Unravelling the genetic puzzle in rectal carcinoma with colonic polyposis

Aishwarya S, Balamurugan TD, Paul AAC, Eswari V

Pdf Page Numbers :- 302-307

Aishwarya S¹, Balamurugan TD², Anston Christo Paul A¹, and Eswari V^1,*

¹Department of Pathology, Meenakshi Medical College Hospital and Research Institute, Kanchipuram - 631552, Tamil Nadu, India

²Department of Surgical Oncology, Meenakshi Medical College Hospital and Research Institute, Kanchipuram - 631552, Tamil Nadu, India

*Corresponding author: Dr. V. Eswari, M.D., Professor and Head, Meenakshi Medical College Hospital and Research Institute, Kanchipuram – 631552, Tamil Nadu, India. Email: dreswarimd@gmail.com

Received 19 March 2025; Revised 16 May 2025; Accepted 29 May 2025; Published 10 June 2025

Citation: Aishwarya S, Balamurugan TD, Paul AAC, Eswari V. Unravelling the genetic puzzle in rectal carcinoma with colonic polyposis. J Med Sci Res. 2025; 13(3):302-307. DOI: http://dx.doi.org/10.17727/JMSR.2025/13-53

Copyright: © 2025 Aishwarya S et al. Published by KIMS Foundation and Research Center. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Abstract

Introduction: Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality worldwide. Hereditary forms, such as familial adenomatous polyposis (FAP) and Lynch syndrome, significantly impact disease onset, progression, and management. This study provides a structured overview of diagnostic approaches in CRC, specifically focusing on Lynch syndrome and FAP, including its attenuated variant.

Methods: A 51-year-old male presented with altered bowel habits and rectal pain, with a family history of endometrial and oropharyngeal cancers. Colonoscopy revealed a rectosigmoid ulcer and multiple sessile polyps throughout the colon. Biopsy confirmed well-differentiated adenocarcinoma with high-grade dysplasia in rectal polyps. He underwent neoadjuvant chemoradiation followed by total proctocolectomy. Immunohistochemistry showed isolated loss of MSH6 protein. Genetic testing revealed a pathogenic APC gene mutation.

Results: This case highlights the complex interaction between APC mutations and mismatch repair (MMR) protein deficiencies. Isolated MSH6 loss may raise suspicion for Lynch syndrome; however, since MSH6 functions with MSH2—an essential component of MMR—the intact expression of MSH2 reduces the likelihood of Lynch syndrome. The presence of ~30 polyps and APC mutation supports a diagnosis of attenuated FAP rather than Lynch syndrome.

Conclusion: This case underscores the importance of integrating molecular diagnostics in CRC evaluation. Genetic testing is essential for differentiating between FAP, Lynch syndrome, and other hereditary syndromes, enabling precise clinical management and family risk assessment.

Keywords: colorectal cancer; APC mutation; attenuated FAP; Lynch syndrome; MMR genes; MSI