Large cell neuroendocrine carcinoma of the colon: A rare and aggressive tumor.

A 74-year old female presented to the emergency room with right lower quadrant abdominal pain, nausea and vomiting for 3 days. Due to a contrast dye allergy, a non-contrast CT scan of the abdomen and pelvis was performed which showed a lesion in the right colon with a dilated cecum and small bowel (Figure 1). Plain X-ray of the chest showed no obvious pathology. An exploratory laparotomy revealed a large obstructing mass at the right colon proximal to the hepatic flexure, with massive lymphadenopathy and abdominal adhesions. Intra-operative palpation and inspection of the liver was unremarkable without evidence of a suspicious mass. The patient underwent right hemicolectomy with anastomosis. Figure 1 Serial non-contrast CT scans of abdomen. (A) CT performed at the time of initial evaluation at admission showed no visible liver lesions. (B) Subsequent CT taken 10 days later showed multiple large liver lesions. The surgical tissue was reviewed by pathology, and on gross specimen, while the ileocecal valve mucosa contained discontinuous deposits of tumor associated with lymphatic tumor emboli, there was no evidence of distant metastasis. On microscopic evaluation the tumor cells had diffuse architecture with necrosis, ample cytoplasm, and numerous mitotic figures (10-20 mitoses per single high power field). Immunohistochemistry showed diffuse cytoplasmic staining for synaptophysin, as well as positive staining for CD-56, CK-7, Ki-67 (in nearly 90% of the cells) and negative staining for CK-20 consistent with large cell neuroendocrine carcinoma (Figure 2). Of the total lymph nodes present in the surgical specimen 17 out of 24 showed metastatic disease. Thus the final pathology was felt to be most compatible with an aggressive high-grade large cell neuroendocrine carcinoma of the colon. Figure 2 Pathologic examination with H&E staining and immunohistochemical analysis. (A) H&E stain showing tumor ulcerating though normal surface epithelium. (B) H&E stain at high magnification showing cytological malignant features such . On post-operative day number 10, the patient developed bilious drainage from the lower portion of the surgical incision. A non-contrast CT of the abdomen and pelvis showed interval development of approximately 5 hypodense lesions within the liver measuring 4-6 cm in size. Comparison of the post-operative scan to the pre-operative CT indicated that the hepatic lesions were new (Figure 1). Given the rapid development of these lesions and concern for potential liver abscesses the decision was made for a drainage procedure. An attempt at interventional radiology guided drainage was unsuccessful and subsequently the patient underwent a surgical exploration. Intra-operative findings were notable for multiple palpable hepatic masses through out both lobes of the liver. By gross inspection the hepatic lesions measured 4-6 cm in size, with complete replacement of the left hepatic lobe and a large firm mass at the surface of the right hepatic lobe. A wedge biopsy of one of the liver masses was performed and frozen section showed morphologic features similar to the previously resected tumor consistent with metastatic large cell neuroendocrine carcinoma. An additional intra-operative finding was a small bowel enterocutaneous fistula 10 cm proximal to the previous anastomotic site, which was resected and reanastomized. Two weeks later, the patients condition deteriorated with development of a second enterocutaneous small bowel fistula. At that time the family withdrew care and the patient subsequently expired.