Tissue sections were stained with routine hematoxylin and eosin (HE). Histological examination revealed a tumor extending into the submucosa and muscularis propria with focal mucosal ulceration. The tumor was composed of epitheloid cells, arranged in trabecular or pseudoglandular pattern, spindle cells, and ganglion cells with abundant cytoplasm and vesicular nuclei (Fig. 2a-e). There was no significant mitotic activity, necrosis or infiltration of the pancreas. No metastasis was found in the regional lymph nodes and omentum.
Immunohistochemical analyses were performed on tissue sections using Ventana Automated Immunostainer. The antibodies used included: cytokeratin AE1/ AE3 cocktail (1:100 dilution, Neomarkers), chromogranin A (monoclonal, 1:1000 dilution, Neomarkers), synaptophysin (27G12, 1:200 dilution, Novocastra), S-100 (4C4.9, 1:200 dilution, Neomarkers), cytokeratin 7 (OV-TL12/30, 1:150 dilution, Neomarkers), cytokeratin 20 (Ks20.8, 1:100 dilution, Neomarkers), and CEA (monoclonal, 1:1000 dilution, Neomarkers). Immunohistochemically, the epitheloid cells were positive for cytokeratin AE1/ AE3 cocktail, chromogranin A, and synaptophysin (Fig. 3b-d). S-100 protein labeled the sustentacular cells and the spindle cell component (Fig. 3a). Ganglion cells were positive for synaptophysin (Fig. 3b). The tumor cells were negative for cytokeratin 7, cytokeratin 20, and CEA.
Figure 1: Endoscopically, an ulcerated polypoid tumor in the periampullary region.
Histologically, GP is an uncapsulated benign triphasic tumor, composed of epitheloid cells, ganglion cells and spindle cells in variable proportions. The general pattern is characterized by the features of carcinoid, paraganglioma, and ganglioneuroma. The tumors show no necrosis or conspicuous mitotic activity. Immunohistochemically, the epitheloid cells are positive for NSE, synaptophysin, chromogranin A and sometimes positive for cytokeratins, similar to our case. The ganglion cells express NSE and synaptophysin whereas spindle cells positively stain for S-100 protein. Although there are many hypothesis about the histogenesis of GPs, there is no clear explanation yet.
It may be difficult to make a differential diagnosis, if endoscopic biopsy specimens do not contain all three histologic components. The spindle cell tumors, epithelial tumors or ganglioneuroma may be recognized according to the presence of three related different elements, as in the current case. The histological differential diagnosis of duodenal GP includes well-differentiated neuroendocrine carcinoma, ganglioneuroma, paraganglioma, and spindle cell malignancies (nerve sheath, smooth muscle, and gastrointestinal stromal tumors)[8]. The lack of immunohistochemical S-100 protein positive spindle cells and ganglion cells favor the diagnosis of well-differentiated neuroendocrine carcinoma. Beside immunohistochemical profile of the tumor, CD117 and CD34 negativity, and the presence of ganglion cells exclude the diagnosis of gastrointestinal stromal tumor. Immunohistochemical expression of smooth muscle markers is not a diagnostic feature of duodenal GP.
Typical duodenal submucosal location without infiltration of the pancreas, without any lymph node metastasis of the tumor, triphasic morphology, immunohistochemical positivity for synaptophysin, chromogranin A, S-100 protein and cytokeratins of the tumor cells are the most important diagnostic features of GP. Although GPs are accepted as a benign tumors, careful assessment is necessary for recurrences or metastases.
1) Dante S, Viale G, Dalla Palma P. Gangliocytic paraganglioma of the duodenum: case report. Tumori 1987;73:425-429.
2) Scheithauer BW, Nora FE, Lechago J, Wick MP, Crawford BG, Weiland LH et al. Duodenal gangliocytic paraganglioma. Clinicopathologic and immunohistological study of 11 cases. Am J Clin Pathol 1986;86:559-565.
3) Dookan DB, Miettinen M, Finkel G, Gibas Z. Recurrent duodenal gangliocytic paraganglioma with lymph node metastasis. Histopathology 1993;22:399-401.
4) Inai K, Kobuke T, Yonehara S, Tokuoka S. Duodenal gangliocytic paraganglioma with lymph node metastasis in a 17 year old boy. Cancer 1989;63:2540-2545.
5) Dahl EV, Waugh JM, Dajin DC. Gastrointestinal ganglioneuroma. Brief review with report of a duodenal ganglioneuroma. Am J Pathol 1957;33:953-965.
6) Nakamura T, Ozawa T, Takehira Y, Kitagawa M, Yamada M, Yasumi K et al. amakoshi K, Kobayashi Y, Nakamura H. Endoscopic resection of gangliocytic paraganglioma of the minot duodenal papilla: case report and review. Gastrointest Endosc 2002;55:270-273.