Microvessel Density as an Adjunctive Immunohistochemical Parameter in the Differential Diagnosis of Parathyroid Carcinoma and Adenoma—An Immunohistochemical Study
Zorka Inić, Katarina Taušanović, Marko Buta, Zoran Kozomara, Ognjen Živković, Nikola Jeftić, Stefan Gačić, Dobrica Stević, Anđela Milićević, Milan ŽegaracBackground/Objectives: Distinguishing parathyroid carcinoma from parathyroid adenoma remains a major diagnostic challenge because these tumors frequently share similar clinical, biochemical, radiological, and histopathological features. Accurate diagnosis is essential for appropriate surgical management, highlighting the need for reliable adjunctive biomarkers. This study evaluated the diagnostic value of tumor angiogenesis, quantified by microvessel density (MVD), for differentiating parathyroid carcinoma from parathyroid adenoma and its association with clinicopathological characteristics. Methods: This retrospective study included 50 patients with primary hyperparathyroidism who underwent surgery at a tertiary endocrine surgery center, including 10 parathyroid carcinomas and 40 parathyroid adenomas. Tumor angiogenesis was assessed by immunohistochemical staining, and MVD was quantified in vascular hot spots using standardized methods. Receiver operating characteristic (ROC) analysis evaluated the diagnostic performance of MVD, while correlations with clinicopathological parameters were analyzed. Results: Parathyroid carcinoma demonstrated significantly higher MVD than parathyroid adenoma (median 901.14 vs. 431.24; p < 0.001). ROC analysis showed excellent diagnostic performance, with an area under the curve of 0.917. Higher MVD was positively associated with Ki-67 expression, preoperative parathyroid hormone and calcium levels, and tumor weight, indicating a close relationship between angiogenesis, tumor proliferation, biochemical disease severity, and tumor burden. No significant associations were observed with age or preoperative phosphate levels. Conclusions: Quantitative assessment of MVD is a promising adjunctive immunohistochemical biomarker for distinguishing parathyroid carcinoma from parathyroid adenoma. Incorporating MVD into conventional histopathological evaluation may improve diagnostic confidence, particularly in morphologically challenging cases. Larger multicenter studies are warranted to validate these findings and further establish the clinical utility of MVD.