Lynch Syndrome: An Unorthodox Presentation

Abstract

Lynch syndrome aka Hereditary Nonpolyposis Colorectal Cancer (HNPCC) is an autosomal dominant condition and the most common cause of inherited colorectal cancer (CRC), characterized by increased risk of a group of malignancies of which CRC is most common. Colon and endometrial cancers are the most common duo in Lynch syndrome but typically coexist at different stages. This is a case of a female with recurrent abdominal abscess found to have synchronous aggressive colon and endometrial cancers A 57-year-old female presented with right lower quadrant (RLQ) abdominal pain, early satiety, 20lbs unintentional weight loss and irregular vaginal bleeding. She was seen 2 months prior at an outside hospital for abdominal abscess that was drained and treated with antibiotics. She had a family history of lung cancer in her father and sister. On admission, BP 118/89, HR 105bpm, RR 18, Temp 98.2F. Physical exam revealed, distended right flank, tender RLQ. Lab findings: WBC 21.3k/mcl, hemoglobin 6.8mg/dl, lactate 2.7mg/dl. CT Abdomen and pelvis revealed fluid collection throughout the right abdomen and pelvis consistent with an abscess. The abscess was drained and cytology was concerning for malignancy. Colonoscopy revealed mucosal edema and congestion at the hepatic flexure which prompted surgery. An excised 3.1cm colon mass revealed Stage IV colonic adenocarcinoma of tubulovillous origin, while a 4.5cm endometrial mass obtained via total abdominal hysterectomy revealed Stage 2 FIGO Grade 1 endometrial adenocarcinoma. Both cancers had loss of expression of PMS2 and MLH1 genes with high frequency of microsatellite instability. Other findings consistent with Lynch syndrome. Lynch syndrome increases risk for synchronous and metachronous cancers, it's often due to germline mutations or gene deletions. In most reported cases, patients had either advanced CRC with early stage Lynch syndrome-associated malignancies or CRC at the time of diagnosis, other associated extracolonic tumors presented later. Workup is often prompted by multigenerational family history of CRC and/or endometrial cancer. Interestingly, our case had 2 aggressive advanced primary cancers occurring concurrently. Also, diagnostic criteria like Amsterdam I&II or Bethesda rely heavily on family history of associated malignancies. This case emphasizes the importance of timely investigation into Lynch syndrome when a patient is diagnosed with either CRC or endometrial cancer without a family history.1522_A Figure 1. Large peripherally enhancing fluid collection (Calipers) throughout the right abdomen and pelvis as well as involving the psoas and right abdominal wall consistent with abscess.1522_B Figure 2. Colon Adenocarcinoma of tubulovillous origin. High magnification of immunostaining for CDX-2, a colon marker.1522_C Figure 3. High magnification of immunostaining for p53 positive for Endometrial cancer. (p53, 40x)