The presence of neuroendocrine features generates a broad differential diagnosis in the fine-needle aspiration of bone and soft tissue neoplasms

Introduction Biopsy of bone and soft tissue (BST) lesions occasionally yields neoplasms with neuroendocrine (NE) features. We identify a differential diagnosis for neoplasms containing NE features when encountered on fine-needle aspiration (FNA) of BST masses. Materials and methods The cytopathology archives of the Johns Hopkins Hospital were searched for any BST FNA specimen diagnosed as a neoplasm with NE features or in which NE immunohistochemical (IHC) markers were ordered. Specimen diagnoses were reviewed and specimens were excluded if neuroendocrine features were not considered at the time of original diagnosis. Results A total of 179 specimens met the inclusion criteria. Of these, 64 (36%) and 115 (64%) neoplasms were primary and metastatic, respectively. A total of 29 distinct entities were identified. Sixteen were entities with established NE differentiation and 13 were entities not typically regarded as having an NE origin. The most commonly encountered neoplasms included small cell carcinoma of all primary locations (38), Ewing sarcoma (37), medullary thyroid carcinoma (24), Merkel cell carcinoma (23), and paraganglioma (10). NE IHC markers were ordered in 45% of cases; 86% were positive by at least one NE marker. Entities with established NE differentiation were more likely to be positive for NE IHC than those not typically regarded as having NE differentiation (100% and 59%, respectively). Conclusions A variety of BST lesions—including neoplasms not typically thought to have neuroendocrine differentiation—can possess NE cytomorphologic features and/or NE IHC marker positivity. The patient's clinical presentation and history can help narrow the differential diagnosis.