RESUMO
BACKGROUND: While the list of fusion-driven soft tissue neoplasms is expanding rapidly, their importance among cutaneous and superficial mesenchymal and adnexal neoplasms remains poorly understood. This challenge is especially evident in cases with ambiguous histopathology that are difficult to classify based on morphology. AIMS: Our goal was to investigate the benefits of next-generation sequencing in diagnosing complex cutaneous neoplasms. MATERIALS & METHODS: Departmental archives were searched for fusion-driven cutaneous neoplasms. Slides were retrieved and clinical information including follow-up was obtained. RESULTS: Fifteen cases occurred in eight female and seven male patients, with a median age of 26 years (range: 1-83) at diagnosis. Tumors involved the extremities (9), scalp (5), and head and neck (1). Predominant features included myoepithelial (5), nested spindled with clear cytoplasm (2), atypical adnexal/squamoid (2), small round blue cell (2), cellular spindled (3), and fibrohistiocytic morphology (1). Most frequently encountered fusions involved EWSR1 (6) fused to ERG (1), FLI1 (1), CREB1 (2), CREM (1), PBX3 (1), followed by PLAG1 (4) with LIFR (2), TRPS1 (1) and CHCHD7. Additional fusions encountered were YAP1::NUTM1, EML4::ALK, SS18::SSX1 (2), and a novel fusion: ACTB::ZMIZ2. Integration of histologic features and molecular findings led to final diagnoses of primary cutaneous Ewing sarcoma (2), soft tissue myoepithelioma (4), cutaneous syncytial myoepithelioma (1), cutaneous adnexal carcinoma (1), porocarcinoma (1), inflammatory myofibroblastic tumor (1), synovial sarcoma (2), clear cell sarcoma (2), and angiomatoid fibrous histiocytoma (1). DISCUSSION AND CONCLUSION: Our results show that fusion testing can be a helpful diagnostic tool, especially in cases with unusual or uncommon morphology in superficial sites. Furthermore, it can allow for the identification of potential therapeutic targets in some instances.
Assuntos
Neoplasias Cutâneas , Humanos , Feminino , Masculino , Adulto , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo , Pessoa de Meia-Idade , Idoso , Criança , Adolescente , Idoso de 80 Anos ou mais , Pré-Escolar , Lactente , Proteínas de Fusão Oncogênica/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Fatores de Transcrição/genética , Neoplasias de Anexos e de Apêndices Cutâneos/patologia , Neoplasias de Anexos e de Apêndices Cutâneos/genética , Neoplasias de Anexos e de Apêndices Cutâneos/diagnóstico , Adulto Jovem , Rearranjo GênicoRESUMO
Cutaneous adnexal tumors form a vast heterogeneous group that include frequent entities that are mostly benign, as well as rare tumors that are occasionally malignant. In contrast to cutaneous tumors arising from the interfollicular epidermis that develop as a result of accumulation of UV-induced DNA damage (basal cell carcinoma, squamous cell carcinoma), the oncogenesis of adnexal tumors is related to a broad spectrum of genetic mechanisms (e.g., point mutation, fusion genes, viral integration, etc.). In this setting, specific and recurrent genetic alterations have been progressively reported, and these allow better classification of these entities. For certain of them, immunohistochemical tools are now available, enabling precise integrated histological and molecular diagnosis since certain entities are linked to well-defined alterations. In this context, we aim in this review to summarize the main molecular tools currently available for the classification of adnexal tumors.
Assuntos
Adenoma , Carcinoma Basocelular , Carcinoma de Células Escamosas , Neoplasias de Anexos e de Apêndices Cutâneos , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/genética , Neoplasias de Anexos e de Apêndices Cutâneos/genéticaRESUMO
Ocular adnexal (OA) sebaceous carcinomas generally demonstrate more aggressive clinical and histopathological phenotypes than extraocular cases, but the molecular drivers implicated in their oncogenesis remain poorly defined. A retrospective review of surgical and ocular pathology archives identified eleven primary resection specimens of OA sebaceous carcinomas with adequate tissue for molecular analysis; two extraocular cases were also examined. Next-generation sequencing was used to evaluate mutations and copy number changes in a large panel of cancer-associated genes. Fluorescence in situ hybridization (FISH) confirmed MYC copy number gain in select cases, and immunohistochemistry to evaluate MYC protein expression. The commonest mutations occurred in TP53 (10/13) and RB1 (7/13). Additional mutations in clinically actionable genes, or mutations with a frequency of at least 25%, included the NF1 (3/12), PMS2 (4/12), ROS1 (3/12), KMT2C (4/12), MNX1 (6/12), NOTCH1 (4/12), PCLO (3/12), and PTPRT (3/12) loci. Low level copy number gain suggestive of amplification of the MYC locus was seen in two cases, and confirmed using FISH. MYC protein expression, as assessed by immunohistochemistry, was present in almost all sebaceous carcinoma cases. Our findings support the concept that alterations in TP53 and RB1 are the commonest alterations in sebaceous carcinoma, and suggest that MYC may contribute to the oncogenesis of these tumors.
Assuntos
Neoplasias Oculares/genética , Neoplasias de Anexos e de Apêndices Cutâneos/genética , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas de Ligação a Retinoblastoma/genética , Neoplasias das Glândulas Sebáceas/genética , Proteína Supressora de Tumor p53/genética , Ubiquitina-Proteína Ligases/genética , Idoso , Idoso de 80 Anos ou mais , Feminino , Dosagem de Genes , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , MutaçãoRESUMO
Cutaneous adnexal tumors recapitulate follicular, sweat gland, and/or sebaceous epithelia, and range from benign tumors to aggressive carcinomas. Adnexal tumors can be hallmarks for inherited tumor syndromes. Oncogenic drivers of adnexal neoplasms modulate intracellular pathways including mitogen-activated protein kinase, phosphoinositide-3-kinase, Wnt/ß-catenin, Hedgehog, nuclear factor κB, and Hippo intracellular signaling pathways, representing potential therapeutic targets. Malignant progression can be associated with tumor suppressor loss, especially TP53. Molecular alterations drive expression of specific diagnostic markers, such as CDX2 and LEF1 in pilomatricomas/pilomatrical carcinomas, and NUT in poromas/porocarcinomas. In these ways, improved understanding of molecular alterations promises to advance diagnostic, prognostic, and therapeutic possibilities for adnexal tumors.
Assuntos
Carcinoma de Apêndice Cutâneo , Neoplasias de Anexos e de Apêndices Cutâneos , Neoplasias Cutâneas , Carcinoma de Apêndice Cutâneo/genética , Humanos , Biologia Molecular , Neoplasias de Anexos e de Apêndices Cutâneos/genética , Neoplasias Cutâneas/genéticaRESUMO
Skin adnexal cancers (SAC) are a heterogeneous group of rare malignancies with histological differentiation towards epithelial adnexa, which lack effective systemic treatments. The aim of this work is to identify any potentially druggable genomic alterations for possible targeted therapies. Cases of primary or recurrent/metastatic (RM) SAC between 2002 and 2014 were identified by searching the institutional cancer registration database. Histological sections of all referral cases were reviewed by a dedicated pathologist to confirm diagnosis. Immunohistochemistry was performed to assess the expression of androgen receptors (AR) and human epidermal growth factor receptor type 2 (HER2). Targeted next-generation sequencing (T-NGS) was performed to identify targetable mutations (panel of 50 genes analyzed by Cancer Hotspot Panel, Ion-Torrent Personal Genome Machine). Mutational analysis of the PTCH1 gene not present in the T-NGS panel was assessed by Sanger sequencing. A total of 45 cases with available histological samples were identified (35 primary, 10 RM). The most frequent histological type was porocarcinoma (n = 12). Globally, 14 cases (31%) were AR+ (6/10 RM, 60%; 8/35 primary, 23%). HER2 was shown as 2+ in eight of 42 (19%) cases (2/9 RM, 22%; 6/33 primary, 18%). DNA was adequate for T-NGS analysis in 25 cases. In the majority of cases (17 cases, 68%) at least one mutation in oncogenes or tumor suppressor genes was found: the most frequent ones involved TP.53 (13 cases, 76% of mutated SAC) and PIK3CA (three cases, 18%). The rate of PTCH1 mutation was 30%. These findings support the use of molecular screening in patients with advanced SAC.
Assuntos
Biomarcadores Tumorais/genética , Recidiva Local de Neoplasia/genética , Neoplasias de Anexos e de Apêndices Cutâneos/genética , Neoplasias das Glândulas Sebáceas/genética , Neoplasias das Glândulas Sudoríparas/genética , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/antagonistas & inibidores , Classe I de Fosfatidilinositol 3-Quinases/antagonistas & inibidores , Classe I de Fosfatidilinositol 3-Quinases/genética , Análise Mutacional de DNA , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Terapia de Alvo Molecular/métodos , Mutação , Taxa de Mutação , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/prevenção & controle , Neoplasias de Anexos e de Apêndices Cutâneos/tratamento farmacológico , Neoplasias de Anexos e de Apêndices Cutâneos/patologia , Receptor Patched-1/antagonistas & inibidores , Receptor Patched-1/genética , Receptor ErbB-2/antagonistas & inibidores , Receptor ErbB-2/genética , Estudos Retrospectivos , Neoplasias das Glândulas Sebáceas/tratamento farmacológico , Neoplasias das Glândulas Sebáceas/patologia , Neoplasias das Glândulas Sudoríparas/tratamento farmacológico , Neoplasias das Glândulas Sudoríparas/patologia , Proteína Supressora de Tumor p53/antagonistas & inibidores , Proteína Supressora de Tumor p53/genéticaAssuntos
Doenças do Cabelo/patologia , Neoplasias de Anexos e de Apêndices Cutâneos/patologia , Neoplasias Cutâneas/patologia , Adulto , Carcinoma Basocelular/patologia , Enzima Desubiquitinante CYLD , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias de Anexos e de Apêndices Cutâneos/genética , Neoplasias de Anexos e de Apêndices Cutâneos/cirurgia , Linhagem , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/cirurgia , Adulto JovemRESUMO
PURPOSE: Ocular adnexal (OA) sebaceous carcinoma is an aggressive malignancy of the eyelid and ocular adnexa that frequently recurs and metastasizes, and effective therapies beyond surgical excision are lacking. There remains a critical need to define the molecular-genetic drivers of the disease to understand carcinomagenesis and progression and to devise novel treatment strategies. EXPERIMENTAL DESIGN: We present next-generation sequencing of a targeted panel of cancer-associated genes in 42 and whole transcriptome RNA sequencing from eight OA sebaceous carcinomas from 29 patients. RESULTS: We delineate two potentially distinct molecular-genetic subtypes of OA sebaceous carcinoma. The first is defined by somatic mutations impacting TP53 and/or RB1 [20/29 (70%) patients, including 10 patients whose primary tumors contained coexisting TP53 and RB1 mutations] with frequent concomitant mutations affecting NOTCH genes. These tumors arise in older patients and show frequent local recurrence. The second subtype [9/29 (31%) patients] lacks mutations affecting TP53, RB1, or NOTCH family members, but in 44% (4/9) of these tumors, RNA sequencing and in situ hybridization studies confirm transcriptionally active high-risk human papillomavirus. These tumors arise in younger patients and have not shown local recurrence. CONCLUSIONS: Together, our findings establish a potential molecular-genetic framework by which to understand the development and progression of OA sebaceous carcinoma and provide key molecular-genetic insights to direct the design of novel therapeutic interventions.
Assuntos
Neoplasias Oculares/genética , Infecções por Papillomavirus/genética , Proteínas de Ligação a Retinoblastoma/genética , Proteína Supressora de Tumor p53/genética , Ubiquitina-Proteína Ligases/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Cisto Epidérmico/genética , Cisto Epidérmico/patologia , Cisto Epidérmico/virologia , Neoplasias Oculares/patologia , Neoplasias Oculares/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Neoplasias de Anexos e de Apêndices Cutâneos/genética , Neoplasias de Anexos e de Apêndices Cutâneos/patologia , Neoplasias de Anexos e de Apêndices Cutâneos/virologia , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Receptores Notch/genética , Análise de Sequência de RNA , Sequenciamento do ExomaRESUMO
Epidermal nevi are hamartomatous lesions derived from the epidermis and/or adnexal structures of the skin; they have traditionally been classified according to their morphology. New variants have been described in recent years and advances in genetics have contributed to better characterization of these lesions and an improved understanding of their relationship with certain extracutaneous manifestations. In the second part of this review article, we will look at nevi derived from the adnexal structures of the skin and associated syndromes.
Assuntos
Neoplasias de Anexos e de Apêndices Cutâneos/classificação , Nevo/classificação , Cisto Epidérmico/classificação , Cisto Epidérmico/patologia , Doenças do Cabelo/classificação , Doenças do Cabelo/patologia , Folículo Piloso/patologia , Humanos , Neoplasias de Anexos e de Apêndices Cutâneos/genética , Neoplasias de Anexos e de Apêndices Cutâneos/patologia , Nevo/genética , Nevo/patologia , Nevo Pigmentado/classificação , Nevo Pigmentado/genética , Nevo Pigmentado/patologia , Nevo Sebáceo de Jadassohn/classificação , Nevo Sebáceo de Jadassohn/genética , Couro Cabeludo , Neoplasias Cutâneas/classificação , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologiaRESUMO
Both antigenic drive and genetic change play critical roles in the development of mucosa-associated lymphoid tissue (MALT) lymphoma, but neither alone is sufficient for malignant transformation, and lymphoma development critically depends on their cooperation. However, which of these different events concur and how they cooperate in MALT lymphomagenesis is totally unknown. To explore this, we investigated somatic mutations of 17 genes and immunoglobulin heavy chain variable region (IGHV) usage in 179 MALT lymphomas from various sites. We showed that: (1) there was a significant association between the biased usage of IGHV4-34 (binds to the carbohydrate I/i antigens) and inactivating mutation of TNFAIP3 [encoding a global negative regulator of the canonical nuclear factor-κB (NF-κB) pathway] in ocular adnexal MALT lymphoma; (2) IGHV1-69 was significantly overrepresented (54%) in MALT lymphoma of the salivary gland, but was not associated with mutation in any of the 17 genes investigated; and (3) MALT lymphoma lacked mutations that are frequently seen in other B-cell lymphomas characterized by constitutive NF-κB activities, including mutations in CD79B, CARD11, MYD88, TNFRSF11A, and TRAF3. Our findings show, for the first time, a significant association between biased usage of autoreactive IGHV and somatic mutation of NF-κB regulators in MALT lymphoma, arguing for their cooperation in sustaining chronic B-cell receptor signalling and driving oncogenesis in lymphoma development. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias Oculares/genética , Rearranjo Gênico , Inativação Gênica , Genes de Cadeia Pesada de Imunoglobulina , Região Variável de Imunoglobulina/genética , Linfoma de Zona Marginal Tipo Células B/genética , Mutação , Neoplasias de Anexos e de Apêndices Cutâneos/genética , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/genética , Biomarcadores Tumorais/imunologia , Análise Mutacional de DNA , Neoplasias Oculares/imunologia , Neoplasias Oculares/patologia , Predisposição Genética para Doença , Humanos , Região Variável de Imunoglobulina/imunologia , Linfoma de Zona Marginal Tipo Células B/imunologia , Linfoma de Zona Marginal Tipo Células B/patologia , Neoplasias de Anexos e de Apêndices Cutâneos/imunologia , Neoplasias de Anexos e de Apêndices Cutâneos/patologia , Fenótipo , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/imunologiaRESUMO
Mammary analogue secretory carcinoma is a low-grade salivary gland carcinoma that exhibits analogous features to secretory carcinoma of the breast including the presence of a t(12;15) translocation resulting in the ETV6-NTRK3 gene fusion. Rare cases of purported secretory carcinoma of the skin adnexa have been reported, but their relationship to true secretory carcinoma of the breast and salivary glands is unclear, as they generally do not harbor ETV6 rearrangements. Cases of cutaneous neoplasms with histologic features identical to secretory carcinoma of the breast and salivary glands were identified from the consultation files of 3 academic medical institutions. Immunohistochemistry was performed for S100 protein, mammaglobin and STAT5a. Break-apart fluorescence in situ hybridization was used evaluate for disruption of the ETV6 gene. Six cases of cutaneous secretory carcinoma were identified. The tumors arose in 4 women and 2 men, ranging from 24 to 71 years in age (mean, 47 y). The carcinomas presented in the skin of the axilla (n=4), ventral neck (n=1), and cheek (n=1). The tumors arose in the superficial dermis in association with adnexal structures. None of the patients had a prior or concurrent breast or salivary gland tumor. They were histologically characterized by well-circumscribed but unencapsulated proliferations of bland, eosinophilic cells arranged in microcysts and follicles with intraluminal secretions. Ectopic breast or salivary gland tissue was not identified. The cases were diffusely positive for S100 protein (6 of 6), mammaglobin (6 of 6), and STAT5a (5 of 5). All 6 cases harbored rearrangements of ETV6. All tumors were treated by simple excision alone. No recurrences or metastases developed in the 2 cases with follow-up. Secretory carcinoma of the skin represents a phenotypic, immunohistochemical, and genetic counterpart to secretory carcinoma of the breast and salivary glands. This tumor entity is less anatomically restricted than previously supposed.
Assuntos
Carcinoma Secretor Análogo ao Mamário/genética , Proteínas de Fusão Oncogênica/genética , Neoplasias Cutâneas/genética , Adulto , Idoso , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carcinoma/genética , Carcinoma/patologia , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Masculino , Carcinoma Secretor Análogo ao Mamário/patologia , Pessoa de Meia-Idade , Neoplasias de Anexos e de Apêndices Cutâneos/genética , Neoplasias de Anexos e de Apêndices Cutâneos/patologia , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/patologia , Neoplasias Cutâneas/patologia , Adulto JovemRESUMO
TMEM207 was first characterized as being an important molecule for the invasion activity of gastric signet-ring cell carcinoma cells. In order to unravel the pathological properties of TMEM207, we generated several transgenic mouse lines, designated C57BL/6-Tg (ITF-TMEM207), in which murine TMEM207 was ectopically expressed under a truncated (by ~200 bp) proximal promoter of the murine intestinal trefoil factor (ITF) gene (also known as Tff3). Unexpectedly, a C57BL/6-Tg (ITF-TMEM207) mouse line exhibited a high incidence of spontaneous intradermal tumors with histopathological features that resembled those of various human cutaneous adnexal tumors. These tumors were found in ~14% female and 13% of male 6- to 12-month-old mice. TMEM207 immunoreactivity was found in hair follicle bulge cells in non-tumorous skin, as well as in cutaneous adnexal tumors of the transgenic mouse. The ITF-TMEM207 construct in this line appeared to be inserted to a major satellite repeat sequence at chromosome 2, in which no definite coding molecule was found. In addition, we also observed cutaneous adnexal tumors in three other C57BL/6-Tg (ITF-TMEM207) transgenic mouse lines. We believe that the C57BL/6-Tg (ITF-TMEM207) mouse might be a useful model to understand human cutaneous adnexal tumors.
Assuntos
Modelos Animais de Doenças , Proteínas de Membrana/genética , Neoplasias de Anexos e de Apêndices Cutâneos/genética , Neoplasias Cutâneas/genética , Animais , Proteínas de Transporte/genética , Feminino , Humanos , Imuno-Histoquímica , Masculino , Proteínas de Membrana/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Regiões Promotoras GenéticasRESUMO
Sebaceous tumors are epithelial tumors with a differentiation towards sebaceous adnexal structures of the skin. They imitate the epithelial cells of mature sebaceous glands, sebaceous ducts, immature (embryonic) sebaceous structures or sebaceous glands that are not stimulated by hormones (mantle structures). This article explains the classification of sebaceous tumors on the basis of the normal histology of sebaceous glands. Clinical and histopathological criteria are given for the most important sebaceous tumors. The differential diagnosis of sebaceoma, sebaceous adenoma and various types of sebaceous carcinoma is emphasized. The importance of a specific diagnosis of adnexal tumors is demonstrated by tumor-associated syndromes with involvement of other organs (e.g., Muir-Torre syndrome and Birt-Hogg-Dubé syndrome). Furthermore, conceptional controversies, problems in differential diagnosis and the impact of immunohistochemical staining in the assessment of sebaceous tumors are considered.
Assuntos
Neoplasias de Anexos e de Apêndices Cutâneos/patologia , Neoplasias das Glândulas Sebáceas/diagnóstico , Neoplasias das Glândulas Sebáceas/patologia , Proliferação de Células/genética , Transformação Celular Neoplásica/classificação , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Diagnóstico Diferencial , Fibroma/classificação , Fibroma/diagnóstico , Fibroma/genética , Fibroma/patologia , Humanos , Hiperplasia/classificação , Hiperplasia/genética , Hiperplasia/patologia , Síndrome de Muir-Torre/classificação , Síndrome de Muir-Torre/diagnóstico , Síndrome de Muir-Torre/genética , Síndrome de Muir-Torre/patologia , Neoplasias de Anexos e de Apêndices Cutâneos/diagnóstico , Neoplasias de Anexos e de Apêndices Cutâneos/genética , Neoplasias das Glândulas Sebáceas/classificação , Neoplasias das Glândulas Sebáceas/genética , Glândulas Sebáceas/patologia , Pele/patologia , Neoplasias Cutâneas/classificação , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologiaRESUMO
Trichoblastoma is a benign cutaneous adnexal tumor, composed mostly of follicular germinative cells. Its pigmented variant is colonized by numerous dendritic melanocytes. So far, only one case in the literature describes a combination of trichoblastoma and melanoma. We report the case of a 62-year-old man who had a slow-growing mass of the left flank present since childhood. This 8-cm mass was surgically removed when it became ulcerated and associated with axillary lymph nodes. Histologically, this tumor was strictly dermal and composed of 2 intermingled components. Large sheets of atypical, proliferating epithelioid cells predominated. Dispersed solid nests or cribriform epithelial islets encased in fibrous tissue were also seen. Some nests displayed a massive colonization by pigmented dendritic melanocytes. On immunohistochemical staining, the sheets of atypical cells expressed focally but strongly S100 protein, MelanA, HMB45, and MiTF. Epithelial structures diffusely expressed pancytokeratin AE1/AE3, KL1, and pleckstrin homology-like domain, family A, member 1. Based on these results, we diagnosed an intradermal melanoma, possibly developed from dendritic melanocytes colonizing a giant pigmented trichoblastoma. Direct sequencing of the melanoma revealed a rarely described NRAS mutation c.34G>T (G12C). Array comparative genomic hybridization displayed a complex profile somewhat divergent from standard melanoma profiles. The patient died of widespread metastatic disease 8 months after initial diagnosis.
Assuntos
Biomarcadores Tumorais/genética , Hibridização Genômica Comparativa , Análise Mutacional de DNA , GTP Fosfo-Hidrolases/genética , Melanoma/genética , Proteínas de Membrana/genética , Neoplasias de Anexos e de Apêndices Cutâneos/genética , Neoplasias Cutâneas/genética , Biomarcadores Tumorais/análise , Biópsia , Evolução Fatal , Humanos , Imuno-Histoquímica , Masculino , Melaninas/análise , Melanócitos/química , Melanócitos/patologia , Melanoma/química , Melanoma/secundário , Pessoa de Meia-Idade , Mutação , Neoplasias de Anexos e de Apêndices Cutâneos/química , Neoplasias de Anexos e de Apêndices Cutâneos/patologia , Neoplasias de Anexos e de Apêndices Cutâneos/cirurgia , Neoplasias Cutâneas/química , Neoplasias Cutâneas/patologia , Fatores de TempoRESUMO
This article reviews the recent dermatopathology literature regarding cutaneous adnexal neoplasms, with emphasis on new and underrecognized entities, "old entities" with new findings, advances in immunohistochemistry, and new findings in relation to inherited disorders associated with cutaneous adnexal neoplasms.
Assuntos
Neoplasias de Anexos e de Apêndices Cutâneos/patologia , Síndromes Neoplásicas Hereditárias/patologia , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Biópsia , Dermatologia/métodos , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Neoplasias de Anexos e de Apêndices Cutâneos/química , Neoplasias de Anexos e de Apêndices Cutâneos/genética , Síndromes Neoplásicas Hereditárias/genética , Síndromes Neoplásicas Hereditárias/metabolismo , Patologia/métodos , Fenótipo , Valor Preditivo dos Testes , PrognósticoRESUMO
The histologic distinction between microcystic adnexal carcinoma (MAC) and desmoplastic trichoepithelioma (dTE) can be challenging in the setting of a superficial biopsy. However, accurate diagnosis has treatment implication because the standard of care for MAC is wide local excision but more conservative care for dTE. We reviewed the histologic features of 30 MAC and 39 dTE cases and performed cytokeratin (CK) 17, CK19, and epidermal growth factor receptor (EGFR) immunostains on 20 MACs and 18 dTEs. MAC cases occurred in older patients in comparison with dTE (median, 67 years vs. 34 years). The head and neck was the most commonly involved site, 88% and 89% for MAC and dTE, respectively. In addition to features previously reported as specific for MAC, such as skeletal muscle and subcutaneous tissue invasion, perineural invasion, and ductal differentiation, we found the presence of mitotic figures to be significantly more frequent in MAC cases (P < 0.0001). In contrast, the presence of keratocyst, keratin granuloma, and calcification was significantly more frequent in dTE cases (P < 0.0001). CK19 seems to be a helpful adjunct because its expression was seen in 70% (14/20) of MAC versus 22% (4/18) of dTE cases (P = 0.0044); however, the clinical usefulness in individual cases may be limited because of the overlapping immunoprofile. CK17 and EGFR expression was seen in all the MAC and dTE cases. Low polysomy of EGFR gene was observed in only one MAC case, suggesting that molecular mechanisms other than gene amplification play a role in EGFR overexpression.
Assuntos
Carcinoma/patologia , Neoplasias de Anexos e de Apêndices Cutâneos/patologia , Neoplasias Cutâneas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Biópsia , Carcinoma/química , Carcinoma/genética , Diagnóstico Diferencial , Receptores ErbB/análise , Receptores ErbB/genética , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Queratina-17/análise , Queratina-19/análise , Masculino , Pessoa de Meia-Idade , Neoplasias de Anexos e de Apêndices Cutâneos/química , Neoplasias de Anexos e de Apêndices Cutâneos/genética , Valor Preditivo dos Testes , Neoplasias Cutâneas/química , Neoplasias Cutâneas/genética , Adulto JovemRESUMO
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.
Assuntos
Mutação , Neoplasias de Anexos e de Apêndices Cutâneos/genética , Neoplasias de Anexos e de Apêndices Cutâneos/patologia , Neoplasias Primárias Múltiplas/genética , Neoplasias Primárias Múltiplas/patologia , Síndromes Neoplásicas Hereditárias/genética , Síndromes Neoplásicas Hereditárias/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Pele/patologia , Proteínas Supressoras de Tumor/genética , Adolescente , Adulto , Idoso , Biópsia , Cromossomos Humanos Par 16 , Análise Mutacional de DNA , Enzima Desubiquitinante CYLD , Feminino , Predisposição Genética para Doença , Hereditariedade , Humanos , Perda de Heterozigosidade , Masculino , Pessoa de Meia-Idade , Fenótipo , Valor Preditivo dos Testes , Estudos RetrospectivosRESUMO
Two unusual Carney complex patients are described. In one of them, several cutaneous biopsies revealed myxoid lesions that were rather more close to authentic adnexal neoplasms with myxoid stroma than to a "myxoma with an epithelial component." These included lesions resembling trichofolliculoma, infundibular cyst, and trichodiscoma. Additionally, 1 soft tissue myxoma was unique in the sense that it greatly resembled a cardiac myxoma, begging the question whether this could represent an embolus from the patient's cardiac myxoma. Given the large size and complexity and heterogeneity of the cutaneous lesions, the authors suggest that these may represent authentic cutaneous neoplasms accompanied by myxoid stroma and not adnexal elements induced by the stroma. However, the latter mechanism is well recognized and demonstrated by our second patient in whom adnexal-type elements in the cutaneous lesion were clearly induced by the myxoid stroma but were unusually complex by manifesting panfollicular and also sebaceous differentiation.
Assuntos
Complexo de Carney/patologia , Neoplasias de Anexos e de Apêndices Cutâneos/patologia , Neoplasias Cutâneas/patologia , Neoplasias de Tecidos Moles/patologia , Adulto , Idoso , Biópsia , Complexo de Carney/genética , Diferenciação Celular , Subunidade RIalfa da Proteína Quinase Dependente de AMP Cíclico/genética , Análise Mutacional de DNA , Feminino , Humanos , Masculino , Mutação , Neoplasias de Anexos e de Apêndices Cutâneos/genética , Neoplasias Cutâneas/genética , Neoplasias de Tecidos Moles/genética , Células Estromais/patologiaRESUMO
Cancers derived from anogenital mammary-like glands are rare, and their identification and selection of treatment for dissemination may be difficult. We encountered two such tumors, which both presented as occult primaries with nodal and hematogenous metastases. They were studied by immunohistochemistry, HER2 receptor assay, and gene expression profiling. Both tumors had some microscopical and immunohistochemical features in common with breast cancer, but lacked estrogen and progesterone receptors. Taxane-platinum-based systemic chemotherapy did not stop progression in a male patient, in whom a developing inguinal skin lesion was the likely primary tumor. The same regimen gave partial remission in a later, female, patient. After the mammary-like, HER2 positive nature of her tumor was confirmed by gene expression profiling using CupPrint and TargetPrint assays, treatment with vinorelbine-trastuzumab induced complete remission that is maintained by trastuzumab alone for almost 4 years after initial diagnosis. Molecular and immunohistochemical characterization of these rare tumors may identify them and sometimes guide systemic chemotherapy away from a non-specific and "broad spectrum" regimen toward a targeted therapy, resulting in greater effectiveness with less side effects.
Assuntos
Perfilação da Expressão Gênica , Metástase Linfática/patologia , Neoplasias de Anexos e de Apêndices Cutâneos/diagnóstico , Neoplasias Primárias Desconhecidas/diagnóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Feminino , Virilha/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias de Anexos e de Apêndices Cutâneos/tratamento farmacológico , Neoplasias de Anexos e de Apêndices Cutâneos/genética , Neoplasias Primárias Desconhecidas/tratamento farmacológico , Neoplasias Primárias Desconhecidas/genética , Receptor ErbB-2/genéticaRESUMO
Adnexal tumors with follicular differentiation in the breast parenchyma are rarely encountered. The authors present a unique case arising in a 64-year-old woman, in whom they observed composite differentiation toward follicular germinative cells of the hair follicle with focal areas of outer root sheath differentiation and pilar-type keratinization. The histogenesis of this tumor is analyzed in light of the peculiar pathological, immunohistochemical, and molecular genetic findings.
Assuntos
Neoplasias da Mama/patologia , Folículo Piloso/patologia , Neoplasias de Anexos e de Apêndices Cutâneos/patologia , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/cirurgia , Transformação Celular Neoplásica , Feminino , Doenças do Cabelo/genética , Doenças do Cabelo/metabolismo , Doenças do Cabelo/patologia , Doenças do Cabelo/cirurgia , Humanos , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Neoplasias de Anexos e de Apêndices Cutâneos/genética , Neoplasias de Anexos e de Apêndices Cutâneos/metabolismo , Neoplasias de Anexos e de Apêndices Cutâneos/cirurgia , beta Catenina/genéticaRESUMO
We report an unusual case of aggressive turban tumor syndrome in a 38-year-old woman with nodules covering her scalp and involving her face, neck, chest, and back. To address concerns regarding hygiene of the scalp and cosmetic disfigurement, she underwent total scalp excision with advancement flap and skin graft reconstruction. Histologic examination of the scalp tumors revealed a predominance of spiradenomas, along with cylindromas and trichoepitheliomas, and tumors containing elements of all 3 of these adnexal neoplasms. We review the literature regarding turban tumor syndrome including the genetic basis for this condition, clinical features, pathology, and treatment.