A case report of diffuse large B-cell lymphoma and gastric signet ring cell adenocarcinoma in the same anatomic site: a clinical and management conundrum

Introduction

Second primary malignancies are uncommon, with reported incidence rates ranging from 1.3% to 5.8% (1). Several risk factors have been proposed, including viral infections, prior exposure to chemotherapy or radiotherapy, genetic susceptibility, smoking, and shared carcinogenic mechanisms among tumors with overlapping biological characteristics (1).

Gastric adenocarcinoma is infrequently associated with active synchronous, metachronous, or second primary cancers (1,2). When reported, colorectal carcinoma represents the most common secondary malignancy occurring in conjunction with primary gastric cancer (3). The occurrence of a synchronous or metachronous primary gastric lymphoma arising at the same anatomical site as a gastric adenocarcinoma is exceedingly rare. While isolated studies and case reports have described an association between extra-nodal lymphomas and subsequent development of gastric adenocarcinoma—particularly following lymphoma-directed therapy—clinical evidence supporting a direct causal relationship remains limited (4-6).

In this report, we describe an unusual case of a histologically confirmed signet ring cell carcinoma (SRCC) on initial biopsy of the stomach, with eventual demonstration of histopathological features consistent with diffuse large B-cell lymphoma (DLBCL) following gastric resection, identified nine months after the initial diagnosis. We present this case in accordance with the CARE reporting checklist (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-0308/rc).

Case presentation

We present a 67-year-old woman with multiple complex medical comorbidities, including single cecal hyperplastic polyp 5 years prior, Roux-en-Y gastric bypass 13 years prior, metabolic-associated steatotic liver disease, a 7.5-pack-year smoking history, smoking about 2 to 4 cigarettes a day, chronic opioid use for chronic musculoskeletal pain, and previous alcohol drinking which stopped 10 years prior. She was admitted following two weeks of intermittent, sharp, right lower quadrant abdominal pain and frequent, large volume, non-bloody, watery, secretory diarrhea. Figure 1 shows her clinical timeline.

Figure 1 Clinical timeline and history. CT, computed tomography; DLBCL, diffuse large B-cell lymphoma; PET, positron emission tomography; R-CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone.

Initial abdominal computed tomography (CT) imaging was concerning for possible ascending colitis. Clostridium difficile (C. diff) testing was nucleic acid amplification testing (NAAT) positive, but toxin negative. Due to her significant symptoms she was presumptively treated for active C. diff infection but diarrhea and abdominal pain persisted.

She had further extensive work-up without a clear etiology for her gastrointestinal symptoms, so an esophagogastroduodenoscopy (EGD) and colonoscopy were performed. The EGD showed mild gastritis in the gastric pouch but with otherwise normal esophagus, gastrojejunostomy anastomosis, and jejunal limb; the remnant stomach was not evaluated (Figure 2). Biopsies were taken from the site of mild gastritis and at random from the gastric pouch and the jejunal limb. Colonoscopy showed normal findings, so random biopsies evaluating for microscopic inflammation were also done.

Figure 2 Upper endoscopy images. (A) Upper endoscopic image of gastric pouch. (B) Upper endoscopic image of gastrojejunostomy anastomosis. (C) Upper endoscopic image of jejunal efferent limb.

Specimens from the gastric pouch showed a proliferation of rounded cells showing central mucin with eccentrically placed nuclei within the lamina propria, infiltrating the mucosa, consistent signet ring cells. The cells tested positive for cytokeratin 7 (CK7) and negative for cluster of differentiation 68 (CD68), overall consistent with SRCC, diffuse type (Figure 3). Mucin stains like Periodic Acid-Schiff (PAS) or Alcian Blue were not used as the immunohistochemical stains were felt to be sufficient by the consulting pathologist. It was reviewed by multiple pathologists who all confirmed the diagnosis. Biopsies from other sites were normal.

Figure 3 The biopsy from the gastric pouch shows a solid, “sheet-like” aggregate of signet cells which are CK7 positive infiltrating the mucosa. Tumor cells are round, relatively uniform, intermediate to large, with a single, central mucin droplet, which displaces the nucleus to the periphery. The mucin droplet has a finely granular, lightly eosinophilic appearance. The background gastric mucosa shows a sprinkling of plasma cells and lymphocytes. No acute gastritis, metaplastic changes, or Helicobacter pylori organisms are present. Immunohistochemical staining for CK7 demonstrates diffuse tumor positivity, which helps confirm the diagnosis of signet ring cell (“diffuse type”) gastric adenocarcinoma. CD68 (a histiocytic marker) is negative. (A) SRCC gastric biopsy (HE staining; 40× magnification). (B) SRCC gastric biopsy (HE staining; 100× magnification). (C) SRCC gastric biopsy (HE staining; 200× magnification). (D) SRCC gastric biopsy (IHC staining; 200× magnification with CK7 stain). (E) SRCC gastric biopsy (IHC staining; 200× magnification with CD68 stain). CD68, cluster of differentiation 68; CK7, cytokeratin 7; HE, hematoxylin and eosin; IHC, immunohistochemistry; SRCC, signet ring cell carcinoma.

Positron emission tomography/computed tomography (PET/CT) imaging did not show focal fluorodeoxyglucose (FDG) avid lesions. Endoscopic ultrasonography (EUS) showed non-specific thickening of the sub-mucosa with intact muscularis mucosa, and so was subsequently staged as Tumor, Node, And Metastasis (TNM) T1bN0M0 (stage 1A) SRCC. A diagnostic laparoscopic guided gastroscopy through a gastrotomy was performed with difficult visualization of the stomach due to difficulty with insufflation, but did not reveal any obvious tumors or abnormalities. Biopsies from the remnant stomach were negative for malignancy. This patient was discussed at the multidisciplinary tumor board where definitive surgical management for stage 1A SRCC was recommended. Her surgery was delayed by about 8 months due to multiple admissions for heart failure exacerbations and one instance of intestinal obstruction due to malrotation of the intestines and volvulus managed with reduction via laparotomy. She needed medical optimization of her co-morbidities to reduce the possibility of an adverse outcome from the gastrectomy. Within this timeframe her diarrhea had worsened but subsequently was controlled on round-the-clock loperamide in addition to her chronic opioid use that was increased for abdominal and chronic musculoskeletal pain control.

Finally, the patient underwent laparotomy with total gastrectomy including gastric pouch and remnant, esophagojejunostomy, and jejunostomy tube placement. The surgery was complex because of dense intra-abdominal adhesions attributable to prior gastric bypass surgery. Emergency splenectomy was performed due to intraoperative bleeding.

Final surgical pathology surprisingly demonstrated DLBCL involving the gastric wall with a linitis plastic-type growth pattern, with extension to the jejunal anastomosis, without splenic or lymph node involvement. Immunophenotyping positive for CD20, CD45, CD79a, and PAX5, and negative for CD3, CD30, CD138, Epstein-Barr virus-encoded RNA (EBER), AE1/AE3, MOC31, EP4, carcinoembryonic antigen (CEA); notably keratin negative (Figure 4). Helicobacter pylori (H. pylori) was negative. No residual adenocarcinoma was found despite extensive sampling. Multiple expert pathology review confirmed the diagnosis of gastric DLBCL in these specimens, as well as SRCC on the prior EGD biopsies, as both specimens were reviewed concurrently to confirm both diagnoses. Both specimens were confirmed to have come from the same patient, from the gastric pouch, and the slides from both cases were reviewed by the multi-disciplinary team as well as external pathologists to confirm the diagnoses.

Figure 4 Sections from the gastric resection specimen show involvement by DLBCL consisting of irregular, loose aggregates of large, atypical lymphocytes present within the submucosa and extending into the muscularis propria. Tumor cells have central irregular nuclei with coarsely granular chromatin, prominent central nucleoli, and small amounts of basophilic to amphophilic cytoplasm. The background gastric mucosa shows mild superficial chronic gastritis and foci of complete-type intestinal metaplasia without atypia. Notably, no residual signet ring cell adenocarcinoma is identified despite extensive sampling. Immunoperoxidase stains show tumor cell positivity against CD45 with dim CD20. No staining is seen against pankeratin AE1/AE3 cocktail, CD3, MOC-31, BerEP4, or CEA. Outside, expert hematopathology consultation was obtained with additional immunohistochemical staining demonstrating positivity of tumor cells against CD79a and PAX5. Tumor cells were negative for all other markers tested, which included CD3, CD30, and CD138. Immunohistochemical staining for EBER was likewise negative. (A) DLBCL gastric biopsy (HE staining; 100× magnification). (B) DLBCL gastric biopsy (HE staining; 200× magnification). (C) DLBCL gastric biopsy (IHC staining; 200× magnification with keratin AE1-AE3 stain). (D) DLBCL gastric biopsy (IHC staining; 200× magnification with CD45 stain). (E) DLBCL gastric biopsy (IHC staining; 200× magnification with CD20 stain). (F) Gastric biopsy (HE staining; 100× magnification showing intestinal metaplasia). CEA, carcinoembryonic antigen; DLBCL, diffuse large B-cell lymphoma; EBER, Epstein-Barr virus-encoded RNA; HE, hematoxylin and eosin; IHC, immunohistochemistry.

Following the diagnosis of gastric DLBCL, subsequent postoperative PET/CT did not show abnormal FDG uptake, and she was managed as stage IIE DLBCL. She was treated with six cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Her clinical course was complicated by recurrent heart failure exacerbations, infections, malnutrition, progressive deconditioning, and failure to thrive.

Post-treatment PET/CT scan done 3 months following her sixth cycle of R-CHOP did not demonstrate suspicious FDG uptake. A contrast enhanced CT of the chest, abdomen, and pelvis was also done due to the lack of suspicious FDG uptake in prior PET/CT scans despite the presence of disease. This showed a new 2.4 centimeter (cm) by 2.5 cm complex lesion in the superior pole of the left kidney which was not present on recent prior CT scans. Further evaluation was planned with magnetic resonance imaging (MRI) of the abdomen and an ultrasound. However, she passed away shortly afterwards following a decision to be placed on comfort measures after an admission with a fall with subsequent hemorrhagic shock and multi-organ failure.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

We present this unusual case of a patient who had biopsy pathology of SRCC and post-gastrectomy pathology of DLBCL within the same anatomical site and were found nine months apart. Both pathology specimens had distinct immunophenotyping and morphology that demonstrates they were completely different. Although rare, signet ring cell lymphomas (SRCL) have been described—most frequently in the context of gastric mucosa-associated lymphoid tissue (MALT) lymphoma and follicular lymphomas, and can be differentiated from SRCCs with the absence of keratin (7,8). B cell lymphomas which stained positive for keratins have been described in the literature (9); but in our case, subsequently diagnosed DLBCL cells were negative for CK7 in metastatic specimens in the gastric pouch and morphologically different from the initial SRCC specimens.

While other forms of indolent lymphomas do transform to DLBCL (10), this is not a phenomenon associated with gastric adenocarcinomas. Rarely are cases of DLBCL and other lymphomas co-existing with gastrointestinal adenocarcinoma or other non-hematologic malignancies reported (4,6,11-14). However, two things are peculiar in our case; first is the absence of the initial SRCC pathology on subsequent post-surgical specimens, and secondly, the identification of both cancers in the same anatomical site, albeit not at the same time. They also did not appear on both PET/CT images prior to treatment, which is unusual especially for DLBCL (15); we believe this to be due to the malignancies being low-bulk at the time of the first scan, or that the DLBCL developed just after the first PET/CT was done, and was subsequently completely or almost completely removed following the surgery before the second PET/CT scan was done where it was either very low-bulk or not present (Figure 1).

DLBCL can sometimes occur in the setting of chronic inflammation, such as in the context of an Epstein-Barr virus (EBV) infection (16), which was evaluated with EBER immunohistochemical stain in our case as negative, and so no further EBV testing was pursued as it ruled out an EBV-associated lymphoproliferative disorder. It is unclear if the presence of the SRCC within the gastric pouch led to chronic inflammation that favored the development of DLBCL within the same anatomical site. However, it would be unusual to have complete resolution of the prior SRCC pathology if this was the case. Spontaneous regression has however been noted with DLBCL (17), but it would be speculative to assume that this was what happened in our case. At this time, we do not have a concrete explanation for the SRCC absence on subsequent specimens, which admittedly added to the clinical challenge and conundrum of the case. Looking into what aspects of the tumor micro-environment, such as cell cannibalism (albeit without cell-in-cell appearance of the DLBCL cells) or nutrient starvation, that could also explain her case, is a considered research gap.

Management of synchronous malignancies poses a challenge especially if they are both active, as treatments can differ, with concerns of sub-optimal treatment and increased toxicity leading to morbidity and mortality (1). In our case, as the SRCC was staged as TNM stage 1A, surgical resection was assessed to be an ideal enough management (18). This allowed the choice of chemoimmunotherapy to be focused on management of DLBCL which she received with the R-CHOP regimen. Post-treatment PET/CT scans did not demonstrate abnormal FDG uptake, however a subsequent CT scan noted an incidental finding of a new complex lesion of the left kidney. As she passed away before further work-up could have been done, it is unclear whether the kidney lesion represents progression of the DLBCL which should ideally show as an abnormality on a PET/CT scan, a new primary malignancy, a benign lesion, or a recurrence of the prior SRCC; lack of a biopsy adds a limitation to the case’s finality.

Conclusions

We highlight an extremely unusual case of DLBCL found within the same anatomical site where an SRCC pathology was identified nine months prior. There may be a yet to be defined connection between both cancers that led to their development, identification of which could help understanding of the pathophysiological processes of both malignancies. We highlight how they were managed and the unusual aspects of the case.

Acknowledgments

We would like to thank Dr. Fisk for his contribution on the pathological descriptions of the specimens.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-0308/rc

Peer Review File: Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-0308/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-0308/coif). A.V.P. reports speakers bureau fees from AstraZeneca, BMS, and Regeneron. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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