RESUMO
Secretory carcinoma of the skin is an extremely rare adnexal tumor, histopathologically identical to homologous lesions in the salivary glands and breast tissue. Although this tumor was previously reported as indolent, we report a case of secretory carcinoma of the skin with metastases and recurrence. The patient, a 31-year-old women, had a subcutaneous mass in the right axilla. The resected specimen contained a circumscribed mass, with proliferating tumor cells that exhibited prominent nucleoli. They exhibited glandular and papillary growth patterns and there were amphophilic secretions in the glands. Immunohistochemically, the tumor cells were positive for mammaglobin and S100. The tumor was surrounded by sweat glands and there was no mammary glandular tissue, suggesting that it was derived from axillary sweat glands. Accordingly, we made a diagnosis of secretory carcinoma of the skin. Four years after the operation, there were metastases in both lungs. The resected specimen revealed a tumor identical to that of the original skin tumor. Next-generation sequencing-based multiplex gene assay performed on the metastatic tissue revealed an ETV6-NTRK3 fusion gene. This is a rare case report of secretory carcinoma of the skin with lymph node metastases and recurrence in both lungs.
Assuntos
Neoplasias Pulmonares/secundário , Metástase Linfática/patologia , Carcinoma Secretor Análogo ao Mamário/diagnóstico , Neoplasias Cutâneas/patologia , Glândulas Sudoríparas/patologia , Adulto , Diagnóstico Diferencial , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Imuno-Histoquímica/métodos , Neoplasias Pulmonares/cirurgia , Metástase Linfática/radioterapia , Carcinoma Secretor Análogo ao Mamário/metabolismo , Carcinoma Secretor Análogo ao Mamário/secundário , Carcinoma Secretor Análogo ao Mamário/cirurgia , Recidiva Local de Neoplasia , Proteínas de Fusão Oncogênica/genética , Proteínas S100/metabolismo , Secretoglobinas/metabolismo , Glândulas Sudoríparas/metabolismo , Cirurgia Torácica Vídeoassistida/métodosRESUMO
Secretory carcinoma of the salivary glands, also known as mammary analogue secretory carcinoma, is a recently described tumor characterized by generally indolent clinical behavior and recurrent ETV6-NTRK3 fusions. However, a small subset of recent cases with high-grade histology, aggressive behavior, or alternate molecular findings are expanding the spectrum of this entity. In this case, a 59-year-old female presented with an infiltrative submandibular gland tumor that was originally classified as a high-grade acinic cell carcinoma, papillary-cystic variant. She developed persistent local disease and, 11 years after initial presentation, was found to have widespread metastases. Rereview of her primary tumor highlighted microcystic, papillary, and solid architecture, eosinophilic cytoplasm, vesicular nuclei with prominent nucleoli, abundant mitotic figures, and necrosis. Immunostains showed the tumor cells to be positive for S100 and mammaglobin and negative for DOG-1, and fluorescence in situ hybridization highlighted an ETV6 rearrangement, supporting a diagnosis of high-grade secretory carcinoma. Finally, next-generation sequencing demonstrated a novel ETV6-MET fusion. To our knowledge, this is the first ETV6-MET fusion reported in secretory carcinoma. This finding further expands the definition of secretory carcinoma while carrying implications for selecting appropriate targeted therapy.
Assuntos
Biomarcadores Tumorais/genética , Fusão Gênica , Carcinoma Secretor Análogo ao Mamário/genética , Proteínas Proto-Oncogênicas c-ets/genética , Proteínas Proto-Oncogênicas c-met/genética , Proteínas Repressoras/genética , Neoplasias das Glândulas Salivares/genética , Biomarcadores Tumorais/análise , Feminino , Predisposição Genética para Doença , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Carcinoma Secretor Análogo ao Mamário/química , Carcinoma Secretor Análogo ao Mamário/secundário , Carcinoma Secretor Análogo ao Mamário/terapia , Pessoa de Meia-Idade , Gradação de Tumores , Fenótipo , Neoplasias das Glândulas Salivares/química , Neoplasias das Glândulas Salivares/patologia , Neoplasias das Glândulas Salivares/terapia , Variante 6 da Proteína do Fator de Translocação ETSRESUMO
BACKGROUND: Salivary gland secretory carcinoma is usually a low-grade neoplasm. However, high-grade transformation can occur and has important implications for clinical outcome. METHODS: A patient presented with an enlarging buccal mass. Magnetic resonance imaging (MRI) showed a tumor with a biphasic appearance along the right parotid duct. Local excision and histopathologic examination confirmed the diagnosis of secretory carcinoma with high-grade transformation. ETV6-NTRK3 translocation and loss of CDKN2A/B were identified. RESULTS: The patient subsequently presented with cough and dyspnea and was found to have pleural metastases. Carboplatin and paclitaxel exacerbated the symptoms. Crizotinib resulted in initial symptomatic and radiographic improvement; however, the patient soon succumbed to progressive intrathoracic disease. CONCLUSIONS: High-grade salivary gland secretory carcinoma can have a biphasic appearance on MRI. Diagnosis is confirmed by the histologic appearance and associated ETV6-NTRK3 fusion. Additional molecular genetic events leading to transformation are unknown; however, loss of CDKN2A/B may have contributed. Treatment with multimodal chemotherapy was of limited benefit.
