Cancers exhibiting a combination of epithelial and neuroendocrine features can occur in various organs. In the WHO classification of neoplasms of the gastrointestinal tract, such tumors are called “mixed adenoneuroendocrine carcinomas”. They may be composite, combined or amphicrine type. We present here a rare case of composite adenocarcinoma and neuroendocrine carcinoma of stomach

Kumar, Ajay

Moothiringode, Savithri

Surendran, Divya

English

Atharva Scientific Publications (E-Jounals)

Surendran et al                              Composite gastric mixed adenoneuroendocrine carcinoma 
Vol 3 Issue 2 Apr – Jun 2017                                                        Indian J Case Reports / 58 
Case Report 
A rare case of composite type of gastric mixed adenoneuroendocrine 
carcinoma 
Divya Surendran, Savithri Moothiringode, Ajay Kumar 
From, the Department of pathology, Amala Institute of Medical Sciences, Thrissur, Kerala, India 
Correspondence to: Dr. Divya Surendran, Amala Institute of Medical Sciences, Thrissur, Kerala, India. Email - 
divyasreehariss@gmail.com.  
Received: 16 Jan 2017    Initial Review: 13 Feb 2017    Accepted:  01 Apr 2017         Published Online: 17 Apr 2017 
ABSTRACT 
Cancers exhibiting a combination of epithelial and neuroendocrine features can occur in various organs. In the WHO 
classification of neoplasms of the gastrointestinal tract, such tumors are called “mixed adenoneuroendocrine carcinomas”. 
They may be composite, combined or amphicrine type. We present here a rare case of composite adenocarcinoma and 
neuroendocrine carcinoma of stomach. 
Keywords: MANEC, Composite tumour, Stomach. 
 
ancers showing epithelial and neuroendocrine 
components are seen in gastrointestinal tract, but 
they are rare in stomach and till 2015, less than 40 
such gastric carcinomas have been reported [1]. These are 
referred to in the WHO classification of tumors of 
gastrointestinal tract as mixed adenoneuroendocrine 
carcinomas (MANEC) [2]. It is important to identify this 
condition and to grade the neuroendocrine component to 
choose the correct treatment modality. Neuroendocrine 
carcinoma (NEC) and adenocarcinomatous components 
are difficult to identify separately by gastroscopy or 
ultrasound. Hence, histopathology along with 
immunohistochemistry (IHC) is of paramount importance. 
According to the morphological and immuno-
histochemical features, they are divided into composite, 
combined or amphicrine types. In composite or collision 
tumors, the two components are separate and in combined 
tumors, the two components are mixed. In amphicrine 
tumors the same tumor cell shows both exocrine and 
endocrine features by IHC [2]. While carcinoma with 
interspersed endocrine cells is the most frequent, the  
 
remaining tumors have rarely been reported in the stomach 
[1]. We report a case of composite type of MANEC. 
CASE REPORT 
A 56 year old lady presented with pain in the abdomen of 
more than five months duration. She was a known 
psychiatric patient on treatment. On general examination, 
pallor was present. No jaundice or lymphadenopathy 
noted. Abdominal examination showed a tender mass in 
the epigastrium. Other systems on examination were 
within normal limits. A neoplastic lesion was suspected 
and oesophago-gastroscopy was done. This revealed an 
ulcer in the antrum with everted edges.  
Biopsy was taken which showed adenocarcinoma. CT 
scan was done and showed focal eccentric wall thickening 
in antro-pyloric region of stomach implying a malignant 
lesion. Small perigastric nodes were also noted. Distal 
radical gastrectomy was done. Macroscopic examination 
of the specimen showed an ulcero-proliferative neoplasm 
measuring 3x1.5x1 cm located towards the distal end. 
C 
Surendran et al                              Composite gastric mixed adenoneuroendocrine carcinoma 
Vol 3 Issue 2 Apr – Jun 2017                                                        Indian J Case Reports / 59 
    
Figures: Fig. 1 - Carcinoma cells arranged in glandular pattern, Fig. 2 - cells with scanty cytoplasm and nucleus showing 
powdery chromatin arranged in nests, Fig. 3 - carcinoma cells positive for CK 
Cut surface was grey white with hemorrhagic areas. 
Microscopy of the H&E stained sections revealed an 
invasive adenocarcinoma in the mucosal aspect (Fig. 1). 
Deeper portions showed smaller cells arranged in nests, 
trabeculae and solid patterns suggesting NEC (Fig. 2). 
Brisk mitotic activity was noted but no necrosis was seen. 
No lymphovascular emboli or perineural invasion were 
seen. The neoplasm involved the sub mucosa. 
Four out of ten dissected lymph nodes showed 
neuroendocrine tumour metastasis without 
adenocarcinoma component. On IHC, both components 
were positive for cytokeratin (Fig. 3). Synaptophysin and 
chromogranin (Fig. 4) were positive in the neuroendocrine 
component while the adenocarcinoma component was 
negative. Final diagnosis of MANEC composite type was 
made on the basis of above mentioned findings. 
 
Figure 4 - Neuroendocrine component showing positivity 
for chromochromogranin 
Patient was put on chemotherapy regimen VI B cycle 
chemo with FOLFOX protocol comprising of injection 
Oxaliplatin, Inj 5 Flourouracil and Leucovorin. Following 
this, patient was given adjuvant radiotherapy. Total dose 
given was 50.Gy/28# to the tumour bed and 45Gy/245# to 
the subclinical disease areas. Patient is currently on follow 
up and is doing well. 
DISCUSSION 
MANECs are of three types. They may be composite or 
collision neoplasms where the neuroendocrine and 
exocrine components occur in separate areas of the same 
lesion or combined neoplasms where they are intimately 
and diffusely admixed. The third one is the amphicrine 
type where exocrine and neuroendocrine features are 
present in the same neoplastic cell and which shows a 
divergent immunophenotype. There are various hypotheses 
regarding the histogenesis of MANECs. It may either be 
the simultaneous proliferation of multiple cell lineages or 
the proliferation of stem cells capable of differentiating 
along multiple cell lines [3,4].  
The presence of amphicrine type of MANEC supports 
the hypothesis of common precursor stem cell which can 
give rise to NEC, squamous cell carcinoma and 
adenocarcinoma. Chromosomal abnormalities are more in 
NEC than adenocarcinoma. The risk factors for NEC and 
adenocarcinoma are said to be the same. This includes 
hereditary, dietary and environmental factors [3]. The 
clinical behavior of composite carcinomas depends on the 
adenocarcinomatous component if the associated 
endocrine component is well differentiated, and upon the 
neuroendocrine component if it is poorly differentiated [2]. 
Our case was MANEC, composite type with the 
superficial portions showing adenocarcinomatous 
component and deeper portions showing NEC component. 
Surendran et al                              Composite gastric mixed adenoneuroendocrine carcinoma 
Vol 3 Issue 2 Apr – Jun 2017                                                        Indian J Case Reports / 60 
Nodal metastasis showed NEC component. NEC and 
adenocarcinomatous components are difficult to identify 
separately by gastroscopy or ultrasound. So, 
histopathology along with IHC is confirmatory. 
Chromogranin and synaptophysin are neuroendocrine 
markers with high specificity for NEC. MEN1 gene 
detection and positron emission tomography (PET) 
scanning have been reported as advanced methods for the 
diagnosis of NEC and adenocarcinomatous components.  
Prognosis is not good for these cases unless they are 
detected very early. Gastrectomy is the treatment of choice 
in such cases. In advanced stage, disease platinum based 
chemotherapy should be considered. 
CONCLUSION 
We report this case because of its rarity. Multimodal 
treatment should be the aim for these patients because of 
the neuroendocrine component of the tumor. 
REFERENCES 
1. Gurzu S, Kadar Z, Bara T, Bara T Jr, Tamasi A, Azamfirei 
L, et al. Mixed neuroendocrine carcinoma of 
gastrointestinal tract: report of two cases. World J 
Gastroenterol. 2015; 21: 1329-33. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2. La Rosa S , Marando A, Sessa F, Capella C. Mixed 
Adenoneuroendocrine Carcinomas (MANECs) of the 
Gastrointestinal Tract: An Update. Cancers 2012; 4: 11-
30. 
3. Li S, Cao X, Jiang C, Wang Q. Combined neuroendocrine 
carcinoma and adenocarcinoma in the stomach: A case 
report, Oncology Letters. 2014; 7: 953–5. 
4. Liu SW, Chen GH, Hsieh PP. Collision tumor of the 
stomach: a case report of mixed gastrointestinal stromal 
tumor and adenocarcinoma. J Clin Gastroenterol. 2002; 
35:332-4. 
5. Kwok C-M. Mixed Adenoneuroendocrine Carcinoma of 
the Stomach. Case Reports in Gastroenterology. 2015; 9: 
241-245. 
 
 
How to cite this article: Surendran D, Moothiringode 
S, Kumar A. A rare case of composite type of gastric 
mixed adenoneuroendocrine carcinoma. Indian J Case 
Reports. 2017; 3(2): 58-60. 
Conflict of interest: None stated, Funding: Nil 


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A rare case of composite type of gastric mixed adenoneuroendocrine carcinoma

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