Path Quiz Case-68:Answer and case discussion

Gangliocytic paragangliomas are rare gastrointestinal tumour of uncertain histogenesis (also known as non-chromaffin paraganglioma).

This entity was first discussed by Dahl et al  in 1957, and subsequently reported by Taylor and Helwig in 1962 .   Kepes and Zacharias named the tumour and described its characteristics in 1971.

The name is derived from its unique histologic features of carcinoid tumor, paraganglioma, and ganglioneuroma.

The tumour has structural and immunohistochemical features of a neuroendocrine tumour.

Though gangliocytic paraganglioma is considered a benign lesion metastatic spread to regional lymph nodes and local recurrence have been reported .

An association with neurofibromatosis, with or without co-existent duodenal somastinoma has been reported.

Site:  These are usually located in the second part of the duodenum close to the ampulla of Vater.  A few cases have been reported in the esophagus, jejunum, pylorus, pancreas, appendix,  cauda equina and superior mediastinum .

Age: This tumour has been reported in patients between 15 to 80 years of age (average age - approximately 52 years ).

Sex: The tumour affects both sexes.

Clinical presentation:  Common presenting symptom is gastrointestinal bleeding, with abdominal pain and occasionally, biliary obstruction. Some patients are asymptomatic and tumours are found incidentally . Clinical signs attributable to hormone secretion have not been reported with duodenal gangliocytic paraganglioma.

Endoscopic finding: Sessile or polypoid submucosal lesion which may be ulcerated.

Gross features: Grossly, gangliocytic paragangliomas are polypoid, sessile or pedunculated lesions upto 14 cm projecting into the duodenal lumen. The cut surface has a firm and pink-tan appearance.

Microscopic features:  The histopathological diagnosis using biopsy specimens taken from the tumor prior to excision is difficult because of its submucosal location.   

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Gangliocytic paragangliomas are centred on the submucosa. The tumour infiltrates smooth muscle and ampullary ducts. The tumour consists of a complex neoplastic proliferation that included a component resembling carcinoid or islet cell tumor, admixed with a proliferation of spindled neurofibrillary cells and larger polygonal cells demonstrating gangliocytic differentiation. There may be some stromal hyalinization in some cases.  Cellular pleomophism may be prominent but mitoses and necrosis are extremely rare,

 The triphasic cellular appearance is characteristic:

1. Spindle cells with a neural phenotype resembling Schwann cells or sustenticular cells.

2. Ganglion cells, often in nests resembling the "zellballen" of classical paragangliomas.

3. Endocrine cells arranges in nests, trabeculae, papillae or gland-like structures.

Immunohistochemistry:  1. Spindle-shaped cells are positive for neurofilament and S-100 protein.     2. Ganglion-like cells show positivity for synaptophysin and glial fibrillary acidic protein.  3. Endocrine cells are positive for pancreatic polypeptide and neurone specific enolase but staining for chromogranin is less consistent and conventional silver stains such as Grimelius are negative.  Endocrine cells may also be positive for somastostatin and psammoma bodies may be present. Amyloid may be found with endocrine cells.

Differential Diagnosis:   The tumour may be misdiagnosed as adenocarcinoma, smooth muscle tumour, nerve sheath tumour or another endocrine tumour.

Electron microscopy:  May show neurosecretory granules and evidence of neuronal differentiation, with prominent rough endoplasmic reticulum in ganglion cell cytoplasm and identifiable axons.

Histogenesis:   It has been suggested that the tumour arises from an embryonic celiac ganglion or from pluripotent stem cells located at the base of the intestinal glands or else that the lesion is due to hamartomatous proliferation of endodermally derived epithelial cells originating from the ventral primodium of the pancreas and neuroectodermally derived ganglion and schwannian cells. However, the findings of regional lymph node metastasis in several reported cases suggest that duodenal gangliocytic paraganglioma is a true neoplasm.

Treatment:    Endoscopic resection is recommended for small duodenal gangliocytic paraganglioma that are localized and with no lymphatic spread . Tumours of the papilla can be resected by endoscopic ampullectomy.   Careful assessment prior to local excision is necessary.  If the lesion is large or if there is suspicion of lymph node involvement, pancreaticoduodenectomy with lymph node dissection is recommended.

Prognosis:   No cases of distant metastasis or of death secondary to this tumour have been reported. Prognosis of gangliocytic paraganglioma is uniformly excellent.