Synchronous lung tumours in a patient with metachronous colorectal carcinoma and a germline MSH2 mutation

Area of Science:

• Oncology
• Genetics
• Pathology

Background:

• DNA mismatch repair (MMR) gene mutations lead to microsatellite instability (MSI), a known factor in carcinogenesis, particularly in hereditary non-polyposis colon carcinoma.
• The role of MMR gene mutations in non-small-cell lung carcinoma (NSCLC) remains less understood, despite their established link to other cancers.

Observation:

• A case study of a male patient with a history of colon carcinoma presented with two synchronous lung tumors, one resembling metastatic colon cancer.
• Immunohistochemistry confirmed a pulmonary origin for both lung lesions.
• MMR protein analysis revealed loss of MSH2 and MSH6 expression in the patient's colonic tumors and one lung tumor exhibiting enteric differentiation.

Findings:

• A deleterious germline mutation in the MSH2 mismatch repair gene was identified in the patient.
• The findings indicate a potential link between MSH2 mutations and the development of synchronous lung and colon tumors, including NSCLC with enteric features.

Implications:

• This case underscores the diagnostic complexities in identifying the primary origin of tumors, especially when lung lesions mimic metastatic disease.
• The study highlights the importance of considering MMR gene mutations in the differential diagnosis of NSCLC, particularly in patients with a history of colorectal cancer.
• Further research is warranted to elucidate the full contribution of MMR gene defects to lung carcinogenesis and to develop targeted diagnostic and therapeutic strategies.