Multiple Trichoepithelioma in a Mother and two Children

Ziprkowski, L.; Schewach-Millet, M

doi:10.1159/000254425

Cited by 34 publications

(16 citation statements)

References 15 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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“…For adnexal skin tumors such as TE, a gatekeeper function may be associated with the functioning of PTCH1, a receptor for hedgehog proteins, which is mutated in BCCs (16). Malignant changes (BCC) have been noted occasionally in cylindromas (36) and TEs (14,37). Experimentally induced BCC in mice tend to be associated with other hair follicle neoplasias such as trichoblastoma, TE, and cylindroma (32).…”

Section: Discussionmentioning

confidence: 99%

Multiple Familial Trichoepithelioma Caused by Mutations in the Cylindromatosis Tumor Suppressor Gene

Salhi

Bornholdt²,

Oeffner³

et al. 2004

Cancer Research

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The recessive oncogene cylindromatosis (CYLD) mapping on 16q12-q13 is generally implicated in familial cylindromatosis, whereas a gene region for multiple familial trichoepithelioma has been assigned to 9p21. Markers from both chromosome intervals were subjected to linkage analysis in a large family with multiple hereditary trichoepithelioma (TE) from Algeria. Linkage to 9p21 was excluded, whereas CYLD remained as a candidate. Mutation analysis identified a single bp germ-line deletion expected to result in truncation or absence of the encoded protein, which segregated with the multiple TE phenotype. In individual tumors, loss of heterozygosity at 16q or a somatic point mutation in the CYLD gene was detected. Hence, mutations of the tumor suppressor gene CYLD at 16q12-q13 may give rise to familial TE indistinguishable from the phenotype assigned to 9p21.

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“…In a recent case study and review of the literature, applying strict diagnostic criteria and critical analysis of illustrations in previously published articles, Pincus et al 12 identified 15 acceptable cases including that of the authors. [13][14][15][16][17][18][19] We report a new case of TE associated with BCC, describing its clinicopathological and molecular features including mutational and loss of heterozygosity (LOH) analysis of the CYLD and PTCH genes. In contrast to the above-cited articles, which describe large nodular or small nodular BCC as the most common associated neoplasms, usually with sharp demarcation of the BCC from the adjacent TE, in our patient, the tumors showed a gradual transition of TE into the BCC-like areas, which were consistent with small nodular BCC and infundibulocystic BCC.…”

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confidence: 99%

Spectrum of Tumors With Follicular Differentiation in a Patient With the Clinical Phenotype of Multiple Familial Trichoepitheliomas: A Clinicopathological and Molecular Biological Study, Including Analysis of the CYLD and PTCH Genes

Kazakov¹,

Vaněček²,

Němcová³

et al. 2009

The American Journal of Dermatopathology

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We report a patient with multiple trichoepitheliomas whose biopsy material also demonstrated a range of other neoplasms with follicular differentiation, including small nodular trichoblastoma, small nodular basal cell carcinoma (BCC), and areas resembling infundibulocystic BCC/basaloid follicular hamartoma. These were all intimately associated with otherwise typical trichoepitheliomas that dominated the microscopic appearances. Peripheral blood and tumor tissues of the patient and his 2 daughters, who apparently had a milder phenotype, were studied for alterations in the CYLD and PTCH genes, but mutations or loss of heterozygosity was not found in either gene. The occurrence of multiple follicular neoplasms within a single lesion adds evidence that, although in most cases BCC and trichoblastoma are distinct lesions, the 2 neoplasms do encompass a morphological spectrum of follicular differentiation, which is probably more overtly expressed in syndromic patients.

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Multiple Trichoepithelioma in a Mother and two Children

Cited by 34 publications

References 15 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

Multiple Familial Trichoepithelioma Caused by Mutations in the Cylindromatosis Tumor Suppressor Gene

Spectrum of Tumors With Follicular Differentiation in a Patient With the Clinical Phenotype of Multiple Familial Trichoepitheliomas: A Clinicopathological and Molecular Biological Study, Including Analysis of the CYLD and PTCH Genes

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