A nationwide study on parathyroid carcinoma

Background: Parathyroid carcinoma (PC) is rare and diagnostically challenging. Reported outcomes are rather poor and the incidence might be increasing.Material and methods: We performed a nationwide study on all cases (n=32) diagnosed in 2000-2011 in Finland, and compared clinical and histopathological characteristics and outcome to atypical parathyroid (APA; n=28) and parathyroid adenomas (PA; n=72). The incidence in years 1955-1999 was compared to that in 2000-2013.Results: Preoperatively, calcium and parathyroid hormone concentrations were higher in PC compared to APA and PA (1.76, 1.56 and 1.44mmol/l, p<.001; and 989, 355 and 160mol/l, p<.001, respectively). Calcium was 1.77mmol/l for all PAs. Hospitalization (44% vs. 22% and 3%, respectively, p=.01), renal (50% vs. 48% vs. 22%, respectively, p=.01) and bone (47% vs. 15% vs. 38%, respectively p=.002) manifestations were more common. PC and APA tumors were larger than PA (p<.001). Histopathological characteristics of PC compared to PA are increased mitotic activity (p=.001), chief cells (p=.003), diffuse growth pattern (p<.001), higher Ki67 (p<.001) and negative parafibromin (p<.001). One PC (1/18) and one APA (1/16) patient had a CDC73 mutation. After 6.7 (2-13.9) years of follow-up, 9.4% of PC had residual, 21% recurrent disease and 12.5% died of disease. Overall mortality did not differ between subgroups (p=.094). Recurrent PC was characterized by vascular invasion, lymph node metastases, high mitotic activity, necrosis and negative parafibromin. Incidence increased from 1.42 (range 0.52-2.14) to 7.14 (range 3.42-10.38)/10.000.000/years; (p<.001).Conclusions: PC associates with severe primary hyperparathyroidism and must be suspected if calcium 1.77mmol/l. The prevalence of CDC73 germline mutations in PC and APA in Finland is 6%. PC has distinct histopathological characteristics and its incidence has increased over the past decades.