Current Knowledge on Atypical Parathyroid Tumors and Emerging Strategies for Risk Stratification

Atypical parathyroid tumors (APTs) are an uncommon subset of parathyroid neoplasms that carry substantial clinical relevance because of their histological and clinical resemblance to parathyroid cancer. Despite this importance, the diagnosis of APTs remains persistently challenging, even for experienced pathologists. Their histopathological features overlap extensively with those of parathyroid cancer, and at present, no specific immunohistochemical markers are available that can reliably distinguish between these entities. Moreover, the clinical manifestations of APTs are indistinguishable from those of parathyroid adenomas or true parathyroid cancer. A major concern is the uncertain malignant potential of APTs, which contributes to difficulties in prognostic prediction and the absence of standardized surveillance guidelines. Although most published studies suggest a benign clinical course for the majority of APTs, these conclusions are frequently limited by relatively short follow-up durations. This limitation is underscored by several case reports describing recurrence or metastatic disease in patients initially diagnosed with APTs, subsequently prompting reclassification as parathyroid cancer. Recent advances in molecular technologies, particularly RNA sequencing and genomic profiling, have facilitated novel approaches to risk assessment and prognostic evaluation in APTs. This review aims to provide a comprehensive overview of the diagnosis, clinical manifestations, and current molecular strategies used to assess the malignant potential of APTs.