Oncocytic Adrenal Tumors: A Tri-Focal Review with Integrated Cytopathological, Pathological, and Molecular Perspectives.

<p>Background: Oncocytic lesions of the adrenal gland pose several diagnostic challenges as they can be associated with both functional and non-functional adrenal disorders and may be either benign or malignant. Summary: Oncocytic tumors are predominantly (>90%) composed of oncocytic cells, characterized by bulky, eosinophilic cytoplasm due to an abundance of mitochondria. Notably, the conventional histopathological criteria for diagnosing adrenal cortical carcinoma (ACC), such as the Weiss criteria, are not recommended for oncocytic tumors, and separate classification algorithms have been proposed for this entity. In addition to their unique cytopathology and histopathology, oncocytic adrenal cortical neoplasms share many driver gene alterations with conventional adrenal tumors, albeit at lower frequencies. However, these tumors also exhibit some distinct genetic changes, particularly deletions of mitochondrial DNA, which are consistent with patterns seen in oncocytic lesions of other endocrine organs. Interestingly, the presence of oncocytic features may correlate with prognosis in ACCs, making this morphological distinction clinically significant. Some studies suggest that oncocytic features could be linked to either a more favorable or unfavorable outcome, depending on other molecular markers. This highlights the importance of accurate diagnostic work-up for these lesions and underscores the critical role of endocrine pathologists in their management. While cytology is not part of the routine work-up for primary adrenal tumors, fine-needle aspiration cytology may still be useful in distinguishing primary adrenal tumors from metastases. Key Messages: This review examines the histological and molecular characteristics of oncocytic adrenal cortical lesions, highlighting their clinically relevant differences from conventional adrenal tumors. It clarifies the limited role of cytology in diagnosing primary adrenal tumors while recognizing its usefulness in distinguishing adrenal metastases. Finally, it underscores the need for a tailored diagnostic approach to effectively manage this complex entity. </p>.