Neuroendocrine Carcinoma of the Paranasal Sinus: A Case Report

Neuroendocrine carcinoma is an uncommon tumor. Primary NEC of the paranasal sinuses is extremely rare; only about 76 cases have been reported in literature. Unfortunately due to the rarity of this neoplasm, there are no specific recommendations regarding management of the disease. While Surgery was used in the past, chemoradiation now seems to be evolving as the treatment of choice. The clinical presentation, imaging studies, histopathological diagnosis with immunohistochemistry correlation, management protocols, and a brief review of literature of this rare tumor is discussed.

Surgery was conducted and medial maxillectomy was done on 6/2/17.
Biopsy of the lesion was done which on microscopy revealed malignant neoplasm, composed of round cells, arranged in sheets and nests, separated by fibrous tissue. There is rosette like structures. Mitosis was noted and diagnosis was high grade malignant neoplasm, consistent with high grade neuroendocrine carcinoma.Differential diagnosis was high grade olfactory neuroblastoma and immunohistochemistry was recommended 9/2/17. Immunohistochemical profile showed tumor cell positivity for Epithelial Membrane Antigen (EMA), pancytokeratin, and focally positive for synaptophysin, The tumor cell was negative for S-100 Protein.

Discussion
Neuroendocrine carcinomas have been classified into from low grade to high grade into four types-carcinoid, atypical carcinoid, large cell neuroendocrine carcinomas, and SNECs 2 .
Extra-pulmonary primary neuroendocrine carcinomas are uncommon malignant neoplasms, whereas primary sites documented may include esophagus, salivary glands, gastrointestinal tract (including small intestine and large intestine), pancreas, larynx, cervix uteri, uterus, urinary bladder, prostate, breast, and lacrimal gland. Primary sinonasal SNECs are extremely rare.
SNECs are thought to arise from a multipotential stem cell. SNEC is a histological sub-type among a broad group of sinonasal malignancies together known as sinonasal The initial presentation of nasal obstruction, nasal discharge, and recurrent epistaxis is practically indistinguishable from that of more benign diseases and hence is likely to result in delay in presentation. Occasionally, the presenting complaint may be swelling of the maxilla and expohthalmos. The aggressiveness coupled with the complex anatomy of this region, ensures that most patients present in an advanced stage of disease. The association between the paraneoplastic endocrine syndrome and SNEC is well documented. However, review of literature showed only in five cases of SNECs of nasal and paranasal sinuses with endocrine syndromes 2 . Our patient did not have any endocrine syndrome except diabetes which was detected 7 years back.
Diagnosis by histological examination is challenging. It is indistinguishable from its pulmonary counterpart. Both consist of smallsized cells arranged in sheets, nests, or cords, with moderate to scanty cytoplasm and hyperchromatic nuclei. It is important to differentiate this tumor from olfactory neuroblastoma, which is a low grade tumor. Definitive diagnosis is made by correlation with immunohistochemistry and/or electron microscopy.
Unfortunately due to the rarity of this neoplasm, there is no specific recommendation on management guidelines, treatment options are generally extrapolated from similar tumors of pulmonary origin. Treatment approaches to this aggressive tumor has varied over the years. Previously, surgery followed by radiotherapy or chemotherapy was preferred 4,5 . In general, these patients usually present in advanced stages, surgery can be extremely disfiguring and may not be curative. Chemotherapy using cisplatin and etoposide followed by high dose proton-photon radiotherapy has been proven by some authors to be an effective line of treatment 6,7 . Surgery is now reserved for nonresponders. Despite presenting in an advanced stage, our patient responded well to a standard combination of chemotherapy and radiotherapy and continues to be in remission.

Conclusion
NECs are aggressive tumors with high potential for local invasion as well as distant metastasis. Metastatic deposits occur in the brain, bones, lungs, and skin.As most patients present in advanced stages, the prognosis is extremely poor.