Goblet Cell Adenocarcinoma in the Stomach: A Case Report

Goblet cell adenocarcinoma (GCA) is known as an amphicrine tumor often seen in the appendix. Here, we report a rare case of GCA in the stomach. An 80-year-old man underwent gastroscopy due to epigastric pain and was diagnosed with gastric cancer. He received total gastrectomy and histology showed a mixture of a moderately-differentiated tubular adenocarcinoma, a mucinous adenocarcinoma, and a tumor composed of goblet-like mucinous cells with neuroendocrine differentiation. The tumor volume ratio was about 4:1:5, respectively, and a final diagnosis of GCA was made. The metastasis of the regional lymph node was occupied by only the component of goblet-like cells. GCA should be recognized as a rare histologic subtype of gastric cancer.


Introduction
Goblet cell adenocarcinoma (GCA) is a rare malignancy often detected in the appendix, which is defined as an amphicrine tumor composed of goblet-like mucinous cells, as well as variable numbers of endocrine cells and Paneth-like cells [1].Historically, it has been called by various names such as goblet cell carcinoid, adenocarcinoid, mucinous carcinoid, and mucin-producing neuroendocrine tumor [1,2].Here, we report a rare case of GCA seen in the stomach, which would be the sixth case in the English literature.

Case Presentation
This is the case of an 80-year-old male patient who presented with epigastric pain and tarry stool for the past month before the consultation.The patient had no relevant medical history and did not report any other general symptoms.Endoscopic examination showed a mass with a bulging and ulcerated surface located at the corpus of the stomach (Figure 1A).Biopsied samples suggested a moderately-differentiated tubular adenocarcinoma.Thereafter, the patient received total gastrectomy and lymph node dissection as the treatment for gastric cancer.

FIGURE 1: Macroscopic images of the gastric tumor
A) A protruding tumor with an ulcerated surface (yellow triangle) was seen on endoscopy.
B) The tumor (yellow triangle) was located at the corpus of the resected stomach.Macroscopically, the resected tumor was approximately 30×25 mm (Figure 1B).Histologically, the tumor consisted of three components: a moderately differentiated tubular adenocarcinoma, a mucinous adenocarcinoma, and a tumor composed of goblet-like mucinous cells (Figures 2A-2B).The tumor volume ratio was about 4:1:5, respectively.The component of the goblet-like cells was the most invasive and was exposed on the serosa surface.Immunohistochemical examination of the goblet-like cells showed positivity for the two neuroendocrine markers, Synaptophysin and Chromogranin A (Figures 2C-2D), which were negative on the other tumor components.Additionally, the Ki-67 proliferative index in the goblet-like cells was more than 70% (Figure 3A).Collectively, a diagnosis of GCA was established.In the non-neoplastic gastric mucosa, chronic atrophic gastritis without apparent evidence of Helicobacter pylori was seen.The metastasis was found in 2 of the 15 regional lymph nodes and occupied by only the goblet-like cells (Figure 3B).The tumor, node, metastasis (TNM) classification was determined as pT4aN1M0 (stage IIIB).Six months after surgery, our follow-up was terminated because he was transferred to a chronic care hospital.At least during the period, no recurrence or metastasis was observed.

Discussion
According to the recent WHO classification (5th) [1], GCA is classified as not a neuroendocrine neoplasm but an adenocarcinoma subtype and can include components of conventional adenocarcinomas.Additionally, the use of the term "mixed adenoneuroendocrine carcinoma (MANEC)" is no longer preferred in the context of GCA.Thus, we determined the diagnosis of the tumor in the present case as just GCA.As the tumor mainly showed tubular or clustered growth, the GCA was graded as 1 on the three-tiered system [1].
Because the majority of reports on GCA have been collected from patients with appendiceal origin, the data on GCA in the stomach is extremely scarce.To our knowledge, there have been just five cases (in four reports) describing GCA of the stomach in the English literature [3][4][5][6].The summary of the reported cases, including ours, is shown in Table 1.Four out of the six cases were over 60 years old.The male/female ratio was 2:1.Interestingly, all the GCAs included other malignant components, such as tubular adenocarcinoma and signet-ring cell adenocarcinoma.The follow-up periods after surgery were diverse, which suggests the difficulty in discussing the prognosis, so far. (

Conclusions
In conclusion, GCA should be recognized as a rare form of gastric malignancy, particularly detected with other types of adenocarcinomas.Further case series are needed to understand the clinical significance of this disease.

FIGURE 3 :
FIGURE 3: Histology and immunostaining for the component of goblet cell adenocarcinoma A) An image of Ki-67 staining in the goblet cell adenocarcinoma of the stomach is shown (visualized using 3,3'Diaminobenzidine, magnification: ×200, scale bar: 50 μm).B) Only the component of goblet-like cells is detected in the metastatic lymph node (Hematoxylin & Eosin staining, magnification: ×200, scale bar: 50 μm).