Faiza Jajja, MD1, Muhammad Qasim Chaudhry, MD1, Abdullah Hafeez, MD1, Omar Alkasabrah, MD1, Sabeeh Akbar, MD2 1Landmark Medical Center, Woonsocket, RI; 2Quaid-e-Azam Medical College, Bellingham, MA Introduction: Colorectal cancer (CRC) with rhabdoid differentiation is rare and associated with poor prognosis. Synchronous involvement of both rectum and ileum by the same tumour is highly unusual. We present a case of metastatic CRC in a young patient harbouring a rare NRAS Q61R mutation and germ line POT1 mutation, complicating management.
Case Description/
Methods: A 42 year old man presented with LLQ pain and hematochezia. Imaging and colonoscopy revealed a recto sigmoid mass and omental nodularity; biopsy confirmed poorly differentiated adenocarcinoma with rhabdoid features, involving both rectum and ileum. PET Scan showed metastatic disease . Next Generation sequencing (NGS) identified an NRAS Q61R mutation (rare), MSI-stable, and no other actionable mutations.He had a diverting colostomy due to severe constipation and began chemotherapy, showing initial improvement. Disease later progressed; further testing revealed no new targets. A POT1 mutation was also found. He received palliative radiation for pain control. Discussion: NRAS mutations are present in only 2-5% of CRCs, with the Q61R variant accounting for less than 1%.These mutations activate the MAPK pathway and are associated with resistance to EGFR-targeted therapies, eliminating a major treatment avenue. Their presence often signals a more aggressive tumour biology, as seen in our patient, who demonstrated early and widespread metastasis despite initial response to multi-agent chemotherapy. Rhabdoid differentiation adds to the poor prognostic profile, correlating with dedifferentiation and rapid disease progression. The coexistence of rectal and ileal tumours from a single origin but with differing morphology suggests early dissemination and intratumoral heterogeneity. The discovery of a germ line POT1 mutation , which confers susceptibility to various cancers , further underscores the importance of genetic evaluation in atypical cases. This case emphasises the need for early genomic profiling to guide personalised treatment in aggressive and rare CRC subtypes.
Disclosures: Faiza Jajja indicated no relevant financial relationships. Muhammad Qasim Chaudhry indicated no relevant financial relationships. Abdullah Hafeez indicated no relevant financial relationships. Omar Alkasabrah indicated no relevant financial relationships. Sabeeh Akbar indicated no relevant financial relationships.
Faiza Jajja, MD1, Muhammad Qasim Chaudhry, MD1, Abdullah Hafeez, MD1, Omar Alkasabrah, MD1, Sabeeh Akbar, MD2. P4674 - A Rare Presentation of Adenocarcinoma of Rectum With NRAS Mutation, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.
