Adrenal Phaeochromocytoma

Histopathology Image1 of Adrenal Phaeochromocytoma

Histopathology Image2 of Adrenal Phaeochromocytoma

Paragangliomas are of two types, sympathetic and parasympathetic, depending on the type of paraganglion in which they arise.

Visit: Extraadrenal Paraganglioma

The term phaeochromocytoma is reserved for tumors arising in the adrenal medulla. These tumours are usually fairly easy to diagnose. However, several areas are the subject of debate, including the identification of malignant potential, the diagnosis of medullary hyperplasia, and the recognition of composite tumors. Some histologic features can cause problems in differential diagnosis. Paragangliomas may have spindle cell morphology or contain pigment, requiring distinction from mesenchymal tumors and melanoma, respectively. Extensive degenerative change in pheochromocytomas may mimic adrenal cortical tumours.

In a typical adrenal phaeochromocytoma there is a packeted arrangement of short spindle cells surrounded by vascular stroma.

Immunohistochemistry would show two cells type -sustentacular cells and chief cells.

Electron microscopy shows dense core neurosecretory granules. In these, noradrenaline gives a characteristic appearance of eccentrically-placed dense cores looking like a fried egg.

The incidence of malignancy in adrenal phaeochromocytoma has been reported as 1-14% but it is probably truly nearer the 1% end of range due to selective reporting of malignant cases and the inclusion in some series of extra-adrenal cases which are widely recognized as having a higher incidence of malignancy.

Short of the documentation of metastases, prediction of malignancy is notoriously difficult.

General features more likely to be associated with malignancy include large tumor size (average 759g versus 157g for benign tumours).

Most malignant examples are functionally active and there is a male predominance.

Histological features more likely to be associated with malignancy include : composition of small cells, extensive confluent necrosis, spindle cell formation (one study only), extensive local or vascular invasion, high mitotic count more than 3 per 30 hpf, coarse nodularity and the absence of hyaline globules and of cells with ganglion-like features.

In one statistical model (Linnoila et al. 1990):

- 71% of malignant paragangliomas had 2 or 3 of the features - extra-adrenal location, coarse nodularity, confluent necrosis and absence of hyaline globules, while

- 89% of benign ones had one or none of these features .There was a greater than 95% probability that more than 70% of the tumors could be correctly classified.

Special techniques have limited value in predicting malignancy.

There is diminished expression of neuropeptides. DNA flow cytometry suggests some evidence that DNA aneuploid tumours are more likely to be malignant.

p53 mutations have been found in both benign and malignant phaeochromocytomas.

Histopathology of benign versus malignant sympathoadrenal paragangliomas: clinicopathologic study of 120 cases including unusual histologic features.Hum Pathol. 1990 Nov;21(11):1168-80.

The clinical and pathologic features of 120 adrenal and extraadrenal paragangliomas were studied in an attempt to identify features which might predict malignant behavior. Clinical follow-up was obtained in 98 cases (82%); 64 tumors were clinically benign, and 34 were malignant as evidenced by regional or distant metastases and/or extensive local invasion. Thirty-two of the 34 malignant tumors (94%) were functionally active. Features noted more frequently in malignant tumors included male predominance (74%; P2 [two-sided P value] = .002), extraadrenal location (52%; P2 less than .0001), greater tumor weight (mean 383 g versus 73 g for nonmalignant tumors), confluent tumor necrosis, and the presence of vascular invasion and/or extensive local invasion. Intracytoplasmic hyaline globules were seen in 59% and 32% of benign and malignant tumors, respectively (P2 = .001). Logistic regression analysis of 16 nonhistologic and histologic parameters showed four of them to be most predictive of malignancy--extraadrenal location, coarse nodularity of the primary tumor, confluent tumor necrosis, and absence of hyaline globules. Most malignant paragangliomas had two or three of these features (71%), while 89% of benign tumors had only one (or none; P less than .0001). According to the statistical model developed, there was better than a 95% probability that more than 70% of tumors could be classified correctly on the basis of the four factors indicated. Although limitations still exist, results of this study provide some basis for evaluating malignant potential of these tumors.

Histological grading of adrenal and extra-adrenal pheochromocytomas and relationship to prognosis: a clinicopathological analysis of 116 adrenal pheochromocytomas and 30 extra-adrenal sympathetic paragangliomas including 38 malignant tumors.Endocr Pathol. 2005 Spring;16(1):23-32.

Pheochromocytomas and extra-adrenal sympathetic paragangliomas show varied histological patterns, and it is difficult to diagnose malignancy or predict the clinical course using current histological criteria. In the present study, we reviewed 146 sympathetic paragangliomas including 116 adrenal (102 unilateral, 14 bilateral) and 30 extra-adrenal tumors including 38 metastatic tumors. We developed a scoring scale according to the following six factors: histological pattern, cellularity, coagulation necrosis, vascular/capsular invasion, Ki-67 immunoreactivity, and types of catecholamine produced. The tumors were classified as well (WD), moderately (MD), and poorly differentiated (PD) types according to their scores. The frequency of these tumor types were 113 WD (77%), 27 MD (19%), and 6 PD (4%). Metastasis was observed in 15 of 113 WD (13%), 17 of 27 MD (63%), and all 6 PD (100%). Five-year survivals of patients with metastases were 92% with WD, 69% with MD, 0% with PD. Respective 10-yr survivals were 83%, 38%, and 0%. Differences between groups were statistically significant. The data show that using this grading scoring system for sympathetic paragangliomas correlates with both metastatic potential and patient survival.

Prediction of malignant behavior of pheochromocytomas and paragangliomas using immunohistochemical techniques. Endocr Pathol. 2002 Summer;13(2):149-56.

Pheochromocytomas and paragangliomas arise from the adrenal glands and extraadrenal paraganglia, respectively. Malignant behavior of these tumors is uncommon and is, in part, dependent on their sites of origin, such as extraadrenal location. Morphologic criteria for malignancy of pheochromocytoma and paragangliomas have not been clearly defined. In this study, to clarify the histologic features that distinguish the benign from malignant pheochromocytomas and paragangliomas, we examined metastatic and nonmetastatic tumors using immunohistochemical techniques. A total of eight cases, five pheochromocytomas from the adrenal glands (four benign and one malignant tumor) and three paragangliomas with invasion or metastasis, were studied. The markers used in this study were chromogranin A, synaptophysin, NCAM (CD56), SNAP25, neuron-specific enolase, S-100 protein, and MIB-1. Our results suggest that MIB-1 immunostaining is a useful adjunct marker to predict malignant behavior in these tumors.