Autophagy-Related Proteins Are Differentially Expressed in Adrenal Cortical Tumor/Pheochromocytoma and Associated with Patient Prognosis

The aim of this research was to evaluate the expression and concomitant implications of LC3A, LC3B, beclin-1, and p62, which are key components of autophagy in human adrenal gland tumors. Tissue microarray was made for 321 cases of adrenal gland tumor (adrenal cortical adenoma (ACA): 115, adrenal cortical carcinoma (ACC): 17, and pheochromocytoma (PCC): 189). Immunohistochemical staining was performed for beclin-1, p62, LC3A, and LC3B, and the results were compared with the patients’ clinicopathologic parameters. LC3A, LC3B, beclin-1, and LC3B isolated single positive cells (ISPC) positivity rates were higher in PCC than in adrenal cortical tumor (ACT), whereas p62 positivity was lower in PCC than in ACT. The proportion of positive LC3B (ISPC) was higher in ACC than in ACA. In addition, the proportion of cells positive for p62 and LC3B (ISPC) was significantly higher in PCCs with a GAPP score of ≥3. In univariate Cox analysis, p62 positivity (p = 0.014) and the presence of p62 (ISPC) (p = 0.001) were associated with shorter disease-free survival in PCC. Moreover, p62 positivity was predictive of shorter overall survival (OS) in patients with PCC by multivariate analysis (relative risk, 6.240; 95% CI, 1.434–27.15; p = 0.015). Differences were found in the expression of autophagy-related proteins according to adrenal gland tumor types. Compared to ACT, the proportion of LC3A, LC3B, beclin-1, and LC3B (ISPC) positivity was higher in PCC, whereas p62 positivity was lower. Similarly, p62 positivity in PCC was associated with patient prognosis of OS.

Unusual Adrenal Cortical Tumor of Unknown Biologic Potential: A Nodule in a Nodule in a Nodule

Adrenocortical tumors are uncommon neoplasms in childhood. Most pediatric adrenal tumors are virilizing and carcinomas are more common than adenomas. Recent molecular data suggest an adenoma-to-carcinoma progression sequence in adrenal cortical neoplasms. We report a case of a 5-year-old boy who presented with virilizing symptoms secondary to an adrenal tumor that was resected laparoscopically. The bulk of the tumor was a large, yellow mass with typical features of an adrenal cortical adenoma. In the center was a well-circumscribed tan-brown nodule that was distinct from the adenoma and had oncocytic features. A third minute focus (3.0 mm) was noted that was not circumscribed or encapsulated, but showed marked pleomorphism and abundant mitoses, including atypical forms and increased Ki67 compared with the outer 2 nodules. Molecular analysis to assess the clonality and mutation rates of the 3 distinct areas showed only 2 genetic loci with allelic imbalances.