Gastric collision tumor with diffuse large B-cell lymphoma and adenocarcinoma: a rare case report and literature review

doi:10.21203/rs.3.rs-2484222/v1

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Case Report

Gastric collision tumor with diffuse large B-cell lymphoma and adenocarcinoma: a rare case report and literature review

https://doi.org/10.21203/rs.3.rs-2484222/v1

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Background

Gastric adenocarcinoma is a common malignant tumor of the digestive system. Primary diffuse large B-cell lymphoma of the stomach is a common lymphoma originating from gastric submucosal lymphoid tissue, and the coexistence of diffuse large B-cell lymphoma and adenocarcinoma is exceedingly rare.

Case presentation:

A 58-year-old woman came to our hospital for treatment due to a choking feeling after eating. During endoscopy, multiple irregular ulcers were seen in the fundus and body of the stomach, and the surrounding mucosa was raised. The biopsy pathology showed poorly differentiated cancer, and the patient did not undergo immunohistochemical detection. Distal gastrectomy was performed. Pathological evaluation of resected specimens showed gastric tubular adenocarcinoma and GC diffuse large B-cell lymphoma. No migration was found at the junction of the two tumors, forming a collision tumor. The patient received two cycles of R-CHOP chemotherapy, and there is no recurrence at present.

Conclusion

We report a case of primary gastric adenocarcinoma colliding with GC-DLBCL. Clinicians and pathologists should pay attention to this issue to avoid missed diagnoses.

Gastric cancer

Collision tumor

Tubular adenocarcinoma

DLBCL

Case report

Collision tumors are defined as two types of independently occurring tumors that are in contact with each other or partially infiltrate and collide with each other[1]. Since the diagnostic criteria was presented by Spagnolo and Heenan in 1980[2], only dozens of cases of gastric collision cancers have been reported, including the collision between gastric adenocarcinoma and neuroendocrine tumor, the collision between gastric adenocarcinoma and MAILT, the collision between gastric adenocarcinoma and gastrointestinal stromal tumor, and the collision between gastric adenocarcinoma and gastric metastatic breast cancer[2–4]. Gastric cancer and diffuse large B-cell lymphoma are rare, with only a few cases reported[5]. Here, we report a case of collision between gastric adenocarcinoma and diffuse large B-cell lymphoma, but the preoperative endoscopic biopsy pathological diagnosis only showed poorly differentiated cancer. Therefore, clinicians and pathologists should be vigilant to avoid missed diagnoses to alleviate the suffering of patients and provide more accurate diagnosis and treatment for tumor patients.

On August 24, 2022, a 51-year-old female with a choking feeling after eating and epigastric dull pain and discomfort was treated at the Outpatient Department of Gastroenterology of the Affiliated Hospital of Chengde Medical College. The patient had a poor appetite and normal urine. The folds of the fundus and body of the stomach were thick, stiff, and poorly inflated. Multiple irregular ulcers and surrounding mucosal protrusions could be seen (Fig. 1A). Poorly differentiated cancer was considered in biopsy pathology, which requires immunohistochemical detection; however, the patient did not undergo immunohistochemical detection.

The patient was hospitalized on August 30, 2022. She had a history of cerebral infarction and hypertension. She had no history of alcohol use or smoking. She also denied recent ingestion of raw foods, overseas travel, or sick contacts. The patient’s family history was unremarkable, with no history of cancer in any blood relatives. Physical examination of the abdomen was unremarkable. The routine blood test results showed that the hemoglobin level (108 g/L) and lymphocyte ratio (4.0%) were decreased, and the white blood cell count (18.96 * 10 ^ 9/L) and neutrophil ratio (92.7%) were increased. Computed tomography (CT) reconstructed the gastric wall thickness, showing multiple ulcer-like changes in the gastric fundus and body and multiple lymph nodes around the cardia (Fig. 1B). Gastrointestinal radiography revealed that barium was slightly blocked through the cardia, the local lumen was irregularly narrow, and mucosal folds were interrupted and destroyed (Fig. 1C). The patient did not undergo immunohistochemical detection but directly underwent radical gastrectomy.

The patient underwent total gastrectomy with lymph node dissection. Macroscopic examination revealed an ulcerative mass measuring 4.5x3x0.3 cm. The dissected surface showed a yellow‒white area surrounding the area of the ulcer. The surrounding mucosa was grayish white with folds. Microscopically, hematoxylin and eosin (HE)-stained tissue sections showed two different types of tumors. One was germinal center type diffuse large B-cell lymphoma (GC-DLBCL), Lugano stage I, and the other was moderately differentiated tubular adenocarcinoma, pT1N0M0 (WHO stage) (Fig. 2A). The lymphoma component involved the mucosa, submucosa and muscle layer, without a complete lymphoid follicular structure or a germinal center, and diffuse infiltration of B cells could be seen. The components of adenocarcinoma were limited to the gastric mucosa and submucosa. The cancer cells were arranged into glandular and cribriform patterns, showing an infiltrative growth pattern. A large number of infiltrating lymphocytes was observed, and lymph follicles could be seen locally. The background mucosa gland was severe chronic atrophic gastritis with glandular intestinal metaplasia. No vessel or nerve invasion was found. No adenocarcinoma or lymphoma was involved in the lymph nodes. Serial sections of the area showed clear boundaries and no histological transition where the two lesions collided. On immunohistochemistry, immuno in situ hybridization: EBER (-). Immunohistochemistry and gene detection were carried out, and the immunohistochemical results were as follows: CK (epithelial component +), LCA (lymphoid tissue +), Vimentin (-), and Ki67 (adenocarcinoma: proliferation index approximately 80%; lymphoma: proliferation index approximately 90%); adenocarcinoma: PMS2 (-), MLH1 (-), MSH2 (+), MSH6 (+), and HER2 (0); lymphoma: CD3 (scattered+), CD5 (scattered+), CD20 (+), CD79a (+), CD10 (+), Bcl-6 (+), CD21 (+), CD23 (-), MUM1 (-), CyclinD1 (individual cells+), Bcl-2 (focal+), c-myc (-), and Helicobacter pylori (+) (Fig. 2B-F). The gene detection results were as follows: mutation of ERBB2 V8421, mutation of BRAF V600E, mutation of MLH1 163mfs * 6, mutation of PIK3CA K111E, and mutation of ARID1A Q1404.

Treatment: The patient underwent two cycles of R-CHOP chemotherapy. The patient developed a gastrointestinal reaction after medication, which improved after symptomatic treatment with metoclopramide.

Follow-up: At present, the patient's condition is stable without recurrence or metastasis.

Collision tumors refer to the contact or mixture of the tissues of two kinds of malignant tumors and are a special type of duplicate cancer. They are very rare in clinical practice, and the pathogenesis is still unclear. Collision tumors can occur in the esophagus, stomach, lung, uterus, kidney, rectum, brain, testis and other parts. The age of onset is generally older, with more males than females[6]. Gastrointestinal collision tumors are rare. Gastric adenocarcinoma with gastric mucosa-associated lymphoma is occasionally reported, and gastric adenocarcinoma with diffuse large B-cell lymphoma is very rare.

There may be common tumorigenic factors in gastric colliding tumors, such as gene mutation, H. pylori[7–9], Epstein‒Barr virus infection, and radiation exposure, but there is no clear test [11]. A Japanese study showed that H. pylori infection was associated with an increased risk of gastric malignant lymphoma. H. pylori-induced lymphoma is a multistep process involving H. pylori virulence factors (such as cagA, vacA and oipA), host factors and environmental conditions. In one study, samples from 23 patients with H. pylori-positive MALT lymphoma and 16 patients with H. pylori-positive gastric DLBCL were collected. CagA, (p) - S473-AKT, PTEN, SHIP and Cyclin A2 were detected by immunohistochemistry. It was found that the localization of cagA was related to the activation of the AKT pathway in MALT and DLBCL lymphoma cells[10]. CagA can directly penetrate the host membrane through interaction with phosphatidylserine, and then it disrupts cellular signal transduction in a way that may lead to tumorigenesis. In view of this, we detected H. pylori positivity in this patient. We found that chronic atrophic gastritis and intestinal metaplasia occurred in the background mucosa, and there was a large number of lymphocytes in the stroma around the gland, even forming lymphoid follicles. It is well known that H. pylori infection leads to chronic atrophic gastritis and intestinal metaplasia[8, 10] and eventually forms gastric cancer. Although chronic mucositis caused by H. pylori can also lead to atrophic gastritis, there is little evidence that atrophic gastritis plays an important role in the formation of gastric lymphoma. A study assessed the association between gastric mucosal atrophy and the risk of gastric lymphoma, and the results failed to show a statistically significant association between atrophic gastritis and the risk of gastric lymphoma. However, gastric MALT lymphoma, DLBCL and other lymphomas were positively correlated with H. pylori. These findings indicate that H. pylori infection can cause gastric lymphoma, but the epithelial changes caused by atrophic gastritis itself do not affect the development of gastric lymphoma. In summary, H. pylori is closely related to the occurrence of lymphoma and adenocarcinoma, that is, collision tumors. H. pylori can cause chronic inflammation of the mucosa. On the one hand, it can induce lymphoma; on the other hand, it can cause chronic atrophic gastritis and intestinal metaplasia, which can lead to gastric cancer.

The general treatment principle of collision tumors is the same as that of single cancers. Surgery is the main treatment, and adjuvant comprehensive treatment includes radiotherapy, chemotherapy, targeted therapy and immunotherapy. This patient underwent radical gastrectomy. The clinical staging on the Lugano system was stage I. Gastric adenocarcinoma belongs to the early stage. The treatment of gastric adenocarcinoma is mainly lymphoma supplemented by chemotherapy with the R-CHOP regimen. At present, the patient's condition is stable, and there is no recurrence. Studies have shown that gastric DLBCL with H. pylori-positive status often has lower invasiveness, less lymph node invasion, earlier clinical staging and a lower IPI score. It is more sensitive to chemotherapy, especially the treatment scheme containing rituximab. The CR, 5-year OS and PFS rates are better, showing a better prognosis[11–13]. Studies have shown that patients with primary lymphoma over 60 years of age, DLBCL, H. pylori infection, chemotherapy and stage II-IV disease have an increased risk of metachronous gastric adenocarcinoma. Therefore, for this patient, who had a history of H. pylori infection and radiotherapy and chemotherapy, H. pylori should be eradicated, and regular gastroscopic and imaging follow-up should be carried out to prevent recurrence of gastric adenocarcinoma.

Acknowledgments

The authors would like to thank Dr. Xinbin Shen, Department of Pathology, for his contribution to the pathological aspects of this case.

Authors’ contributions

Meiling Hao wrote the manuscript. Yuyang Zhao, Xingbin Shen and Chunhui Li critically reviewed the manuscript. All authors approved the final manuscript.

Funding

This study was supported by the 2020 Chengde Science and Technology Research and Development Plan Project (202006A042) and the Natural Science Foundation of Hebei Province (H2019406073).

Availability of data and materials

Not applicable.

Ethics approval and consent to participate

Not applicable.

Consent for publication

The patient provided written informed consent for the publication of this manuscript and images.

Competing interests

The authors have no competing interests to declare.

Author details

[author unit] Department of Pathology, Affiliated Hospital of Chengde Medical College, Chengde 067000, Hebei

[introduction to the first author] Meiling Hao (1989 -), female, Chengde City, Hebei Province, attending physician, mainly engaged in tumor diagnosis, email: [email protected], Tel.: 15632495450, Department of Pathology, Affiliated Hospital of Chengde Medical College, No. 36, Nanyingzi Street, Shuangqiao District, Chengde City, Hebei Province

Corresponding author: Chunhui Li (1965 -), male, chief physician in Chengde City, Hebei Province, mainly engaged in tumor diagnosis, email: [email protected], Tel.: 15633142839, Department of Pathology, Affiliated Hospital of Chengde Medical College, No. 36, Nanyingzi Street, Shuangqiao District, Chengde City, Hebei Province

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No competing interests reported.

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Gastric collision tumor with diffuse large B-cell lymphoma and adenocarcinoma: a rare case report and literature review

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