| Abstract|| |
A 50-year-old male patient presented with pain abdomen of 6 months duration. Computed tomography scan revealed a large mass in the stomach occluding the lumen. Histopathology revealed a triple composite tumor comprising of tubular adenocarcinoma arising on a background of high-grade dysplasia, hepatoid adenocarcinoma (positive for Hep Par-1 and alpha fetoprotein) and large cell neuroendocrine carcinoma (positive for synaptophysin and chromogranin) with nodal metastasis.Triple composite tumors are distinctly rare with few reports in literature.
Keywords: Alpha fetoprotein, composite tumors, hepatoid adenocarcinoma, neuroendocrine
|How to cite this article:|
Lipi L, Sachdev R, Gautam D, Singh J, Mohapatra I. Triple composite tumor of stomach: A rare combination of alpha fetoprotein positive hepatoid adenocarcinoma, tubular adenocarcinoma and large cell neuroendocrine carcinoma. Indian J Pathol Microbiol 2014;57:98-100
|How to cite this URL:|
Lipi L, Sachdev R, Gautam D, Singh J, Mohapatra I. Triple composite tumor of stomach: A rare combination of alpha fetoprotein positive hepatoid adenocarcinoma, tubular adenocarcinoma and large cell neuroendocrine carcinoma. Indian J Pathol Microbiol [serial online] 2014 [cited 2019 May 24];57:98-100. Available from: http://www.ijpmonline.org/text.asp?2014/57/1/98/130912
| Introduction|| |
The gastrointestinal tract is the site of 70% of synchronous cancers. Most gastric cancers are adenocarcinomas and may co-exist with carcinoid tumors and B cell non-Hodgkin lymphoma.  While alpha fetoprotein producing carcinoma (AFPC) is rare in the stomach,  few cases of gastric carcinoma consisting of AFPC/hepatoid adenocarcinoma (HAC) and neuroendocrine carcinoma (NEC) have been reported. 
| Case Report|| |
This was a case report of a 50-year-old male patient who presented with the complaints of pain abdomen since 6 months. Computed tomography scan abdomen revealed thickening of gastric cardia with a polypoidal mass projecting in the lumen. Positron emission tomographyscan revealed metabolically active, FDG avid lesion in gastric cardia and adjacent proximal body (SUV max 19.56). No other abnormal uptake was noted elsewhere in the body.
A total gastrectomy was performed. Grossly, a polypoidal and ulcerating growth measuring 85 mm × 65 mm × 45 mm was identified, located in the cardia [Figure 1]. Histopathology revealed high grade dysplasia with foci of tubular adenocarcinoma merging with sheets of poorly differentiated, large cells and another tumor comprising of glandular component with clear cells arranged in cords and trabeculae.
The tumor cells that were arranged in sheets showed nuclei with salt and pepper chromatin and brisk mitosis. On immunohistochemistry (IHC), these tumor cells stained for cytokeratin (CK) (CK, clone AE 1 and AE3), Synaptophysin (Syn) (Syn, clone SY38), chromogranin (CG) (CG, clone IS02) and were negative for alpha fetoprotein (AFP) (AFP, clone IS500. Ki 67 index was 80% [Figure 2], [Figure 3], [Figure 4]. The clear cell adenocarcinoma showed cells, which were positive for CK, AFP and Hep Par-1(clone OCH1E5). The tumor cells were negative for CG and Syn.
|Figure 1: Gastrectomy specimen showing a polypoidal and ulcerative growth located in cardia|
Click here to view
|Figure 2: (a) H and E stained slide showing triple composite tumors in the same field (H and E, ×10), (b) High power view of the neuroendocrine tumor (H and E, ×40) (c and d) Alpha fetoprotein,(c) Hep Par-1, (d) positivity in the hepatoid adenocarcinoma component (×40)|
Click here to view
|Figure 3: (a and b) Low (H and E, ×10) and high power (H and E, ×40) view of neuroendocrine carcinoma (NEC) and hepatoid adenocarcinoma in same field, (c and d) NEC showing positivity for chromogranin, (c) synaptophysin (d), ×40|
Click here to view
|Figure 4: (a) H and E stained slide showing tubular adenocarcinoma and neuroendocrine carcinoma (NEC) (H and E, ×40), (b and c) Cytokeratin immunohistochemistry showing dot like pattern in NEC and membranous staining in adenocarcinoma (×40), (d) High Ki 67 labeling index in the NEC (×40)|
Click here to view
10 out of 12 lymph nodes isolated showed metastasis. Interestingly, the metastatic component comprised primarily of AFP positive HAC.
Based on histopathological and IHC findings, a diagnosis of Triple composite tumor, stomach: Components of clear cell HAC, tubular adenocarcinoma (on a background of high grade surface dysplasia) and large cell NEC was made.
The patient is on Cisplatin + VP 16 based chemotherapy, has received 2 cycles so far and is currently afebrile and hemodynamically stable.
| Discussion|| |
Collision tumor characteristically has two types of tumors, juxtaposed to each other but not admixed like as in our case, when the term composite tumor is preferred. The term amphicrine tumor is preferred when there is dual differentiation within the same tumor cell.  Most of the collision tumors of stomach described in literature include adenocarcinoma with lymphomas, carcinoid and GIST or neuroendocrine tumors. Triple composite tumors are rare and require diligent sampling and comprehensive IHC for definite characterization. Only a few cases have been reported. A study by Nagaoka et al. described a composite tumor comprised of AFP producing adenocarcinoma and NEC.  In our case also had a surface tubular adenocarcinoma arising on a background of high grade dysplasia, which was AFP negative.
While carcinoids are generally more indolent in nature, they may demonstrate a greater degree of malignant potential if there is a concomitant gastric adenocarcinoma.  Hence in such patients, surgical resection is generally preferred.
In our case, the AFP positive component metastasized widely to neighboring lymph nodes, indicating its relative aggressiveness. It is known that HAC produces alpha-1 antitrypsin and/or alpha-1 anti-chymotrypsin (ACT) as well as AFP. AAT and ACT have immunosuppressive and protease-inhibitor properties that enhance invasiveness.  AFP has a suppressive effect on lymphocyte transformation. Furthermore, these tumors are known to be resistant to chemotherapy.  A study by Chong et al. described a patient treated for gastric cancer, later presenting as triple collision tumor comprising of hepatocellular carcinoma, gastric composite tumor comprising of adenocarcinoma with large B cell lymphoma. 
Our case was H pylori negative unlike that observed by Chong et al.  Various risk factors have been proposed, including age, H pylori and genetic factors, though no definite etiological factor can be certain until date. Amongst the possible theories, particularly in rats with hypergastrinemia, enterochromaffin-like cells were shown to have the capacity to dedifferentiate and become potential precursors of gastric adenocarcinomas.  Some authors have postulated proliferation of a pluripotent precursor cell and studies describing common genetic alterations in the glandular and neuroendocrine component of mixed tumors support the latter hypothesis. 
| References|| |
|1.||Chang YC, Nagasue N, Abe S, Taniura H, Kumar DD, Nakamura T. Comparison between the clinicopathologic features of AFP-positive and AFP-negative gastric cancers. Am J Gastroenterol 1992;87:321-5. |
|2.||Okamoto T, Ogasahara K, Fujiki M, Takagi H, Ikeda H, Makino T, et al. Primary coexistent neuroendocrine carcinoma, hepatoid adenocarcinoma, and tubular adenocarcinoma of the stomach with focal trophoblastic differentiation in metastatic lymph nodes. JGastroenterol 2003;38:608-10. |
|3.||Kim TY, Chae HD. Composite neuroendocrine carcinoma with adenocarcinoma of the stomach misdiagnosed as a giant submucosal tumor. J Gastric Cancer 2011;11:126-30. |
|4.||Nagaoka S, Toyoshima H, Bandoh T, Isoyama T, Kasahara D, Kusafuka K, et al. Composite carcinoid-adenocarcinoma tumor of the stomach: Report of a case. Surg Today 1996;26:184-8. |
|5.||Kumashiro Y, Yao T, Aishima S, Hirahashi M, Nishiyama K, Yamada T, et al. Hepatoid adenocarcinoma of the stomach: Histogenesis and progression in association with intestinal phenotype. Hum Pathol 2007;38:857-63. |
|6.||Chong VH, Idros A, Telisinghe PU. Triple synchronous gastrointestinal malignancies: A rare occurrence. Singapore Med J 2010;51:e176-7. |
A 803, Plot No 7 A. Navrattan Apartments, Sector 23, Dwarka, New Delhi - 110 077
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3], [Figure 4]