Contributed by Pier Luigi Di Patre, Ildiko Szalay, and Jacqueline DelavelleDIAGNOSIS: NASOPHARYNGEAL PARAGANGLIOMA
DISCUSSION:
Paragangliomas of the head and neck are uncommon tumors that may arise from any of the paraganglia distributed along the parasympathetic chain, including the carotid bodies, jugulotympanic ganglia, ganglion nodosum of the vagus, and microscopic paraganglia aggregates dispersed in the mouth, nose, nasopharynx, larynx, and orbit (6). The most frequent form is the carotid body tumor, while paragangliomas of the nasal cavity, paranasal sinuses and nasopharynx are rare. In a study of 71 patients with paragangliomas of the head and neck, only three of the tumors were located in the nasal cavity (7). Paragangliomas originating unequivocally from the nasopharynx are truly exceptional and have a striking tendency for intracranial and intraorbital invasion (5, 9).
If anatomical location is typical, the histological diagnosis of paraganglioma is easy. Microscopically, the nests of neoplastic cells ("zellballen") create an organoid pattern that recapitulates the morphology of normal paraganglia: this pattern is usually present in all cases, regardless of anatomical site. Nuclear pleomorphism is mild, and mitotic figures are absent or rare. Tumor cells retain a strong expression of neuroendocrine markers such as synaptophysin and chromogranin, while sustentacular cells at the periphery of "zellballen" are S-100 positive. Head and neck paragangliomas may synthesize a wide range of neuroendocrine products (e.g. serotonin, leu-enkephalin, gastrin, substance P, VIP, etc.), although rarely endocrine activity results in clinical symptoms (2). Ultrastructural studies demonstrate cytoplasmic dense-core granules.
In the present case, the midline location of the tumor and its apparent lack of relationship with major vessels seemed in apparent contrast with the topographical distribution of major paraganglia. The morphologic features and immunohistochemical profile, on the other hand, were highly characteristic of paragangliomas, ruling out diagnostic alternatives such as olfactory neuroblastoma, nasopharyngeal carcinoma, and sinonasal undifferentiated carcinoma. The unusual location of this paraganglioma can be explained by an orgin from one of the microscopic paraganglia, which are found in the upper airways without connection with major vascular structures or parasympathetic ganglia. A jugulotympanic or vagal orgin is unlikely, since tumors arising from these paraganglia develop in a lateral location, not along the midline (5, 6, 9). Paragangliomas have also been reported in other atypical sites, such as the orbit (4) sella turcica (3), and pineal gland (10). These rare tumors, therefore, should be added to an already long list of primary and metastatic neoplasms to consider in the differential diagnosis of a skull base mass (8).
Malignant paragangliomas are said to represent approximately 10% of all cases (6), but morphologic criteria alone do not distinguish unmistakably benign from malignant forms. Features said to be associated with an unfavorable clinical outcome include necrosis, mitotic activity and vascular invasion (7); other authors found that aggressive tumors contain fewer sustentacular cells than benign ones (1). A study of three cases of nasal and paranasal paragangliomas suggested that quantitative DNA analysis and proliferation markers may have prognostic significance (11), but the validity of this approach must be corroborated on larger series of cases. As of now, metastatic spread remains the only unequivocal criterion of malignancy.
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Contributed by Pier Luigi Di Patre, Ildiko Szalay, and Jacqueline Delavelle
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