Final Diagnosis -- Extraadrenal Paragangliomas


CASE 1: Extraadrenal Paraganglioma.

CASE 2: Malignant Extraadrenal Paraganglioma with metastasis to the lesser curvature of the stomach and one right sacral neural foramina lymph node.


Paragangliomas are rare tumors arising from the extraadrenal paraganglia of the autonomic nervous system, which are distributed from the skull base to the pelvis. Paragangliomas may arise from either the parasympathetic ganglia or sympathetic ganglia. Those arising from parasympathetic ganglia are usually found in the head and neck region and include paragangliomas of the carotid body, nodose ganglion of the vagus nerve, in the tympanic branch of cranial nerve IX, auricular branch of cranial nerve X (jugulotympanic paraganglia), paraganglia in the larynx, and aorticopulmonary paraganglia (1,2). Pheochromocytomas of the adrenal medulla have been shown to be virtually identical to extra-adrenal paragangliomas in morphology. Other paragangliomas of the parasympathetic system include those arising in the organ of Zuckerkandl (3), and paravertebral and retroperitoneal ganglia (4). Both pheochromocytomas and paragangliomas can produce catecholamines and other peptides, although this is less common in paragangliomas (5).

Judgement of malignancy of paragangliomas is a controversial subject. While extensive local invasion by tumor and metastasis undoubtably indicate the malignant nature of the tumor, correlation of histopathologic findings with prognosis remains unreliable. Usual indicators of malignancy (increased mitotic rate, cellular atypia, necrosis, and vascular invasion) have been unreliable in predicting prognosis of these tumors. A 1990 study of 120 paragangliomas by Linnoila et. al. (6) showed by logistic regression analysis that the four most predictive indicators of malignancy are extraadrenal location, coarse nodularity of primary tumor, confluent tumor necrosis, and absence of hyaline globules. An earlier 1988 study by Linnoila et. al. (7) showed a correlation between decreased neuropeptide expression and malignancy. In 1989, Kliewar et. al. (8) found tumor grade to be inversely related to sustentacular cell density (S-100 protein positive) and chief cell staining (neuron specific enolase, chromogranin positive). A 1994 study by Montresor et. al. (9) showed a correlation between good prognosis and detection of sustentacular cells within the lesion (S-100 protein positive). In that same study, no correlation between chromogranin A, neuron specific enolase staining and malignancy was found. Thus, diagnosis of malignancy remains controversial and dependent on clinical correlation.


  1. Lack, E., Cubila, A., Woodruff, J., and Farr, H. Paragangliomas of the head and neck region. Cancer. 39: 1977, 397-409.
  2. Gallivan, M., Chun, B., Rowden, G., Lack, E. Laryngeal paraganglioma. Case report with ultrastructural analysis and literature review. American Journal of Surgical Pathology. 3:1989, 85-92.
  3. Ober, W. Emil Zuckerkandl and His Delightful Little Organ. Pathology Annuals. 18(pt. 1): 1983, 103-119.
  4. Lack, E., Cubilla, A., Woodruff, J., Lieberman, P. Extra-adrenal paragangliomas of the retroperitoneum. American Journal of Surgical Pathology. 4: 1980, 109-120.
  5. Kuvshinoff, B., Nussbaum, M., Richards, A., Bloustein, P., and McFadden, D. Neuropeptide Y Secretion from a Malignant Extraadrenal Retroperitoneal Paraganglioma. Cancer. 70(9):1992, 2350-3.
  6. Linnoila, R., Keiser, H., Steinberg, S., and Lack, E. Histopatholgoy of Benign Versus Malignant Sympathoadrenal Paragangliomas: Clinicopathologic Study of 120 Cases Including Unusual Histologic Features. Human Pathology. 21(11):1990, 1169-1179.
  7. Linnoila, R., Lack, E., Steinberg, S., and Keiser, H. Decreased Expression of Neuropeptides in Malignant Paragangliomas: An Immunohistochemical Study. Human Pathology 19(1): 1988, 41-50.
  8. Kliewer, K., Wen, D., Cancilla, P., Cochran, A. Paragangliomas: Assessment of Prognosis by Histologic , Immunohistochemical, and Ultrastructural Techniques. Human Pathology. 20(1): 1989, 29-39.
  9. Montresor, E., Iacono, C., Nifosi, F., Zanza, A., Modena, S., Zamboni, G., Bernardello, F., and Serio, G. Retroperitoneal Paragangliomas: Role of Immunohistochemistry in the Diagnosis of Malignancy and in Assessment of Prognosis. European Journal of Surgery.160: 1994, 547-552.

Contributed by Christine Dorvault, M.D., Shaila Fernandes, M.D. and Samuel Yousem, M.D.

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