DIAGNOSIS AND DISCUSSION:
MODERATELY DIFFERENTIATED ADRENAL CORTICAL CARCINOMA WITH ADRENAL VEIN INVASION (10 cm, 250 gm).
In a case of a retroperitoneal neoplasm such as this one, a few issues are important to address:
1. Is this an adrenal or a renal neoplasm? Certainly, the location of this neoplasm in the adrenal gland is compatible with a primary adrenal neoplasm. However, ruling out the possibility of a metastasis requires the use of ancillary studies such as immunostaining. Work up on this case revealed the neoplasm to be positive for Vimentin and Synaptophysin and negative for Cytokeratin (AE1/AE3), Epithelial Membrane Antigen, and Chromogranin. The lack of finding a mass in the kidney and the negative EMA stain are against this neoplasm being a renal cell carcinoma. Molecular analysis may also assist in the findings of Von-Hippel Lindau gene mutation and/or loss of heterozygosity favors renal cell carcinoma.
2. If adrenal, is this a cortical neoplasm or a pheochromocytoma? While classic cases of each of these neoplasms are easily distinguished from one another, there are cases with overlapping features. Both neoplasms may have oncocytic or eosinophilic cytoplasm and both may contain intracytoplasmic lipid. Although, the clinical constellation of hypertension, flushing, and palpitations are characteristic for pheochromocytoma, these symptoms along with elevated serum or urine catecholamine levels have also been reported in adrenal cortical adenomas and carcinomas. Neuroendocrine differentiation as demonstrated by synaptophysin, neuron specific enolase, and neurofilament positivity may be seen in adrenocortical neoplasms. However chromogranin is negative even in adrenocortical neoplasms which show neuroendocrine differentiation by other markers. Electron microscopic studies in these neoplasms demonstrate very few membrane bound neurosecretory granules. Pheochromocytoma characteristically demonstrate strong chromogranin positivity and numerous neurosecretory granules by EM. Cytokeratin is characteristically negative in Pheochromocytoma but a subset of cortical carcinomas are negative as well. Finally, molecular analysis may be a useful ancillary tool in that point mutation in exons 10, 11, or 16 of the ret oncogent would indicate a pheochromocytoma.
3. If it is an adrenal cortical neoplasm, is it benign or malignant? A number of studies have addressed this issue but there several parameters which are probably more important than others. These include weight, mitotic count, atypical mitotic figures, tumor necrosis, capsular and vascular invasion, and diffuse growth pattern. Typically adenomas are less than 100 grams, demonstrate less than 2 mitoses per 10 high powered fields, show no necrosis, capsular or vascular invasion, and grow in nests. For most cortical neoplasms, this distinction is not a problem, however like neoplasms in other organ systems a few borderline cases are recognized occasionally.
4. If malignant, what are the significant prognostic indicators? Studies by Weiss, van Slooten, and Evans state the prognostic importance of mitotic counts. However, the numerical cutoff is different from study to study and ranges from 20/50 hpf to 20/10 hpf. The significance of nuclear pleomorphism has also been addressed but this parameter has not been widely accepted as a prognostic determinant.
This case shows many of the cardinal features of an adrenal cortical carcinoma. The distinction from a pheochromocytoma is made by the lack of chromogranin immunoreactivity. While most adrenal neoplasms are readily classified, some may fall into a borderline category after assessing multiple parameters.
Contributed by N. Paul Ohori, M.D. and Sydney D. Finkelstein, M.D.