Fibrous dysplasia (FD) is associated with increased risk for breast and thyroid cancer and for the pre-malignant intraductal papillary mucinous neoplasm (IPMN), possibly due to extra-skeletal tissue distribution of GNAS-mutations. Data on further associations of FD with malignant tumors are scarce. Since these associations may have significant clinical implications, we performed a cohort study on tumor occurrence in FD.

Pathology reports from FD patients were retrieved from the Dutch National pathology registry (PALGA). Incidence rates for malignant tumors were compared between FD patients and the general Dutch population by calculating standardized morbidity ratios (SMR). In this study, SMRs were calculated for all FD/GNAS-associated and bone tumors. We also studied the FD associated risk for the three most common malignancies in the Netherlands, e.g. prostate, colorectal and skin cancer; our data on breast cancer have been reported previously.

Of the 1146 PALGA FD patients, 177 (M/F; 79/98) also had histological evidence for a malignant tumor. Mean age at FD diagnosis was 47.0 years (1-86yr) and mean age at diagnosis of malignancy was 49.7 years (2-92yr). 207 malignant tumors were documented. Among known GNAS-related and bone tumors, SMR was increased for thyroid cancer (3.71[95%CI 1.13-7.76]) and for osteosarcoma (26.31[95%CI 6.58-59.20]). For the three most prevalent malignancies in The Netherlands, SMRs were increased for prostate cancer (3.08[95%CI 1.82-4.63]) and melanoma (1.99[95%CI 1.05-2.94]), but not for colorectal cancer.

Our data confirm that patients with FD have an increased risk for thyroid cancer and osteosarcoma. We also report an increased risk of other malignancies in FD such as melanoma and prostate cancer, both associated with GNAS-mutations, but no increased risk for pancreatic cancer. Our findings raise awareness for the risk of malignancy in FD, although caution should be exerted in their interpretation, as the specific role of GNAS mutations in the pathophysiology of FD-related tumors is as yet to be unraveled.