title: Evaluation of malignant parathyroid tumours in two European cohorts of patients with sporadic primary hyperparathyroidism.
abstract: OBJECTIVE
  Parathyroid carcinoma (PC) is remarkable for its rare occurrence and challenging diagnostics. PC accounts for 0.1-5 % cases of primary hyperparathyroidism (PHPT). The differentiation from benign tumours is difficult even by morphological criteria. To address these issues, we assessed the PC frequency in two separate European PHPT cohorts and evaluated the demographic, clinical, morphological and molecular background.
  
  
  METHODS
  A retrospective study was carried out, using continuously maintained database (2005-2014) of PHPT patients from two tertiary referral university hospitals in Europe. The demographic, clinical data and frequency of PC among surgically treated PHPT was detected. Immunohistochemistry (IHC) was performed to detect parafibromin, representing protein product of HRPT2 gene and proliferation marker Ki-67.
  
  
  RESULTS
  Both PHPT cohorts were characterised by close mean age values (58.6 and 58.0 years) and female predominance. The frequency of PC differed significantly between the cohorts: 2.1 vs. 0.3 %; p = 0.004. PC was characterised by invariable complete loss of parafibromin contrasting with parathyroid adenomas. The proliferation fraction was similar in both PC cohorts (10.6 and 11.0 %). PC showed significantly higher proliferation fraction than typical parathyroid adenomas (1.6 %), atypical adenomas (1.6 %) or adenomas featuring focal loss of parafibromin (2.2 %).
  
  
  CONCLUSIONS
  PC frequency can range significantly between the two European cohorts. The differences can be attributable to selection bias of patients referred for surgery and are not caused by discordant definition of malignant parathyroid histology. Diffuse loss of parafibromin and increased proliferation fraction by Ki-67 are valuable adjuncts in PC diagnostics due to significant differences with various clinical and morphological subtypes of adenoma.
authors.affiliation: Department of Surgery, Riga Stradins University, Dzirciema Street 16, LV-1007, Riga, Latvia. arturs.ozolins@rsu.lv.
authors.forename: Arturs
authors.initials: A
authors.lastname: Ozolins
authors.affiliation: Department of Surgery, Riga Stradins University, Dzirciema Street 16, LV-1007, Riga, Latvia.
authors.forename: Zenons
authors.initials: Z
authors.lastname: Narbuts
authors.affiliation: Department of Surgery, Riga Stradins University, Dzirciema Street 16, LV-1007, Riga, Latvia.
authors.forename: Andrejs
authors.initials: A
authors.lastname: Vanags
authors.affiliation: Department of Pathology, Riga Stradins University, Riga, Latvia.
authors.forename: Zane
authors.initials: Z
authors.lastname: Simtniece
authors.affiliation: Department of Surgery, Riga Stradins University, Dzirciema Street 16, LV-1007, Riga, Latvia.
authors.forename: Zane
authors.initials: Z
authors.lastname: Visnevska
authors.affiliation: Department of Surgery, Lukas Hospital, Neuss, Germany.
authors.forename: Aycan
authors.initials: A
authors.lastname: Akca
authors.affiliation: Department of Surgery, Lukas Hospital, Neuss, Germany.
authors.forename: Denis
authors.initials: D
authors.lastname: Wirowski
authors.affiliation: Department of Surgery, Riga Stradins University, Dzirciema Street 16, LV-1007, Riga, Latvia.
authors.forename: Janis
authors.initials: J
authors.lastname: Gardovskis
authors.affiliation: Department of Pathology, Riga Stradins University, Riga, Latvia.
authors.forename: Ilze
authors.initials: I
authors.lastname: Strumfa
authors.affiliation: Department of Surgery, Lukas Hospital, Neuss, Germany.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Goretzki
mesh_terms: D000236:Adenoma / Q000175:diagnosis* / Q000453:epidemiology* / Q000378:metabolism; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005060:Europe; D005260:Female; D006801:Humans; D049950:Hyperparathyroidism, Primary / Q000150:complications* / Q000378:metabolism / Q000473:pathology*; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010282:Parathyroid Neoplasms / Q000175:diagnosis* / Q000453:epidemiology* / Q000378:metabolism; D015995:Prevalence; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: C454900:CDC73 protein, human; D019394:Ki-67 Antigen; D025521:Tumor Suppressor Proteins
keywords: Immunohistochemistry; Ki-67; Parafibromin; Parathyroid carcinoma; Primary hyperparathyroidism