified in pediatric carcinomas as well, and this has become a new frontier in pathologic diagnosis. This article provides an overview of pediatric carcinoma as well as a detailed review of selected types of carcinoma that in particular can present diagnostic difficulty to the practicing pathologist and illustrate new and emerging concepts in pediatric carcinoma.

  10. The dog as a natural animal model for study of the mammary myoepithelial basal cell lineage and its role in mammary carcinogenesis.

    PubMed

    Rasotto, R; Goldschmidt, M H; Castagnaro, M; Carnier, P; Caliari, D; Zappulli, V

    2014-01-01

    Basal-like tumours constitute 2-18% of all human breast cancers (HBCs). These tumours have a basal myoepithelial phenotype and it has been hypothesized that they originate from either myoepithelial cells or mammary progenitor cells. They are heterogeneous in morphology, clinical presentation, outcome and response to therapy. Canine mammary carcinomas (CMCs) have epidemiological and biological similarities to HBCs, are frequently biphasic and are composed of two distinct neoplastic populations (epithelial and myoepithelial). The present study evaluates the potential of CMCs as a natural model for basal-like HBCs. Single and double immunohistochemistry was performed on serial sections of 10 normal canine mammary glands and 65 CMCs to evaluate expression of cytokeratin (CK) 8/18, CK5, CK14, α-smooth muscle actin (SMA), calponin (CALP), p63 and vimentin (VIM). The tumours were also evaluated for Ki67 and human epidermal growth factor receptor (HER)-2 expression. A hierarchical model of cell differentiation was established, similar to that for the human breast. We hypothesized that progenitor cells (CK5(+), CK14(+), p63(+) and VIM(+)) differentiate into terminally-differentiated luminal glandular (CK8/18(+)) and myoepithelial (CALP(+), SMA(+) and VIM(+)) cells via intermediary luminal glandular cells (CK5(+), CK14(+) and CK8/CK18(+)) and intermediary myoepithelial cells (CK5(+), CK14(+), p63(+), SMA(+), CALP(+) and VIM(+)). Neoplastic myoepithelial cells in canine complex carcinomas had labelling similar to that of terminally-differentiated myoepithelial cells, while those of carcinomas-and-malignant myoepitheliomas with a more aggressive biological behaviour (i.e. higher frequency of vascular/lymph node invasion and visceral metastases and higher risk of tumour-related death) were comparable with intermediary myoepithelial cells and had significantly higher Ki67 expression. The majority of CMCs examined were negative for expression of HER-2. The biphasic appearance of

  11. Distribution of lectin UEA-I in trichilemmal carcinoma, squamous cell carcinoma, and other epithelial tumors of the skin.

    PubMed

    Ko, T; Muramatsu, T; Shirai, T

    1996-06-01

    Trichilemmal carcinoma (TLC) is a cutaneous appendage tumor. In some cases, the histological distinction between TLC and squamous cell carcinoma (SCC) is difficult with hematoxylin & eosin staining. In the present study, in order to establish a simple and reliable method for distinguishing between TLC and SCC, we examined the lectin Ulex europaeus agglutinin-I (UEA-I)-binding patterns of TLC (4 cases), SCC (10 cases), malignant proliferating trichilemmal cyst (MPTC) (3 cases), Bowen's disease (4 cases), Bowen's carcinoma (4 cases), actinic keratosis (4 cases), basal cell carcinoma (8 cases), and eccrine porocarcinoma (1 case). In normal skin samples, UEA-I was strongly positive in the outer root sheath cells of the hair follicle and weakly positive in the granular layers of the epidermis. UEA-I stained the tumor cells of TLC clearly and some MPTC and Bowen's disease cells weakly. This result indicates that histochemical staining with UEA-I is a simple and useful method for distinguishing between TLC and SCC of the skin.

  12. Hepatocellular carcinoma

    SciTech Connect

    Nakashima, T.; Kojiro, M.

    1986-01-01

    With the remarkable recent diagnostic and therapeutic advances and the discovery of a possible pathogenetic role of hepatitis B virus, the study and treatment of hepatocellular carcinoma are entering a new era. Parallel developments in the pathological study of this malignancy are also to be expected. To coincide with this new era, this book presents the authors' accumulated pathomorphological knowledge of hepatocellular carcinoma. The detailed coverage is based on the examination findings of 439 cases of hepatocellular carcinoma autopsied at the authors' department in the last twenty years.

  13. Adrenocortical carcinoma

    MedlinePlus

    ... Adrenocortical carcinoma (ACC) is a cancer of the adrenal glands . The adrenal glands are two triangle-shaped glands. One gland is ... unknown. Symptoms Symptoms of increased cortisol or other adrenal gland hormones may include: Fatty, rounded hump high on ...

  14. SOX2 and PI3K Cooperate to Induce and Stabilize a Squamous-Committed Stem Cell Injury State during Lung Squamous Cell Carcinoma Pathogenesis

    PubMed Central

    Kim, Bo Ram; Van de Laar, Emily; Tarumi, Shintaro; Hasenoeder, Stefan; Wang, Dennis; Virtanen, Carl; Bandarchi, Bizhan; Pham, Nhu An; Lee, Sharon; Keshavjee, Shaf; Tsao, Ming-Sound; Moghal, Nadeem

    2016-01-01

    Although cancers are considered stem cell diseases, mechanisms involving stem cell alterations are poorly understood. Squamous cell carcinoma (SQCC) is the second most common lung cancer, and its pathogenesis appears to hinge on changes in the stem cell behavior of basal cells in the bronchial airways. Basal cells are normally quiescent and differentiate into mucociliary epithelia. Smoking triggers a hyperproliferative response resulting in progressive premalignant epithelial changes ranging from squamous metaplasia to dysplasia. These changes can regress naturally, even with chronic smoking. However, for unknown reasons, dysplasias have higher progression rates than earlier stages. We used primary human tracheobronchial basal cells to investigate how copy number gains in SOX2 and PIK3CA at 3q26-28, which co-occur in dysplasia and are observed in 94% of SQCCs, may promote progression. We find that SOX2 cooperates with PI3K signaling, which is activated by smoking, to initiate the squamous injury response in basal cells. This response involves SOX9 repression, and, accordingly, SOX2 and PI3K signaling levels are high during dysplasia, while SOX9 is not expressed. By contrast, during regeneration of mucociliary epithelia, PI3K signaling is low and basal cells transiently enter a SOX2LoSOX9Hi state, with SOX9 promoting proliferation and preventing squamous differentiation. Transient reduction in SOX2 is necessary for ciliogenesis, although SOX2 expression later rises and drives mucinous differentiation, as SOX9 levels decline. Frequent coamplification of SOX2 and PIK3CA in dysplasia may, thus, promote progression by locking basal cells in a SOX2HiSOX9Lo state with active PI3K signaling, which sustains the squamous injury response while precluding normal mucociliary differentiation. Surprisingly, we find that, although later in invasive carcinoma SOX9 is generally expressed at low levels, its expression is higher in a subset of SQCCs with less squamous identity and

  15. Familial Investigations of Childhood Cancer Predisposition

    ClinicalTrials.gov

    2017-04-12

    Acute Leukemia; Adenomatous Polyposis; Adrenocortical Carcinoma; AML; BAP1 Tumor Predisposition Syndrome; Carney Complex; Choroid Plexus Carcinoma; Constitutional Mismatch Repair Deficiency Syndrome; Diamond-Blackfan Anemia; DICER1 Syndrome; Dyskeratosis Congenita; Emberger Syndrome; Familial Acute Myeloid Leukaemia; Familial Adenomatous Polyposis; Fanconi Anemia; Familial Cancer; Familial Wilms Tumor; Familial Neuroblastoma; GIST; Hereditary Breast and Ovarian Cancer; Hereditary Paraganglioma-Pheochromocytoma Syndrome; Hodgkin Lymphoma; Juvenile Polyposis; Li-Fraumeni Syndrome; Lynch Syndrome; MDS; Melanoma Syndrome; Multiple Endocrine Neoplasia Type 1; Multiple Endocrine Neoplasia Type 2; Neuroblastoma; Neurofibromatosis Type 1; Neurofibromatosis Type II; Nevoid Basal Cell Carcinoma Syndrome; Non Hodgkin Lymphoma; Noonan Syndrome and Other Rasopathy; Overgrowth Syndromes; Pancreatic Cancer; Peutz-Jeghers Syndrome; Pheochromocytoma/Paraganglioma; PTEN Hamartoma Tumor Syndrome; Retinoblastoma; Rhabdoid Tumor Predisposition Syndrome; Rhabdomyosarcoma; Rothmund-Thomson Syndrome; Tuberous Sclerosis; Von Hippel-Lindau Disease

  16. Adhesion systems in normal breast and in invasive breast carcinoma.

    PubMed Central

    Glukhova, M.; Koteliansky, V.; Sastre, X.; Thiery, J. P.

    1995-01-01

    To analyze the role of various elements of the adhesion system in the organization of the normal mammary gland and in breast carcinoma, we have studied simultaneously the expression of integrins, E- and P-cadherins, and cytoplasmic constituents of adherens junctions. In the normal gland, E-cadherin and alpha-catenin are present in luminal epithelial and myoepithelial cells, whereas integrins are more abundant in acinar epithelial and in myoepithelial cells. We demonstrate here that, in addition, myoepithelial cells express much more vinculin and alpha-actinin than luminal epithelial cells, whereas talin and focal adhesion kinase (pp125FAK) are restricted to the basal cell layer. In invasive carcinoma, E-cadherin is usually present although often in reduced amount; different integrin subunits are expressed either by a fraction or by all of the cells or are absent. However, the cytoplasmic components of adherens junctions, such as alpha-catenin, vinculin, alpha-actinin, talin, and pp125FAK, are expressed at low levels or cannot be detected in the carcinoma cells. Our data suggest that 1), in the normal mammary gland, the myoepithelial cells, being particularly rich in integrins and cytoplasmic components of the adherens junctions, play an important role in the maintenance of tissue integrity; 2), in invasive carcinoma, cell aggregates may be maintained due to varying levels of expression of E-cadherin and/or integrins; and 3), interaction of the transmembrane adhesion molecules with the cytoskeleton in carcinoma may be impaired as revealed by reduced levels of expression of alpha-catenin, vinculin, alpha-actinin, talin, and pp125FAK. Importantly, carcinoma cells, when exposed to stroma during invasion, do not acquire the adhesion apparatus characteristic of normal cells in contact with the extracellular matrix. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:7887451

  17. From Normal Skin to Squamous Cell Carcinoma: A Quest for Novel Biomarkers

    PubMed Central

    Ghita, Mihaela; Moraru, Liliana; Voiculescu, Suzana; Greabu, Maria

    2016-01-01

    Squamous cells carcinoma (SCC) is the second most frequent of the keratinocyte-derived malignancies after basal cell carcinoma and is associated with a significant psychosocial and economic burden for both the patient himself and society. Reported risk factors for the malignant transformation of keratinocytes and development of SCC include ultraviolet light exposure, followed by chronic scarring and inflammation, exposure to chemical compounds (arsenic, insecticides, and pesticides), and immune-suppression. Despite various available treatment methods and recent advances in noninvasive or minimal invasive diagnostic techniques, the risk recurrence and metastasis are far from being negligible, even in patients with negative histological margins and lymph nodes. Analyzing normal, dysplastic, and malignant keratinocyte proteome holds special promise for novel biomarker discovery in SCC that could be used in the future for early detection, risk assessment, tumor monitoring, and development of targeted therapeutic strategies. PMID:27642215

  18. Neglected skin cancer in the elderly: a case of basosquamous cell carcinoma of the right shoulder

    PubMed Central

    Bisgaard, Erika; Tarakji, Michael; Lau, Frank; Riker, Adam

    2016-01-01

    Skin cancer remains the most common cancer worldwide, and basal cell carcinoma represents the largest portion of non-melanomatous skin cancers with over 3 million cases diagnosed annually. Locally advanced disease is frequently seen in the elderly posing clinical challenges regarding proper treatment. We report on an 86-year-old female presenting with fatigue, anemia and a large ulcerated skin lesion along the right upper back. A biopsy of the lesion revealed a basosquamous cell carcinoma. She underwent a wide local excision with complex wound reconstruction. Neglected skin cancers in the elderly can present difficult clinical scenarios. There are associated adjuvant therapies that should be considered following resection, such as local radiation therapy and other novel therapies. Newer therapies, such as with vismodegib, may also be considered. A comprehensive, multimodal approach to treatment should be considered in most cases of locally advanced, non-melanoma skin cancers. PMID:27534889

  19. Neglected skin cancer in the elderly: a case of basosquamous cell carcinoma of the right shoulder.

    PubMed

    Bisgaard, Erika; Tarakji, Michael; Lau, Frank; Riker, Adam

    2016-08-17

    Skin cancer remains the most common cancer worldwide, and basal cell carcinoma represents the largest portion of non-melanomatous skin cancers with over 3 million cases diagnosed annually. Locally advanced disease is frequently seen in the elderly posing clinical challenges regarding proper treatment.We report on an 86-year-old female presenting with fatigue, anemia and a large ulcerated skin lesion along the right upper back. A biopsy of the lesion revealed a basosquamous cell carcinoma. She underwent a wide local excision with complex wound reconstruction.Neglected skin cancers in the elderly can present difficult clinical scenarios. There are associated adjuvant therapies that should be considered following resection, such as local radiation therapy and other novel therapies. Newer therapies, such as with vismodegib, may also be considered. A comprehensive, multimodal approach to treatment should be considered in most cases of locally advanced, non-melanoma skin cancers.

  20. Histopathogenesis of carcinoma in situ of the uterine cervix*

    PubMed Central

    Wahi, P. N.; Kehar, Usha; Mali, S.; Misra, G. D.

    1962-01-01

    Cancer of the cervix is amenable to treatment provided it is diagnosed at the preinvasive stage, and it is therefore imperative to be able to identify cases of symptomless cervical cancer, which invariably presents no visible alteration in the appearance of the mucous membrane. Fortunately, this is possible by study of vaginal smears for exfoliated cells. In view of the ease with which carcinoma of the uterine cervix can be induced in mice and of its similarity to analogous lesions in women, it was thought that study of early cytological and morphological changes in cervical carcinoma of the mouse—especially at the in situ stage—might prove valuable for biological and therapeutic studies of human cervical carcinoma. This paper reports on study of the progressive epithelial changes in the mouse cervix by means of exfoliated cells in vaginal smears and histological examination of the cervical epithelium after intravaginal painting with 3,4-benzpyrene. The authors consider that basal cell hyperplasia and the early grades of dysplasia are reversible if the carcinogenic agent is withdrawn, but that the lesion is likely to be invasive and progressive once the presence of large numbers of squamoid cells indicates that the dysplastic changes involve the superficial layers. ImagesFIG. 1-5FIG. 6-10FIG. 11-15FIG. 16-20FIG. 21-25 PMID:14004393

  1. Adenoid cystic carcinoma of breast: Recent advances

    PubMed Central

    Miyai, Kosuke; Schwartz, Mary R; Divatia, Mukul K; Anton, Rose C; Park, Yong Wook; Ayala, Alberto G; Ro, Jae Y

    2014-01-01

    Adenoid cystic carcinoma (ACC) of the breast is a rare special subtype of breast cancer characterized by the presence of a dual cell population of luminal and basaloid cells arranged in specific growth patterns. Most breast cancers with triple-negative, basal-like breast features (i.e., tumors that are devoid of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression, and express basal cell markers) are generally high-grade tumors with an aggressive clinical course. Conversely, while ACCs also display a triple-negative, basal-like phenotype, they are usually low-grade and exhibit an indolent clinical behavior. Many discoveries regarding the molecular and genetic features of the ACC, including a specific chromosomal translocation t(6;9) that results in a MYB-NFIB fusion gene, have been made in recent years. This comprehensive review provides our experience with the ACC of the breast, as well as an overview of clinical, histopathological, and molecular genetic features. PMID:25516849

  2. Nasopharyngeal carcinoma

    SciTech Connect

    Ho, J.H.C.

    1985-07-01

    In this editorial comment, the author presents a review of recent achievements in the diagnosis and treatment of squamous cell carcinoma of the nasopharynx. The value of the use of CT scans for differentiating between cranial nerve involvement by recurring tumors and irradiation neuropathy, and between temporal lobe irradiation encephalopathy and other nonneoplastic neurologic disorders and meningeal metastasis is discussed. Magnetic resonance imaging is said to be superior to CT for finding soft tissue involvement or abnormalities in the brain. 13 references.

  3. Adrenocortical Carcinoma

    PubMed Central

    Kim, Alex C.; Sabolch, Aaron; Raymond, Victoria M.; Kandathil, Asha; Caoili, Elaine M.; Jolly, Shruti; Miller, Barbra S.; Giordano, Thomas J.

    2014-01-01

    Adrenocortical carcinoma (ACC) is a rare endocrine malignancy, often with an unfavorable prognosis. Here we summarize the knowledge about diagnosis, epidemiology, pathophysiology, and therapy of ACC. Over recent years, multidisciplinary clinics have formed and the first international treatment trials have been conducted. This review focuses on evidence gained from recent basic science and clinical research and provides perspectives from the experience of a large multidisciplinary clinic dedicated to the care of patients with ACC. PMID:24423978

  4. Reviewing the genetic alterations in high-risk cutaneous squamous cell carcinoma: A search for prognostic markers and therapeutic targets.

    PubMed

    Ashford, Bruce G; Clark, Jonathan; Gupta, Ruta; Iyer, N Gopalakrishna; Yu, Bing; Ranson, Marie

    2017-04-03

    Cutaneous squamous cell carcinoma (SCC) is second only in incidence to basal cell carcinoma (BCC), effecting up to 500 000 people in the United States annually. Metastasis to regional lymph nodes occurs in approximately 5% of cases and imparts significant morbidity. Standard treatment in this group involves a combination of surgery and adjuvant radiation. Currently, there are no clinically useful biomarkers of metastatic potential in primary cutaneous SCC and histological predictors can be unreliable. The high level of mutational burden in normal UV-exposed skin has hampered the search for novel drivers of invasive disease, and indeed metastatic potential. This review outlines the clinical problems in high-risk and metastatic cutaneous SCCs, reviews the known genetic events and molecular mechanisms in high-risk primary cutaneous SCC and metastasis, and identifies avenues for further investigation and potential therapy.

  5. Oral Rigosertib for Squamous Cell Carcinoma

    ClinicalTrials.gov

    2016-05-18

    Head and Neck Squamous Cell Carcinoma; Anal Squamous Cell Carcinoma; Lung Squamous Cell Carcinoma; Cervical Squamous Cell Carcinoma; Esophageal Squamous Cell Carcinoma; Skin Squamous Cell Carcinoma; Penile Squamous Cell Carcinoma

  6. GLUT-1 Expression in Cutaneous Basal and Squamous Cell Carcinomas.

    PubMed

    Abdou, Asmaa Gaber; Eldien, Marwa Mohammad Serag; Elsakka, Daliah

    2015-09-01

    Glucose uptake is a key regulating step in glucose metabolism and is mediated by facilitative glucose transporters (GLUTs), and GLUT-1 is the predominant glucose transporter in many types of human cells. Cutaneous basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) represent the most common skin cancer in Egypt. The present study aimed at evaluation of the pattern and distribution of GLUT-1 in cutaneous BCC (16 cases) and SCC (16 cases) by means of immunohistochemistry. GLUT-1 was expressed in all SCC (100%) and in 62.5% of BCC. Membranous pattern of GLUT-1 was seen in 62.5% of SCC and 31.25% of BCC. Positivity (P = .02) and percentage (P = .000) of GLUT-1 expression were in favor of SCC in comparison to BCC. The high percentage of GLUT-1 expression was associated with high grade in SCC (P = .03). The immunoreactivity for GLUT-1 was more in the periphery of malignant nests of SCC while it was more in the center of BCC nests. GLUT-1 is overexpressed in cutaneous non-melanoma skin cancer. Its expression in SCC is related to differentiation status, and its expression in BCC is intimately associated with squamous metaplastic areas.

  7. Extended immunologic and genetic lineage of mammary analogue secretory carcinoma of salivary glands.

    PubMed

    Ni, Hao; Zhang, Xue-Ping; Wang, Xiao-Tong; Xia, Qiu-Yuan; Lv, Jing-Huan; Wang, Xuan; Shi, Shan-Shan; Li, Rui; Zhou, Xiao-Jun; Rao, Qiu

    2016-12-01

    Mammary analogue secretory carcinoma (MASC) of salivary glands is a newly recognized tumor entity. To explore a more practical and convenient immunohistochemical approach to distinguish MASC from other tumors arising from salivary glands as well as to expand the immunologic and genetic lineage of MASC, we examined 17 MASCs using clinicopathologic, immunohistochemical, and molecular analyses. Eighteen cases of acinic cell carcinoma, 18 cases of adenoid cystic carcinoma, 22 cases of mucoepidermoid carcinoma, and 14 cases of basal cell adenocarcinoma were brought in for comparison. Seventeen MASCs shared similar architectures with not only intraluminal or intracellular secretion but also low-grade vesicular nuclei. In addition, they were all immunoreactive for S-100 and SOX-10, whereas only 3 of 17 demonstrated reactivity for GATA-3 and P63, and 4 of 17 were focally positive for CD117. ETV6 translocation was detected in 10 cases by fluorescence in situ hybridization, whereas intact ETV6 was noted in 2 cases. Our data proposed a combined immunohistochemical panel to distinguish MASC from other tumors arising from salivary glands and expanded the immunologic and genetic lineage of MASC.

  8. Carcinoma gallbladder.

    PubMed

    Biswas, P K

    2010-07-01

    Carcinoma gallbladder (CaGb) is a rare disease. The aetiology of CaGb is yet not known. However the risk of CaGb is increased in anomalous pancreaticobiliary duct junction (APBDJ), gall stones, xanthogranulomatus cholecystitis, calcified or porcelain gallbladder, cholelithiasis with typhoid carriers, gallbladder adenoma, red meat consumption and tobacco uses. There are protective effects of vegetables on CaGb. Most of the cases present with advanced disease. In early carcinoma of a gallbladder sign and symptoms mimic benign disease. The diagnosis is established by ultrasonography, computerized tomography and guided fine needle aspiration cytology (FNAC). Biochemical tests are of very little value in making a diagnosis. The treatment depends on the clinical stage at presentation. Surgery offers the best chance of cure. In stage T1a, laparoscopic or open cholecystectomy alone is curative, and in T1b, cholecystectomy with hepatoduodenal lymph node dissection without combined resection of an adjacent organ is required. Segment S4a+5 hepatectomy combined with extrahepatic bile duct resection (BDR) and D2 lymph node dissection is a highly recommended operation for the treatment of T2 and T3 CaGb. The dye injection method is useful in determining the appropriate extent of hepatic resection for advanced CaGb. Resurgery is required only in those cases where tumour has invaded the serosa and/ or adjacent structures when diagnosed postoperatively. Biliary bypass is required for palliation. Prognosis depends on early diagnosis and appropriate surgical excision.

  9. Immunomodulatory Effectiveness of Fish Oil and omega-3 Fatty Acids in Human Non-melanoma Skin Carcinoma Cells.

    PubMed

    Rehman, Khurram; Mohd Amin, Mohd Cairul Iqbal; Yuen, Ng Pei; Zulfakar, Mohd Hanif

    2016-01-01

    Fish oil is composed of various fatty acids among which omega-3 fatty acids are considered as most beneficial. The effects of fish oil on the activity of a topical anticancer drug, imiquimod, and the immunomodulatory activity of omega-3 fatty acids was investigated in human basal and squamous cell carcinoma cell lines. Imiquimod-fish oil mixture exhibited higher carcinoma cell growth inhibition and immunomodulatory activity than imiquimod alone, especially against squamous cell carcinoma cells. Omega-3 fatty acids exhibited growth inhibition of both basal cell and squamous cell carcinoma cell lines and modulated the immune response. Omega-3 fatty acids of fish oil serve as inducers of interleukin-10, an anti-inflammatory cytokine, and as suppressors of interleukin-6 and tumor necrosis factor-alpha, which not only depress tumor growth but also adequately control the inflammatory side effects of imiquimod. Thus, imiquimod administration with fish oil could be beneficial for inhibition of non-melanoma skin carcinoma cells but further in vivo studies are needed to understand their role in skin cancer.

  10. p40 (ΔNp63) is superior to p63 for the diagnosis of pulmonary squamous cell carcinoma.

    PubMed

    Bishop, Justin A; Teruya-Feldstein, Julie; Westra, William H; Pelosi, Giuseppe; Travis, William D; Rekhtman, Natasha

    2012-03-01

    Immunohistochemistry has recently emerged as a powerful ancillary tool for differentiating lung adenocarcinoma and squamous cell carcinoma-a distinction with important therapeutic implications. Although the most frequently recommended squamous marker p63 is extremely sensitive, it suffers from low specificity due to its reactivity in a substantial proportion of lung adenocarcinomas and other tumor types, particularly lymphomas. p40 is a relatively unknown antibody that recognizes ΔNp63-a p63 isoform suggested to be highly specific for squamous/basal cells. Here we compared the standard p63 antibody (4A4) and p40 in a series of 470 tumors from the archives of Memorial Sloan-Kettering Cancer Center and The Johns Hopkins Hospital, which included lung squamous cell carcinomas (n=81), adenocarcinomas (n=237), and large cell lymphomas (n=152). The p63 was positive in 100% of squamous cell carcinomas, 31% of adenocarcinomas, and 54% of large cell lymphomas (sensitivity 100%, specificity 60%). In contrast, although p40 was also positive in 100% of squamous cell carcinomas, only 3% of adenocarcinomas, and none of large cell lymphomas had p40 labeling (sensitivity 100%, specificity 98%). The mean percentage of p63 versus p40-immunoreactive cells in squamous cell carcinomas was equivalent (97 vs 96%, respectively, P=0.73). Rare adenocarcinomas with p40 labeling had reactivity in no more than 5% of tumor cells, whereas the mean (range) of p63-positive cells in adenocarcinomas and lymphomas was 26% (1-90%) and 48% (2-100%), respectively. In summary, p40 is equivalent to p63 in sensitivity for squamous cell carcinoma, but it is markedly superior to p63 in specificity, which eliminates a potential pitfall of misinterpreting a p63-positive adenocarcinoma or unsuspected lymphoma as squamous cell carcinoma. These findings strongly support the routine use of p40 in place of p63 for the diagnosis of pulmonary squamous cell carcinoma.

  11. Thyroid cancer - medullary carcinoma

    MedlinePlus

    Thyroid - medullary carcinoma; Cancer - thyroid (medullary carcinoma); MTC; Thyroid nodule - medullary ... in children and adults. Unlike other types of thyroid cancer, MTC is less likely to be caused by ...

  12. Liver cancer - hepatocellular carcinoma

    MedlinePlus

    Primary liver cell carcinoma; Tumor - liver; Cancer - liver; Hepatoma ... Hepatocellular carcinoma accounts for most liver cancers. This type of cancer occurs more often in men than women. It is usually diagnosed in people age 50 or ...

  13. Neurocutaneous Syndromes and Brain Tumors.

    PubMed

    Ullrich, Nicole J

    2016-10-01

    The etiology of most childhood cancer remains largely unknown, but is likely attributable to random or induced genetic aberrations in somatic tissue. However, a subset of children develops cancer in the setting of an underlying inheritable condition involving a germline genetic mutation or chromosomal aberration. The term "neurocutaneous syndrome" encompasses a group of multisystem, hereditary disorders that are associated with skin manifestations as well as central and/or peripheral nervous system lesions of variable severity. This review outlines the central nervous system tumors associated with underlying neurocutaneous disorders, including neurofibromatosis type 1, neurofibromatosis type 2, schwannomatosis, tuberous sclerosis complex, Von Hippel Lindau, and nevoid basal cell carcinoma syndrome. Recognizing the presence of an underlying syndrome is critically important to both optimizing clinical care and treatment as well as genetic counseling and monitoring of these affected patients and their families.

  14. KCOT Occurring in Bilateral Maxillary Sinus in Non-Syndromic Patient

    PubMed Central

    Newaskar, Vilas; Rajmohan, Sushmita; Dashore, Dolly

    2016-01-01

    Odontogenic Keratocyst (OKC) also termed as Keratocystic Odontogenic Tumour (KCOT) (WHO 2005) is a pathology with unique behavior because of which it is under much scrutiny and continued study. The pathology usually presents itself commonly in mandible and less commonly in maxilla. The occurrence of KCOT in maxillary sinus is reported as rare and multiple occurrences are mostly associated along with the presence of Nevoid Basal Cell Carcinoma (NBCC) syndrome. Here, we present a rare case of bilateral Maxillary OKC involving maxillary sinuses, without the presence of NBCC syndrome. An interesting feature of this case is the presence of left upper third molar in ectopic position in maxillary sinus and a vertically impacted right third molar suggesting an origin from the dental lamina. PMID:27656578

  15. One germline mutation of PTCH gene in a Chinese family with non-syndromic keratocystic odontogenic tumours.

    PubMed

    Wang, X; Lu, Y; Shen, G; Chen, W

    2011-08-01

    Keratocystic odontogenic tumours (KOCTs) are common benign cystic tumours that arise sporadically or associated with nevoid basal cell carcinoma syndrome (NBCCS). PTCH mutation can be found in sporadically or NBCCS associated KOCTs. Few PTCH mutations in families with non-syndromic KOCTs have been reported. Through PCR and gene sequence analysis, the authors discovered one missense mutation c.3277G>C in exon 19 of PTCH gene in a Chinese family with non-syndromic KOCTs. This mutation causes one highly conserved glycine residue transit to arginine on the 10th transmembrane region of PTCH protein. This work revealed that the missense mutation of PTCH is the causative and dominant gene of KOCTs in this family.

  16. Multiple non-syndromic odontogenic keratocysts in three siblings

    PubMed Central

    Nirwan, Amit; Wanjari, Sangeeta Panjab; Saikhedkar, Rashmi; Karun, Vinayak

    2013-01-01

    Occurrence of multiple cysts (MC) involving the jaw is rare. When multiple, it is usually associated with a syndrome. Occurrence of MC without syndromic association is extremely rare. Multiple odontogenic cysts mostly could be odontogenic keratocysts or dentigerous cysts. Odontogenic keratocyst shows involvement of mandible over maxilla, with peak incidence in second and third decade and it is exceedingly rare before 10 years of age. However multiple odontogenic keratocysts found in children are often reflective of nevoid basal cell carcinoma syndrome. Here is a case report which documents multiple jaw cysts involving both the jaws, in three siblings of ages 10, 13 and 17 years with negative parental history. All three reported cases were free of any systemic involvement. As odontogenic keratocyst spreads through bone marrow, destruction is more before any clinical manifestation. Therefore, early detection and intervention are essential in preventing extensive destruction. PMID:23505078

  17. Multiple non-syndromic odontogenic keratocysts in three siblings.

    PubMed

    Nirwan, Amit; Wanjari, Sangeeta Panjab; Saikhedkar, Rashmi; Karun, Vinayak

    2013-03-14

    Occurrence of multiple cysts (MC) involving the jaw is rare. When multiple, it is usually associated with a syndrome. Occurrence of MC without syndromic association is extremely rare. Multiple odontogenic cysts mostly could be odontogenic keratocysts or dentigerous cysts. Odontogenic keratocyst shows involvement of mandible over maxilla, with peak incidence in second and third decade and it is exceedingly rare before 10 years of age. However multiple odontogenic keratocysts found in children are often reflective of nevoid basal cell carcinoma syndrome. Here is a case report which documents multiple jaw cysts involving both the jaws, in three siblings of ages 10, 13 and 17 years with negative parental history. All three reported cases were free of any systemic involvement. As odontogenic keratocyst spreads through bone marrow, destruction is more before any clinical manifestation. Therefore, early detection and intervention are essential in preventing extensive destruction.

  18. Hepatocellular carcinoma.

    PubMed

    Tang, Z Y

    2000-10-01

    Hepatocellular carcinoma (HCC) has ranked second in cancer mortality in China since the 1990s and is increasing in frequency among males in many countries. Hepatitis B and C viruses, aflatoxin and algal toxin in the contaminated drinking water remain major aetiological factors and hepatitis G virus and transfusion-transmitted virus can not be excluded. A prospective randomized control trial screening for HCC in a high-risk population using alpha fetoprotein (AFP) and ultrasonography has demonstrated a decrease in HCC mortality. Rapidly progressing medical imaging has continuously contributed to the improving treatment results. Surgical resection still plays a major role in influencing prognosis of HCC. Studies on recurrence and metastasis after curative resection have become a key issue for further improvement of the surgical outcome. Regional cancer therapies are progressing rapidly, based on the advances in early diagnosis. The advantages and disadvantages of these are noted. Multimodality combination and sequential treatment has been accepted as an important approach for unresectable HCC and cytoreduction and sequential resection have attracted attention. Conformal radiotherapy has shown important potential for HCC treatment. Intra-arterial chemotherapy has been repeatedly proved effective; however, systemic chemotherapy for HCC remains disappointing. The effects of tamoxifen are questionable, whereas alpha-interferon has been shown to have significant potential, particularly in prevention of recurrence. All of these treatments have resulted in continuing improvement of HCC prognosis in some centres.

  19. Gorlin-Goltz Syndrome: A Rare Case Report of a 11-Year-Old Child

    PubMed Central

    Tandon, Sandeep; Chauhan, Yashwant; Jain, Manish

    2016-01-01

    Gorlin-Goltz Syndrome, also known as nevoid basal cell carcinoma syndrome (NBCCS), is an autosomal dominant trait caused due to mutations in the patched tumor suppressor gene (PTCH) gene found on the long arm of chromosome 9. The syndrome is characterized by the presence of odontogenic keratocysts (OKCs), basal cell carcinomas, and skeletal malformations. Early diagnosis of the syndrome can be done by pedodontist as OKC is one of the early manifestations of the syndrome. Early diagnosis and treatment is important for long-term prognosis of the syndrome by reducing the severity of cutaneous carcinomas and deformities due to jaw cyst. The present case describes an 11-year-old patient with some typical features of NBCCS, which were diagnosed through its oral and maxillofacial manifestations. This case emphasizes the importance of pedodontist in early recognition of the syndrome. How to cite this article Tandon S, Chauhan Y, Sharma M, Jain M. Gorlin-Goltz Syndrome: A Rare Case Report of a 11-Year-Old Child. Int J Clin Pediatr Dent 2016;9(3):264-268. PMID:27843260

  20. Nonfunctioning parathyroid carcinoma

    SciTech Connect

    Klink, B.K.; Karulf, R.E.; Maimon, W.N.; Peoples, J.B. )

    1991-07-01

    Parathyroid carcinoma is a rare clinical entity accounting for only 4 per cent of all cases of parathyroid neoplasia. Nonfunctioning parathyroid carcinoma is even rarer. Previously, virtually all patients with these lesions were treated for a nonspecific neck mass. However, in the present case, a preoperative diagnosis of nonfunctioning parathyroid carcinoma was made based on the technetium pertechnetate/thallium 201 subtraction scan. The authors report on the 14th case of nonfunctioning parathyroid carcinoma, a review of the literature, and guidelines for the preoperative and operative evaluation of neck masses suspected to be parathyroid carcinoma.22 references.

  1. Squamoid eccrine ductal carcinoma*

    PubMed Central

    Saraiva, Maria Isabel Ramos; Vieira, Marcella Amaral Horta Barbosa; Portocarrero, Larissa Karine Leite; Fraga, Rafael Cavanellas; Kakizaki, Priscila; Valente, Neusa Yuriko Sakai

    2016-01-01

    Squamoid eccrine ductal carcinoma is an eccrine carcinoma subtype, and only twelve cases have been reported until now. It is a rare tumor and its histopathological diagnosis is difficult. Almost half of patients are misdiagnosed as squamous cell carcinoma by the incisional biopsy. We report the thirteenth case of squamoid eccrine ductal carcinoma. Female patient, 72 years old, in the last 6 months presenting erythematous, keratotic and ulcerated papules on the nose. The incisional biopsy diagnosed squamoid eccrine ductal carcinoma. After excision, histopathology revealed positive margins. A wideningmargins surgery and grafting were performed, which again resulted in positive margins. The patient was then referred for radiotherapy. After 25 sessions, the injury reappeared. After another surgery, although the intraoperative biopsy showed free surgical margins, the product of resection revealed persistent lesion. Distinction between squamoid eccrine ductal carcinoma and squamous cell carcinoma is important because of the more aggressive nature of the first, which requires wider margins surgery to avoid recurrence. PMID:28099603

  2. Squamoid eccrine ductal carcinoma.

    PubMed

    Saraiva, Maria Isabel Ramos; Vieira, Marcella Amaral Horta Barbosa; Portocarrero, Larissa Karine Leite; Fraga, Rafael Cavanellas; Kakizaki, Priscila; Valente, Neusa Yuriko Sakai

    2016-01-01

    Squamoid eccrine ductal carcinoma is an eccrine carcinoma subtype, and only twelve cases have been reported until now. It is a rare tumor and its histopathological diagnosis is difficult. Almost half of patients are misdiagnosed as squamous cell carcinoma by the incisional biopsy. We report the thirteenth case of squamoid eccrine ductal carcinoma. Female patient, 72 years old, in the last 6 months presenting erythematous, keratotic and ulcerated papules on the nose. The incisional biopsy diagnosed squamoid eccrine ductal carcinoma. After excision, histopathology revealed positive margins. A wideningmargins surgery and grafting were performed, which again resulted in positive margins. The patient was then referred for radiotherapy. After 25 sessions, the injury reappeared. After another surgery, although the intraoperative biopsy showed free surgical margins, the product of resection revealed persistent lesion. Distinction between squamoid eccrine ductal carcinoma and squamous cell carcinoma is important because of the more aggressive nature of the first, which requires wider margins surgery to avoid recurrence.

  3. Interstitial brachytherapy of periorificial skin carcinomas of the face: A retrospective study of 97 cases

    SciTech Connect

    Rio, Emmanuel . E-mail: e-rio@nantes.fnclcc.fr; Bardet, Etienne; Ferron, Christophe; Peuvrel, Patrick; Supiot, Stephane; Campion, Loic; Beauvillain De Montreuil, Claude; Mahe, Marc Andre; Dreno, Brigitte

    2005-11-01

    Purpose: To analyze outcomes after interstitial brachytherapy of facial periorificial skin carcinomas. Patients and Methods: We performed a retrospective analysis of 97 skin carcinomas (88 basal cell carcinomas, 9 squamous cell carcinomas) of the nose, periorbital areas, and ears from 40 previously untreated patients (Group 1) and 57 patients who had undergone surgery (Group 2). The average dose was 55 Gy (range, 50-65 Gy) in Group 1 and 52 Gy (range, 50-60 Gy) in Group 2 (mean implantation times: 79 and 74 hours, respectively). We calculated survival rates and assessed functional and cosmetic results de visu. Results: Median age was 71 years (range, 17-97 years). There were 29 T1, 8 T2, 1 T3, and 2 Tx tumors in Group 1. Tumors were <2 cm in Group 2. Local control was 92.5% in Group 1 and 88% in Group 2 (median follow-up, 55 months; range, 6-132 months). Five-year disease-free survival was better in Group 1 (91%; range, 75-97) than in Group 2 (80%; range, 62-90; p = 0.23). Of the 34 patients whose results were reassessed, 8 presented with pruritus or epiphora; 1 Group 2 patient had an impaired eyelid aperture. Cosmetic results were better in Group 1 than in Group 2 with, respectively, 72% (8/11) vs. 52% (12/23) good results and 28 (3/11) vs. 43% (10/23) fair results. Conclusions: Brachytherapy provided a high level of local control and good cosmetic results for facial periorificial skin carcinomas that pose problems of surgical reconstruction. Results were better for untreated tumors than for incompletely excised tumors or tumors recurring after surgery.

  4. Radiation-induced skin carcinomas of the head and neck

    SciTech Connect

    Ron, E.; Modan, B.; Preston, D.; Alfandary, E.; Stovall, M.; Boice, J.D. Jr. )

    1991-03-01

    Radiation exposures to the scalp during childhood for tinea capitis were associated with a fourfold increase in skin cancer, primarily basal cell carcinomas, and a threefold increase in benign skin tumors. Malignant melanoma, however, was not significantly elevated. Overall, 80 neoplasms were identified from an extensive search of the pathology logs of all major hospitals in Israel and computer linkage with the national cancer registry. Radiation dose to the scalp was computed for over 10,000 persons irradiated for ringworm (mean 7 Gy), and incidence rates were contrasted with those observed in 16,000 matched comparison subjects. The relative risk of radiogenic skin cancer did not differ significantly between men or women or by time since exposure; however, risk was greatest following exposures in early childhood. After adjusting for sex, ethnic origin, and attained age, the estimated excess relative risk was 0.7 per Gy and the average excess risk over the current follow-up was 0.31/10(4) PY-Gy. The risk per Gy of radiation-induced skin cancer was intermediate between the high risk found among whites and no risk found among blacks in a similar study conducted in New York City. This finding suggests the role that subsequent exposure to uv radiation likely plays in the expression of a potential radiation-induced skin malignancy.

  5. [Radiotherapy of oropharynx carcinoma].

    PubMed

    Servagi Vernat, S; Tochet, F; Vieillevigne, L; Pointreau, Y; Maingon, P; Giraud, P

    2016-09-01

    Indication, doses, technique of radiotherapy and concomitant chemotherapy for oropharynx carcinoma are presented. The recommendations for delineation of the target volumes and organs at risk are detailed.

  6. Constitutive activation of the shh-ptc1 pathway by a patched1 mutation identified in BCC.

    PubMed

    Barnes, Elizabeth A; Heidtman, Keely J; Donoghue, Daniel J

    2005-01-27

    Mutations in the transmembrane receptor patched1 (ptc1) are responsible for the majority of basal cell carcinoma (BCC) cases. Many of these mutations, including ptc1-Q688X, result in premature truncation of the ptc1 protein. ptc1-Q688X has been identified in patients with both BCC and nevoid basal cell carcinoma syndrome, an inheritable disorder causing a predisposition to cancer susceptibility. Here we describe a mechanism by which ptc1-Q688X causes constitutive cellular signaling. Cells expressing ptc1-Q688X demonstrate an increase in cell cycle progression and induce cell transformation. The ptc1-Q688X mutant enhances Gli1 activity, a downstream reporter of sonic hedgehog (shh)-ptc1 signaling, independent of shh stimulation. In contrast to wild-type ptc1, ptc1-Q688X fails to associate with endogenous cyclin B1. Expression of nuclear-targeted cyclin B1 derivatives promotes Gli1-dependent transcription, which correlates temporally with cyclin B1-cdk1 kinase activity. Coexpression of wild-type ptc1 with a nuclear-targeted cyclin B1 derivative, mutated to mimic constitutive phosphorylation, dramatically decreases Gli1 activity. In addition, the coexpression of this constitutively nuclear cyclin B1 derivative with ptc1-Q688X substantially enhances foci formation. These studies therefore describe a molecular mechanism for the aberrant activity of ptc1-Q688X that includes the premature activation of the transcription factor Gli1.

  7. Xeroderma pigmentosum skin: an immune privilege site for tumor development.

    PubMed

    Abid, Kalthoum; El Mezni, Faouzi; Kamoun, Mohamed Ridha; Fazaa, Becima; Zermani, Rachida; Hadouchi, Chokri; Hamzaoui, Kamel

    2010-04-01

    A unique feature of the skin immune system is its proximity to cells continuously exposed to sun rays, as it is located in the interface between the body and the environment. In this study, we aimed to determine the impact of DNA damaged keratinocytes on the expression of apoptotic-related molecules, in T-cells of the inflammatory component of the tumor environment. Immunohistochemistry was performed on tissue sections derived from skin biopsies of basal cell carcinomas (BCCs) of xeroderma pigmentosum (XP) patients, non-XP patients and nevoid basal cell carcinoma syndrome (NBCCS) patients, using antibodies against B-cell lymphoma/leukemia-2 (Bcl-2), Bcl-2 associated X protein (Bax), CD95, CD3, CD8 and CD56. Our results showed significantly lower levels of expression of the antiapoptotic Bcl-2 molecule, in XP, in comparison with non-XP and NBCCS T-lymphocytes, leading to the highest Bax/Bcl-2 ratio for XP T-cells. For the CD95 receptor expression levels, there were significant differences among T-cells of the three patient subgroups as well. The higher propensity of XP T-cells to undergo apoptosis may have evolved in individual XP patients, apparently during the course of their disease, to maintain a special skin as an immune privilege site for tumors' development.

  8. Skeletal stigmata as keys to access to the composite and ancient Gorlin-Goltz syndrome history: The Egypt, Pompeii and Herculaneum lessons.

    PubMed

    Ponti, Giovanni; Pellacani, Giovanni; Tomasi, Aldo; Sammaria, Giuliano; Manfredini, Marco

    2016-09-10

    There are several genetic diseases with a wide spectrum of congenital bone stigmata in association to cutaneous and visceral benign and malignant neoplasms. Gorlin-Goltz syndrome, also named nevoid basal cell carcinoma syndrome, is an autosomal dominant systemic disease with almost complete penetrance and high intra-familial phenotypic variability, caused by germline mutations of the gene PTCH1. The syndrome is characterized by unusual skeletal changes and high predisposition to the development of multiple basal cell carcinomas, odontogenic keratocysts tumors and other visceral tumors. The Gorlin syndrome, clinically defined as distinct syndrome in 1963, existed during Dynastic Egyptian times, as revealed by a costellation of skeletal findings compatible with the syndrome in mummies dating back to 3000years ago and, most likely, in the ancient population of Pompeii. These paleogenetic and historical evidences, together with the clinical and biomolecular modern evidences, confirm the quite benign behavior of the syndrome and the critical value of the multiple and synchronous skeletal anomalies in the recognition of these rare and complex genetic disease.

  9. Gorlin-Goltz syndrome in twin brothers: an unusual occurrence with review of the literature.

    PubMed

    Anchlia, Sonal; Vyas, Siddharth; Bahl, Sumit; Nagavadiya, Vipul

    2015-08-21

    Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome, is caused by genetic alteration produced by a mutation in the 'patched' tumour suppressor gene, and is inherited in a dominant autosomal way. Although sporadic cases have been found, this syndrome has rarely been reported in twin patients. The syndrome is characterised by a wide range of developmental abnormalities and has a predisposition to neoplasms such as multiple pigmented basal cell carcinomas and keratocysts in jaws; it also has other features such as palmar and/or plantar pits and calcification of falx cerebri. Owing to the critical oral and maxillofacial manifestations of this syndrome, it is important to recognise its characteristics in order to make a diagnosis, and to plot early preventive treatment and establish the right genetic evidence. Based on a combination of imaging, clinical and histopathological findings, we present a diagnosed case of Gorlin-Goltz syndrome in 18-year-old twin brothers. All cystic lesions were enucleated and 1 year follow-up showed no recurrence.

  10. Multiple tumor types including leiomyoma and Wilms tumor in a patient with Gorlin syndrome due to 9q22.3 microdeletion encompassing the PTCH1 and FANC-C loci.

    PubMed

    Garavelli, Livia; Piemontese, Maria Rosaria; Cavazza, Alberto; Rosato, Simonetta; Wischmeijer, Anita; Gelmini, Chiara; Albertini, Enrico; Albertini, Giuseppe; Forzano, Francesca; Franchi, Fabrizia; Carella, Massimo; Zelante, Leopoldo; Superti-Furga, Andrea

    2013-11-01

    Gorlin syndrome or nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant condition mainly characterized by the development of mandibular keratocysts which often have their onset during the second decade of life and/or multiple basal cell carcinoma (BCC) normally arising during the third decade. Cardiac and ovarian fibromas can be found. Patients with NBCCS develop the childhood brain malignancy medulloblastoma (now often called primitive neuro-ectodermal tumor [PNET]) in 5% of cases. The risk of other malignant neoplasms is not clearly increased, although lymphoma and meningioma can occur in this condition. Wilms tumor has been mentioned in the literature four times. We describe a patient with a 10.9 Mb 9q22.3 deletion spanning 9q22.2 through 9q31.1 that includes the entire codifying sequence of the gene PTCH1, with Wilms tumor, multiple neoplasms (lung, liver, mesenteric, gastric and renal leiomyomas, lung typical carcinoid tumor, adenomatoid tumor of the pleura) and a severe clinical presentation. We propose including leiomyomas among minor criteria of the NBCCS.

  11. Gorlin-Goltz syndrome--a medical condition requiring a multidisciplinary approach.

    PubMed

    Kiwilsza, Małgorzata; Sporniak-Tutak, Katarzyna

    2012-09-01

    Gorlin-Goltz syndrome is a rare genetic condition showing a variable expressiveness. It is inherited in a dominant autosomal way. The strongest characteristic of the disease includes multiple basal cell carcinomas, jaw cysts, palmar and plantar pits, skeletal abnormalities and other developmental defects. Owing to the fact that the condition tends to be a multisystemic disorder, familiarity of various medical specialists with its manifestations may reduce the time necessary for providing a diagnosis. It will also enable them to apply adequate methods of treatment and secondary prevention. In this study, we present symptoms of the disease, its diagnostic methods and currently used treatments. We searched 2 scientific databases: Medline (EBSCO) and Science Direct, for the years 1996 to 2011. In our search of abstracts, key words included nevoid basal cell carcinoma syndrome and Gorlin-Goltz syndrome. We examined 287 studies from Medline and 80 from Science Direct, all published in English. Finally, we decided to use 60 papers, including clinical cases and literature reviews. Patients with Gorlin-Goltz syndrome need particular multidisciplinary medical care. Knowledge of multiple and difficult to diagnose symptoms of the syndrome among professionals of various medical specialties is crucial. The consequences of the disease pose a threat to the health and life of patients. Therefore, an early diagnosis creates an opportunity for effective prevention and treatment of the disorder. Prevention is better than cure.

  12. Sporadic medulloblastomas contain PTCH mutations.

    PubMed

    Raffel, C; Jenkins, R B; Frederick, L; Hebrink, D; Alderete, B; Fults, D W; James, C D

    1997-03-01

    Nevoid basal cell carcinoma syndrome (NBCCS), or Gorlin's syndrome, is an autosomal dominant disorder that predisposes to developmental defects and various forms of cancer. PTCH was recently proposed as a candidate gene for NBCCS due to its frequent mutation in basal cell carcinomas, the cancer most often associated with this syndrome. Another NBCCS-associated cancer is medulloblastoma, a common central nervous system tumor in children. Most medulloblastomas, however, occur without indication of an inherited predisposition. We have examined 24 sporadic medulloblastomas for loss of heterozygosity (LOH) at loci flanking as well as within PTCH. In cases with LOH, single-strand conformational polymorphism and sequencing analysis were performed to determine the status of the remaining PTCH allele. Microsatellite analysis indicated LOH of PTCH in 5 of 24 tumors, and in three of these cases a mutation of the remaining allele was identified. Two of the mutations were duplication insertions, and the third consisted of a single base deletion. It is interesting that all three mutations occur in exon 17 of the PTCH gene. These data suggest that inactivation of PTCH function is involved in the development of at least a subset of sporadic medulloblastomas.

  13. Analysis of the PTCH coding region in human rhabdomyosarcoma.

    PubMed

    Calzada-Wack, Julia; Schnitzbauer, Udo; Walch, Axel; Wurster, Karl-Heinz; Kappler, Roland; Nathrath, Michaela; Hahn, Heidi

    2002-09-01

    Inherited mutations of the human tumor suppressor gene Patched (PTCH) lead to an autosomal dominant disorder known as Nevoid Basal Cell Carcinoma Syndrome (NBCCS). The syndrome is characterized by a combination of developmental abnormalities and a predisposition to tumor formation. Tumors in patients with NBCCS include basal cell carcinoma, medulloblastoma, fibroma and rhabdomyosarcoma (RMS). RMS are also present in 15 % of mice haplodeficient for Ptch. To investigate whether mutations in PTCH are a general feature in rhabdomyosarcomagenesis we sequenced the protein-coding region in sporadic human cases of these tumors. For this purpose we first determined the distribution and frequency of polymorphisms in 23 exons of PTCH in 48 healthy caucasians. Ten new polymorphisms were identified (IVS11 + 15-17del AAA; IVS14 + 25T>C; 2485G>A; IVS15 + 9G>C; IVS17 + 21A>G; 3033T>C; 3149T>C; 3387T>C; 3617G>A; 4080C>T). Next, the PTCH coding region in 14 RMS was sequenced. Whereas one case with LOH at the PTCH locus was detected, none of the cases showed nonsense or missense mutations in the coding region of PTCH. These data do not support the existence of frequent mutations in the protein-coding region of PTCH in RMS.

  14. Gorlin–Goltz syndrome: A case series of 5 patients in North Indian population with comparative analysis of literature

    PubMed Central

    Lata, Jeevan; Verma, Nitin; Kaur, Amandeep

    2015-01-01

    Objective: In Indian scenario, Gorlin–Goltz syndrome (nevoid basal cell carcinoma syndrome [NBCCS]) has been rarely reported. The clinical, radiological, and histopathological findings and major and minor criteria in five cases of NBCCS in North Indian population have been presented along with a discussion of the role of gene mutation analysis in early diagnosis of syndrome. Materials and Methods: The diagnostic findings of Gorlin–Goltz syndrome in 5 patients were compared with other reports in Indian population and with reports of this syndrome in other parts of the world. Results: The most common features seen were keratocystic odontogenic tumors (100%), calcifications of falx cerebri (60%), palmar-plantar pits (80%), rib anomalies (80%), macroencephaly (60%), ocular hypertelorism (80%), and frontal bossing (60%) in our series. Retained deciduous teeth seen in 80% patients whose association has not been previously reported has been presented. None of our patients had basal cell carcinoma, syndactyly or polydactyly, pectus deformity, bridging of sella turcica, pigmented nevi, or family history of this syndrome in contrast to such findings in other Indian patients. Medulloblastoma has not been reported in any Indian patient so far compared to this finding in other studies conducted worldwide. Conclusions: Combining the features of 48 patients in 38 cases of NBCCS being published in Indian literature with five cases of our series and on comparison with other studies in the world, a wide disparity in different ethnic groups and a wide variation in presentation of syndrome within the same population is suggested. PMID:26604574

  15. [Breast carcinoma in men].

    PubMed

    Zigić, B; Balvanović, D; Rac, S; Bilbija, S

    1989-01-01

    The authors describe 8 cases of carcinoma of the male breast treated at the Clinic of Surgery, Clinical Medical Center Banja Luka in the period 1968-1988. In their discussion, the authors review contemporary findings concerning the genesis, evolution and treatment of this carcinoma.

  16. Glyoxalase I is differentially expressed in cutaneous neoplasms and contributes to the progression of squamous cell carcinoma.

    PubMed

    Zou, Xiao-Yan; Ding, Dong; Zhan, Na; Liu, Xiao-Ming; Pan, Cheng; Xia, Yu-Min

    2015-02-01

    Glyoxalase I (GLO1) is a methylglyoxal detoxification enzyme being implicated in the progression of multiple malignancies. However, currently, the role of GLO1 in human nonmelanoma skin tumors remains unclear. To explore the expression of GLO1 in cutaneous neoplasms and its role in the pathogenesis of skin cancers, we determined the GLO1 expression in multiple subtypes of cutaneous neoplasms and cell lines harboring different tumorigenicity. Also, the GLO1 siRNA transfection was performed in squamous cell carcinoma (SCC)-13 cells or SCC in the xenograft model. The results show that GLO1 was overexpressed by SCC, basal cell carcinoma, and verrucous carcinoma but weakly expressed by several benign neoplasms. Human papilloma virus 16 E6/E7-transfected keratinocytes expressed more GLO1 than did normal keratinocytes, although both of them had lower levels of GLO1 than SCC-13 cells. Moreover, the knockdown of GLO1 by siRNA was related to enhanced apoptosis of SCC-13 cells in the presence of tumor necrosis factor-related apoptosis-inducing ligand and inhibited cell invasion and migration, which was mirrored by the suppressed growth of SCC xenografts in mice. Finally, the GLO1 regulation of SCC-13 cells might be relevant to methylglyoxal-induced p53 translocation. Therefore, GLO1 is prevailingly expressed in cutaneous neoplasms of higher malignancy and contributes to the progression of SCC.

  17. The hereditary renal cell carcinoma 3;8 translocation fuses FHIT to a patched-related gene, TRC8.

    PubMed

    Gemmill, R M; West, J D; Boldog, F; Tanaka, N; Robinson, L J; Smith, D I; Li, F; Drabkin, H A

    1998-08-04

    The 3;8 chromosomal translocation, t(3;8)(p14.2;q24.1), was described in a family with classical features of hereditary renal cell carcinoma. Previous studies demonstrated that the 3p14.2 breakpoint interrupts the fragile histidine triad gene (FHIT) in its 5' noncoding region. However, evidence that FHIT is causally related to renal or other malignancies is controversial. We now show that the 8q24.1 breakpoint region encodes a 664-aa multiple membrane spanning protein, TRC8, with similarity to the hereditary basal cell carcinoma/segment polarity gene, patched. This similarity involves two regions of patched, the putative sterol-sensing domain and the second extracellular loop that participates in the binding of sonic hedgehog. In the 3;8 translocation, TRC8 is fused to FHIT and is disrupted within the sterol-sensing domain. In contrast, the FHIT coding region is maintained and expressed. In a series of sporadic renal carcinomas, an acquired TRC8 mutation was identified. By analogy to patched, TRC8 might function as a signaling receptor and other pathway members, to be defined, are mutation candidates in malignant diseases involving the kidney and thyroid.

  18. Mediator subunits MED1 and MED24 cooperatively contribute to pubertal mammary gland development and growth of breast carcinoma cells.

    PubMed

    Hasegawa, Natsumi; Sumitomo, Akiko; Fujita, Azusa; Aritome, Nami; Mizuta, Shumpei; Matsui, Keiji; Ishino, Ruri; Inoue, Kana; Urahama, Norinaga; Nose, Junko; Mukohara, Toru; Kamoshida, Shingo; Roeder, Robert G; Ito, Mitsuhiro

    2012-04-01

    The Mediator subunit MED1 is essential for mammary gland development and lactation, whose contribution through direct interaction with estrogen receptors (ERs) is restricted to involvement in pubertal mammary gland development and luminal cell differentiation. Here, we provide evidence that the MED24-containing submodule of Mediator functionally communicates specifically with MED1 in pubertal mammary gland development. Mammary glands from MED1/MED24 double heterozygous knockout mice showed profound retardation in ductal branching during puberty, while single haploinsufficient glands developed normally. DNA synthesis of both luminal and basal cells were impaired in double mutant mice, and the expression of ER-targeted genes encoding E2F1 and cyclin D1, which promote progression through the G(1)/S phase of the cell cycle, was attenuated. Luciferase reporter assays employing double mutant mouse embryonic fibroblasts showed selective impairment in ER functions. Various breast carcinoma cell lines expressed abundant amounts of MED1, MED24, and MED30, and attenuated expression of MED1 and MED24 in breast carcinoma cells led to attenuated DNA synthesis and growth. These results indicate functional communications between the MED1 subunit and the MED24-containing submodule that mediate estrogen receptor functions and growth of both normal mammary epithelial cells and breast carcinoma cells.

  19. Concomitant cetuximab and radiation therapy: A possible promising strategy for locally advanced inoperable non-melanoma skin carcinomas

    PubMed Central

    DELLA VITTORIA SCARPATI, GIUSEPPINA; PERRI, FRANCESCO; PISCONTI, SALVATORE; COSTA, GIUSEPPE; RICCIARDIELLO, FILIPPO; DEL PRETE, SALVATORE; NAPOLITANO, ALBERTO; CARRATURO, MARCO; MAZZONE, SALVATORE; ADDEO, RAFFAELE

    2016-01-01

    Non-melanoma skin cancers (NMSCs) include a heterogeneous group of malignancies arising from the epidermis, comprising squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Merkel cell carcinoma and more rare entities, including malignant pilomatrixoma and sebaceous gland tumours. The treatment of early disease depends primarily on surgery. In addition, certain patients present with extensive local invasion or metastasis, which renders these tumours surgically unresectable. Improving the outcome of radiotherapy through the use of concurrent systemic therapy has been demonstrated in several locally advanced cancer-treatment paradigms. Recently, agents targeting the human epidermal growth factor receptor (EGFR) have exhibited a consolidated activity in phase II clinical trials and case series reports. Cetuximab is a monoclonal antibody that binds to and completely inhibits the EGFR, which has been revealed to be up-regulated in a variety of SCCs, including NMSCs. The present review aimed to summarize the role of anti-EGFR agents in the predominant types of NMSC, including SCC and BCC, and focuses on the cetuximab-based studies, highlighting the biological rationale of this therapeutic option. In addition, the importance of the association between cetuximab and radiotherapy for locally advanced NMSC is discussed. PMID:27073643

  20. [Medullary thyroid carcinoma and other rare types of thyroid carcinoma].

    PubMed

    Obara, Takao

    2007-11-01

    Among 4 major traditional groups of thyroid carcinoma, papillary and follicular carcinomas are most common, and other forms, anaplastic and medullary carcinomas, are relatively rare. The 2003 WHO histological classification of thyroid tumor separated 7 other malignant thyroid tumors into distinct pathological entities, such as poorly differentiated, squamous cell, mucinous carcinomas, carcinoma showing thymus-like differentiation (CASTLE), etc. Although they are also extremely rare, recognition of their clinicopathologic features are very important. In this review, not only diagnostic and therapeutic strategies for the rare forms of thyroid carcinomas, specifically focussed on medullary carcinoma and CASTLE, but also their histogenetic abnormalities were discussed.

  1. Mammary Analogue Secretory Carcinoma.

    PubMed

    Stevens, Todd M; Parekh, Vishwas

    2016-09-01

    Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland tumor that shares the same histologic appearance and ETV6 gene (12p13) rearrangement as secretory carcinoma of the breast. Prior to its recognition, MASC cases were commonly labeled acinic cell carcinoma and adenocarcinoma, not otherwise specified. Despite distinctive histologic features, MASC may be difficult to distinguish from other salivary gland tumors, in particular zymogen-poor acinic cell carcinoma and low-grade salivary duct carcinoma. Although characteristic morphologic and immunohistochemical features form the basis of a diagnosis of MASC, the presence of an ETV6-NTRK3 gene fusion is confirmatory. Given its recent recognition the true prognostic import of MASC is not yet clearly defined.

  2. Squamous-cell Carcinoma of the Anus and Anal Canal: An Analysis of 55 Cases

    PubMed Central

    Gabriel, W. B.

    1941-01-01

    The analysis is of 55 cases admitted into St. Mark's Hospital from 1922 to 1940. The incidence was 3.35% of all cases of cancer of the rectum, anal canal and anus admitted during this period. Sex distribution—27 males and 28 females. The average age (61.7 years) is higher than that of columnar-cell carcinoma of the rectum (57.4 years). Histology.—The cases have been graded into three grades of malignancy—low grade, medium grade, and high grade. Low grade squamous carcinoma is twice as frequent in men as in women, and generally originates at the anal margin. Medium grade squamous carcinoma is equally distributed between men and women; it may arise at the anus or in the anal canal. High grade squamous carcinoma is much more common in the female sex and is almost entirely limited to the anal canal. Quadrant affected—about one-third of the anal margin growths and one-half of the anal canal growths were situated anteriorly. Differential diagnosis from simple papilloma, simple ulcer, chronic inflammation, tuberculous ulcer, tuberculide, primary chancre, amœbic ulcer, basal-cell carcinoma, columnar-cell carcinoma. Biopsy and grading essential before treatment is decided upon. The results of treatment in the three grades of malignancy are described. The best results were obtained in the early low-grade cases treated by interstitial radium needling. In the medium and high grades only three five-year survivals can be reported and these followed excision of the rectum. The management of the inguinal glands is discussed and the importance of a very close post-operative supervision emphasized. Squamous carcinoma of the anal canal may cause lymphatic metastases in the superior hæmorrhoidal glands; there have been four such cases in this series. Diathermy perineal excision is indicated in these cases. ImagesFig. 1Fig. 2Fig. 3Fig. 5Fig. 6aFig. 6bFig. 7Fig. 1Fig. 2Fig. 3Fig. 4 PMID:19992316

  3. Accessory Breast Carcinoma

    PubMed Central

    Youn, Hyun Jo; Jung, Sung Hoo

    2009-01-01

    Summary Background Ectopic breast tissue usually develops along the mammary ridges, and the incidence has been reported to be 2–6% of the general population. Occurrence of primary carcinoma in ectopic breast tissue is rare. Case Report We report the case of 59-year-old woman with accessory breast carcinoma in her left axilla. Conclusion Because an accessory areola or nipple is often missing and awareness of physicians and patients about these unsuspicious masses is lacking, clinical diagnosis of accessory breast carcinoma is frequently delayed. Therefore, a mass along the ‘milk line’ should be examined carefully, and any suspicious lesions should be evaluated. PMID:20847887

  4. Breast carcinoma metastases.

    PubMed

    Bodzin, G A; Staren, E D; Faber, L P

    1998-02-01

    With careful selection of patients, complete resection of pulmonary metastases from breast carcinoma may be a useful therapeutic option. Such a treatment appears to offer a significant survival benefit when compared with medical treatment alone, or with incomplete resection.

  5. [Multiple primary pulmonary carcinomas].

    PubMed

    Guitart, A C; Gómez, G; Estrada, G; Rodríguez, C; León, C; Cornudella, R

    1991-02-01

    Three cases of multiple simultaneous primary lung carcinomas are presented, in which diagnosis was established by post-surgery pathological exam. In all three cases, chest X-ray showed pulmonary masses suggestive or clinical malignancy, and pre-surgery pathological diagnosis or squamous lung carcinoma. During thoracotomy or in the resected segment, a second lesion we confirmed which made resection necessary being this second lesion classified as lung adenocarcinoma.

  6. [Imaging renal cell carcinoma].

    PubMed

    Bazan, F; Busto, M

    2014-01-01

    Renal cell carcinoma is the eighth most common malignancy in adults and the most common malignancy in the kidney. It is thus a very common disease for radiologists. This review aims to provide a general overview of the imaging techniques used to diagnose, characterize, and help plan the treatment of renal cell carcinoma as well as to review basic aspects related to staging, imaging-guided percutaneous treatment, and follow-up in the most common clinical scenarios.

  7. [Pulmonary sarcomatoid carcinoma].

    PubMed

    Antoine, Martine; Vieira, Thibault; Fallet, Vincent; Hamard, Cécile; Duruisseaux, Michael; Cadranel, Jacques; Wislez, Marie

    2016-01-01

    Pulmonary sarcomatoid carcinomas are a rare group of tumors accounting for about one percent of non-small cell lung carcinoma (NSCLC). In 2015, the World Health Organization classification united under this name all the carcinomas with sarcomatous-like component with spindle cell or giant cell appearance, or associated with a sarcomatous component sometimes heterologous. There are five subtypes: pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma and pulmonary blastoma. Clinical characteristics are not specific from the other subtypes of NSCLC. Epithelial to mesenchymal transition pathway may play a key role. Patients, usually tobacco smokers, are frequently symptomatic. Tumors are voluminous more often peripherical than central, with strong fixation on FDG TEP CT. Distant metastases are frequent with atypical visceral locations. These tumors have poorer prognosis than the other NSCLC subtypes because of great aggressivity, and frequent chemoresistance. Here we present pathological description and a review of literature with molecular features in order to better describe these tumors and perhaps introduce new therapeutics.

  8. Transplantable pancreatic acinar carcinoma

    SciTech Connect

    Warren, J.R.; Reddy, J.K.

    1981-03-15

    Fragments o