Basal cell carcinomas arising within multiple trichoepitheliomas

Pincus, Laura B.; McCalmont, Timothy H.; Neuhaus, Isaac M.; Kasper, Richard; Oh, Dennis H.

doi:10.1111/j.1600-0560.2008.01002.x

Cited by 36 publications

(37 citation statements)

References 37 publications

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“…Less common patterns included areas reminiscent of tumor of the follicular infundibulum, lymphadenoma-like areas, spiradenoma-like areas, small nodular trichoblastoma, large nodular trichoblastoma with focal sebaceous differentiation, and development of BCC. The latter event is rarely seen in patients with MFT 8,34,[44][45][46][47][48][49][50] Areas reminiscent of tumor of the follicular infundibulum were produced by superficial horizontal anastomosing cords of isthmic cells. This rare neoplasm has recently received attention because of opposing views of its histogenesis.…”

Section: Discussionmentioning

confidence: 99%

Multiple (Familial) Trichoepitheliomas: A Clinicopathological and Molecular Biological Study, Including CYLD and PTCH Gene Analysis, of a Series of 16 Patients

Kazakov

Vaněček²,

Zelger³

et al. 2011

The American Journal of Dermatopathology

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Multiple familial trichoepitheliomas (MFT) constitute an autosomally inherited syndrome possibly related to Brooke-Spiegler syndrome (BSS). Although some early studies suggested a role for the PTCH gene on chromosome 9q22.3 in the etiopathogenesis of MFT, recent studies of occasional patients with the MFT clinical phenotype identified mutations in the CYLD gene on chromosome 16q12-q13, a gene responsible for BSS. A systematic investigation of PTCH and CYLD mutations in patients with MFT has never been performed. Our main objective was to collect a reasonably large series of patients with MFT to (1) study the clinicopathological spectrum of the disease, (2) determine whether the PTCH gene is implicated in the pathogenesis of MFT, and if so (3) determine the relative frequency of CYLD and PTCH mutations, (4) establish if there may be any possible genotype-phenotype correlations, and (5) study the spectrum of somatic mutations. Clinical analysis including family histories, histopathological investigations, and molecular genetic studies were performed. There were 9 female and 7 male patients ranging in age from 11 to 63 years. They presented with multiple, small, discrete and sometimes confluent, skin-colored to pink, asymptomatic nodules preferentially located on the face, being especially prominent and confluent in the nasolabial folds and inner aspects of the eyebrows. A total of 66 conventional trichoepitheliomas (TEs) were studied microscopically. Aside from typical features of TE, some also exhibited variant morphological patterns including areas reminiscent of other benign adnexal neoplasms and melanocytic hyperplasia. In none of the 9 patients tested was a germline mutation of the PTCH gene identified. Germline CYLD mutations were detected in 6 of 13 patients tested (identical in 2 unrelated patients) including 2 novel mutations, whereas the remaining 7 individuals showed wild-type alleles. Two patients with germline wild-type CYLD showed, however, a somatic mutation in the gene (1 duplication, 1 substitution mutation). Neither CYLD nor PTCH germline mutations were found in the 5 patients in whom both genes were analyzed. MFT seems to be a phenotypic variant of BSS. The PTCH gene is rarely, if ever, involved in the pathogenesis of MFT. Absence of a germline mutation of the CYLD gene in cases harboring a somatic mutation may be explained by large deletions in the gene or by mutation in intronic sequences or in the promoter region. Considering our 5 patients with no mutation in either gene, the final possibility is that another, as yet undescribed gene (neither CYLD nor PTCH) is implicated in the pathogenesis of some patients with MFT.

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Section: Discussionmentioning

confidence: 99%

Multiple (Familial) Trichoepitheliomas: A Clinicopathological and Molecular Biological Study, Including CYLD and PTCH Gene Analysis, of a Series of 16 Patients

Kazakov

Vaněček²,

Zelger³

et al. 2011

The American Journal of Dermatopathology

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“…Also, the evolution of malignant phenotype (AFX) can occur in a background of benign lesions (benign fibrous histiocytoma). This evolution is analogous to evolution of the following malignancies: malignant melanomas in a background of nevi (including dysplastic nevi) [88], basal cell carcinomas in a background of trichoepitheliomas or trichoblastomas [89] or hidradenocarcinomas in a background of hidradenomas [87,90,91].…”

Section: Molecular Pathology Of Afxmentioning

confidence: 94%

Atypical fibroxanthoma: new insights

Hussein

2014

Expert Review of Anticancer Therapy

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Atypical fibroxanthoma (AFX) is an ultraviolet radiation-associated dermal neoplasm. To address the clinicopathologic and molecular features of this particular neoplasm. The author conducted a literature review using PubMed searching for articles relating to AFX. AFX usually appears as a rapidly growing nodular or nodulo-ulcerative lesion. It occurs on sun-exposed skin of elderly peoples. AFX may be composed predominantly of pleomorphic, spindle, epithelioid cells, or admixture of these cells. The differential diagnosis of AFX includes pleomorphic dermal sarcoma, squamous cell carcinoma, malignant melanoma and leiomyosarcoma. Several observations favor a mesenchymal origin for AFX. These reviews address the clinicopathologic features, molecular pathology, prognosis and treatment of this neoplasm.

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“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14] These cutaneous adnexal neoplasms may infrequently undergo malignant transformation. [15][16][17][18][19] Morphologically similar neoplasms may rarely arise in the salivary glands [20][21][22][23] and exceptionally in the breast. 24,25 Alterations of the CYLD gene are detected in a majority of familial cases of BSS and allelic disorders.…”

Section: Introductionmentioning

confidence: 99%

Large Germline Deletions of the CYLD Gene in Patients With Brooke–Spiegler Syndrome and Multiple Familial Trichoepithelioma

Vaněček

Halbhuber

Kacerovská

et al. 2014

The American Journal of Dermatopathology

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Brooke-Spiegler syndrome (BSS) and its phenotypic variants, multiple familial trichoepithelioma (MFT) and familial cylindromatosis, are rare autosomal dominant hereditary diseases. They are characterized by the presence of multiple adnexal tumors, especially cylindromas, spiradenomas, spiradenocylindromas, and trichoepitheliomas. Implicated in the pathogenesis of the disease is the gene CYLD, which is localized on the long arm of chromosome 16. This gene encodes an evolutionarily conserved protein belonging to the deubiquitinating enzymes family, which plays a key role in many signaling pathways, especially in NF-κB, JNK, and Wnt. Less than 90 germline mutations of CYLD have been identified in patients with BSS/MFT. These mutations are mostly small alterations in the coding sequence and at exon-intron junction sites. One patient with an intronic mutation and another with a large CYLD deletion have also been recorded. In this study, the authors have analyzed a cohort of 14 patients with BSS/MFT from 13 families for large genome rearrangements by array comparative genome hybridization followed by confirmatory sequencing. We identified 2 large deletions, namely c.-34111_*297858del378779 and c.914-6398_1769del13642ins20 in patients with MFT and BSS, respectively. All other analyzable patients did not reveal any copy number alteration. It is concluded that the large rearrangements are relatively rare in patients without a germline CYLD mutation demonstrable by conventional sequencing. The pathogenetic mechanisms in patients with BSS/MFT lacking germline sequence alterations or large rearrangements in the CYLD gene remain to be clarified.

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Basal cell carcinomas arising within multiple trichoepitheliomas

Cited by 36 publications

References 37 publications

Multiple (Familial) Trichoepitheliomas: A Clinicopathological and Molecular Biological Study, Including CYLD and PTCH Gene Analysis, of a Series of 16 Patients

Multiple (Familial) Trichoepitheliomas: A Clinicopathological and Molecular Biological Study, Including CYLD and PTCH Gene Analysis, of a Series of 16 Patients

Atypical fibroxanthoma: new insights

Large Germline Deletions of the CYLD Gene in Patients With Brooke–Spiegler Syndrome and Multiple Familial Trichoepithelioma

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