GP is a rare neuroendocrine tumor and up to three hundred cases have been reported until now. GPs affect individuals ranging from 15 to 84 years old with mean of about 53 years old, and are a little more prevalent in males with a male-to-female ratio of 1.5:1 . A majority of GPs were documented to be located in the duodenum, accounting for nearly 90%. Involvement of other sites, such as spinal cord, respiratory system and digestive tracts was also reported .
The presenting symptoms and complaints of GPs in digestive tracts include gastrointestinal bleeding, abdominal pain or anemia and so on, which have no reliably diagnostic signs. Imaging examinations always demonstrates a mass lesion .
GPs range in size from 0.5 cm to 10 cm with average 2.5 cm in maximum diameter. Pathological investigation always displays a well-circumscribed, non-encapsulatedtumor whereas some cases are infiltrative focally or even mostly. GPs in duodenum are located or anchored in submucosa, expanding to nearby lamina propria or muscularis propria . Therefore, preoperative pathological diagnosis is difficult through endoscopic biopsy due to relatively deep location, and definite diagnosis requires resection of the mass .
GP consists of three distinct cellular elements, including the epithelioid, ganglion-like and spindle cells . The epithelioid cells have eosinophilic abundant cytoplasm and a round nucleus with inconspicuous or conspicuous nucleoli. They arranged in nest or zellballen pattern. Immunohistochemically, Syn and CgA are positive, and S-100 and SOX-10 are positive in sustentacular cells around. In sum, they resemble paraganglioma in cytological, architectural and immunostaining features. The ganglion-like cells are larger than the epithelioid cells, and of abundant cytoplasm and eccentric vesicular nuclei with prominent round nucleoli. They are always scattered or sometimes merged into epithelioid or spindle cellular areas, individually or arranging in small clusters. The immunophenotypes of the ganglion-like cells are similar with those of the epithelioid cells, while NF is positive uniquely. The spindle cells arrange in fascicular clusters, and are bland in morphology and positive for S-100 and SOX-10, which resemble neurofibroma. The neoplasm is absent from mitosis and necrosis.
The proportion of the three cellular types is variable. In tumors predominant of spindle cells, the differential diagnosis includes spindle cell neoplasms especially schwannoma and gastrointestinal stromal tumor (GIST) . The presence of epithelioid and ganglion-like cells, although perhaps rare, is the most important clue against schwannoma. Negative immunohistochemical expression for DOG-1 and CD117 provides compelling evidence against GIST.
In tumors predominant of ganglion-like or epithelioid cells, the differential diagnosis includes epithelial tumors, melanoma and well-differentiated neuroendocrine tumors. The first two neoplasms are supposed to be excluded by immunohistochemistry of epithelial or melanic markers. Since the concept was introduced by the World Health Organization (WHO) classification in 2010, neuroendocrine tumor (NET) has been widely diagnosed according to mitotic activity and Ki-67 proliferation index. GP is generally classified among NETs . However, diversity of GP is different from relative consistence of NET in morphology, and GP has a more indolent clinical behavior and improved prognosis than NET . Thus, GP is supposed to be differentiated from NET Grade 1.
The entity of GP remains a problem. It is noted that paraganglioma is a distinct entity among NET menu, which is not graded according to proliferation index. Some authors pointed out that histological differences between pheochromocytoma-ganglioneuromas and GPs were not clear . Some areas of ganglioneuroma or ganglion-like cells were reported to be present in paragangliomas. In our opinion, since pathology of GP is supposed to be divided into two neoplastic proportions, paraganglioma and ganglioneuroma, GP is preferred as paraganglioma-ganglioneuroma, a kind of composite paraganglioma. Thus immature ganglion cells are supposed to be explored to exclude possibility of paraganglioma-neuroblastoma, especially in the young cases.
Origin of GP need be elucidated. GP is always located in submucosa, inducing hypothesis of origin related with meissner plexus . Recent studies and our report displayed that the epithelioid cells expressed PR just as the same as pancreatic isletcells, which indicated that GP may originate from pancreas islet remnant or ectopia .
Although clinical behavior of GP is usually benign, up to 10% of cases occurred regional lymph node metastasis and a few were reported to occur distant metastasis to bone, liver or pelvic cavity . Age, tumor size and depth of invasion appear to be related with metastasis . The general immunohistochemical prognostic factors in NETs, such as Ki-67, P53 and Bcl-2, are not indicative for malignant potential. It is noted that all the three cellular components are supposed to be present in metastasis. The patients with metastasis have favorable prognosis with long survival periods, whereas one case followed an aggressive clinical course and died of the disease . Endoscopic resection of duodenal GP appears to be enough for most cases, while additional surgery was managed in cases for positive margin. Adjuvant therapies, including chemotherapy and irradiation appear no effect and necessity even in cases with metastasis.
In conclusion, we presented a rare case of 51-year-old malewith GP as a polyp in the descending portion of duodenum. Pathological examination showed aneoplasm located in submucosa, infiltrating into lamina propria. The tumor was composed of epithelioid, ganglion-like and spindle cells. Syn, MAP-2 and CgA were positive in epithelioid and ganglion-like cells in variety and NF highlighted the ganglion-like cells. S-100 and SOX-10 were positive in the sustentacular cells around the epithelioid cells and spindle cell proliferation. PR was also positive. GP is supposed to be distinguished with NET G1 and designated as paraganglioma-ganglioneuroma, a kind of composite paraganglioma. Most GPs displayed benign clinical biological behaviors and a few occurred regional lymph node metastasis or distant metastasis. A large majority of cases follow favorable prognosis, even with metastasis.