Malignant pheochromocytoma with negative biochemical markers: Is it time to reclassify pheochromocytomas?

Abstract

Pheochromocytomas are catecholamine producing tumors of adrenal gland generally diagnosed by presence of these markers in urine or plasma. However, a few may be marker-negative and challenging for clinicians. Several reports of these marker-negative pheochromocytomas may warrant necessity for a new classification of these tumors. Adrenergic blockade before surgery is one of the main reasons for recognition of these cases. We present a case of marker-negative pheochromocytoma which turned out to be malignant on its recurrence. To our knowledge, this is the only case of malignant marker-negative pheochromocytoma reported in literature so far.

Ocular muscle metastasis as the initial presentation of a malignant pheochromocytoma: A unique case

“…Some hypotheses were suggested for the mechanism of normotensive pheochromocytomas, including different blood pressure basis and/or variable cardiovascular response to catecholamine and metanephrine released among different individuals. Thus, in the same elevated levels of catecholamines, different blood pressure values were observed 9‐13 . Also, we assume that in huge malignant pheochromocytomas the nature and function of tumor changes and severe malignancy process lead to poor differentiation of chromaffin cells, contributing to the advent of a nonfunctional or minimally functional tumor.…”

“…[3][4][5][6] The most common metastatic sites of malignant pheochromocytoma are as follows: bone, intra-abdominal organs, lungs, and pleura. [5][6][7][8][9][10][11][12][13] Although skull metastasis is quite common, 2 there has never been a reported case of ocular…”

“…The most common metastatic sites of malignant pheochromocytoma are as follows: bone, intra‐abdominal organs, lungs, and pleura 5‐13 . Although skull metastasis is quite common, 2 there has never been a reported case of ocular muscle involvement as the initial presentation of malignant pheochromocytoma.…”

“…Nonetheless, some studies hypothesized that the size of the tumor and its metabolic rate relative to its size are also important factors in the levels of catecholamine products and the clinical picture presented. [6][7][8][9][10][11][12][13] We believe that this linear relationship does not continue until the late stages, in which because of tumor necrosis and the undifferentiated nature of advanced tumors, the metanephrine levels drop so much that they could be in the upper limits of normal (like our case) or even less.…”

“…1,8 Despite the lack of definite criteria for the detection of malignancy, there are some histopathological findings such as nuclear pleomorphism, cellular hyperchromatism, bizarre mitotic figures, and vascular and capsular invasion. 9,10 Unfortunately, these findings have poor predictive value, because they are also seen in benign lesions. Immunohistochemical staining is not helpful in the prediction of the biological behavior of pheochromocytoma.…”