Duodenal Neuroendocrine tumors constitute 5% of all gastrointestinal neuroendocrine tumors 12. Most of these show well-differentiated features and are classified as carcinoids or somatostatinomas 3456. Occurrence of carcinoma is rare, and carcinomas with anaplastic character, which are classified as small-cell carcinomas, are even less frequent 789101112. The most common small-cell neuroendocrine carcinoma (NEC) is the small-cell undifferentiated carcinoma of the lung 1314. Although the features of these pulmonary tumors are well defined, the characteristics of their extrapulmonary counterparts are still unknown. We report a case of small-cell NEC in the duodenum that had unique morphological features and exceptionally good clinical outcome.

A 57-year-old man presented with sudden gastrointestinal tract bleeding and episode of fainting. Duodenoscopy (Figure 1a) and hypotonic duodenography (Figure 1b) revealed a 3 × 3 cm protruding tumor with two ulcerations located opposite the ampulla of Vater in the second part of the duodenum. Laboratory data showed no abnormalities in blood chemistry, tumor markers (CEA, CA19-9, NSE, proGRP) and endocrine markers (somatostatin, gastrin, glucagons, serotonin, VIP) except a moderate anemia (9.5 g/dl hemoglobin). No abnormal findings were observed in the chest X-ray and computed tomography (CT).

A laparotomy was performed. As there was no serosal invasion or regional lymphadenopathy wide local excision of the tumor was performed. On gross examination, the tumor showed two ulcerations and two different morphological components (Figure 2a and 2b). One component (component A) was round in shape with a round ulceration on the top, and the other component (component B), which enclosed the round component, was crescent in shape with a spindle-shaped ulceration on the top. The two components showed different histopathological and immunohistochemical features (Table 1). The round component contained fibrous tissue, small nuclei, and clear nucleoli. Histopathologically, the crescent component had more anaplastic features typical of small-cell carcinoma, such as sheets of tightly packed anaplastic cells with round nuclei and scanty cytoplasm (Figure 2c, 2d). Neuroendocrine differentiation was investigated using immunohistochemical and ultrastructural techniques. Both components showed neuroendocrine features, with immunochemistry identifying synaptophysin and AE1/AE3 (Figure 3a and 3b), and electron microscopy identifying dense core granules (Figure 4). Immunochemistry also showed that the crescent component expressed less cytokeratin, vimentin and CD56, and more MIB-1 than the round component.

The patient was discharged three weeks after operation with uneventful postoperative period. Four cycles of monthly adjuvant chemotherapy with 5-fluoro uracil (5-FU) (325 mg/m²) and leucovorin (20 mg/m²) were administered. The patient showed no sign of recurrence and is disease-free 48 months after surgery.

Neuroendocrine carcinomas (NEC) in the duodenum are extremely rare, and are classified as either 'small-cell' or 'non small-cell' types. The small-cell NEC occurring in the duodenum and elsewhere in gastrointestinal tract are similar to the small-cell carcinoma of the lung 78. Only eight cases of small-cell NEC in the duodenum have been reported, with the present case being the ninth (Table 2) 789101112. Most cases occurred in middle-aged or geriatric males with lesions in the ampulla of Vater. Extra-ampullary small-cell NECs in the duodenum are extremely rare, with only two cases reported previously 78.

The natural course of small-cell NECs in the duodenum is still not clear. Most cases reported in the literature show rapid progress of the disease, with radical surgery and/or chemotherapy not altering the clinical course, and thus a poor prognosis. In six of the previous eight cases, patients underwent pancreaticoduodenectomy for removal of the tumor, while the remaining two did not undergo surgery because of multiple liver metastasis or poor general condition. In spite of radical resection with or without adjuvant chemotherapy, most cases showed rapid recurrence and metastasis. Of the eight reported cases, one was unusual as it occurred in a middle-aged female with rapid progress of the disease but effective response to adjuvant chemotherapy using 5FU, tumor necrosis factor, and interferon this patient survived for more than eighteen months 10. The present case was treated by a local excision of the tumor followed by adjuvant chemotherapy using 5-FU and leucovorin, and showed a distinctively unique clinical course, with the patient surviving for more than 48 months without any sign of recurrence. This case was presented with gastrointestinal bleeding, which contributed to early diagnosis, whereas the other previous cases in literature presented either with abdominal pain or jaundice. Hence, the good prognosis in present case could also be due to its earlier presentation. The lesion in the present case showed a different immunohistological character from that in other cases, such as no immunoreactivity to neuron-specific enolase (NSE) or chromogranin A. These differences too might partly explain the different character of this case.

This report identifies a new subtype of small-cell NEC in the duodenum. This subtype appears to have a much better prognosis, and may be amenable to local excision, if the lesion is away from the ampulla of Vater.

None declared.

NS, MT, MK, KY, KK, HN took part in the operation, performed the literature search and drafted the manuscript for submission. HN supervised the preparation of the manuscript and edited the final version for publication. TS, KS performed pathological investigations and contributed to the pathological content of the manuscript.

All authors read and approved the manuscript.