Moderately Differentiated Neuroendocrine Carcinoma (Atypical Carcinoid) of the Parotid Gland: Report of Three Cases with Contemporary Review of Salivary Neuroendocrine Carcinomas

Abstract

Primary neuroendocrine carcinomas (NECs) of the salivary glands are rare. Most reported NECs in that region are small cell carcinomas with few cases of large cell undifferentiated carcinoma and typical carcinoid tumors. Only two moderately differentiated NECs (atypical carcinoid tumors) have been previously reported. In the current series, the authors report three additional moderately differentiated NECs (atypical carcinoid tumors) of the parotid gland; two occurred in women and one in a man. All patients were initially treated with parotidectomy, with selective lymph node excision in one, and radiation therapy in another. Follow-up was available for two cases (18 and 79 months). One patient had two local recurrences, developing lymph node and liver metastases requiring further surgery and chemotherapy. Currently, she is alive with disease, on supportive care. The second patient is alive with no signs of recurrence. Patients' work-up excluded the possibility of metastatic NECs to the salivary glands in all cases. Histologically, the tumors demonstrated infiltrating nests, cords and trabeculae of round, oval to spindle shaped cells with moderate to focally abundant eosinophilic cytoplasm, small to prominent nucleoli and chromatin stippling. Scattered rosette-like structures were prominent in one tumor. The highest mitotic counts for the three tumors ranged from 5 to 8 mitotic figures/10hpfs. Necrosis, focal but distinct, was noted in two tumors, vascular invasion in two tumors and perineural invasion in one tumor. Immunohistochemical staining was diagnostic of neuroendocrine carcinoma, showing uniform positive labeling with broad-spectrum cytokeratin (with a paranuclear punctuate pattern in one case), chromogranin and synaptophysin antibodies. CK20 was negative in two tumors and stained rare cells (\1 %) in the third.

Neuroendocrine Neoplasms of the Head and Neck: Some Suggestions for the New WHO Classification of Head and Neck Tumors

“…Wenig et al [3] in their series of ''moderately differentiated'' NEC reported that 38 % (18/48) of patients had died with tumor. One of two patients with ''moderately differentiated NEC'' of parotid gland described by Said-Al-Naief [28] was alive with liver metastases whereas the patient illustrated by Modlin et al [29] was alive with stable metastatic disease in the liver 10 years after initial diagnosis. We stress the need of collaborative studies with current diagnostic criteria to determine the differences in behavior, prognosis, and molecular genetic underpinnings between the old ''atypical carcinoid tumors'' and ''LC-NECs'' in the head and neck.…”

“…Lower grade neuroendocrine carcinomas (''typical carcinoid'' and ''atypical carcinoid'' tumors) of salivary gland origin are extremely rare [4,28,29,41]. The recognition of LC-NEC in salivary glands was hampered by the absence of well defined microscopic criteria for their diagnosis and the lack of ancillary techniques to demonstrate neuroendocrine differentiation; however, NEC, large cell-type (LC-NEC) in the major salivary glands was recognized in 1990 by Hui et al [21] in what is probably the most cited study of ''undifferentiated'' carcinomas of the salivary glands.…”

Small Cell Neuroendocrine Carcinoma of the Salivary Glands of the Palate: Report of a Rare Case and a Review of the Literature

“…SmCC has also been referred to as oat cell carcinoma, poorly differentiated neuroendocrine carcinoma, small cell undifferentiated carcinoma, or anaplastic cell carcinoma (2,5). SmCC may also occur in non-pulmonary organs in which it is classified as extra-pulmonary small cell carcinoma (EPSmCCs).…”

“…The cells are typically identified by ill-defined borders, sparse eosinophilic cytoplasm, and pyknotic nuclei, with fine evenly-dispersed clumped chromatin. Nuclear molding and crush artifact may also be observed in these cases, and the nucleoli are inconspicuous (3,5).…”

“…They are round or oval, and are arranged in solid sheets and nest patterns (5). Therefore, the differential diagnosis of SmCC should include metastatic small cell lung carcinoma, Merkel cell carcinoma, metastatic melanoma, lymphoma, poorly differentiated carcinoma, and other small round cell tumors (3).…”