Preoperative CALLY Index for Identifying Atypical Parathyroid Tumors

Atypical parathyroid tumors (APTs) are diagnostically challenging neoplasms that display worrisome histopathological features but do not meet the criteria for carcinoma. Conventional biochemical and imaging parameters have limited discriminatory accuracy, and no validated preoperative biomarker exists to identify APT reliably. This study evaluated the diagnostic performance of the C-reactive protein-albumin-lymphocyte (CALLY) index as a composite immunonutritional marker for distinguishing APT from typical parathyroid adenomas (TPA).

This retrospective observational study with a matched analytical case-control design included adult patients who underwent parathyroidectomy for primary hyperparathyroidism between June 2020 and December 2025. All histopathologically confirmed APT cases were included, and age- and sex-matched TPA controls were selected from a larger institutional database. The primary diagnostic outcome was histopathologically confirmed APT. Diagnostic accuracy was assessed using receiver operating characteristic (ROC) analysis, and independent predictors of atypical pathology were identified using multivariable logistic regression.

A total of 50 APT cases and 156 matched TPA controls formed the analytical cohort (n = 206). The CALLY index was significantly lower in APT than in TPA (median 3.11 vs. 10.55; p < 0.001). ROC analysis demonstrated excellent discriminatory performance for APT-TPA differentiation (AUC = 0.941), with an optimal cutoff of ≤ 5.73 yielding 88.0% sensitivity, 86.5% specificity, and 95.7% negative predictive value. Low CALLY remained the strongest independent predictor of APT (OR: 37.29; p < 0.001), outperforming serum calcium, PTH, and tumor diameter.

The preoperative CALLY index may serve as a simple and accessible adjunctive marker for identifying patients with an increased likelihood of atypical parathyroid pathology before surgery. Its clinical value appears to lie primarily in preoperative APT-TPA discrimination and risk stratification rather than prediction of postoperative recurrence. Prospective multicenter validation is warranted before routine clinical implementation.