On CT scans, pheochromocytomas appear as welldemarcated and circumscribed nonhomogeneous tumors. The lack of homogeneity is due to hemorrhage, necrosis, and cystic degeneration. The ¹³¹I-MIBG scan using a radioactive material that is taken up by neuroendocrine tumors is diagnostically useful.

Sporadic pheochromocytomas are usually single, unilateral tumors, 2 to 10 cm in diameter but can attain a large size. Multiple and bilateral tumors are common in a hereditary setting. The cut surface is gray to pink-tan or red with areas of recent hemorrhage. Areas of old hemorrhage, fibrosis, and cystic degeneration and necrosis are frequent in large neoplasms (Fig. 14.1). The tumor takes the deep mahogany color after exposure to air. Following immersion in a dichromate solution, the tumor turns deep brown as a result of oxidation of the catecholamines.

Histologically, most are encapsulated. Pheochromocytomas demonstrate various growth patterns such as trabecular with anastomosing cell cords, alveolar or nesting (Zellballen), and diffuse (Fig. 14.2A-J). Pseudoacinar, pseudopapillary, or perivascular arrangement may occur. Spindle cell patterns are occasionally observed (see Fig. 14.9D). The tumors are very vascular, with a prominent network of delicate capillaries surrounding groups of neoplastic cells. The predominant cell type is large polygonal with moderate-to-abundant granular cytoplasm that is eosinophilic to amphophilic (Fig. 14.2F). The cytoplasm may be vacuolated or clear and contain melanin pigment. Some cells mimic ganglion cells. Intracytoplasmic eosinophilic hyaline globules have been detected in 47% of the cases. Intranuclear inclusions are commonly seen. Pheochromocytomas also demonstrate

giant multinucleated bizarre cells. Stromal amyloid has been reported in 70% of the cases.

The specimens for cytologic diagnosis almost always represent fine needle aspiration (FNA) biopsies. The fine needle biopsy procedure is usually not recommended when pheochromocytoma is clinically suspected due to possible complications during the procedure. The documentation of cytologic features in literature is rather lean. The cytologic findings presented in this chapter represent both, the scrape preparations of the surgically excised neoplasms and FNA biopsies.

The cytologic features of pheochromocytomas vary widely from case to case and are dependent on the growth pattern, cell composition, as well as the cell characteristics (Table 14.1; Figs. 14.3,14.4,14.5,14.6,14.7,14.8,14.9,14.10,14.11,14.12 and 14.13). The aspirates tend to be bloody. The cellularity of the aspirate is variable and often compromised due to excessive blood. The neoplastic cells appear isolated, in loosely cohesive groups and in syncytial tissue fragments, without any architectural patterns. The neoplastic cells vary in size and range from small to large with frequent giant forms. The cells in a given case can be monomorphic or pleomorphic. They can be round, cuboidal, plasmacytoid, polygonal, racquet shaped, caudate, or spindle shaped. The characteristic large polygonal cells with deep eosinophilic cytoplasm, seen in histologic preparations, are only rarely appreciated in cytologic smears. The cell borders are well to poorly defined. Their nuclei are central to eccentric, round to ovoid with stippled chromatin (salt-pepper) and small nucleoli. The nuclear pleomorphism may be striking with the presence
of giant forms with pyknosis (Figs. 14.6B,C and 14.8C). Intranuclear inclusions may also be present. Their cytoplasm of pheochromocytoma cells is variable. The nuclear/cytoplasmic ratios likewise vary. Some cells appear large and ganglion-like (Fig. 14.8C), while some exhibit wispy cytoplasmic processes (Fig. 14.8B). It is not unusual to encounter disruption of the lipid-rich cytoplasm resulting in a large population of uniform naked nuclei (Figs. 14.12 and 14.13A). The cytoplasm of the pheochromocytoma cells may contain eosinophilic, periodic acid-Schiff (PAS)-positive globules. Red cytoplasmic granules are seen in Romanowsky-stained preparations. Old and new hemorrhage and degenerative changes are frequent.