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INTRODUCTION: Primary carcinomas of the trachea are rare, with a reported annual incidence of one in a million. We present a case of a previously undescribed polypoid high-grade neuroendocrine carcinoma of the trachea. Resection of the carcinoma revealed only superficial invasion of the mucosa and without evidence of local or distant metastatic disease. Histologically, the tumor had high-grade features with necrosis and a high mitotic index. METHODS: Characterization of this rare neuroendocrine carcinoma of the trachea was performed by immunohistochemistry and whole-genome sequencing. RESULTS: Immunohistochemistry result was positive for neuroendocrine markers, p16 and an elevated Ki-67. Whole-genome sequencing of the lesion was performed and revealed a very unusual and very distinct mutational signature without relationship to other relevant neuroendocrine carcinomas. Neither known driver nor targetable mutations were found by whole-genome sequencing. Analysis of the sequence of numerous viral elements of human papillomavirus-18 suggests that the pathogenesis of the lesion is related to viral integration. The patient developed distal recurrence, which progressed to widespread pulmonary dissemination, presumably through aerogenous spread of disease. CONCLUSIONS: This is the first characterization of this type of tracheal tumor, including genomic findings, pathogenesis, and natural history.
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High-grade transformation (HGT) or "dedifferentiation" is an uncommon phenomenon among salivary gland carcinomas including adenoid cystic carcinoma (ACC), which is important to recognize because it is associated with increased tumor aggressiveness, with a high propensity for lymph node and distant metastases. ACC with HGT is histologically characterized by a distinct population of poorly differentiated cells with loss of the typical biphasic ductal and myoepithelial differentiation seen in conventional ACC, associated with pleomorphism, necrosis and increased mitotic activity. We report the cytologic features of a case of metastatic ACC-HGT in cervical lymph node and effusion, which, to the best of our knowledge, have not been described previously. When ACC presents both in atypical locations and with HGT, the danger of misdiagnosis is increased if the clinical history is lacking, incomplete or inaccurate. Since ACC-HGT are rare (and possibly underdiagnosed) and do not have a specific set of cytological and/or immunohistochemical features, it is important for practicing cytopathologists to be aware of the possibility of encountering them, especially in specimens from patients with a history of ACC, in order to render the correct diagnosis.
