Pathology of the Head and Neck

274 M. A Luna · K. Pineda-Daboin9Fig. 9.12. Zellballen pattern in a carotid body tumourthis section, only neoplasms of the carotid body and intravagalparaganglia are discussed.Carotid body paragangliomas are the most commontumours of the head and neck paraganglia, making up60–70% of the tumours of this type [30, 61, 100]. Lack etal. found 69 paragangliomas of the head and neck in morethan 600,000 operations (0.12%), and only 1 in 13,400 autopsiesat Memorial Hospital in New York city [61].The tumour, typically located in the carotid bifurcation,is typically found in individuals of either sex in thethird to the eighth decades of life. It often presents as apainless, slowly enlarging mass. It is the only neoplasmthat arises in that particular location. Carotid angiographyis a valuable diagnostic aid. The risk of developingthis tumour is higher in persons living at high altitudesthan those living at sea level [100]. Carotid body paragangliomaswith endocrine activity are rare. The tumour seldomundergoes malignant transformation; histologic criteriaare of little prognostic value. The incidence of metastasisis estimated to be less than 10% [14, 61].The vagal region is the third most frequent site of involvementafter the carotid body and jugulotympanicregion. Unlike the circumscribed carotid body, the vagalparaganglioma represents collections of microscopicnests located along the vagus nerve distal to the ganglionnodosum. Because of the variability in location of thenormal vagal paraganglia, paragangliomas arising fromthese structures also vary in location. At the time of diagnosis,patients are usually in the fourth to fifth decadeof life, and there is a female predominance [14, 30].Patients generally report a slowly growing neck mass,and, because of the intimate relationship with the vagusnerve, cranial nerve palsies may also be present [14, 30].Vagal paragangliomas displace the carotid vessels anteriorly,are grossly round or fusiform, and abut the baseof the skull. Multiple, also bilateral, and familial occurrencesof paragangliomas have been documented.Paragangliomas have a tan, soft cut surface. Paragangliomasfrom all regions of the head and neck arehistologically similar. They are well circumscribed andcomposed of chief cells arranged in nests known as Zellballen(Fig. 9.12). The tumour cells have granular cytoplasmand round nuclei with prominent nucleoli. Nuclearpleomorphism may be present, but mitosis is rare, andnecrosis is usually present only if the patient underwentpreoperative embolisation or if the nests of cells are verylarge. Compressed sustentacular cells and a rich capillarynetwork surround each nest. A reticulin stain highlightsthe Zellballen arrangement of the cells. Malignantvarieties are difficult to distinguish on histologic examination,but generally they have a higher mitotic rate andmore necrosis than benign tumours. Vascular invasionmay be present in both benign and malignant paragangliomas.The chief cells are positive for neuroendocrine markerssuch as chromogranin and synaptophysin. They areusually negative for cytokeratin, but an occasional casehas been reported to be positive [55]. The sustentacularcells are positive for S-100 protein [55].Electron microscopy studies show the tumour cellsto contain neurosecretory granules. The cells have cytoplasmicprocesses that surround neighbouring cells,and the cytoplasm contains abundant large mitochondriaand inconspicuous Golgi apparatus, smooth andrough endoplasmic reticulum.Although histologic findings are generally quite distinctive,the differential diagnosis of paragangliomas ofthe head and neck may include endocrine neoplasms arisingfrom the thyroid (medullary carcinoma) or parathyroidglands and other neuroendocrine carcinomas. Lesscommonly, alveolar soft part sarcoma, melanoma, granularcell tumour and metastatic renal cell carcinoma are includedin the differential diagnosis [14, 30, 55, 61].Surgery is the treatment of choice for paragangliomas.If the neoplasm is completely excised, recurrence isrelatively rare; recurrence rates are 10% for carotid bodytumours and 5–25% for vagal paragangliomas [14, 30,55, 61]. Radiotherapy may be useful as a palliative methodfor those tumours that cannot be controlled by surgicalmeans. Local infiltration of vagal body tumours andextension into the cranial cavity represent significantproblems in disease control. The rate of metastasis in intravagaltumours is estimated at 16%, but most of theseare to regional lymph nodes [14, 30].9.6 Unknown Primaryand Secondary Tumours9.6.1 DefinitionIn head and neck oncology, the term “ unknown primarytumour” means a primary neoplasm that has not beenfound in a patient with neck metastasis, even after a