|Year : 2016 | Volume
| Issue : 3 | Page : 236-239
A very rare case of neuroendocrine carcinoma of stomach
Abhishek Purkayastha1, Neelam Sharma1, Virender Suhag1, Vibha Dutta2
1 Department of Radiation Oncology, Army Hospital Research and Referral, New Delhi, India
2 Department of Pathology and Molecular Sciences, Army Hospital Research and Referral, New Delhi, India
|Date of Web Publication||9-Jun-2016|
Department of Radiation Oncology, Army Hospital Research and Referral, Delhi Cantonment - 110 010, New Delhi
Source of Support: None, Conflict of Interest: None
We report an extremely rare case of neuroendocrine carcinoma (NEC) of the stomach, which is known for its aggressive behavior and poor prognosis. To the best of our knowledge, only a few cases have been reported in the world till date and our case may be one of the very few of this rare pathology. A 42-year-old male presented with vague abdominal pain and significant weight loss. Upper gastrointestinal endoscopy revealed ulceroproliferative growth in the pylorus. Computed tomography of the abdomen showed thickening of the pylorus with locoregional lymphadenopathy. Positron emission tomography scan showed localized disease. A distal gastrectomy with D1 dissection was performed. Postoperative histopathology revealed high grade NEC of the stomach with cytokeratin-20, epithelial membrane antigen, chromogranin, and CDX-2 positivity on immunohistochemistry. He was treated with adjuvant chemotherapy followed by locoregional radiotherapy with significant response to treatment. Presently on regular follow-up without any evidence of recurrence or distant metastasis.
Keywords: Gastric neuroendocrine neoplasms, neuroendocrine carcinoma, radiotherapy, stomach
|How to cite this article:|
Purkayastha A, Sharma N, Suhag V, Dutta V. A very rare case of neuroendocrine carcinoma of stomach. CHRISMED J Health Res 2016;3:236-9
|How to cite this URL:|
Purkayastha A, Sharma N, Suhag V, Dutta V. A very rare case of neuroendocrine carcinoma of stomach. CHRISMED J Health Res [serial online] 2016 [cited 2020 May 31];3:236-9. Available from: http://www.cjhr.org/text.asp?2016/3/3/236/183759
| Introduction|| |
Gastric neuroendocrine neoplasms (NENs) are rare tumors accounting for <1% of all gastrointestinal tract malignancies  while neuroendocrine carcinoma (NEC) of stomach represents <10% of gastric NENs. , Such rarity and lack of randomized clinical trials have made it difficult to understand precisely their biological nature and therefore to establish optimal treatment options. NEC should always be considered in a patient presenting with abdominal pain and ulceroproliferative gastric growth on endoscopy in view of its dismal prognosis. Surgery remains the upfront treatment approach while chemotherapy  and radiotherapy (RT)  are used as adjuvant therapeutic modalities.
| Case report|| |
A 42-year-old male with no known comorbidities presented with a history of vague abdominal pain, decreased appetite, and dyspepsia associated with significant weight loss of 8-month duration. There was no history of vomiting, hematemesis, or malena. Upper gastrointestinal endoscopy (UGIE) showed a large ulceroproliferative growth in pylorus [Figure 1] with a gastroesophageal junction at 40 cm with biopsy revealing well differentiated adenocarcinoma with neuroendocrine differentiation.
|Figure 1: Upper gastrointestinal endoscopy showing ulceroproliferative growth at pylorus (yellow pointer)|
Click here to view
Ultrasonography abdomen and pelvis showed irregular wall thickening in antro-pyloric region of stomach. Contrast enhanced computed tomography of chest, abdomen and pelvis [Figure 2] showed circumferential thickening of the walls of pylorus and antrum. The fat planes with liver and pancreas were maintained. Few enlarged locoregional lymph nodes were seen, largest measuring 14 mm × 10 mm. The positron emission tomography scan showed a localized disease.
|Figure 2: Computed tomography scan of chest, abdomen and pelvis showing circumferential thickening of the walls of pylorus and antrum (yellow pointer)|
Click here to view
The patient underwent distal gastrectomy with D1 dissection. Peroperatively the growth was seen infiltrating the pancreas. Postoperative histopathological report [Figure 3] showed tumor cells in form of glands, well-defined nests, cords and trabecular pattern infiltrating into wall of stomach up to the serosal fat suggestive of high grade NEC with tumor deposits in three perigastric and one omental lymph nodes with perinodal spill. Immunohistochemistry (IHC) revealed cytokeratin 20 (CK 20) [Figure 4], epithelial membrane antigen (EMA) [Figure 5], chromogranin [Figure 6], and CDX-2 positivity with Ki-67 labeling index of 45% while CK-7, PDX-1 and thyroid transcription factor (TTF-1) were immunonegative.
|Figure 3: Postoperative histopathological report showing tumor cells in form of glands, well-defined nests, cords and trabecular pattern infiltrating into wall of stomach up to the serosal fat suggestive of high grade neuroendocrine carcinoma (H and E, ×10)|
Click here to view
|Figure 4: Immunohistochemistry showing cytokeratin 20 (CK-20) positivity (×40)|
Click here to view
|Figure 5: Immunohistochemistry showing epithelial membrane antigen positivity (×40)|
Click here to view
The patient was treated with adjuvant chemotherapy, three cycles of injection cisplatin and injection etoposide (EP) followed by locoregional RT to stomach bed by three-dimensional conformal RT technique to dose of 45 Gray (Gy) in 25 fractions, followed by three more cycles of EP. The patient tolerated treatment well and is presently on regular follow-up without any evidence of recurrence or distant metastasis.
| Discussion|| |
Gastric NENs are relatively rare tumors that account for <1% of all gastric tumors  while NECs of the stomach are still rarer, representing <10% of gastric NENs. , Gastric NENs were differentiated by the WHO, in 2010, into neuroendocrine tumors (NETs) and NECs based on local tumor behavior, tumor size, depth of tumor infiltration, and lymphovascular embolization.  While NETs show a slow clinical course and good prognosis, NECs of the stomach exhibit a highly malignant and aggressive behavior with a dismal prognosis  in view of local tumor recurrence and early metastasis.
Histopathological analysis shows a predominant solid growth pattern followed by lesser variants such as trabecular, tubular, and scirrhous types.  ASH1 and NKX2.2 are two new neuroendocrine markers expressed by these tumor cells on IHC apart from chromogranin, synaptophysin, and CD56.  The level of cellular proliferation of NECs is based on mitotic index per high power field and Ki-67 proliferative index status.  Our patient's gastrectomy specimen showed malignant growth with the lymphatic involvement of perigastric and omental nodes associated with perinodal spill which indicated a high grade nature this disease.
IHC was positive for chromogranin, CK-20, and EMA with a high Ki-67. CDX2, a homeobox gene that plays an important role in proliferation and differentiation of gastric epithelial cells was positive. Since peroperatively the tumor was seen infiltrating the pancreas, IHC for CK-7, PDX-1, and TTF-1 was done which was negative, thus proving the malignant growth to be of gastric origin and not a pancreatic or pulmonary component. CK-20 is expressed alone in the majority of intestinal adenocarcinoma and in Merkel cell carcinomas, whereas CK7 is present without CK20 in most breast, lung, and ovarian adenocarcinomas and with CK20 in urothelial and pancreatic carcinomas.
Gastric NECs occur mostly in adults with a slight predilection for females and very rarely in children.  Tumor size more than 4.6 cm, stage, lymph node status, and treatment have a potential impact on the overall prognosis.  Surgery remains the mainstay of treatment helping reduce tumor burden and symptoms thus prolonging survival. However adjuvant treatment options are still a subject of discussion, though Rindi et al.  used adjuvant chemotherapy in a postgastrectomy patient with some success. Since NEC accounts for 20% of lung carcinomas of which 14% are small cell lung carcinomas (SCLCs) and most oncologists use pulmonary classification for extra-pulmonary NEC, we used cisplatin with EP which is usually exhibited to patients of SCLC as this regimen had shown a 5 years survival of 88.9%. 
RT is, in general, given after adjuvant chemotherapy in patients with regional lymph node metastasis as happened in our case, as they have a high rate of local recurrence and overall worse prognosis if treated with surgery alone,  keeping in mind the high grade and malignant nature of this pathological entity. In our case, the patient responded very well to initial three cycles of chemotherapy and therefore to consolidate the gain of systemic therapy it was decided to start RT in view of perinodal spill to achieve a better local control as it was easier to encompass the entire treatment volume at this juncture in the RT portals.
| Conclusion|| |
The diagnosis of NEC of stomach should always be considered whenever any patient presents with vague abdominal discomfort and a gastric growth on UGIE so as to enable a prompt initiation of appropriate treatment. By reporting this case, we emphasize the need of an appropriate adjuvant treatment algorithm and recommend the use of chemotherapy regimens used for SCLC including platinum agents and EP, followed by locoregional RT in the case of nodal metastasis as a preferred therapeutic option.
We thank the patient for allowing us to publish the case report and use the images taken during his stay in the hospital.
Ethical approval: Written informed consent to publication was obtained from the patient.
We also like to extend our gratitude to Department of Surgical and Medical Oncology, Command Hospital Western Command Chandimandir, Departments of Medical Oncology, Nuclear Medicine and Radiology, Army Hospital Research and Referral, New Delhi, India.
The manuscript has been read and approved by all the authors, the requirements for authorship have been met, and each author believes that the manuscript represents honest work.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Modlin IM, Lye KD, Kidd M. Carcinoid tumors of the stomach. Surg Oncol 2003;12:153-72.
Rindi G, Bordi C, Rappel S, La Rosa S, Stolte M, Solcia E. Gastric carcinoids and neuroendocrine carcinomas: Pathogenesis, pathology, and behavior. World J Surg 1996;20:168-72.
Chiba N, Suwa T, Hori M, Sakuma M, Kitajima M. Advanced gastric endocrine cell carcinoma with distant lymph node metastasis: A case report and clinicopathological characteristics of the disease. Gastric Cancer 2004;7:122-7.
Mackley HB, Videtic GM. Primary carcinoid tumors of the lung: A role for radiotherapy. Oncology (Williston Park) 2006;20:1537-43.
Bosman FT, Carneiro F, Hruban RH, Theise ND, editors. WHO Classification of Tumors of the Digestive System. 4 th
ed. Lyon, France: International Agency for Research on Cancer; 2010.
Ishida M, Sekine S, Fukagawa T, Ohashi M, Morita S, Taniguchi H, et al.
Neuroendocrine carcinoma of the stomach: Morphologic and immunohistochemical characteristics and prognosis. Am J Surg Pathol 2013;37:949-59.
Klimstra DS, Modlin IR, Coppola D, Lloyd RV, Suster S. The pathologic classification of neuroendocrine tumors: A review of nomenclature, grading, and staging systems. Pancreas 2010;39:707-12.
Bordi C, Yu JY, Baggi MT, Davoli C, Pilato FP, Baruzzi G, et al.
Gastric carcinoids and their precursor lesions. A histologic and immunohistochemical study of 23 cases. Cancer 1991;67:663-72.
Yuan D, Yan R, Li K, Zhu K, Jia Y, Dang C. Small-cell neuroendocrine carcinoma of the stomach: A clinical and prognostic analysis of 21 cases. Zhonghua Zhong Liu Za Zhi 2015;37:227-30.
Iyoda A, Hiroshima K, Moriya Y, Iwadate Y, Takiguchi Y, Uno T, et al.
Postoperative recurrence and the role of adjuvant chemotherapy in patients with pulmonary large-cell neuroendocrine carcinoma. J Thorac Cardiovasc Surg 2009;138:446-53.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]