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Fig. 7.11. Paraganglioma. a Characteristic arrangement into "Zellballen" composed of central chief and peripheral sustentac-

ular cells. b Chief cells stain immunohistochemically for synap-tophysin

Fig. 7.11. Paraganglioma. a Characteristic arrangement into "Zellballen" composed of central chief and peripheral sustentac-

ular cells. b Chief cells stain immunohistochemically for synap-tophysin cells typically have an eosinophilic, finely granular cytoplasm and central vesicular nuclei. Cellular pleomor-phism may be present and is occasionally prominent, but prognostically unimportant. Rare mitoses can be found, usually less than 2-3 per 10 high power fields. The supporting cells are usually inconspicuous, spindle-shaped, and most frequently found at the edge of the cell balls [18, 375].

Immunohistochemical findings are characteristic and decisive for the diagnosis. The chief cells are positive for neuroendocrine markers, such as chromogranin, synaptophysin and neuron-specific enolase (Fig. 7.11b).

The paragangliomas usually stain negatively for epithelial markers, such as cytokeratin, epithelial membrane antigen, carcinoembryonic antigen, and calcitonin. Sustentacular cells are positively stained with S-100 protein and glial fibrillary acid protein [18, 375].

Laryngeal paragangliomas must be primarily differentiated from typical and atypical carcinoids. The most reliable aid is positivity for both epithelial (cytokeratin, epithelial membrane antigen and carcinoembryonic antigen) and neuroendocrine markers in both types of carcinoids [107, 110]. Other, more remote differential diagnostic possibilities include malignant melanoma, renal cell carcinoma and medullary thyroid carcinoma. Melanoma can be confirmed by melan A and HMB-45 pos-itivity. Renal cell carcinoma, in contrast to paragangli-oma, does not express neuroendocrine markers. Medullary carcinoma expresses positive staining for calcito-nin, amyloid and CEA [18, 106, 375].

Since paragangliomas are only exceptionally malignant, conservative surgical treatment is suggested [18, 20, 110]. There are no histological criteria that could reliably predict the biological behaviour of the lesion [18].

In a recent genetic study, it was postulated that sporadic head and neck paragangliomas have deletions at the same or closely related loci (11q13 and 11q22-23) as their family counterparts [33].

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