title: Histopathological analysis of spontaneous large necrosis of adrenal pheochromocytoma manifested as acute attacks of alternating hypertension and hypotension: a case report.
abstract: BACKGROUND
  Pheochromocytomas are rare catecholamine-producing neuroendocrine tumors. Hypertension secondary to pheochromocytoma is often paroxysmal, and patients occasionally present with sudden attacks of alternating hypertension and hypotension. Spontaneous, extensive necrosis within the tumor that is associated with catecholamine crisis is an infrequent complication of adrenal pheochromocytoma, but its pathogenesis remains unclear.
  
  
  METHODS
  A 69-year-old Japanese man developed acute-onset episodic headaches, palpitations, and chest pains. During the episodes, both marked fluctuations in blood pressure (ranging from 40/25 to 300/160 mmHg) and high plasma levels of catecholamines were found simultaneously. Radiological findings indicated a 4-cm left adrenal pheochromocytoma. These episodic symptoms disappeared within 2 weeks with normalization of plasma catecholamine levels. Two months later, the patient underwent adrenalectomy. Microscopic examinations revealed pheocromocytoma with a large central area of coagulative necrosis. The necrotic material was immunohistochemically positive for chromogranin A. Granulation tissue was adjacent to the necrotic area, accompanied by numerous hemosiderin-laden macrophages and histiocytes with vascular proliferation. Viable tumor cells, detected along the periphery of the tumor, demonstrated pyknosis, and the Ki-67 labeling index was 2 % in the hot spot. No embolus or thrombus formation was found in the resected specimen harboring the whole tumor. The Pheochromocytoma of the Adrenal gland Scaled Score was 2 out of 20. The patient's postoperative course was unremarkable for > 7 years.
  
  
  CONCLUSIONS
  Presumed causal factors for the extensive necrosis of adrenal pheochromocytoma in previously reported cases include hemorrhage into the tumor, hypotension induced by a phentolamine administration, embolic infarction, high intracapsular pressure due to malignant growth of the tumor, and catecholamine-induced vasoconstriction. In the present case, histopathological and clinical findings suggest that under conditions of chronic ischemia due to catecholamine-induced vasoconstriction, an acute infarction occurred after sudden attacks of alternating hypertension and hypotension. Over the subsequent 2 weeks, repetitive massive release of catecholamines from the infarcts into circulation likely accelerated infarction progression by causing repeated attacks of alternating hypertension and hypotension and resulted in the large necrosis. This case highlights the need for physicians to consider acute spontaneous tumor infarction accompanying episodic catecholamine crisis as a rare but severe complication of pheochromocytoma.
authors.affiliation: Department of Endocrinology and Metabolism, Nagaoka Red Cross Hospital, 2-297-1 Senshu, Nagaoka, Niigata, 940-2085, Japan. oharan@med.niigata-u.ac.jp.|Department of Endocrinology and Metabolism, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Niigata, Japan. oharan@med.niigata-u.ac.jp.
authors.forename: Nobumasa
authors.initials: N
authors.lastname: Ohara
authors.affiliation: Department of Endocrinology and Metabolism, Nagaoka Red Cross Hospital, 2-297-1 Senshu, Nagaoka, Niigata, 940-2085, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Uemura
authors.affiliation: Department of Endocrinology and Metabolism, Nagaoka Red Cross Hospital, 2-297-1 Senshu, Nagaoka, Niigata, 940-2085, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Mezaki
authors.affiliation: Department of Endocrinology and Metabolism, Nagaoka Red Cross Hospital, 2-297-1 Senshu, Nagaoka, Niigata, 940-2085, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Kimura
authors.affiliation: Department of Endocrinology and Metabolism, Nagaoka Red Cross Hospital, 2-297-1 Senshu, Nagaoka, Niigata, 940-2085, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Kaneko
authors.affiliation: Department of Cardiovascular Medicine, Nagaoka Red Cross Hospital, Niigata, Japan.
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Kuwano
authors.affiliation: Department of Cardiovascular Medicine, Nagaoka Red Cross Hospital, Niigata, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Ebe
authors.affiliation: Department of Cardiovascular Medicine, Nagaoka Red Cross Hospital, Niigata, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Fujita
authors.affiliation: Department of Urology, Nagaoka Red Cross Hospital, Niigata, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Komeyama
authors.affiliation: Department of Pathology, Nagaoka Red Cross Hospital, Niigata, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Usuda
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Miyagi, Japan.
authors.forename: Yuto
authors.initials: Y
authors.lastname: Yamazaki
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Miyagi, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Maekawa
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Miyagi, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
authors.affiliation: Department of Endocrinology and Metabolism, Nagaoka Red Cross Hospital, 2-297-1 Senshu, Nagaoka, Niigata, 940-2085, Japan.
authors.forename: Kenzo
authors.initials: K
authors.lastname: Kaneko
authors.affiliation: Department of Internal Medicine, Ojiya General Hospital, Niigata, Japan.|Center of Diabetes, Endocrinology and Metabolism, Joetsu General Hospital, Niigata, Japan.
authors.forename: Kyuzi
authors.initials: K
authors.lastname: Kamoi
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000150:complications / Q000175:diagnosis* / Q000601:surgery; D000315:Adrenalectomy; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage; D044466:Asian People; D001794:Blood Pressure; D002395:Catecholamines / Q000378:metabolism; D002637:Chest Pain; D006261:Headache; D006801:Humans; D006973:Hypertension / Q000209:etiology* / Q000503:physiopathology; D007022:Hypotension / Q000209:etiology* / Q000503:physiopathology; D010535:Laparoscopy; D008297:Male; D009336:Necrosis / Q000473:pathology*; D010673:Pheochromocytoma / Q000150:complications / Q000175:diagnosis* / Q000601:surgery; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D002395:Catecholamines
keywords: Adrenalectomy; Chest pain; Coagulative necrosis; Hypertension; Hypotension; Immunohistochemistry; Metaiodobenzylguanidine scintigraphy; Pheochromocytoma