A large hemorrhagic pheochromocytoma (275 g) is described in a 38-year-old obese woman who had no history of sustained or sporadic hypertension. The tumor was unusual histologically because of the striking presence of oncocytic cells. Immunohistochemical studies revealed the positivity for neuron-specific enolase, synaptophysin, and cytokeratin CAM 5.2. Electron microscopy demonstrated neurosecretory dense core granules characteristic of a pheochromocytoma. Oncocytic pheochromocytoma was briefly documented in previous case reports but has not been well recognized. The expression of cytokeratin by pheochromocytoma is also very rare and has been described in a single study in the literature. This case had both unusual clinical and pathologic manifestations and is the first report of a pheochromocytoma with coexistence of oncocytic changes and cytokeratin immunoreactivity.
1. Goldflen A. Pheochromocytoma. Clin Endocrinol Metab10:607-630, 1981
2.
2. Lack EE. In: Lack EE (ed). Pathology of adrenal and extra-adrenal paraganglioma. The series major problems in pathology, V29. WB Saunders, Philadelphia, pp. 220-272, 1994
3.
3. Sheps SG, Jiang NS, Klee GG. Diagnostic evaluation of pheochromocytoma. Endocrinol Metabol Clin North Am17:397-414, 1988
4.
4. Bravo EL. Pheochromocytoma: New concepts and future trends. Kidney Int40:544-556, 1991
5.
5. Page LB, Raker JW, Berberich FR. Pheochromocytoma with predominant epinephrine secretion. Am J Med47:648-652, 1969
14. Sasano H, Suzuki T, Sano T, Kameya T, Sasano N, Nagura H. Adrenocortical oncocytoma. A true nonfunctioning adrenocortical tumor. Am J Surg Pathol15:949-956, 1991
15.
15. Kimura N, Sasano N, Miura Y, Kobayashi K. Adrenal and extra-adrenal pheochromocytomas: An ultrastructural and formaldehyde-induced fluorescence study with catecholamine content. Tohoku J Exp Med142:1-14, 1984
16.
16. Kimura N, Nakazato Y, Nagura H, Sasana N. Expression of intermediate filaments in neuroendocrine tumors. Arch Pathol Lab Med114:506-510, 1990
17.
17. Lioyd RV, Sisson JC, Shapiro B, Verhofstad AAJ. Immunohistochemical localization of epinephrine, norepinephrine catecholamine-synthesizing enzymes, and chromogranin in neuroendocrine cells and tumors. Am J Pathol125:45-54, 1986
18.
18. Herrera MF, Stone E, Deitel M, Asa SL. Pheochromocytoma producing multiple vasoactive peptides. Arch Surg127:105-108, 1992
19.
19. Fried G, Wikstrom LM, Hoog A, et al. Multiple neuropeptide immunoreactivities in a renin-producing human paraganglioma. Cancer74:142-151, 1994
20.
20. Osamura RY, Tsutsumi Y, Yanaihara N, Imura H, Watanabe K. Immunohistochemical studies for multiple peptide-immunoreactivities and co-localization of Met-enkephalin-Arg-Gly-Leu, neuropeptide Y and somatostatin in human adrenal medulla and pheochromocytomas. Peptide8:77-87, 1987
21.
21. O'Connor DT, Frigon RP, Deftos LJ. Immunoreactive calcitonin in catecholamine storage vesicles of human pheochromocytoma. J Clin Endocrinol Metab56:582-585, 1983
22.
22. Sipple JH. The association of pheochromocytoma with carcinoma of the thyroid gland. Am J Med31: 163-166, 1961
23.
23. Glushien AS, Mansuy MM, Littman DS. Pheochromocytoma: Its relationship to neurocutaneous syndromes. Am J Med14:318-327, 1953
24.
24. Horton WA, Wong V, Eldridge R. Von Hippel-Lindau disease: Clinical and pathological manifestations in nine families with 50 affected members. Arch Intern Med136:769-777, 1976
25.
25. Ramsay JA, Asa SL, van Nostrand AWP, Hassaram ST, de Harven EP. Lipid degeneration in pheochromocytomas mimicking adrenal cortical tumors. Am J Surg Pathol11:480-486, 1987
26.
26. Unger PD, Cohen JM, Thung SN, Gordon R, Pertsemlidis D, Dikman SH. Lipid degeneration in a pheochromocytoma histologically mimicking an adrenal cortical tumor. Arch Pathol Lab Med114: 892-894, 1990
27.
27. Aiba M, Hirayama A, Ito Y, Fujimoto Y, Nakagami Y, Demura H, Shizume K. A compound adrenal medullary tumor (pheochromocytoma and ganglioneuroma) and a cortical adenoma in the ipsilateral adrenal gland: A case report with enzyme histochemical and immunohistochemical studies. Am J Surg Pathol12:559-566, 1988
28.
28. Sasano N, Sasano H. The adrenal cortex. In Kovacs K, Asa SL (eds): Functional endocrine pathology. Blackwell, Oxford, pp. 546-584, 1990
30. O'Brien T, Young Jr WF, Davila DG, et al. Cushing's syndrome associated with ectopic production of corticotrophin-releasing hormone, corticotrophin and vasopressin by a pheochromocytoma. Clin Endocrin37:460-467, 1992
31.
31. Beaser RS, Guay AT, Lee AK, Silverman ML, Flint LD. An adrenocorticotropic hormone-producing pheochromocytoma: Diagnostic and immunohistochemical studies. J Urology135:10-13, 1986
32.
32. Komminoth P, Roth J, Schroder S, Saremaslani P, Heitz PU. Overlapping expression of synaptophysin mRNA in pheochromocytomas and adrenocortical carcinomas: Implications for the differential diagnosis of adrenal gland tumors. Lab Invest72:424-431, 1995
33.
33. Miettinen M. Neuroendocrine differentiation in adrenocorticcal carcinoma. New immunohistochemical findings supported by electron microscopy. Lab Invest66:169-174, 1992
34.
34. Tannenbaum M. Ultrastructural pathology of adrenal medullary tumors. Pathol Annu5:145-171, 1970
35.
35. Hoefler H, Lackinger E, Helleis G, Polak JM, Heitz Ph U. Immunocytochemical demonstration of intermediate filament cytoskeleton proteins in human endocrine tissues and (neuro-) endocrine tumors. Virchows Arch [Pathol Anat]409:609-626, 1986
36.
36. Gown AM, Vogel AM. Monoclonal antibodies to human intermediate filament proteins, III: Analysis of tumors. Am J Clin Pathol84:413-424, 1985
37.
37. Wilander E, Scheibenpflug L. Cytokeratin expression in small intestinal and appendiceal carcinoma. A basis for classification. Acta Oncologica32:131-134, 1993
38.
38. Sasaki A, Yumita S, Kimura S, Miura Y, Yoshinaga K. Immunoreactive corticortrophin-releasing hormone, growth hormone-releasing hormone, somatostatin, and peptide histidine methionine are present in adrenal pheochromocytomas, but not in extraadrenal pheochromocytoma. J Clin Endocrinol Metab70:996-999, 1990
39.
39. Johnson TL, Zarbo RJ, Lloyd RV, Crissman JD. Paragangliomas of the head and neck: Immunohistochemical neuroendocrine and intermediate filament typing. Mod Pathol1:216-223, 1988
40.
40.Van Muijen GNP, Ruiter DJ, Huiskens-van Der Mey CH, Warnaar SO. Monoclonal antibodies with different specificities against cytokeratins: An immunohistochemical study of normal tissues and tumors. Am J Pathol114:9-17, 1984
41.
41. Unger PD, Hoffman K, Thung SN, Pertsemlidis D, Wolfe D, Kaneko M. S100 protein-positive sustentacular cells in malignant and locally aggressive adrenal pheochromocytomas. Arch Pathol Lab Med115:484-487, 1991
