Oncocytic adrenal cortical tumor with cytoplasmic inclusions and hyaline globules

Abstract

Adrenal cortical tumors, particularly oncocytic tumors, have been reported to contain a variety of intracytoplasmic and intramitochondrial inclusions. Oncocytic cortical tumors can also morphologically mimic pheochromocytomas. We report an unusual, partially oncocytic cortical neoplasm with nesting architecture, intranuclear inclusions, and hyaline globules reminiscent of pheochromocytoma, together with numerous, small, brightly eosinophilic, periodic acid-Schiff-positive cytoplasmic inclusions and typical cytoplasmic lipid droplets. Ultrastructural study revealed oncocytes containing numerous mitochondria with intramitochondrial crystals and lipid droplets. Immunohistochemistry and immunoblots were utilized to further characterize the tumor. Immunohistochemistry demonstrated immunoreactivity of both the eosinophilic inclusions and the hyaline globules for adipose differentiation-related protein (ADRP), which is one of a group of proteins associated with storage of neutral lipids in many cell types. Immunoblots confirmed the presence of ADRP and demonstrated an imbalance between ADRP and perilipin, another neutral lipid-associated protein, in tumor tissue compared to normal adrenal cortex. The findings suggest that mitochondrial dysfunction in oncocytic cortical tumors may lead to abnormal processing of proteins related to the lipid-storing functions of the adrenal cortex, resulting in unusual cytoplasmic inclusions and extracellular globules resembling the globules in pheochromocytomas. The finding of ADRP as a constituent of inclusions in adrenal cortical tumors has not been previously reported.

Aldosterone-Producing Adrenal Cortical Adenoma with Oncocytic Change and Cytoplasmic Eosinophilic Globular Inclusions

“…Seo et al reported two cases of oncocytic adrenal cortical tumors (one carcinoma and the other of unknown potential) with intracytoplasmic crystalline inclusions located within the membrane-bound cisterns of rough endoplasmic reticulum [19]. Recently, Al-Zaid et al published an oncocytic adrenal cortical tumor exhibiting hyaline globules reminiscent of pheochromocytoma, together with multiple cytoplasmic inclusions and cytoplasmic lipid droplets [20]. They demonstrated the immunoreactivity of both the eosinophilic inclusions and the hyaline globules for adipose differentiation-related protein, which is one group of proteins associated with storage of neutral lipid in oncocytic cells.…”

Oncocytic adrenocortical neoplasms—a clinicopathologic study of 13 new cases emphasizing the importance of their recognition

“…The tumor cells are usually arranged in a diffuse sheet-like pattern, although trabecular, alveolar, and glandular [8] architectures can be focally seen. Eosinophilic intranuclear pseudoinclusions, bizarre multinucleated giant cells, and lymphoid infiltrates are well-described features [2], whereas spindle cell areas [3], cytoplasmic globular inclusions [9], extracellular hyaline droplets [10], fibromyxoid stroma, and dystrophic calcification are less common. In our series, we report the first case of a myelolipomatous component occurring in association with a malignant OAN (case 3; Fig.…”

Psammomatoid Calcification-Rich Oncocytic Thyroid Adenoma With Clear-Cell Change

“…The heterogeneous expression with focal lack of cytoplasmic thyroglobulin in several nodule thyrocytes, in agreement with the observations of Kniseley and Andrews, 16 sustains the hypothesis of a necrobiotic-type change. Interestingly, markers of intracytoplasmic lipid-droplets adipophilin (already reported for oncocytic adrenal adenomas) 17 and Figure 1. The thyroid nodule showed multiple, confluent calcifications, most of psammomatoid-type (A, B, C, and E: black arrows).…”