Abstract
INTRODUCTION: Lynch syndrome is an autosomal dominant disorder caused by germ line mutations in DNA mismatch repair (MMR) genes. It is characterized by an increased risk of colon cancer, endometrial cancer, and ovarian cancer. Sarcoma is not a typical cancer associated with Lynch syndrome but has been reported. We report a case of sarcoma in a patient who was eventually diagnosed with Lynch Syndrome. CASE REPORT: A 71-year-old woman with personal history of endometrial cancer treated with total abdominal hysterectomy and radiation therapy 20 years ago, presented with a 2-month history of left leg pain and weakness. Family history was significant for both daughter and sister diagnosed with synchronous ovarian and uterine cancer at ages 42 and 48 respectively. Physical examination revealed weakness of the left quadriceps and decreased sensation to L4 dermatome. Magnetic resonance imaging of the lumbar spine showed an 8cm enhancing mass in the left psoas muscle, causing complete erosion and collapse of the L4 vertebral body, with moderate to severe spinal stenosis. Biopsy of the psoas mass showed high-grade sarcoma of unknown primary. As the patient's family history was suspicious of Lynch syndrome, microsatellite instability testing of the sarcoma by immunohistochemical staining of MMR proteins was performed. Results of MMR testing showed loss of expression of MSH2 protein in malignant cell nuclei. MSH2 gene testing was positive for deleterious mutation R621X, confirming the diagnosis of Lynch syndrome. The patient underwent palliative radiation therapy with improved pain control. Her relatives at risk were informed of MSH2 gene mutation in the family and counseled about screening and medical management of healthy individuals who test positive for the mutation. This case illustrates the importance of family history in identifying patients at risk for Lynch syndrome. Identification of specific mutations in an index case is very helpful in order to identify relatives at risk of inheriting the mutation. Appropriate screening can then be offered to affected relatives to reduce cancer risk. Although sarcoma is not a typical tumor of Lynch syndrome, the absence of MSH2 protein on immunohistochemistry suggests that a germ line mutation contributed to the development of sarcoma. Sarcoma may be part of the hereditary nonpolyposis colorectal cancer (HNPCC) tumor spectrum, and Lynch syndrome should be considered in patients with family history of sarcoma.