Eeva M Ryhänen1, Helena Leijon2, Saara Metso3, Eija Eloranta4, Pirkko Korsoff5, Petteri Ahtiainen6, Päivi Kekäläinen7, Marjo Tamminen8, Raija Ristamäki9, Otto Knutar10, Eliisa Löyttyniemi11, Leo Niskanen1, Mika Väisänen12, Ilkka Heiskanen12, Matti J Välimäki1, Markku Laakso13, Caj Haglund12,14, Johanna Arola2, Camilla Schalin-Jäntti1. 1. a The Division of Endocrinology , Abdominal Center, University of Helsinki and Helsinki University Hospital , Helsinki , Finland. 2. b Department of Pathology , Huslab and University of Helsinki , Helsinki , Finland. 3. c Department of Internal Medicine , Tampere University Hospital , Tampere , Finland. 4. d Department of Internal Medicine , Oulu University Hospital , Oulu , Finland. 5. e Department of Internal Medicine , Satakunta Central Hospital , Pori , Finland. 6. f Department of Internal Medicine , Central Finland Central Hospital , Jyväskylä , Finland. 7. g Department of Internal Medicine , North Carelia Central Hospital , Joensuu , Finland. 8. h Department of Internal Medicine , Kymenlaakso Central Hospital , Kotka , Finland. 9. i Department of Oncology , Turku University Hospital , Turku , Finland. 10. j Department of Internal Medicine , Vaasa Central Hospital , Vaasa , Finland. 11. k Department of Biostatistics , University of Turku , Turku , Finland. 12. l Department of Surgery , University of Helsinki, Helsinki University Hospital , Helsinki , Finland. 13. m Institute of Clinical Medicine, Internal Medicine , University of Eastern Finland and Kuopio University Hospital , Finland. 14. n Research Programs Unit, Translational Cancer Biology , University of Helsinki , Helsinki , Finland.
Abstract
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 1.44 mmol/l, p < .001; and 989, 355 and 160 μmol/l, p < .001, respectively). Calcium was ≤1.77 mmol/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 ≥1.77 mmol/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.
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 1.44 mmol/l, p < .001; and 989, 355 and 160 μmol/l, p < .001, respectively). Calcium was ≤1.77 mmol/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 APAtumors 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 ≥1.77 mmol/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.
Authors: Sung Hye Kong; Jung Hee Kim; Man Young Park; Sang Wan Kim; Chan Soo Shin Journal: J Cancer Res Clin Oncol Date: 2021-03-18 Impact factor: 4.553