Indian Journal of Pathology and Microbiology
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Year : 2019  |  Volume : 62  |  Issue : 3  |  Page : 505-507
A case of multifocal EBV associated gastric carcinoma with focal squamous differentiation

1 Department of Surgery, University of Ulsan College of Medicine, Gangneung Asan Hospital, Gangneung, Republic of Korea
2 Department of Pathology, University of Ulsan College of Medicine, Gangneung Asan Hospital, Gangneung, Republic of Korea

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Date of Web Publication26-Jul-2019

How to cite this article:
Ji-Hoon K, Dae-Woon E. A case of multifocal EBV associated gastric carcinoma with focal squamous differentiation. Indian J Pathol Microbiol 2019;62:505-7

How to cite this URL:
Ji-Hoon K, Dae-Woon E. A case of multifocal EBV associated gastric carcinoma with focal squamous differentiation. Indian J Pathol Microbiol [serial online] 2019 [cited 2021 Jun 13];62:505-7. Available from: https://www.ijpmonline.org/text.asp?2019/62/3/505/263469


Uncommon histologic variants represent approximately 5% of gastric carcinomas and include squamous carcinoma (SCC) and gastric carcinoma with lymphoid stroma (GCLS). Here, we report a rare case of GCLS with focal squamous differentiation.

A 58-year-old man complained of several occurrences of hematemesis and melena for three days. Gastric endoscopy disclosed an ulcerative lesion with oozing bleeding in the posterior wall of the high body and an ulcer scar-like lesion in the angle along the side of less curvature. Endoscopic biopsy was performed and the lesions were diagnosed as poorly differentiated adenocarcinomas. Subsequently, he underwent total gastrectomy and adjacent lymphadenectomy. On gross examination, the resected stomach showed two separate lesions of a slightly depressed EGC IIb lesion (1.1 × 1.1 × 0.7 cm) in the angle along the less curvature side and a shallow ulcerative lesion EGC type IIc (3 × 2 × 0.3 cm) in the posterior wall of high body [Figure 1]a and [Figure 1]b.
Figure 1: A total gastrectomy, an EGC IIb lesion in the angle (lower circle), and an ulcerated lesion in the high body (upper circle) (a). Tumor mapping, gray areas indicate squamous carcinoma component (inlet) (b)

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Histologically, the first tumor consisted of two components [Figure 2]a and [Figure 2]b. One component was GCLS accounting for 85% of the total neoplasm and extended up to the deep submucosa (SM3). The tumor cells had eosinophilic cytoplasm and enlarged nuclei with prominent nucleoli and vesicular chromatin with moderately or poorly differentiated tubular structures. Marked infiltration of lymphocytes was observed in the stromal background [Figure 2]a. The other component was SCC which occupied 15% of the total neoplasm and was mainly located in superficial portion of the tumor. These cells showed clear or dense eosinophilic cytoplasm and intercellular bridges with infiltrative features [Figure 2]b. No mucin-containing cells were noted. Some transitional areas between the two components were observed.
Figure 2: GCLS (a) and SCC (b) components in the angle. GCLS in the high body (c) and metastatic tumor in the lymph node (d) (×200, H and E)

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The second tumor was composed of carcinoma with lymphoid stroma showing poorly differentiated tubular structures associated with prominent lymphoid stromal infiltration [Figure 2]c and extended to the superficial submucosa (SM1). GCLS component was metastasized in eight lymph nodes out of 39 dissected lymph nodes [Figure 2]d.

On immunohistochemistry, the tumor cells showing squamous differentiation were diffusely positive for p63 [Figure 3]a and keratin 903. Some nuclei of the SCC component were weakly positive for EBER, and the tumor cells of GCLS component were diffusely positive for EBER [Figure 3]b. PD-L1 was focally expressed in a few SCC cells (approximately 5%) [Figure 3]c. The tumor cells of the SCC component were focally positive for p53, and the tumor cells of GCLS component were diffusely positive for p53 [Figure 3]d.
Figure 3: Diffusely positive for p63 in SCC (a). Weakly positive for EBV in SCC (strong in GCLS, inlet) (b). Positive for PDL1 in SCC (negative in GCLS, inlet) (c). Focally positive for p53 in SCC; diffusely positive GCLS (inlet) (d)

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Carcinoma with lymphoid stroma (lymphoepithelioma) was primarily described in the nasopharynx. Although similar histologic features have been described in many other organs, Epstein-Barr virus (EBV) is frequently found in the carcinomas arising in the stomach, lung, thymus, and salivary gland. GCLS, constituting approximately 1–4% of all gastric carcinomas, tends to occur in old age with a male predominance and arises in the cardia or middle portion of the stomach.[1] Gastric SCC is an extremely rare malignancy with an incidence of 0.04–0.07%.[2] The prognosis of gastric SCC is probably less favorable than that of adenocarcinoma due to its higher frequency of lymphovascular and serosal invasions.

Our case is unique due to the rare histological combination with aggressive prognostic behavior; multiple metastases in the dissected lymph nodes by the GCLS component despite early T stage and early recurrence of the cancer (12 months) causing patient death (25 months) after surgery.

Although the pathogenesis of the coexistence of two components is unknown, there might be three possible origins of both components in the stomach. First, the two tumors seem to collide and form one mass. Second, the two tumors originated from a multipotential precursor cell able to differentiate along the lines of EBV-associated adenocarcinoma and the other demonstrated squamous differentiation. Third, squamous metaplasia or squamous differentiation occurred in a pre-existing GCLS. Considering the presence of a transition area between the two components and the superficial location of the squamous component, we suggest the last possibility. The role of EBV in the carcinogenesis of SCC is unclear in the stomach. Interestingly, Takita et al. detected EBV in surgical specimens of the tumor by polymerase chain reaction and proposed that EBV infection may be involved in the pathogenesis of certain cases of gastric SCC.[3]

Programmed death ligand 1 (PD-L1), which is a cell surface protein of B7 family, serves as negative regulators of T cell-mediated immunity. High PD-L1 expression in tumor cells has been suggested to be an important immune evasion mechanism. Some studies have confirmed the high expression of PD-L1 in EBV-associated malignancies, including specific subtypes of lymphomas, nasopharyngeal carcinoma, and EBV-associated gastric carcinoma.[4] In gastric cancer, it has been reported that high PD-L1 expression is correlated with aggressive clinicopathological features and poor prognosis.[5] Interestingly, in the present case, PD-L1 was only expressed in the squamous component. The prognostic significance of PD-L1 expression in our case is uncertain because the metastatic tumor was entirely composed of carcinoma with lymphoid stroma.

We reported a rare case of multifocal GCLSs with focal squamous differentiation with an aggressive behavior. Clinicians and pathologists should keep in mind that such a tumor may occur in the stomach, and further studies are necessary to define the pathogenesis and biological behavior.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

This research was supported by a grant (2015-011) from the Gangneung Asan Hospital Biomedical Research Center Promotion Fund.

Conflicts of interest

There are no conflicts of interest.

   References Top

Sousa H, Pinto-Correia AL, Medeiros R, Dinis-Ribeiro M. Epstein-Barr virus is associated with gastric carcinoma: The question is what is the significance? World J Gastroenterol 2008;14:4347-51.  Back to cited text no. 1
Boswell JT, Helwig EB. Squamous cell carcinoma and adenoacanthoma of the stomach. A clinicopathologic study. Cancer 1965;18:181-92.  Back to cited text no. 2
Takita J, Kato H, Miyazaki T, Nakajima M, Fukai Y, Masuda N, et al. Primary squamous cell carcinoma of the stomach: A case report with immunohistochemical and molecular biologic studies. Hepatogastroenterology 2005;52:969-74.  Back to cited text no. 3
Dong M, Wang HY, Zhao XX, Chen JN, Zhang YW, Huang Y, et al. Expression and prognostic roles of PIK3CA, JAK2, PD-L1, and PD-L2 in Epstein-Barr virus-associated gastric carcinoma. Hum Pathol 2016;53:25-34.  Back to cited text no. 4
Geng Y, Wang H, Lu C, Li Q, Xu B, Jiang J, et al. Expression of costimulatory molecules B7-H1, B7-H4 and Foxp3+Tregs in gastric cancer and its clinical significance. Int J Clin Oncol 2015;20:273-81.  Back to cited text no. 5

Correspondence Address:
Eom Dae-Woon
Department of Pathology, Gangneung Asan Hospital, University of Ulsan College of Medicine, 38 Bangdong-gil, Sacheon-myeon, Gangneung 25440
Republic of Korea
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJPM.IJPM_174_18

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