diagnostic pathology has shown remarkable improvement in recent years , and routine use of immunohistochemistry and electron microscopy has enabled more precise diagnoses . the availability of improved pathological methods for diagnosis of neuroendocrine tumors has also resulted in the recent recognition that these neoplasms have a wider spectrum .
the incidence of unknown primary neuroendocrine tumors has not been determined ; however , they have been estimated to account for approximately 3% of all malignancy of unknown primary sites .
these tumors , which represent a subset of unknown primary carcinomas , have a relatively favorable prognosis .
however , poorly differentiated neuroendocrine carcinoma ( pdnec ) has an aggressive biology and the median survival duration is only 10 months [ 1 - 3 ] .
most of these patients had several sites of metastasis , often with predominant tumor in bones , liver , and lymph nodes ( particularly the retroperitoneal and mediastinal nodes ) .
however , involvement of a single lymph node ( ln ) is very rare . here , we present a case of pdnec in a perigastric ln only with no identifiable primary site .
a 52-year - old male patient was diagnosed as having early gastric cancer at the lesser curvature of the antrum by routine esophagogastroduodenoscopy in june 2008 .
results of a subsequent endoscopic biopsy resulted in a histological diagnosis of well - differentiated adenocarcinoma .
computed tomography ( ct ) of the abdomen showed no evidence of ln enlargement or distant metastases .
he was diagnosed as having type iic early gastric cancer , which met the indications for endoscopic submucosal dissection ( esd ) .
1a ) , and the resected specimen confirmed the presence of well differentiated adenocarcinoma , with negative resection margins , and the absence of lymphovascular or perineural invasion by hematoxylin and eosin ( h&e ) staining ( fig .
however , six months later , a ln enlargement measuring 2.0 cm at the lesser curvature side of the stomach was observed on a routine abdominal and pelvic ct scan ( fig .
he had no symptoms , and physical examination failed to reveal evidence of peripheral lymphadenopathy , and a meticulous skin examination revealed no suspicious lesions .
he underwent subtotal gastrectomy and regional ln dissection under a suggestive preoperative diagnosis of gastric adenocarcinoma with perigastric ln metastasis .
microscopically , no residual tumor was found in the stomach , and the pathologic findings of the single perigastric ln differed completely from those of gastric adenocarcinoma .
3a ) . results of immunohistochemical staining showed that tumor cells were positive for cytokeratin 20 ( 1 : 200 , leica , newcastle - upon - tyne , uk ) , cd56 ( 1 : 150 , leica ) ( fig .
3b ) , synaptophysin ( 1 : 200 , neomarkers , fremont , ca ) ( fig .
3d ) , but negative for cytokeratin 7 ( 1 : 600 , neomarkers ) , thyroid transcription factor-1 ( 1 : 300 , leica ) , s-100 ( 1 : 800 , dako , glostrup , demark ) , and human melanoma black 45 ( 1 : 150 , leica ) . therefore , based on histological and immunohistochemical findings
we performed immunohistochemistry in order to rule out neuroendocrine differentiation in previous well - differentiated adenocarcinoma from the esd specimen ; according to the results , all of the tumor cells were negative for cd56 , synaptophysin , and chromogranin .
in addition , when the esd specimen and the specimen resected after subtotal gastrectomy were mapped , no other primary site was identified in the stomach specimen . in our search for the primary site , we also performed chest ct , bronchoscopy , colonoscopy , and a positron emission tomography - ct scan .
after an extensive work up , no primary site was identified and no further metastatic lesions were found .
he has remained disease - free for more than two years after surgical resection . written informed consent
this report described a case of pdnec in a single perigastric ln from a presumed unknown primary site .
there are two models of tumor progression for these nodal neuroendocrine carcinomas from an unknown primary site : nodal neuroendocrine carcinoma originates from the ln via formation of malignant precursor cells ; and it originates from a spontaneously regressed primary lesion . according to a study reported by kuwabara et al .
, primary nodal neuroendocrine carcinoma follows a less aggressive course than its metastatic nodal involvement . if nodal neuroendocrine carcinoma is the primary disease , wide surgical resection is the treatment of choice for localized disease . on the other hand ,
if nodal neuroendocrine carcinoma is formed by systemic metastasis from an unknown primary site , in view of the aggressive behavior of this tumor , platinum - based adjuvant chemotherapy is required after surgical resection .
however , determination of whether nodal neuroendocrine carcinoma is primary or metastatic at initial presentation is difficult , thus , localized therapy combined with chemotherapy and regular close follow - up is essential .
first , a perigastric ln involvement is unique . in a recent update that included 99 patients with pdnec with an unknown primary site ,
the majority of patients had multiple sites of metastasis , and commonly involved sites included the retroperitoneum in 20.2% , peripheral ln in 14.1% , mediastinum in 12.1% , liver in 12.1% , and bone in 11.1% .
second , in almost all previous reports , only chemotherapy ( usually platinum - based ) was administered , whereas , given the unusual setting and a tumor limited to a single site , we adopted surgical resection followed by chemotherapy . a small number of previous case reports
reported two cases of pdnec of unknown primary origin in an inguinal and a pancreaticoduodenal ln , respectively , which were treated by surgical resection alone .
considering the fact that both patients achieved long - term disease - free survival with ln dissection only , their cases probably could have originated from the affected ln itself .
however , in general , pdnec is highly aggressive , with a high rate of metastases and recurrence .
in addition , this disease group represents a favorable subset of unknown primary carcinomas that are sensitive to platinum - based combination chemotherapy .
therefore , aggressive treatment of pdnec of unknown origin following guidelines similar to those for small cell lung cancer is advised and if possible , a platinum - base adjuvant chemotherapy should be considered .
neuroendocrine carcinoma of unknown primary origin is very rare , and its diagnosis is difficult . in this unusual
setting , because a minority of patients could enjoy long - term and disease - free survival , we recommend treatment of patients with a single or localized pdnec from an unknown primary site with an aggressive local therapy .
in addition to definitive local therapy , the authors believe that these patients should also receive either neoadjuvant or adjuvant chemotherapy .
 neuroendocrine carcinomas from an unknown primary site are uncommon . 
 the authors report on a case of neuroendocrine carcinoma in a perigastric lymph node ( ln ) with no primary site . a 52-year - old male patient with early gastric adenocarcinoma underwent treatment by endoscopic submucosal dissection , and , six months later 
 , findings on a computed tomographic scan of the abdomen revealed a ln enlargement measuring 2.0 cm in the perigastric region . 
 the patient underwent subtotal gastrectomy and regional ln dissection under a suggestive preoperative diagnosis of gastric adenocarcinoma with ln metastasis . 
 however , microscopically , no residual tumor was found in the stomach , and the perigastric ln showed poorly differentiated neuroendocrine carcinoma ( pdnec ) . 
 after an extensive workup , no primary site was identified . 
 the patient also received four cycles of etoposide and cisplatin . despite its extremely rare incidence 
 , this case suggests that pdnec of an unknown primary site is limited to a single site , and that resection should be considered in combination with chemotherapy . 
Introduction
Case Report
Discussion