The scrape preparations show cells occurring singly and in loosely cohesive aggregates. The cytoplasm is stripped from some cells, while others retain small to moderate amounts of pale to wispy cytoplasm. Cell shape ranges from ovoid to spindled. Chromatin is finely granular and small nucleoli can be seen. Some markedly enlarged, pleomorphic nuclei are evident. Rare intranuclear cytoplasmic inclusions were identified.
Tumor sections show a relatively uniform pattern of round-oval clusters (zellballen) and anastomosing cords of polygonal cells with abundant pale eosinophilic cytoplasm, separated by an extensive, delicate vascular network. As in the cytologic preparations, occasional enlarged, irregular and hyperchromatic nuclei are noted (above right). Immunohistochemical staining is positive for neuroendocrine-associated markers, including chromogranin (below left). S-100 staining is positive in spindled cells at the periphery of cell nests and trabeculae, consistent with sustentacular cells (below right).
Diagnosis: Paraganglioma
Discussion
Paraganglia can be classified on the basis of anatomic location. Head and neck paraganglia, which often have chemoreceptor function, are associated with the parasympathetic nervous system and include the carotid body, jugulotympanic and aorticopulmonary paraganglia. The sympathoadrenal system includes the adrenal medullae, organs of Zuckerkandl and collections of neuroendocrine tissue in organs such as the urinary bladder. All tumors arising from paraganglionic tissue may be designated paragangliomas, although neoplasms deriving from the adrenal medullae are referred to as pheochromocytomas.
Paragangliomas characteristically contain neurosecretory granules and produce catecholamines. They may contain peptide hormones such as ACTH and calcitonin. Functional activity varies, with most tumors arising from parasympathetic ganglia not responsible for symptoms due to neuroendocrine dysfunction. Regardless of site, paragangliomas tend to manifest similar gross, histologic and cytologic features.
Fine needle aspirates and other cytologic preparations obtained from these tumors incorporate cells with epithelioid, spindled and ganglion cell-like forms. Loose cell clusters and dispersed single cells are seen. Zellballen are not common in smears, while spindle cells corresponding to sustentacular cells may be present. Atypia in the form of cells with large, pleomorphic nuclei and prominent nucleoli may be alarming, and lead to a misdiagnosis of adrenocortical or metastatic carcinoma. Small reddish cytoplasmic granules on Diff-Quik-stained smears (representing neurosecretory granules) aid in classification. Sarcomas enter into the differential diagnosis of neoplasms with abundant spindle cells. Prominent intranuclear cytoplasmic inclusions may raise the possibility of melanoma. Immunostaining for neuroendocrine markers such as chromogranin and synaptophysin may be helpful; staining for synaptophysin and neuron-specific enolase has been reported in carcinomas. Use of these markers does not aid in differentiating paragangliomas from other neuroendocrine neoplasms with a similar cytologic appearance, i.e. carcinoid tumors. Demonstration of S-100 positive sustentacular cells at the edge of neoplastic chief cell nests is a characteristic feature of paragangliomas which may be demonstrated on cell block preparations.
It should be noted that while many paragangliomas have been aspirated without complication, there remains a risk of significant hemorrhage. FNA of pulsatile neck masses should be avoided. Aspiration of sympathoadrenal paragangliomas (notably pheochromocytomas) may result in fatal hypertensive crisis.
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