Sigmoid colon adenocarcinoma with isolated loss of PMS2 presenting in a patient with synchronous prostate cancer with intact MMR: Diagnosis and analysis of the family pedigree

Lynch syndrome (LS) patients with isolated PMS2 loss in the colon cancer, while intact MMR in the prostate cancer, are exceedingly rare. Herein, we report such a case. A 71-year-old male was found to have increased serum PSA (10 ng/ml) after treatment for his urinary tract infection. Prostate biopsies showed foci of prostate cancer with Gleason score 7 (3+4) (grade grope 2) involving 10% of two cores. Through work up for treatment of the prostate cancer, he was found to have focal thickening of his sigmoid colon with adjacent lymphadenopathy in CT scans. Colon biopsy showed a tubular adenoma with high-grade dysplasia and deep invasive carcinoma could not be excluded. A low anterior resection of the rectosigmoid colon was performed and a sigmoid colon adenocarcinoma (pT2N1b, AJCC 8th edition) was confirmed. Immunostaining showed that the colon cancer was positive for CDX2, SATB2, had a loss of PMS2 and intact expression of MLH1, MSH2 and MSH6, negative for AMACR, while the prostate cancer was positive for AMACR, had intact expression of PMS2, MLH1, MSH2 and MSH6, and negative for CDX2 and SATB2. MSI-H phenotype and PMS2 mutation in the colon cancer were confirmed by microsatellite instability (MSI) PCR and nextgeneration sequencing (NGS), respectively. Through genetic counseling and analysis of the family pedigree, LS was confirmed with colon cancer present in multiple maternal family members and his brother also had metachronous colon and prostate cancers. To the best of our knowledge, this is the first documented case of synchronous colon and prostate cancers, with isolated PMS2 loss present in the colon cancer while intact DNA mismatch repair (MMR) protein expressions present in the prostate cancer, in the English literature. The pathogenesis, diagnosis and prognosis of this entity are discussed.