P4718 - Incidental Detection of Low-Grade Rectal Mixed Adenoneuroendocrine Carcinoma During Immunotherapy for Metastatic Gallbladder Adenocarcinoma

Steven Luong, BS¹, Quynh Ton, BS¹, Aleaa Rana, MS², Rana Khan, MBBS³, James Gulizia, MD, PhD⁴
1Touro University California, Clovis, CA; 2Touro University California, Vallejo, CA; 3Mercy Medical Center, Sacramento, CA; 4Inform Diagnostics, Sacramento, TX

Introduction:

Mixed adenoneuroendocrine carcinomas (MANECs) are rare neoplasms comprising both adenocarcinoma and neuroendocrine components, each accounting for ≥30% of the lesion. Often found in the colon and rectum, MANECs vary in behavior based on grade and differentiation. High-grade neuroendocrine components predict poor prognosis, while low-grade, superficial tumors may allow conservative management.

Case Description/

Methods:

A 76-year-old woman was diagnosed in 2023 with metastatic gallbladder adenocarcinoma after PET/CT revealed an FDG-avid gallbladder mass with extensive hepatic, pulmonary, osseous, and nodal metastases. Liver biopsy confirmed adenocarcinoma of hepatobiliary origin. Molecular profiling showed ERBB2 amplification, TP53 mutation, CDKN2A/B loss, and microsatellite stability. She underwent 8 cycles of gemcitabine, oxaliplatin, and durvalumab, followed by maintenance durvalumab, achieving a partial metabolic response with ECOG 1 status.

In 4/2025, surveillance PET/CT showed new rectal FDG uptake. Colonoscopy revealed a 30mm distal rectal polyp. Histopathology demonstrated a superficially invasive adenocarcinoma (2.5mm) and neuroendocrine tumor (1.9mm) arising within an adenomatous polyp, consistent with low-grade rectal MANEC. The lesion was completely excised endoscopically. Absence of high-risk features (e.g., lymphovascular invasion, tumor budding) supported a non-operative, surveillance-based approach given the patient’s ongoing management for stage IV gallbladder cancer.

Discussion:

A low-grade rectal MANEC was incidentally identified on PET/CT in a stable patient undergoing systemic therapy for metastatic gallbladder adenocarcinoma. Although no direct link exists between immunotherapy and MANEC, checkpoint inhibitors may unmask indolent tumors or alter the tumor microenvironment, while improved survival and frequent imaging increase the likelihood of detecting secondary malignancies. Histology revealed superficially invasive adenocarcinoma and a well-differentiated neuroendocrine tumor within a tubular adenoma, with no high-risk features. Complete endoscopic resection was achieved, and conservative management was pursued. In contrast, high-grade MANECs with poorly differentiated neuroendocrine components are aggressive, requiring radical resection and platinum-based chemotherapy. Therapeutic options include FOLFOX, FLOT, S1 with cisplatin, XELOX, EP, IP, and streptozocin. This case emphasizes the need for diagnostic vigilance during surveillance in metastatic cancer patients.

Disclosures:
Steven Luong indicated no relevant financial relationships.
Quynh Ton indicated no relevant financial relationships.
Aleaa Rana indicated no relevant financial relationships.
Rana Khan indicated no relevant financial relationships.
James Gulizia indicated no relevant financial relationships.

Steven Luong, BS¹, Quynh Ton, BS¹, Aleaa Rana, MS², Rana Khan, MBBS³, James Gulizia, MD, PhD⁴. P4718 - Incidental Detection of Low-Grade Rectal Mixed Adenoneuroendocrine Carcinoma During Immunotherapy for Metastatic Gallbladder Adenocarcinoma, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.