Large-Cell Neuroendocrine Cancer of the Colon following Rituximab-Based Lymphoma Treatment

A 58-year-old man was referred in June 1991 with rectal bleeding for a colonoscopy that showed a sigmoid adenocarcinoma. Anterior resection revealed extension into, but not through, the muscularis propria, as well as 18 benign lymph nodes. Annual colonscopies were performed for five years, then every three years. In 2002, he underwent prostatectomy for prostate carcinoma. In 2008, a stage IVA, diffuse large B-cell right testicular lymphoma was treated with right orchidectomy, scrotal radiation and six cycles of CHOP-R (cyclophosphamide-doxorubicin-vincristine-prednisolone-rituximab). In 2008, colonoscopy and computed tomography (CT) scans of the head, abdomen and pelvis were normal, with no evidence of lymphoma. While travelling in southern France and Spain in June 2011, he developed abdominal pain and diarrhea for three days. This resolved for approximately one week and then recurred over a two-week period after his return to Canada. His physical examination was normal and laboratory studies revealed a mild anemia (hemoglobin level 122 g/L), but a normal white blood cell count and no left shift or eosinophilia. Fecal studies for bacteria and parasites were negative. A CT scan showed circumferential thickening of the hepatic flexure along with hepatic hypodense lesions, and colonoscopy showed an obstructing carcinoma. A right hemicolectomy and partial hepatectomy revealed a large cell neuroendocrine carcinoma invading through the colonic wall and involving seven of 14 regional lymph nodes and the liver. Microscopic evaluation showed predominately trebecular and insular architecture; the nests comprised of relatively monomorphous, but large cells, with moderate amounts of cytoplasm, an open nuclear chromatin pattern and a high mitotic apoptotic rate (Figure 1). Immunohistochemical staining for synaptophysin was stongly positive (Figure 2). Chromogranin was also positive. Subsequent chemotherapy treatment included carboplatin and etoposide. Figure 1) Trebecular/insular arrangement of high-grade malignancy of hepatic flexure with monomorphous large epithelioid cells with an open nuclear chromatin pattern and a high mitotic/apoptotic rate. Hematoxylin and eosin stain (original magnification ×200) ... Figure 2) Immunohistochemical stain for synaptophysin showing strong cytoplasmic positivity in the malignant cells. Original magnification ×200