Oncocytic adrenocortical neoplasm arising from adrenal rest in the broad ligament of the uterus.

Oncocytic adrenocortical neoplasm is characterized by abundant eosinophilic cytoplasm containing mitochondria, occasional nuclear atypia and diffuse growth pattern. Oncocytic adrenocortical neoplasm arising in adrenal rest is, however, extremely rare. We report a case of oncocytic adrenocortical neoplasm arising in adrenal rest of the broad ligament with associated marked lipomatous metaplasia. A well circumscribed tumor was accidentally detected in the pelvic cavity of a 29 year old Japanese woman, adjacent to the broad ligament of the uterus. The tumor was composed of large eosinophilic cells associated with diffuse growth pattern and abundant mature adipose tissue admixed with foci of clear cells. Both steroidgenic factor 1 (SF-1) and alpha-inhibin were immunohistochemically positive in tumor cells. Abundant mitochondria detected by immunohistochemical and electron microscopic examination confirmed the diagnosis of oncocytic adrenocortical neoplasm. The absence of necrosis, capsular and vascular invasion as well as the low mitotic index indicated the benign potential of this tumor. The tumor cells were also positive for dehydroepiandrosteron-sulfotransferase (DHEA-ST), 17ß-hydroxysteroid dehydrogenase type 5 (17ß-HSD5), 3ß-hydroxysteroid dehydrogenase (3ß-HSD) and steroid 17α-hydroxylase (P450-c17), suggesting a possible production of testosterone of this tumor. This is the first reported case of oncocytic adrenocortical adenoma arising in adrenal rest of the broad ligament.

Tumor Cell Subtypes Based on the Intracellular Hormonal Activity in KCNJ5-Mutated Aldosterone-Producing Adenoma.

Aldosterone-producing adenomas (APAs) harbor marked intratumoral heterogeneity in terms of morphology, steroidogenesis, and genetics. However, an association of biological significance of morphologically identified tumor cell subtypes and genotypes is virtually unknown. KCNJ5 mutation is most frequently detected and generally considered a curable phenotype by adrenalectomy. Therefore, to explore the biological significance of KCNJ5 mutation in APA based on intracellular hormonal activities, 35 consecutively selected APAs (n=18; KCNJ5 mutated, n=17; wild type) were quantitatively examined in the whole tumor areas by newly developed digital image analysis incorporating their histological and ultrastructural features (14 cells from 2 KCNJ5-mutated APAs and 15 cells from 1 wild type) and CYP11B2 immunoreactivity. Results demonstrated that KCNJ5-mutated APAs had significantly lower nuclear/cytoplasm ratio and more abundant clear cells than wild type. CYP11B2 immunoreactivity was not significantly different between these genotypes, but a significant correlation was detected between the proportion of clear cells and CYP11B2 immunoreactivity in all of the APAs examined. CYP11B2 was predominantly immunolocalized in clear cells in KCNJ5-mutated APAs. Quantitative ultrastructural analysis revealed that KCNJ5-mutated APAs had significantly more abundant and smaller-sized mitochondria with well-developed cristae than wild type, whereas wild type had more abundant lipid droplets per unit area despite the small number of the cases examined. Our results did provide the novel insights into the morphological features of APA based on their biological significance. KCNJ5-mutated APAs were characterized by predominance of enlarged lipid-rich clear cells possibly resulting in increased neoplastic aldosterone biosynthesis.