Paraganglioma

* A pigmented left atrial paraganglioma was found at autopsy in a 40-year-old black man who died unexpectedly. The cause of death was ascribed to coronary artery disease. The atrial mass was sharply demarcated and polypoid, measured 4 cm in greatest dimension, and had a cut surface that revealed dark red-brown soft tumor tissue. Histopathologically, the neoplasm exhibited a classic organoid clustering of cells (zellballen) with a prominent capillary network. The chief cells contained a brown-black pigment with histochemical characteristics of melanin. We report a case of pigmented cardiac paraganglioma because of its rarity. To our knowledge, no mention has been made of the presence of pigment in previously reported cases of cardiac paragangliomas.

(Arch Pathol Lab Med. 2001;125:680-682)

Intrinsic cardiac tumors are uncommon. With the exception of endodermal heterotopia of the atrioventricular node, primary cardiac tumors rarely cause sudden death.' Among benign primary cardiac tumors, paraganglioma, a neuroendocrine neoplasm that arises from the extra-adrenal paraganglia of the autonomic nervous system, accounts for less than 1%.2,3 The sites of origin in the heart parallel the anatomic distribution of visceral autonomic paraganglionic tissue, chiefly arising from the roof of the atria and atrial septum and from the branchiomeric aortopulmonary paraganglia. A singularly unique feature in our case was the presence of melanin, which is rarely encountered in paragangliomas.

REPORT OF A CASE

A 40-year-old black man was found dead, lying on the living room floor of his house. Scene investigation yielded no suspicious dues. He was a smoker. No medical history was available, which precluded documentation of hypertensive manifestations. There was no evidence of trauma. Reportedly, the last time he was seen alive, he had no complaints.

PATHOLOGIC FINDINGS

Gross Findings

At autopsy, the salient findings in this 58-kg, 179-cm, 40-year-old, youthful-appearing, thin, muscular black man were in the heart. A structurally unremarkable 330-g heart (expected size, 290 to 330 g) with a right dominant coronary arterial distribution showed pronounced obstructive lesions.

The right coronary artery was 80% narrowed by an atherosclerotic plaque at 1.2 cm from its origin. A section of the right coronary artery taken at 2.2 cm from the origin showed an atherosclerotic plaque with an accumulation of cholesterol clefts and calcific deposits. The major branches of the left anterior descending coronary artery were free of significant obstructive lesions. A small diagonal branch of the left anterior descending coronary artery was 50% narrowed by a plaque at 2.8 cm from its origin. The left circumflex artery was 90% obstructed by a plaque at 2.8 cm from its origin. No thrombus was detected. A welldemarcated 4.0 x 2.0 x 1.6-cm sessile, smooth surfaced, gently lobulated, gray-tan polypoid mass projected into the left atrial cavity. The exophytic mass bulged from the roof of the left atrium between the atrial septum and the orifices of the pulmonary veins. Cut surface revealed dark red-brown soft tumor tissue that resembled an encapsulated blood clot (Figure 1).

Histologic Findings

The left atrial tumor was pseudoencapsulated by an attenuated and discontinuous layer of fibrous connective tissue and had pushing margins that formed a sharply demarcated interface with the atrial myocardium and epicardial fat. The tumor was composed of nests of polyhedral epithelial-like cells set in a delicate, richly vascularized stroma in a prototypical zellballen pattern with focal lumen formation. The rather ample cytoplasms of the chief cells were amphophilic to clear and contained a variable number of coarse brown-black pigment granules (Figures 2 and 3, A). A sprinkling of pleomorphic and hyperchromatic cells was noted amid an otherwise monomorphic, seemingly nonproliferating cell population. Fontana-Masson stain revealed clusters of black cytoplasmic granules (Figure 3, B) that disappeared after melanin bleach. Acid fast and iron stains were negative. No autofluorescence was detected. The mass effect of the tumor was probably inconsequential. The myocardium was free of contraction band necrosis. Severe coronary artery disease was ascertained as the cause of death.

COMMENT

An estimated 25 individuals die suddenly due to a primary cardiac tumor in the United States every year. Although seldom ascribable to primary cardiac tumors, conductive or obstructive-compressive events that result in sudden death are chiefly caused by microscopically benign lesions.1 Tamponade due to pericardial effusion; impaired valvar function; coronary ostial obstruction; tumor emboli with cardiac, pulmonary, or central nervous system impact; and hypertension due to vasoactive secreting tumors are additional effects of primary cardiac tumors that may prove fatal. Approximately half of the cases of pheochromocytoma manifest characteristic hypertensive crises.

Primary cardiac tumors are rare and paragangliomas among the rarest.2 Paragangliomas are neuroendocrine, often functional tumors that in decreasing order of frequency originate from paraganglia of the autonomic nervous system in the head and neck, retroperitoneum, and thorax.3 A search for publications indexing cardiac pheochromocytomas, chemodectomas, and paragangliomas yielded mostly single surgical case reports. Adjustment was made for repeat publications.

Paragangliomas occur in patients between the ages ot 12 and 76 years (average age, 39 years), affect equally males and females (21 males and 19 females), and are occasionally familial. A significant proportion are functional (hypertension), but catecholamine secretion was not always associated with hypertension (case 15). They rarely cause dysphagia (case 40). The left atrium and aortocoronary-pulmonary trunk region are the most common sites of origin. A few are multicentric (cases 5 and 7). They rarely behave in a malignant fashion (case 10). Imaging techniques (iodine 131 iobenguane sulfate 1 123) greatly facilitate tumor localization and surgical planning. The tumors vary in size between 3 and 15 cm (average size, 6.1 cm). Their prominent vascularization poses a risk of hemorrhage. Finally, there is no reliable histopathologic predictor of behavior, and although surgically challenging, most are cured by resection (Table).

Generally, when a cardiac paraganglioma is recognized clinically, surgical management is technically challenging but feasible and the outcome favorable. Their critical location, highly vascularized nature, and 5% to 10% incidence of recurrence or metastatic potential are unfavorable factors. When a cardiac paraganglioma is detected incidentally at autopsy, it may be interpreted as an associated finding, not necessarily the cause of death.

Regarding the presence of melanin, only a paucity of pigmented paragangliomas have been documented, namely in the uterus, orbit, spine, retroperitoneum, bladder, and posterior mediastinum.4,5 Admittedly, the distinction between melanin and lipofuscin by histochemical and even ultrastructural analysis proves to be much more difficult than anticipated. Melanin, other than imparting a peculiar pigmentation, does not seem to confer any clinical behavioral significance to paragangliomas. The function of neuromelanin has yet to be worked out. However, it has been suggested that neuromelanin in catecholamineproducing cells may have a detoxifying function.6 We describe a 40-year-old black man who died suddenly and was incidentally found to have a left atrial paraganglioma, which is of further interest because it was pigmented.

References

1. Cina SJ Smialek JE, Burke AP, Virmani R, Hutchins GM. Primary cardiac tumors causing sudden death: a review of the literature. Am J Forensic Med Pathol. 1996;17:271-281.

2. Burke A, Virmani R. Tumors of the Heart and Great Vessels. Washington, DC: Armed Forces Institute of Pathology; 1995. Atlas of Tumor Pathology, 3rd series, fascicle 16.

3. Lack EE. Tumors of the Adrenal Gland and Extra-adrenal Paraganglia. Washington, DC: Armed Forces Institute of Pathology; 1997. Atlas of Tumor Pathology; Irl eis. fascicle 19.

4. Moran CA, Albores-Saavedra J, Wenig BM, Mena H. Pigmented extraadrenal paragangliomas: a clinicopathologic and immunohistochemical study of five cases. Cancer. 1997;79:398-402.

5. Lack EE, Kim H, Reed K. Pigmented ("black") extraadrenal paraganglioma. Am] Surg Pathol. 1998;22:265-269.

6. Smythies J. On the function of neuromelanin. Proc R Soc Lond B Biol Sci. 1996;263:487-489.

Irina Mikolaenko, MD; Carlos A. Galliani, MD; Gregory G. Davis, MD

Accepted for publication September 21, 2000.

From the Department of Pathology, University of Alabama at Birmingham, Birmingham, Ala (Drs Mikolaenko and Davis); and Department of Pathology, Cook Children's Medical Center, Fort Worth, Tex (Dr Galliani).

Reprints: Gregory G. Davis, MD, Department of Pathology, University of Alabama at Birmingham, 1515 Sixth Ave S, Birmingham, AL 35233-1601.

Copyright College of American Pathologists May 2001
Provided by ProQuest Information and Learning Company. All rights Reserved