Annals of Surgical Oncology

, Volume 21, Issue 2, pp 426–433 | Cite as

Negative Parafibromin Staining Predicts Malignant Behavior in Atypical Parathyroid Adenomas

  • Schelto KruijffEmail author
  • Stan B. Sidhu
  • Mark S. Sywak
  • Anthony J. Gill
  • Leigh W. Delbridge
Endocrine Tumors



The histopathological criteria for carcinoma proposed by the World Health Organization (WHO) are imperfect predictors of the malignant potential of parathyroid tumors. Negative parafibromin (PF) and positive protein gene product 9.5 (PGP9.5) staining are markers of CDC73 mutation and occur commonly in carcinoma but rarely in adenomas. We investigated whether PF and PGP9.5 staining could be used to predict the behavior of atypical parathyroid adenomas—tumors with atypical features that do not fulfill WHO criteria for malignancy.


Long-term outcomes were compared across four groups: group A, WHO-positive criteria/PF-negative staining; group B, WHO+/PF+, group C; WHO/PF; and group D, WHO/PF+.


Eighty-one patients were included in the period 1999–2012: group A (n = 13), group B (n = 14), group C (n = 21), and group D (n = 33). Mortality and recurrence rates, respectively, for group A were 15 and 38 %, for group B 7 and 36 %, for group C 0 and 10 %, and for group D 0 and 0 %. The PGP9.5+ ratios for groups A to D were 85, 78, 71, and 12 %, further informing prognosis. Five-year disease-free survival for groups A to D were 55, 80, 78, and 100 %, respectively. Tumor recurrence was significantly associated with PF (p = 0.048) and PGP9.5 (p = 0.003) staining.


Although WHO criteria are essential to differentiate parathyroid carcinoma from benign tumors, the presence of negative PF staining in an atypical adenoma predicts outcome better, whereas PF-positive atypical adenomas do not recur and can be considered benign. PF-negative atypical adenomas have a low but real recurrence risk and should be considered tumors of low malignant potential.


Adenoma Parathyroid Carcinoma Parathyroid Tumor Minimal Invasive Parathyroidectomy Parathyroid Cancer 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Conflict of interest

The authors declare no conflict of interest.


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Copyright information

© Society of Surgical Oncology 2013

Authors and Affiliations

  • Schelto Kruijff
    • 1
    Email author
  • Stan B. Sidhu
    • 1
  • Mark S. Sywak
    • 1
  • Anthony J. Gill
    • 2
    • 3
  • Leigh W. Delbridge
    • 1
  1. 1.Endocrine Surgical UnitUniversity of SydneySydneyAustralia
  2. 2.Department of PathologyRoyal North Shore HospitalSt. LeonardsAustralia
  3. 3.Department of PathologyUniversity of SydneySydneyAustralia

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