Pheochromocytoma

PHEOCHROMOCYTOMA

• Pheochromocytoma is a paraganglioma arising in the adrenal medulla

• Incidence – accounts for about 6% of primary adrenal tumors

• Age – peak age at diagnosis is 5th decade of life

• Shows equal sex incidence

• They have been termed as 10% tumor due to

  • 10% tumors are bilateral

  • 10% tumors are extra adrenal

  • 10% tumors are malignant

  • 10% tumors occur in childhood

• In familial cases 50% are bilateral and patients are of earlier age .

• Tumors occurring in paediatric age group are mostly bilateral, multicentric and extraadrenal tumors.

Clinical features

• Presents with diagnostic triad of diaphoresis, headache and paroxysmal hypertension

• Sustained hypertension in Nor-epinephrine secreting tumors

• Episodic hypertension in tumors secreting both epinephrine and nor-epinephrine.

• Patients are normotensive in dopamine secreting tumors.

Morphology

Gross –

• Tumor presents as rounded, unicentric mass with peripheral rim of normal adrenal gland.

• size – 1 to 10cms

• Malignant tumors are heavier than benign tumors

• Cut section – circumscribed tumor with pseudocapsule. Tumor is grey white with areas of congestion, hemorrhage, necrosis, fibrosis and cystic change. Dystrophic calcifications can also be present.

• Infiltration into adjacent structures like kidney, liver and extension into inferior vena cavae, right atrium indicates malignancy.

Microscopic features

• Various architectural patterns seen in this tumor are alveolar, trabecular, Zell-ballen pattern (means “balls of cells” in German)

• Spindle cell pattern can also be seen

• Non – neoplastic cortical cells and adrenal medulla cell can also be seen intermingled with tumor cells

• Tumor cells are polygonal and have eosinophilic, finely granular or amphophilic to basophilic cytoplasm. vacuolated cytoplasm can also be seen.

• Occasionally tumor cells partially envelop other cells (Cell embracing).

• Nuclei show pseudoinclusions.

• Intracytoplasmic hyaline globules may be present.

• Melanin pigment has also been reported

• Stroma shows areas of sclerosis and amyloid deposition. Lakes of eosinophilic proteinaceous material with vacuoles at the periphery may be present.

Chromaffin reaction

• Dichromate containing fixatives may produce the chromaffin reaction on fresh tumor tissue resulting in a dark brown colour.

• Freshly cut tumor tissue when immersed in Potassium dichromate(pH of 5 to 6), it turns dark brown due to oxidation of stored catecholamines synthesized by tumor cells.

Pheochromocytoma with malignant behavior

Pheochromocytoma of adrenal gland scoring scale (PASS)

• Largest nests or diffuse growth (>10% of tumor volume)                 –   score   2

• Central or confluent tumor necrosis                                                   –   score   2

• high cellularity                                                                                      –   score   2

• Cellular monotony                                                                                –   score   2

• Tumor cell spindling                                                                             –   score   2

• Mitotic figures  (>3/10 hpf)                                                                   –   score   2

• Atypical mitotic figures                                                                       –   score   2

• Extension into adipose tissue                                                            –   score   2

• Vascular invasion                                                                                 –   score   1

• Capsular invasion                                                                                –   score   1

• Profound nuclear pleomorphism                                                        –   score   1

• Nuclear hyperchromasia                                                                     –   score   1

PASS score >4 was potentially aggressive behavior and less than 4 are benign.