An Aggressive Case of Colorectal Adenocarcinoma with Neuroendocrine Features

Introduction: Colorectal carcinoma with neuroendocrine differentiation (CRC-NE) may present as a pure neuroendocrine carcinoma or as a mixed adeno-neuroendocrine carcinoma (MANEC). Compared to conventional colorectal adenocarcinoma, CRC-NE is more frequently located in the right colon and presents at more advanced stage. Neuroendocrine differentiation, BRAF mutation without microsatellite instability, and signet ring histology are all associated with poor overall survival. Case description/methods: We present the case of a 75 year old female who underwent an average risk screening colonoscopy which revealed a 2 cm ulcerated non-obstructing mass in the hepatic flexure. Biopsy was significant for mixed neoplasm with glandular and neuroendocrine differentiation. Immunohistochemical stains showed strong positivity for CDX2, CK7, chromogranin and synaptophysin as well as patchy positivity for CK20. Stains for mismatch repair proteins MLH1, PMS2, MSH2, and MSH6 did not reveal loss of expression. She underwent right hemicolectomy and ileocolonic anastomosis (T1N0Mx). Given T1 disease she did not receive adjuvant chemotherapy. One-year follow up and surveillance imaging showed no evidence of disease recurrence. Two years after the initial resection the patient presented to the hospital with abdominal pain. Computed tomography (CT) showed new retroperitoneal adenopathy and multiple liver lesions. A retroperitoneal lymph node biopsy showed recurrent adenocarcinoma with neuroendocrine differentiation, with KRAS wild type, BRAF V600E, and microsatellite stable mutational analysis. Due to disease recurrence she was treated with multiple palliative chemotherapy regimens over the subsequent year before eventually succumbed to her disease. Discussion: NEC and MANEC are frequently misdiagnosed as adenocarcinoma or another malignant tumor requiring a detailed endoscopic and histological investigation. Both NEC and MANEC are rare and often follow an aggressive disease course. Although early stage at initial diagnosis, this patient experienced disease recurrence. Per the National Comprehensive Cancer Network (NCCN) guidelines, surgical resection and post operative observation remain the mainstay treatment for T1 colon cancer. While early diagnosis and survival is reported, most patients are diagnosed with advanced disease, even if presenting with small tumors. These cancers tend to be aggressive, and patients should be considered for multidisciplinary oncologic management.Figure 1:: Resected Juvenile Polyp.