Ganglioneuroma of Parapharyngeal Region

Ganglioneuroma is a well-differentiated tumor of the sympathoadrenal nervous system. These tumors belong to a family of neoplasms that exhibit a wide range of differentiation, with neuroblastoma at one end and ganglioneuroma at the other. Ganglioneuroma can be found anywhere along the sympathetic chain, but its most common localizations are the posterior mediastinum and retroperitoneum. They occur over a wide age range (0–70 years), with the adrenal tumors tending to occur in patients older than 10 years.1,2 The clinical behavior of ganglioneuroma is invariably benign, although the occurrence of chronic diarrhea due to tumor elaboration of vasoactive intestinal peptide has been described.3 Moreover, catecholamine synthesis is frequently observed in this tumor, which rarely induces hypertension as a clinical sequela.2 We describe a case of ganglioneuroma observed in an unusual location, the parapharyngeal space.

The patient, a 27-year-old woman, presented at the otolaryngologic hospital division with a complaint of throat pain and with a self-appreciated nodule in the right neck, which had been present for several months. No systemic symptoms were reported. On ultrasonographic examination, the parapharyngeal lesion was hypoechoic and hypovascular. A fine-needle aspiration biopsy was performed. The smear contained rare and scattered large cells with granular cytoplasm and was considered inadequate for diagnosis. The nodule was surgically excised.

The material was fixed in 10% buffered formalin for histology and immunohistochemistry. Routine sections were stained with hematoxylin-eosin. Immunohistochemistry was performed with a TECHMATE 500 automated system (Dako, Glostrup, Denmark), which employs the streptavidin-biotin technique with diaminobenzidine as a substrate. The following antibodies were used: high-molecular-weight cytokeratins (34BetaE12, Dako), vimentin (V9, Menarini, Firenze, Italy), neuron-specific enolase (NSE H14, Dako), neurofilaments (2F11, Dako), and S100 (Dako). All antibodies are monoclonal, except S100. Appropriate positive and negative controls were included.

Grossly, the 4 × 3-cm tumor was well circumscribed with a brown fibrous capsule. The cut surface was whitish and had a whorled pattern. Low-power microscopy revealed an encapsulated tumor with low cellularity and a variably loose stroma. Two distinct cellular subgroups were identified microscopically: large ganglion cells variably distributed but more concentrated near the tumor periphery (Figure, A) and Schwann cells. The latter were arranged as short intersecting fascicles and were separated by a loose myxoid stroma (Figure, B). Ganglion cells were isolated in clusters or nests as well. The degree of neuronal differentiation varied. The less mature neurons had abundant pink cytoplasm with central to slightly eccentric nuclei and conspicuous nucleoli. With maturation, cells expressed more abundant cytoplasm, occasionally with Nissl substance, and more prominent nuclei, similar to normal neurons. No mitotic activity, necrosis, or calcification was present.

Immunohistochemical stains for vimentin, neurofilaments, neuron-specific enolase, and S100 demonstrated variable intensity in neoplastic cells. Staining for cytokeratins was negative.

Tumors of the sympathetic nervous system include neuroblastoma, ganglioneuroblastoma, and ganglioneuroma. All are derived by neural crest cells and are considered as different maturational steps of a unique neoplasm. As their names indicate, the least differentiated lesion, neuroblastoma, contains primitive neuroblasts, whereas the better differentiated, ganglioneuroma, contains mature Schwann and ganglion cells. Ganglioneuroblastoma has an intermediate cell population. The differentiation of these tumors reflects their clinical behavior. Neuroblastoma and ganglioneuroblastoma are malignant neoplasms,1,2,4 and the proportion of neuroblastoma elements within any given tumor is used to determine the histologic grading and the prognosis. Ganglioneuroma is a benign neoplasm that occurs along the sympathetic chain. It is located most frequently in the posterior mediastinum5 and the retroperitoneum. Other sites of origin are much less common.6–8 In the Armed Forces Institute of Pathology series of 88 cases of ganglioneuroma (1970–1980), which classified tumors according to patient age and anatomical distribution, only 1 patient had a tumor in the parapharyngeal region. The most common sites were the mediastinum (34 cases) and the retroperitoneum (27 cases).1 

Recently, one case report described a parapharyngeal ganglioneuroma diagnosed by cytology.9 The patient was a 4-year-old girl with a mass in the left parapharyngeal region that had been present since birth. The authors described an aspirate that showed a cluster of large oval to polygonal cells with voluminous granular cytoplasm and 1 to 3 large, vesicular, eccentrically placed nuclei. Occasional spindle-shaped cells were also present. The cytologic diagnosis of ganglioneuroma was confirmed histologically after surgical excision of the nodule. However, no immunohistochemical studies were reported. In our case, a fine-needle aspiration biopsy was also performed, but the results, although partially similar to the previous case, were considered inadequate for diagnosis due to the paucity of material.

Two additional case reports have discussed the cytologic diagnosis of ganglioneuroma in the pelvis10 and the adrenal gland.11 To our knowledge, this case is one of the few examples of parapharyngeal ganglioneuroma reported in the literature.