If at first you don't succeed making the right diagnosis eventually.

Abstract

In 2006, a patient presented to Genetic Health Queensland (GHQ) with a history of premenopausal breast cancer, bilateral dermoid ovarian cysts and multiple basal cell carcinomas (BCC). Her firstdegree relatives had histories of pre- and post-menopausal breast cancer, papillary thyroid cancer, bladder cancer and esophageal cancer. Based on her BRCAPRO score, testing for hereditary breast and ovarian cancer syndrome (BRCA1 & BRCA2) was undertaken and no pathogenic mutations were identified. The differential diagnosis of Cowden syndrome (CS) was then considered given the family tumour spectrum; premenopausual breast cancer, thyroid cancer, and BCCs. However, macrocephaly was absent in the proband. Genetic testing of PTEN was undertaken and no pathogenic mutation was found. In 2010, the proband represented to GHQ with a sebaceous adenoma that demonstrated immunohistolological loss of MSH2, one of five mismatch repair (MMR) genes responsible for Lynch syndrome. Genetic testing consequently found the proband to be a carrier a truncating MSH2 mutation. Lynch syndrome (HNPCC) is a dominantly inherited disorder characterized by the development of a variety of cancers, predominantly colorectal and endometrial malignancies. However no commonly associated tumours have been reported in this family. This case outlines some cancer genetic counseling issues that evolved and the emerging implications for family members with the culmination of the diagnosis Lynch syndrome - specifically Muir-Torre syndrome.<br />