A 54-year-old man presented at local hospital with complaint of pain upper abdomen for past one month. Pain was insidious in onset and progressive in nature and aggravated after meals. He had loss of appetite and weight loss. On presentation, serum biochemistry showed total serum bilirubin 0.4, AST 33u/l, ALT 39u/l, alkaline phosphatase 84, serum urea 24mg/dl and creatinine 0.7mg/dl. He underwent CECT of abdomen which showed hepatomegaly and multiple liver mets. PET-CT showed hypermetabolic eccentric circumferential mural thickening involving lower third of esophagus and hypermetabolic diffuse hepatic and lymphatic metastasis. He further underwent upper GI endoscopy which revealed growth at 33cm from incisors. Histopathology diagnosis was poorly differentiated neuroendocrine carcinoma, which was positive for cytokeratin and INSM-1and negative for synaptophysin on IHC. Tumor markers chromogranin A level was high (705ng/ml) and CEA 5.55ng/ml.

He was started on chemotherapy as liver metastasis was present on presentation. After obtaining informed consent chemotherapy based on cisplatin 80mg/m² and etoposide 100mg/m² intravenously on days 1-3, repeated after every 3 weeks. After receiving 4 cycles of chemotherapy CECT chest and abdomen revealed heterogeneously enhancing circumferential thickening of lower esophagus with liver metastasis. He was symptomatically relieved of symptoms and was further planned for 3 more cycles of same chemotherapy.

Esophageal neuro-endocrine tumors are extremely rare, ranging between 0.4 -2% of all malignancies of esophagus [1]. Esophageal neuroendocrine carcinomas are aggressive neoplasm. Patients usually present in advanced stage with multiple metastasis and prognosis is poor [2]. Patient usually present with vague symptoms like progressive dysphagia with weight loss, chest pain or pressure. Dysphagia is more common than carcinoid symptoms [3]. Most of the esophageal carcinoma present as large ulceroproliferative growth with deep infiltration into esophageal wall.

Microscopically neuroendocrine tumors show features of either large cell and small cell. Large cell neuroendocrine tumor are more common than small cell. Results of IHC markers like chromogranin A, synaptophysin, NCAM, CD56 and neuron specific enolase are usually positive, with synaptophysin being the most sensitive diagnostic marker [2]. IHC features in our patient showed positivity for pancytokeratin and KI-67 index was 70%, and was diagnosed as poorly differentiated neuroendocrine carcinoma.

According to WHO 2010 criteria neuroendocrine neoplasms of esophagus are defined as neoplasms with neuroendocrine differentiation and are further classified as G1(carcinoid), G2 and large cell and small cell carcinomas on the basis of KI-67 levels [4]. Prognosis correlates with grade and stage of disease and prognosis is better in patients with loco-regional disease.

Patients with loco-regional disease are treated with curative intent with esophagectomy, and /or radiotherapy combined with adjuvant or neo-adjuvant chemotherapy [5]. Cisplatin, etoposide, cyclophosphamide and doxorubicin are the components of mostly used drug regimens. A commonly used regimen consist of cisplatin and etoposide. Recently, stomatostatin antagonist octreotide [6] and amrubicin chloride have been used in neuroendocrine tumors of gastrointestinal tract. In our patient combination chemotherapy regimens of cisplatin and etoposide was used as he presented with liver metastasis. After 4 cycles of chemotherapy he was relieved of pain abdomen, serum chromogranin a levels within normal limits but CECT showed thickening in lower esophagus and liver metastasis. He was further planned for 3 more cycles of chemotherapy.

1. Yun, J.P. et al. “Primary Small Cell Carcinoma of the Esophagus: Clinicopathological and Immunohistochemical Features of 21 Cases.” BMC Cancer, vol. 7, 2007, p. 38. https://doi.org/10.1186/1471-2407-7-38.

2. Maru, D.M. et al. “Retrospective Study of Clinicopathologic Features and Prognosis of High-Grade Neuroendocrine Carcinoma of the Esophagus.” The American Journal of Surgical Pathology, vol. 32, no. 9, September 2008, pp. 1404–1411. https://doi.org/10.1097/PAS.0b013e31816bf41f.

3. Modlin, I.M. et al. “An Analysis of 8,305 Cases of Carcinoid Tumors.” Cancer, vol. 79, 1997, pp. 813–829. https://doi.org/[insert DOI if available].

4. Bosman, F.T. et al. WHO Classification of Tumors of the Digestive System. 4th ed., International Agency for Research on Cancer Publisher, Lyon, 2010.

5. Vos, B. et al. “Small Cell Carcinoma of the Esophagus: A Multicentre Rare Cancer Network Study.” Diseases of the Esophagus, vol. 24, no. 4, May 2011, pp. 258–264.

6. Volante, M. et al. “Somatostatin Receptor Type 2A Immunohistochemistry in Neuroendocrine Tumors: A Proposal of Scoring System Correlated with Somatostatin Receptor Scintigraphy.” Modern Pathology, vol. 20, no. 11, November 2007, pp. 1172–1182.