RESUMO
BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive malignant neuroendocrine tumour. There are two subsets of MCC, one related to Merkel cell polyomavirus (MCPyV) and the other to ultraviolet radiation (UVR). MCPyV-positive and MCPyV-negative MCCs have been considered to be different tumours, as the former harbour few DNA mutations and are not related to UVR, and the latter usually arise in sun-exposed areas and may be found in conjunction with other keratinocytic tumours, mostly squamous cell carcinomas. Two viral oncoproteins, large T antigen (LT; coded by MCPyV_gp3) and small T antigen (sT; coded by MCPyV_gp4), promote different carcinogenic pathways. OBJECTIVES: To determine which genes are differentially expressed in MCPyV-positive and MCPyV-negative MCC; to describe the mutational burden and the most frequently mutated genes in both MCC subtypes; and to identify the clinical and molecular factors that may be related to patient survival. METHODS: Ninety-two patients with a diagnosis of MCC were identified from the medical databases of participating centres. To study gene expression, a customized panel of 172 genes was developed. Gene expression profiling was performed with nCounter technology. For mutational studies, a customized panel of 26 genes was designed. Somatic single nucleotide variants (SNVs) were identified following the GATK Best Practices workflow for somatic mutations. RESULTS: The expression of LT enabled the series to be divided into two groups (LT positive, n = 55; LT negative, n = 37). Genes differentially expressed in LT-negative patients were related to epithelial differentiation, especially SOX9, or proliferation and the cell cycle (MYC, CDK6), among others. Congruently, LT displayed lower expression in SOX9-positive patients, and differentially expressed genes in SOX9-positive patients were related to epithelial/squamous differentiation. In LT-positive patients, the mean SNV frequency was 4.3; in LT-negative patients it was 10 (P = 0.03). On multivariate survival analysis, the expression of SNAI1 [hazard ratio (HR) 1.046, 95% confidence interval (CI) 1.007-1.086; P = 0.02] and CDK6 (HR 1.049, 95% CI 1.020-1.080; P = 0.001) were identified as risk factors. CONCLUSIONS: Tumours with weak LT expression tend to co-express genes related to squamous differentiation and the cell cycle, and to have a higher mutational burden. These findings are congruent with those of earlier studies.
Merkel cell carcinoma (MCC) is an aggressive form of skin tumour. There are two subtypes of MCC: one of them is related to a virus called Merkel cell polyomavirus (MCPyV); the other one is related to persistent exposure to sunlight. The aim of this research was to find differences between these subtypes in their molecular behaviour (the genes that are expressed and the mutations that may be found). To do this, we carried out two studies, one to investigate gene expression (the process cells use to convert the instructions in our DNA into a functional product such as a protein) and one to look at gene mutations (changes in the DNA sequence). We found that the tumours that were not related to MCPyV expressed genes related to epithelial differentiation (the process by which unspecialized cells gain features characteristics of epithelial cells, which, among other things, make up the outer surface of the body), which means that the origin of both MCC subtypes may be different. We also found that MCPyV-related tumours had fewer mutations. Our findings are important because they help us to understand the biology of the MCC subtypes and could help with the development of new treatments for people diagnosed with skin tumours.
Assuntos
Antígenos Virais de Tumores , Carcinoma de Célula de Merkel , Poliomavírus das Células de Merkel , Infecções por Polyomavirus , Fatores de Transcrição SOX9 , Neoplasias Cutâneas , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antígenos Virais de Tumores/genética , Carcinoma de Célula de Merkel/virologia , Carcinoma de Célula de Merkel/genética , Carcinoma de Célula de Merkel/patologia , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Poliomavírus das Células de Merkel/genética , Poliomavírus das Células de Merkel/isolamento & purificação , Mutação , Infecções por Polyomavirus/genética , Infecções por Polyomavirus/virologia , Neoplasias Cutâneas/virologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Fatores de Transcrição SOX9/genética , Infecções Tumorais por Vírus/genética , Infecções Tumorais por Vírus/virologiaRESUMO
Mycosis fungoides (MF) has been widely reported to mimick a considerable number of different dermatoses, including scarring alopecia, bullous dermatoses or cysts, and comedones. In atypical presentations, histopathology is essential for the diagnosis. We present two cases of MF with clinical urticarial lesions and a striking blood involvement that responded to mogamulizumab treatment. Histopathologically, both cases had classic MF features and shared a peculiar immunophenotype, with positivity for CD25 and FOXP3. Differential diagnoses included urticarial lymphomatoid drug reactions and other lymphomas, like T-cell prolymphocytic leukemia, atypical Sézary syndrome, or adult T-cell lymphocytic leukemia. A low suspicion threshold is necessary for the diagnosis of atypical presentations of MF.
Assuntos
Imunofenotipagem , Micose Fungoide , Neoplasias Cutâneas , Humanos , Micose Fungoide/patologia , Micose Fungoide/diagnóstico , Neoplasias Cutâneas/patologia , Masculino , Imunofenotipagem/métodos , Diagnóstico Diferencial , Pessoa de Meia-Idade , Feminino , Urticária/patologia , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Idoso , Fatores de Transcrição ForkheadRESUMO
ABSTRACT: Perineural infiltration refers to a neoplastic cell involvement in, around, and through the nerves. It is considered as one of the neoplastic dissemination pathways. Thus, its identification is crucial to establish the prognosis of some malignant skin neoplasms, such as squamous cell carcinoma, and explains the locally aggressive behavior of cutaneous neoplasms, such as microcystic adnexal carcinoma. We have conducted a review of malignant and benign skin tumors in which perineural infiltration has been described, and we also discuss some histopathological findings that may simulate perineural infiltration.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Anexos e de Apêndices Cutâneos , Neoplasias Cutâneas , Humanos , Prognóstico , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/terapia , Neoplasias Cutâneas/patologia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/patologiaRESUMO
Papillary dermal elastolysis is a rare acquired disease of the elastic tissue that mainly affects elderly women with a clinical presentation of small firm papules in the neck, the supraclavicular areas and the upper back. Histopathologically, it is characteristic to find a complete or almost complete absence of elastic fibers in the papillary dermis with stains such as orcein or Verhoeff-Van Gieson. We present the case of an adult female patient presenting a clinical picture of years of evolution of elastic skin-colored papules on her neck, occasionally pruritic. Two biopsies were performed. In one of them an inflammatory infiltrate affecting the hair follicles was observed, and she was diagnosed with mycosis fungoides. The other biopsy showed a total absence of elastic fibers in the papillary dermis and was diagnosed as elastolysis of the papillary dermis. In early stages of papillary dermal elastolysis, a perivascular and periadnexal lymphocytic inflammatory infiltrate has been described, as is the case described above. It is important for dermatopathologist to know this atypical but possible presentation, as it may require a differential diagnosis with other entities such as follicular mycosis fungoides.
Assuntos
Cútis Laxa , Micose Fungoide , Neoplasias Cutâneas , Adulto , Feminino , Humanos , Idoso , Tecido Elástico/patologia , Micose Fungoide/diagnóstico , Micose Fungoide/patologia , Cútis Laxa/patologia , Derme/patologia , Neoplasias Cutâneas/patologiaRESUMO
BACKGROUND: Median raphe cysts (MRC) are epithelial-lined cystic lesions of the genital area that do not communicate with the urethra or the overlying epidermis. Immunohistochemically, MRC show positivity for cytokeratin (CK) 5-6, CK 7, carcinoembryonic antigen, p63 and uroplakin III (URO III). GATA3 and human milk fat globulin 1 (HMFG1) are immunohistochemical markers that have been not previously studied in MRC. METHODS: We conducted a study of 52 patients diagnosed with MRC in the Pathology Departments of eight hospitals between 1990 and 2016. The monoclonal antibodies used were CK5-6, CK7, CK20, URO III, p63, GATA3, and HMFG1. HMFG1 was studied in five cases of apocrine hidrocystomas and compared with five cases of MRC from our series. RESULTS: CK 5-6, CK7, and p63 expression showed strong positivity in the urothelial epithelium of 48 cases. CK20 was focally positive in areas of mucinous differentiation in three cases. GATA3 showed intense nuclear staining in 30 cases. HMFG1 was positive in three cases of MRC and in three cases of apocrine hidrocystoma. CONCLUSION: Positivity of GATA3 and CK7 in MRC supports the urothelial origin of these cysts. We found no differences in HMFG1 expression between MRC and apocrine hidrocystomas.
Assuntos
Cistos , Hidrocistoma , Neoplasias das Glândulas Sudoríparas , Humanos , Imuno-Histoquímica , Cistos/patologia , Biomarcadores Tumorais/metabolismoRESUMO
Pigmented epidermotropic breast cancer metastases are a rarity, often clinically misdiagnosed as melanocytic lesions. Histopathologically, they show a dermal proliferation of neoplastic metastatic cells that extend to the overlying epidermis in a pattern identical to that seen in primary Paget disease (PD). Differential diagnosis should be established with entities with a similar presentation, such as pigmented mammary PD and malignant melanoma. Immunohistochemistry may be useful for this purpose. We present a new case of pigmented epidermotropic breast cancer metastases with a particularly unusual feature: the absence of dermal infiltration by neoplastic cells, thus considered as pure epidermotropic metastatic involvement.
Assuntos
Neoplasias da Mama , Melanoma , Neoplasias Cutâneas , Adulto , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/secundário , Diagnóstico Diferencial , Feminino , Humanos , Melanoma/diagnóstico , Melanoma/metabolismo , Melanoma/patologia , Metástase Neoplásica , Doença de Paget Mamária/diagnóstico , Doença de Paget Mamária/metabolismo , Doença de Paget Mamária/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Melanoma Maligno CutâneoRESUMO
ABSTRACT: Circumscribed palmar or plantar hypokeratosis is a focal disorder of keratinization that consists of a reduction in the thickness of the corneal layer of the epidermis of palms or soles. Although it is considered a benign entity, the thinning of the stratum corneum facilitates ultraviolet damage in the affected skin, which may result in an increased risk of developing focal epidermal dysplasia. Other factors, such as immunosuppression in transplanted patients, may play a role as well. We present a case of circumscribed palmar or plantar hypokeratosis with features of Bowen disease limited to the hypokeratotic epidermis.
Assuntos
Neoplasias do Ânus , Doença de Bowen , Dermatoses da Mão , Ceratose , Neoplasias Cutâneas , Humanos , Doença de Bowen/patologia , Ceratose/patologia , Dermatoses da Mão/patologia , Epiderme/patologia , Neoplasias do Ânus/patologia , Hiperplasia/patologia , Neoplasias Cutâneas/patologiaRESUMO
ABSTRACT: Tattoos are characterized by the introduction of exogenous pigments into the dermis. Tattoos usually serve cosmetic purposes, although they may have other causes, such as traumatic pigment implants in accidents or medical-related tattoos in the context of radiotherapy. Dermatologic adverse reactions are relatively uncommon, and they include infections, immune-mediated reactions, cutaneous lesions secondary to the Koebner phenomenon, exacerbation of preexisting dermatosis, benign and malignant neoplasms, and a miscellaneous group of dermatologic conditions that may appear in a preexisting tattoo. The aim of this study is to review the types of histopathologic reactions that may appear in a preexisting permanent tattoo.
Assuntos
Dermatopatias , Tatuagem , Humanos , Dermatopatias/etiologia , Dermatopatias/patologia , Tatuagem/efeitos adversosRESUMO
ABSTRACT: The presence of neoplastic melanocytes within the eccrine apparatus into the reticular dermis and/or subcutaneous tissue is extremely rare. The staging of syringotropic melanomas and their biological behavior are still controversial. We present 6 new cases of syringotropic melanoma and their main histopathologic features; review the previous literature; and discuss about the origin, staging, and prognosis of this rare variant of melanoma.
Assuntos
Melanócitos/patologia , Melanoma/patologia , Neoplasias Cutâneas/patologia , Glândulas Sudoríparas/patologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Biópsia , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Masculino , Melanócitos/química , Melanoma/química , Melanoma/cirurgia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Neoplasias Cutâneas/química , Neoplasias Cutâneas/cirurgia , Glândulas Sudoríparas/química , Glândulas Sudoríparas/cirurgia , Resultado do TratamentoRESUMO
Microcystic adnexal carcinoma (MAC) is a low-grade adnexal carcinoma with controversial lines of differentiation. We present here an example of MAC showing histopathologic findings of germinative follicular differentiation in the form of solid aggregates of trichoblastoma intermingled with neoplastic aggregates of MAC. Immunohistochemical findings, showing positivity for PHLDA1 and negativity for BerEp4 in neoplastic aggregates of trichoblastoma, also supported a germinative follicular differentiation. Follicular differentiation in MAC supports an apocrine line of differentiation for this neoplasm.
Assuntos
Neoplasias de Anexos e de Apêndices Cutâneos/patologia , Neoplasias Cutâneas/patologia , Idoso , Diferenciação Celular , Humanos , Masculino , Nariz/patologiaRESUMO
Targeted anticancer therapy is being used with greater frequency and dermatologic toxicities are among the most frequent adverse events of these drugs. However, histopathological features of these adverse events are not yet well characterized. We present two cases of clinically different cutaneous toxicities on two patients with hematologic neoplasia. They were treated with different drugs and in both cases medications shared inhibition of PI3K as mechanism of action. The skin biopsy specimen showed endothelial cell atypia with large nuclei and mitotic figures. To the best of our knowledge, no other cases with these striking histopathologic findings have been reported with PI3K inhibitors or other anticancer targeted therapy.
Assuntos
Toxidermias/patologia , Exantema/induzido quimicamente , Neoplasias Hematológicas/tratamento farmacológico , Terapia de Alvo Molecular/efeitos adversos , Inibidores de Fosfoinositídeo-3 Quinase/efeitos adversos , Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Idoso , Antineoplásicos/toxicidade , Benzotiazóis/efeitos adversos , Benzotiazóis/uso terapêutico , Biópsia , Toxidermias/tratamento farmacológico , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/uso terapêutico , Feminino , Neoplasias Hematológicas/complicações , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/uso terapêutico , Pessoa de Meia-Idade , Compostos de Fenilureia/efeitos adversos , Compostos de Fenilureia/uso terapêutico , Inibidores de Fosfoinositídeo-3 Quinase/uso terapêutico , Pirazóis/efeitos adversos , Pirazóis/uso terapêutico , Pirimidinas/efeitos adversos , Pirimidinas/uso terapêutico , Pirrolidinas/efeitos adversos , Pirrolidinas/uso terapêutico , Pele/patologia , Resultado do TratamentoRESUMO
Toker cells (TCs) are sometimes present in the nipple epidermis as oval cells with pale cytoplasm and roundish nuclei. In most cases, TCs may be easily distinguished from cancerous cells of Paget disease of the nipple (PCs). Especially in TC hyperplasia, in which mild-to-moderate atypia may be present, it may be challenging to distinguish between TCs and PCs. The combination of chronic inflammatory changes in the nipple, in the context of Zuska disease, and TC hyperplasia, may easily lead to an erroneous diagnosis of mammary Paget disease.
Assuntos
Abscesso/diagnóstico , Abscesso/patologia , Doenças Mamárias/diagnóstico , Doenças Mamárias/patologia , Fístula/diagnóstico , Fístula/patologia , Mamilos/patologia , Adulto , Neoplasias da Mama/patologia , Diagnóstico Diferencial , Feminino , Humanos , Hiperplasia/diagnóstico , Hiperplasia/patologia , Doença de Paget Mamária/patologia , Fumar/efeitos adversosRESUMO
ABSTRACT: Microcystic adnexal carcinoma (MAC) is a low-grade malignant neoplasm of slow growth and low metastatic potential, but locally aggressive. Architecturally, MAC is usually a poorly circumscribed neoplasm that tends to extend deeply into the dermis and subcutaneous tissue. We present here a lesion in which the histopathologic study showed a well-demarcated nodular lesion involving the mid dermis and composed of small cystic keratinous structures, solid aggregates of pale squamous cells without cytologic atypia and ductal structures. Although these neoplastic components resembled those of MAC, the sharp delimitation of the lesion as well as the absence of deep extension and perineural involvement supported the benign nature of this lesion. We have named this neoplasm microcystic adnexal adenoma, as the benign counterpart of MAC.
Assuntos
Adenoma/patologia , Doenças do Pé/patologia , Neoplasias de Anexos e de Apêndices Cutâneos/patologia , Neoplasias Cutâneas/patologia , Adenoma/cirurgia , Derme/patologia , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
BACKGROUND/OBJECTIVES: Primary cutaneous lymphomas are rare in pediatric patients. The clinical and histopathological manifestations may differ from those in adults. Due to their low frequency and the insidious clinical picture, the diagnosis is usually delayed. The Spanish Primary Cutaneous Lymphoma Registry was initiated in 2016 as a multicenter registry that would allow better insight into the epidemiological, clinical, histopathological, and treatment response characteristics of patients with primary cutaneous lymphomas. METHODS: We conducted a prospective observational cohort study of primary cutaneous lymphomas in pediatric patients participating in the Spanish Academy of Dermatology and Venereology (AEDV) Primary Cutaneous Lymphoma Registry. RESULTS: At the time of the analysis, 10 patients under 18 years of age out of 799 all-age cases (1.25%) had been included in the registry (7 males, 3 females). The mean age at diagnosis was 9.7 years (SD: 4.8). Seven (70%) had mycosis fungoides, 2 of them had the folliculotropic variant; and 3 (30%) had primary cutaneous marginal zone B-cell lymphoma. CONCLUSIONS: Primary cutaneous lymphomas are extremely rare in pediatric patients and usually have a good prognosis. Therefore, a high level of suspicion is necessary for the diagnosis. We suggest management by experienced physicians and follow-up into adulthood.
Assuntos
Dermatologia , Micose Fungoide , Neoplasias Cutâneas , Venereologia , Adolescente , Adulto , Criança , Humanos , Estudos Prospectivos , Sistema de Registros , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/terapiaRESUMO
Pagetoid reticulosis (PR) is a rare lymphoproliferative disorder with indolent behavior considered a variant of mycosis fungoides. It is characterized by marked epidermotropism of the neoplastic lymphocytes. Since its original description, five cases have been reported in children. We report a new case of PR with an immunohistochemical profile not previously described in children.
Assuntos
Imuno-Histoquímica/métodos , Reticulose Pagetoide/metabolismo , Neoplasias Cutâneas/patologia , Administração Tópica , Adolescente , Biópsia , Criança , Pré-Escolar , Clobetasol/administração & dosagem , Clobetasol/uso terapêutico , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Imunofenotipagem/métodos , Linfócitos/patologia , Linfócitos/ultraestrutura , Transtornos Linfoproliferativos/patologia , Masculino , Micose Fungoide/patologia , Pele/patologia , Resultado do TratamentoRESUMO
BACKGROUND: Non-neural granular cell tumor (NNGCT) is an uncommon neoplasm of controversial histogenesis and its histopathologic differential diagnosis includes, in addition to conventional GCT, other dermal tumors that may exhibit granular cell change. METHODS: Three patients with a diagnosis of NNGCT were identified in the authors' files. Hematoxylin and eosin-stained sections and immunohistochemical studies were performed. RESULTS: Histopathological study of the three lesions showed dermal proliferation of granular cells arranged in thick fascicles between collagen bundles. The lesions showed positivity for Factor XIIIa, CD163, CD68, NKIC3, vimentin, ALK, fascin, and cyclin D1. CONCLUSION: To our knowledge, positivity for cyclin D1 has not been reported to date in NNGCT. In borderline cases, where the diagnosis is unclear despite histopathologic and immunohistochemical findings, positivity for cyclin D1 may favor the diagnosis of NNGCT. Further investigations to assess the differentiation of this rare neoplasm are needed.