Sebaceous neoplasms with an organoid pattern (rippled, labyrinthine/sinusoidal, carcinoid-like, and petaloid) are rare. Previous studies suggested that the above patterns likely represent variations along a morphological continuum. The objectives of this study were to (1) validate this proposition by studying a large number of cases, (2) determine whether there are specific associations with clinical features, (3) establish their frequency, and (4) determine whether they have any association with Muir-Torre syndrome. Fifty-seven sebaceous neoplasms (54 sebaceomas and 3 sebaceous carcinomas) with organoid growth patterns were studied. These occurred in 36 men and 18 women (sex unknown in 3), with ages at diagnosis ranging from 22 to 89 years (mean, 63 years). All patients presented with a solitary nodule (mean size, 11 mm) on the head and neck area. Of the 57 tumors, 24 manifested a single growth pattern, 23 had a combination of 2 patterns, and 10 a combination of 3 patterns, indicating that these patterns are part of a morphological continuum of changes. The carcinoid-like pattern was the most frequent in the "monopatterned" neoplasms (13 cases), whereas the labyrinthine/sinusoidal pattern comprised most of the "polypatterned" lesions, in which various combinations occurred. Immunohistochemically, mismatch repair protein deficiency was detected in 3 of the 22 cases studied, whereas 5 of the 33 patients with available follow-up had an internal malignancy/premalignancy. In conclusion, sebaceous neoplasms with organoid growth patterns are predominantly sebaceomas having a predilection for the scalp, occurring as solitary lesions in elderly patients (male to female ratio of 2:1). Such patterns are expected to be found in a quarter of sebaceomas. In most cases, more than one of the organoid patterns is present. These lesions do not appear to be associated with internal malignancy or mismatch repair deficiency in most cases. However, confirmation of the absence of any significant association with Muir-Torre syndrome syndrome will require genetic studies.
- MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- nádory mazových žláz etiologie patologie MeSH
- oprava chybného párování bází DNA genetika MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Torrého-Muirův syndrom komplikace MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The normal histology of anogenital mammary-like glands (AGMLG) has been studied previously, but some aspects, including glandular depth, presence of columnar epithelium resembling columnar cell change/hyperplasia as defined in mammary pathology, and distribution of elastic fibers, have not been previously investigated. To address these issues, we studied 148 AGMLG identified in 133 paraffin blocks sampled from 64 vulvar wide excision or vulvectomy specimens (64 patients, various indications for surgery). The depth of AGMLG ranged from 0.64 to 3.9 mm. Epithelial columnar cell change was noted in 33.1% of all AGMLG, whereas columnar cell hyperplasia was detected in 10.1%. Occasionally, combinations of cuboidal epithelium and columnar cell change were seen within 1 histological section. Of 22 specimens stained for elastic fibers, in only 6 (27.3%) cases were elastic fibers found around glands. Periductal elastic fibers were demonstrated around 3 of the only 5 ducts, which were available for analysis in slides stained for elastic fibers. The depth of AGMLG should be taken into account when planning topical and surgical therapies for lesions derived or evolving from AGMLG. Alterations identical to columnar cell change may represent a normal variation of AGMLG.
To determine whether a subset of primary extramammary Paget disease (EMPD) may originate in anogenital mammary-like glands (AGMLG), the authors studied 181 specimens of EMPD, detailing alterations in AGMLG. The latter were identified in 33 specimens from 31 patients. All patients were women, ranging in age from 38 to 93 years (median, 65 y). In all cases, lesions involved the vulva and in 1 patient the perianal skin was affected. Histopathologically, AGMLG manifested changes identical to columnar cell change (CCC) (87.1%), usual ductal hyperplasia (22.6%), columnar cell hyperplasia (CCH) (9.7%), oxyphilic (apocrine) metaplasia (6.5%), and atypical duct hyperplasia (3.2%). Four cases (12.9%), in addition to intraepidermal carcinoma, harbored invasive carcinoma. In all 4 of these, AGMLG displayed a range of alterations including ductal carcinoma in situ, CCC, and CCH. Three further cases (9.7%) showed ductal carcinoma in situ without any definite invasive carcinoma. Colonization of AGMLG by neoplastic Paget cells was noted in 6 cases. As CCC and CCH may be encountered in normal AGMLG, these alterations are unlikely to play a significant role in the pathogenesis of the disease. However, by analogy with mammary Paget disease, rare cases of primary EMPD may originate in AGMLG with a subsequent upward migration of the neoplastic cells into the epidermis and possible later breach through the basal membrane. Usual ductal hyperplasia and atypical duct hyperplasia can then be regarded as earlier precursor lesions, linking both ends of the spectrum.
- MeSH
- anální kanál patologie MeSH
- dospělí MeSH
- extramamární Pagetova nemoc etiologie patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory anu etiologie patologie MeSH
- nádory vulvy etiologie patologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- vulva patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Lesions affecting anogenital mammary-like glands (AGMLG) are histopathologically very similar to those seen in the breast but whether this morphological similarity is also reflected at the genetic level is unknown. To compare the underlying molecular mechanisms in lesions of AGMLG and their mammary counterparts, we analyzed the mutational profile of 16 anogenital neoplasms including 5 hidradenomas papilliferum (HP), 1 lesion with features of HP and fibroadenoma (FA), 7 FA, 3 phyllodes tumors (PhT)) and 18 analogous breast lesions (6 intraductal papillomas (IDP), 9 FA, and 3 PhT) by high-coverage next generation sequencing (NGS) using a panel comprising 50 cancer-related genes. Additionally, all cases were analyzed for the presence of a mutation in the MED12 gene. All detected mutations with allele frequencies over 20% were independently validated by Sanger sequencing (concordance: 100%). Mutations in PIK3CA, AKT1, MET, ABL1 and TP53 genes were found in lesions of AGMLG and also their mammary counterparts. The PI3K-AKT cascade plays a role in tumors arising at both sites. It appears that some histopathologically similar anogenital and breast lesions develop along similar molecular pathways.
- Klíčová slova
- AKT1, Anogenital mammary-like glands, Breast, Fibroadenoma, Hidradenoma papilliferum, Intraductal papilloma, PIK3CA, Phyllodes tumor, Vulva,
- MeSH
- adenomy potních žláz metabolismus patologie MeSH
- cystosarcoma phyllodes metabolismus patologie MeSH
- fibroadenom metabolismus patologie MeSH
- fosfatidylinositol-3-kinasy třídy I metabolismus MeSH
- fosfatidylinositol-3-kinasy metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- mutace genetika MeSH
- nádory prsu genetika patologie MeSH
- nádory vulvy patologie MeSH
- papilom intraduktální metabolismus patologie MeSH
- prsy patologie MeSH
- senioři MeSH
- vysoce účinné nukleotidové sekvenování metody MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- fosfatidylinositol-3-kinasy třídy I MeSH
- fosfatidylinositol-3-kinasy MeSH
- PIK3CA protein, human MeSH Prohlížeč
Extramammary Paget disease (EMPD) is a rare neoplasm usually presenting in the anogenital area, most commonly in the vulva. Adnexal involvement in primary EMPD is a very common feature and serves as a pathway for carcinoma to spread into deeper tissue. The depth of carcinomatous spread along the appendages and the patterns of adnexal involvement were studied in 178 lesions from 146 patients with primary EMPD. Hair follicles and eccrine ducts were the adnexa most commonly affected by carcinoma cells. The maximal depth of involvement was 3.6 mm in this series. When planning topical therapy or developing novel local treatment modalities for EMPD, this potential for significant deep spread along adnexa should be taken into account.
- MeSH
- biopsie MeSH
- dospělí MeSH
- ekrinní žlázy patologie MeSH
- extramamární Pagetova nemoc patologie terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory anu patologie terapie MeSH
- nádory kožních adnex patologie terapie MeSH
- nádory potních žláz patologie terapie MeSH
- nádory vulvy patologie terapie MeSH
- prognóza MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- vlasový folikul patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- Geografické názvy
- Evropa MeSH
- Západní Austrálie MeSH
Hidradenoma papilliferum (HP), also known as papillary hidradenoma, is the most common benign lesion of the female anogenital area derived from anogenital mammary-like glands (AGMLG). HP can be viewed conceptually as the cutaneous counterpart of mammary intraductal papilloma. The authors have studied 264 cases of HP, detailing various changes in the tumor and adjacent AGMLG, with emphasis on mammary-type alterations. In many HP, the authors noticed changes typical for benign breast lesions, such as sclerosing adenosis-like changes, usual, and atypical ductal hyperplasia. Almost in a third of cases, remnants of AGMLG adjacent to the lesion were evident, manifesting columnar changes reminiscent of those seen in breast lesions. This study shows that the histopathological changes in HP run a broad spectrum comparable with that in the mammary counterpart and benign breast disease.
- MeSH
- akrospirom patologie MeSH
- anální kanál patologie MeSH
- biopsie MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mléčné žlázy lidské patologie MeSH
- nádory análních žláz patologie MeSH
- nádory potních žláz patologie MeSH
- nádory vulvy patologie MeSH
- prediktivní hodnota testů MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Brooke-Spiegler syndrome (BSS) is a rare, inherited, autosomal dominant disorder characterized by development of multiple adnexal cutaneous neoplasms including spiradenoma, cylindroma, spiradenocylindroma, and trichoepithelioma. The syndrome of multiple familial trichoepitheliomas (MFT) is considered a phenotypic variant of BSS in which patients present with trichoepitheliomas only. We studied germline and somatic mutations of the CYLD gene by direct sequencing in patients with BSS (n = 49) and MFT (n = 18) using peripheral blood and 90 samples of frozen or formalin-fixed paraffin-embedded tumor tissue selected from 379 available histology specimens. Germline CYLD mutations were found in 51 patients (76%) from 36 families (75%). Germline CYLD mutations were found in 43 of the 49 patients with BSS (88%) but in only 8 of 18 MFT cohort (44%). Twenty-one frameshift, 15 nonsense, 3 missense, and 4 splice site mutations were found in patients with BSS, whereas 1 frameshift, 5 nonsense, and 2 splice site mutations were identified in the MFT cohort. Five novel mutations were identified including 4 frameshift mutations (c.1027dupA/p.T343NfsX7, c.2155dupA/p.M719NfsX5, c.2288_2289delTT/p.F763X, and c.2641delG/p.D881TfsX32) and 1 nonsense mutation (c.2713C>T/p. Q905X). Of the 76 tumors from 32 patients with a germline CYLD mutation, 12 were spiradenomas, 15 spiradenocylindromas, 26 cylindromas, 15 trichoepitheliomas, and 7 were other tumor types. Somatic mutations were detected in 67 specimens of these 76 tumors (88%). Of the 67 somatic mutations, 21 (31%) represented a sequence alteration and 46 (69%) showed loss of heterozygosity. In the remaining 9 cases (12%), the somatic changes remained unknown. A germline CYLD mutation was not detected in 14 tumor samples from 8 patients. In these 14 tumors, somatic mutations were identified in 6 samples (43%), all consisting of sequence alterations (1 sample showed 2 different sequence alterations). In the remaining 8 samples (53%), neither germline nor somatic mutations were found in the lesional tissue. Our study increases the catalog of known CYLD mutations in patients with BSS/MFT to 86 and documents the variability of somatic mutations that may occur in them. We confirm the absence of firm genotype-phenotype correlations and the existence of a subset of patients with BSS/MFT who lack a demonstrable germline CYLD mutation. Further studies are needed to explain the reasons for this phenomenon.
- MeSH
- biopsie MeSH
- dědičné nádorové syndromy genetika patologie MeSH
- deubikvitinizační enzym CYLD MeSH
- dospělí MeSH
- fenotyp MeSH
- genetická predispozice k nemoci MeSH
- kůže patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- missense mutace MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mutace * MeSH
- mutační analýza DNA MeSH
- nádorové supresorové proteiny genetika MeSH
- nádory kůže genetika patologie MeSH
- nesmyslný kodon MeSH
- posunová mutace MeSH
- rodokmen MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- zalévání tkání do parafínu MeSH
- zárodečné mutace MeSH
- zmrazené řezy MeSH
- ztráta heterozygozity MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- CYLD protein, human MeSH Prohlížeč
- deubikvitinizační enzym CYLD MeSH
- nádorové supresorové proteiny MeSH
- nesmyslný kodon MeSH
We report 11 individuals, each presenting with few (2-4) adnexal neoplasms histologically confirmed as belonging to the spectrum of lesions typical for Brooke-Spiegler syndrome (BSS) and/or multiple familial trichoepitheliomas. These include spiradenoma, cylindroma, spiradenocylindroma, and trichoblastoma variants. Our objective was to clarify whether this is merely a sporadic, albeit unusual, occurrence of multiple neoplasms in these patients or whether they are related to BSS and its phenotypic variant, multiple familial trichoepithelioma. Six patients presented with 2 neoplasms, 4 had 3 lesions and the last had 4 lesions. In none was there any family history of similar lesions. The 28 neoplasms consisted of 7 spiradenomas, 6 cylindromas, 5 spiradenocylindromas, and 11 trichoblastomas (6 trichoepitheliomas and 5 with mixed patterns). In 1 patient only with 2 spiradenomas, both tumors harbored identical CYLD sequence alterations (c.1112C>A/S371X) in the CYLD gene and both showed loss of heterozygosity on chromosome 16q. The remaining cases yielded neither germ line nor somatic alterations in CYLD. It is concluded that the presentation with few (2-4) cylindromas, spiradenomas, spiradenocylindromas, and trichoepitheliomas is a sporadic occurrence, and that these patients do not have any relationship to BSS.
- MeSH
- biopsie MeSH
- dědičné nádorové syndromy genetika patologie MeSH
- dědičnost MeSH
- deubikvitinizační enzym CYLD MeSH
- dospělí MeSH
- fenotyp MeSH
- genetická predispozice k nemoci MeSH
- kůže patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lidské chromozomy, pár 16 MeSH
- mladiství MeSH
- mnohočetné primární nádory genetika patologie MeSH
- mutace * MeSH
- mutační analýza DNA MeSH
- nádorové supresorové proteiny genetika MeSH
- nádory kožních adnex genetika patologie MeSH
- nádory kůže genetika patologie MeSH
- prediktivní hodnota testů MeSH
- retrospektivní studie MeSH
- senioři MeSH
- ztráta heterozygozity MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- CYLD protein, human MeSH Prohlížeč
- deubikvitinizační enzym CYLD MeSH
- nádorové supresorové proteiny MeSH
Cutaneous adnexal neoplasms are complex lesions, including benign and malignant neoplasms in addition to malformations and hamartomas. They show one or several features of differentiation along follicular, sebaceous, apocrine, and eccrine lines. Rarely, cutaneous adnexal neoplasms or their mimics may arise outside the skin. In some organs, such as the parotid gland, a number of tumors comprise well-established entities, whereas in the majority of cases an extracutaneous occurrence of cutaneous-type adnexal lesions is a rare and often diagnostically challenging finding. This review discusses various authentic cutaneous-type adnexal neoplasms or related lesions presented according to the organ involved.
- MeSH
- lidé MeSH
- nádory kožních adnex patologie MeSH
- nádory kůže patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
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.
- MeSH
- dědičné nádorové syndromy genetika patologie MeSH
- deubikvitinizační enzym CYLD MeSH
- dítě MeSH
- dospělí MeSH
- exprese genu MeSH
- karcinom kožních adnex genetika patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mutace MeSH
- mutační analýza DNA MeSH
- nádorové supresorové proteiny genetika MeSH
- nádory kůže genetika patologie MeSH
- Patched receptory MeSH
- polymerázová řetězová reakce MeSH
- receptor Patched 1 MeSH
- receptory buněčného povrchu genetika MeSH
- stanovení celkové genové exprese MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- CYLD protein, human MeSH Prohlížeč
- deubikvitinizační enzym CYLD MeSH
- nádorové supresorové proteiny MeSH
- Patched receptory MeSH
- PTCH1 protein, human MeSH Prohlížeč
- receptor Patched 1 MeSH
- receptory buněčného povrchu MeSH