Poorly Differentiated Large-Cell Neuroendocrine Carcinoma of the Cecum: A Rare Malignancy

Abstract

Abstract Poorly differentiated neuroendocrine carcinomas (PDNECs) are rare tumors that can arise anywhere in the gastrointestinal tract. They often present at advanced stage and portend a poor prognosis when compared to adenocarcinomas of the same stage. A 65-year-old female presented with progressively worsening bilateral proximal muscle weakness of 3 months’ duration. It was associated with fatigue, decreased appetite, and unintentional weight loss (8 lbs). She was also found to have hypercalcemia (serum calcium 12.1 mg/dL), anemia (hemoglobin 9.9 g/L), and abnormal liver panel (Alk phos 336, AST 85, GGTP 737). CT abdomen showed abnormal thickening and mass-like enhancement in the cecum measuring 2.9 × 3.7 cm and an enlarged 22-cm liver with numerous rounded masses, the largest measuring 4.6 × 8.2 cm. Colonoscopy revealed a large ulcerated mass distal to the ileocecal valve and extending to the proximal ascending colon. Histology revealed an ulcerated invasive pleomorphic large cell neoplasm with focal squamous differentiation and a tubular adenoma. Initial positive immunostains were AE1/AE3, CK5, and p63. CK7, CK20, S100, and calretinin were negative. Strong, diffuse expression of synaptophysin confirmed neuroendocrine carcinoma; high Ki-67 (80%) confirmed grade 3. CDX2 and TTF1 were positive but are not lineage specific in PDNECs. A liver biopsy had identical histology with diffuse expression of CD56, another confirmatory neuroendocrine marker. Elevated random urine 5-hydroxyindoleacetic acid (5HIAA) supported the diagnosis. Mismatch repair (MMR) protein immunostains did not reveal deficient MMR. Colonic NECs are extremely rare, accounting for 0.6% of patients with colorectal carcinoma; of these, only 0.2% are classified as large cell NECs. A panel of immunostains confirms the diagnosis. They most often arise in the cecum or rectum with early liver metastases and median survival of 9 months. Rare cases have responded to checkpoint inhibitors, which may be a therapeutic option.