EP678 - Serendipitous Success: Excellent Response of Colorectal Small Cell Neuroendocrine Carcinoma to FOLFOX Chemotherapy Following Initial Misdiagnosis as Poorly Differentiated Carcinoma

Purpose/Background: Small Cell Neuroendocrine Carcinoma (SCNEC) of the gastrointestinal tract is uncommon, comprising less than 1% of colorectal cancers. It exhibits aggressive behavior, with rapid progression, high mitotic activity, and early dissemination. These tumors typically present at an advanced stage and are associated with poor outcomes, with 5-year survival rates far lower than those for conventional adenocarcinomas. Standard treatment approaches are not well-established due to the rarity of the disease, though management often mirrors that of small cell lung cancer, including platinum-etoposide chemotherapy regimens. In this case, a standard colorectal adenocarcinoma regimen (FOLFOX) was used inadvertently and led to an excellent response, raising important considerations for treatment approaches in atypical SCNEC presentations.

Methods/Interventions: A 54-year-old woman presented with one month of progressive lower abdominal pain. CT imaging revealed an exophytic mass arising from the rectosigmoid colon with associated retroperitoneal lymphadenopathy. Colonoscopy showed a near obstructive lesion at 15 cm from the anal verge. Biopsy revealed a poorly differentiated carcinoma, favoring an intestinal primary. Histologic sections demonstrated small, densely packed cells with high nuclear-to-cytoplasmic ratios, arranged in cords and trabeculae, without overt glandular or squamous differentiation. IHC at that stage was inconclusive. PET/CT revealed a rectosigmoid mass (7.0 × 4.2 cm, SUV 11.8), retroperitoneal lymphadenopathy (largest of note being 3.1 × 1.6 cm, SUV 12.5), and a small hepatic lesion (SUV 3.4). The diagnosis of clinical stage IV poorly differentiated colorectal carcinoma was made. Neoadjuvant FOLFOX 6 cycles were administered.

Results/Outcomes: MRI performed four weeks later showed reduced tumor burden, nodal regression, and no identifiable liver lesion. After completion of 6 cycles, PET/CT demonstrated further regression: primary tumor reduced to 2.8 × 1.1 cm (SUV 2.8), and the previously discussed retroperitoneal node regressed to 1.1 × 1.0 cm (SUV 3.3). The previously hypermetabolic hepatic lesion was no longer observed. Patient's case was presented at multidisciplinary tumor board, and the decision was made to pursue surgical resection. Patient underwent low anterior resection with creation of diverting loop ileostomy, total abdominal hysterectomy with bilateral Salpingo-oophorectomy, and paraaortic and paracaval nodal sampling. Final surgical pathology showed primary SCNEC of the rectosigmoid tissue and metastatic SCNEC of the lymph nodes. Based on SCNEC protocols and extrapolated small cell lung cancer data, the decision was made to proceed with adjuvant therapy using a platinum-based regimen. The patient completed four cycles of carboplatin and etoposide over four months. She tolerated treatment, and follow-up imaging showed no radiographic evidence of recurrence at the time of this report.

Conclusion/Discussion: This case highlights the challenges in diagnosing colorectal SCNEC and the importance of recognizing limitations and unreliability of superficial biopsy. It also presents a rare instance of excellent response to FOLFOX in high-grade SCNEC. These findings suggest flexibility in chemotherapy approaches may be beneficial in selected patients. They also highlight the need for further research and discussion in the application of FOLFOX in non-traditional colorectal neoplasms.

Synaptophysin: Positive
Ki-67: 99%