Gangliocytic paraganglioma has been known as a rare and benign neuroendocrine tumor. This condition occurs at the gastrointestinal tract, especially at the second portion of the duodenum [1
]. Major clinical symptoms of the disease include abdominal pain, nausea, vomiting, and gastrointestinal bleeding. Biliary obstruction has rarely been reported as a devastating complication [6
]. Histopathological diagnosis of the disease should require a confirmation of three identical components comprising epithelioid cells, spindle-shaped cells, and ganglion-like cells [1
]. Carcinoid tumor, paraganglioma, ganglioneuroma or spindle cell tumors (including nerve sheath tumors, smooth muscle tumors and gastrointestinal stromal tumors) should be referred as diseases for differential diagnosis in cases of histopathological investigation [6
]. To identify the three cellular components, in addition to the detailed microscopic examination of hematoxylin and eosin double stained sections, phenotypical expression analysis by immunohistochemical examination has been regarded as an important diagnostic clue [8
]. Although gangliocytic paraganglioma has been regarded as a benign tumor, we found nine cases showing lymph node metastasis among the literature [Table ]. The table surmises major clinical data of ten cases of gangliocytic paraganglioma with lymph node metastasis including the present case were analyzed. Patient age ranged from 17 to 74 (mean: 46.4). Male-to-female ratio was 3:7. Tumor sizes ranged from 14 to 65 mm (mean: 32.9). Nine cases occurred at duodenum, but one occurred at pancreas. Although present patient was older, its location and size follows characteristic manner of the disease. One case had irradiation as an adjuvant therapy [10
], no recurrence or distant metastasis, however, was described in all patients who we had extracted from the previously reported cases. Therefore, we decided to avoid any adjuvant therapy from the present case. The results of immunohistochemical examinations are summarized in Table with those of previously reported cases of gangliocytic paraganglioma with lymph node metastasis. In the present case, three identical components were clearly identified by phenotypical expression analysis, which correspond to those previously reported with the exception of positive reactivity for chromogranin A. In addition, the present case also showed lymphatic involvement of tumor cells of an epithelioid cell type at the primary focus and regional lymph node metastasis. Furthermore, there was a study suggesting approximately 5% of gangliocytic paraganglioma demonstrate malignant behavior [10
], an importance of imaging examinations before an operation should be emphasize to determine the most suitable method of surgical intervention [11
]. On the other hand, several studies conducting to neuroendocrine tumor have reported that bcl-2 and/or p53 expression might be correlated with malignant behavior of them [2
], whereas no studies were found of which investigation was limited in gangliocytic paraganglioma.
Summary of phenotypical expression analysis by immunohistochemical examination
Therefore, we unfortunately have to conclude an immunohistochemical evaluation using bcl-2 or p53 in gangliocytic paraganglioma has a limited prognostic value mostly due to its rarity. In fact, some studies indicated that bcl-2 and/or p53 expression was not correlated with malignant behavior in gastrointestinal neuroendocrine tumors [12
]. In addition, MIB-1 (Ki-67) has been known as a prognostic indicator in neuroendocrine tumor [14
]. However, none of previously reported cases of gangliocytic paraganglioma with lymph node metastasis described the MIB-1 (Ki-67) labeling index and that of the present case estimated less than 1% in both primary and metastatic foci. These finding suggests that immunohistochemical evaluation using MIB-1 (Ki-67) has also a limited prognostic value in gangliocytic paraganglioma.
In the meantime, Hagemeyer et al. reported the case of pulmonary paraganglioma with p53 expression after Tschernobyl radiation [15
]. They suggested that the irradiation had little influence on development of pulmonary paraganglioma, but smoking or irradiation could be associated with p53 expression. A part of their notion may be supported because our patient showed no p53 expression who had history of neither smoking nor irradiation. However, it should be unripe that smoking or irradiation has a relationship to p53 expression of tumor cell in gangliocytic paraganglioma. We wish to emphasize the importance of imaging examinations to monitor for recurrence or metastasis after the operation, because appropriate prognostic indicators have not been accepted using immunohistochemical evaluation.
The operation of our patient resulted in success, and he still maintains a high quality of life six months after that. Neither chemotherapy nor radiation has started because consensus on the adjuvant therapy for this tumor has not been reached at present.