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/10 hpfs. 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.

Fig. 1

The tumor cells in case 1 demonstrated marked nesting with an organoid growth pattern with focal ductal differentiation. The cells also demonstrated slight nuclear pleomorphism, a moderate amount of eosinophilic cytoplasm, vesicular chromatin, prominent nucleoli, and up to 6 mitotic figures/10 HPF (arrow). Vascular invasion was also identified (insert). (Hematoxylin and eosin stain, original magnification ×100, Insert ×40)

Fig. 2

Immunohistochemistry staining of cases 1–3 showing characteristic paranuclear dot staining with cytokeratin in case 1 (a1) and areas with diffuse staining with cytokeratin in cases 2 {a2} and 3 {a3}, respectively. Tumor cells from all 3 cases reacted positively with chromogranin (cases1 {b1}, 2 {b2} and 3 {b3}). Similarly, strong and diffuse positive staining with synaptophysin was seen in cases 1{c1}, 2 {c2}, and 3 {c3}, respectively

Fig. 3

The tumor cells in case 2 were predominantly organized in spindle and trabecular patterns. The cells have moderate to abundant amounts of cytoplasm and nuclei showed moderate pleomorphism with mitosis (arrow). Rosette-like structures were also appreciated (insert). (Hematoxylin and eosin stain, original magnification ×100, Insert ×20)

Fig. 4

Axial images from a contrast enhanced CT scan of the neck in case 3 (a is slightly cephalad to b), showing an enhancing oval mass arising from the inferior aspect of the deep lobe of the parotid gland (arrows) and extending medially into the parapharyngeal space, bordered posteriorly by the sternocleidomastoid muscle and anteriorly by the mandible, with mass effect on the retromandibular vein. The intratumoral enhancement pattern is somewhat heterogeneous, suggesting areas of central necrosis

Fig. 5

a A low power photomicrograph of case 3 showing lobules of small round blue tumor with prominent connective tissue necrosis identified in the background (arrows) (Hematoxylin and eosin stain, original magnification ×20). b The tumor cells in case 3 were arranged in solid cords and nests and the cells displayed moderate amounts of eosinophilic cytoplasm with moderate nuclear pleomorphism and prominent nucleoli. Perineural invasion was noted as well (insert). (Hematoxylin and eosin stain, original magnification ×80, Insert ×40)