**4. Pathological findings**

Adrenal adenomas are generally encapsulated, have variable volume and weight, and in most cases have a diameter of 2–4 cm. In nonfunctioning tumors, clear cells of the fasciculate zone, filled with lipids (cholesterol), predominate microscopically, which gives the yellowish coloration. Functioning tumors are usually of varied colors, reddish-brown, with yellowish areas or striae, showing in microscopy the predominance of compact cells, associated with clear cell nests (**Figure 1**). Cortisolproducing adenomas are accompanied by hypotrophy of the adrenal cortex of the affected gland and the contralateral adrenal gland due to adrenocorticotropic hormone (ACTH) (suppression in contrast to aldosterone-producing adenomas in which this aspect is not observed) [3].

### **Figure 1.**

*Microscopy of an adrenal cortex adenoma showing one or more cell types (A) separated from each other by fibrous septa containing blood vessels (H&E 100×). High increase showing cells in the zona glomerulosa, fasciculate zone, and reticular zone forming nests and strands (H&E 400×).*

Adrenal carcinomas are usually larger than 4 cm and occasionally weigh more than 1 kg. Microscopically, the picture is varied: in some cases, the tumor is very similar to the adenoma, but in some cases, the tumor appears anaplastically, being composed of cells with large pleomorphism, bizarre nuclei, and atypical mitoses. Vascular or capsular invasion is a predictive sign of malignant behavior, being a sign of local extension [3, 4].

Differentiation with adenomas can be difficult and is based on macroscopic (tumor weight, hemorrhage, and capsule integrity) and microscopic aspects using the modified Weiss scoring system. The five criteria used in the updated Weiss system include >6 mitoses/50 high potency fields, ≤25% clear tumor cells in the cytoplasm, abnormal mitoses, necrosis, and capsular invasion. Each criterion is scored 0 when absent or 2 for the first two criteria and 1 for the last three when present. The adrenal carcinoma can be diagnosed by the presence of a total score ≥ 3 [5].

Tumors are functioning in approximately 60% of all cases, but the presence of symptoms of hormonal hypersecretion is present in only 40%, possibly by the secretion of large quantities of biologically inactive hormones [5, 6].

In general, adrenal carcinomas rarely produce and secrete a single steroid hormone and are usually associated with overproduction and hypersecretion of multiple hormones and precursors. Most cases produce different types of steroid hormones [7–9]. Thus, hypersecretion of a single adrenocortical steroid usually indicates the benign nature of adrenocortical neoplasia. The most frequently seen combination is hypersecretion of cortisol and androgens [10].
