J Hematol

Journal of Hematology, ISSN 1927-1212 print, 1927-1220 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Hematol and Elmer Press Inc

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Review

Volume 14, Number 6, December 2025, pages 281-296

Primary Gastrointestinal B-Cell Lymphomas: A Clinicopathological Review

Figures

Figure 1. Representative pathology image of a gastrointestinal follicular lymphoma. (a) Low power view of the colon biopsy with a polypoid appearance due to the underlying lymphoid infiltrate. The neoplastic lymphocytes are arranged in a follicular/nodular architecture and are based in the lamina propria with focal extension into the mucosa and submucosa (H&E, × 4). (b) High power view showing a mixture of small elongated cleaved cells (centrocytes) and large round/oval cells with prominent nucleoli (centroblasts) (H&E, × 40). The neoplastic lymphocytes show co-expression of both BCL6 (c, × 4) and BCL2 (d, × 4). H&E: hematoxylin and eosin.

Figure 2. Representative case of a primary gastrointestinal mantle cell lymphoma. (a) Low power view shows a nodular lymphocyte infiltrate in the lamina propria of a colon biopsy (H&E, × 4). (b) The neoplastic lymphocytes are small to medium sized with angulated nuclei (H&E, × 40). These cells are positive for CD5 (c, × 20) and cyclin D1 (d, × 20). H&E: hematoxylin and eosin.

Figure 3. Representative case for extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue in the stomach. (a) Low power view showing a diffuse lymphoid infiltrate in the mucosa, submucosa and lamina propria (H&E, × 4). (b) High power view of the neoplastic lymphocytes that appear small to medium sized with some showing a monocytoid morphology. The neoplastic lymphocytes are noted infiltrating in and around the glands forming lymphoepithelial lesions (H&E, × 40). (c) CD20 highlights the neoplastic lymphocytes confirming their B-cell lineage (× 5). (d) H. pylori immunohistochemical stain is positive (red arrow) (× 40). Molecular studies for B-cell clonality were also positive. H&E: hematoxylin and eosin.

Figure 4. Representative image of a diffuse large B-cell lymphoma involving the small bowel. (a) Low power view showing sheets of neoplastic lymphocytes with full thickness involvement of the bowel wall and surface ulceration of the mucosa (yellow arrow). A few normal appearing lymphoid follicular are noted at the right edge (red arrows) (H&E, × 1). (b) The cells are growing in sheets and appear large and pleomorphic with scattered atypical mitotic figures (H&E, × 40). (c) CD21 stain highlighting the lack of follicular dendritic meshwork and intact meshwork (orange arrow) in the benign lymphoid follicles (acting as an internal control) (× 1). (d) The Ki-67 proliferative index is high reaching around 70% (× 40). H&E: hematoxylin and eosin.

Figure 5. Representative case of a Burkitt lymphoma involving the stomach. (a) The endoscopic image of the stomach mass with central ulceration. (b) Low power view of a neoplastic lymphoid proliferation in sheets involving the mucosa of the stomach and infiltrating around the glands (H&E, × 4). (c) Higher power image of medium sized neoplastic lymphocytes with cytological atypia and scattered apoptotic bodies showing a “starry sky” appearance (H&E, × 20). The neoplastic cells are positive for CD20 (d, × 40), CD10 (e, × 40) and Epstein-Barr virus-encoded RNA (EBER) in situ hybridization (f, × 40). H&E: hematoxylin and eosin.

Figure 6. Representative case of a plasmablastic lymphoma. (a) Highlights sheets of neoplastic proliferation of medium to large immunoblasts and plasmablasts (with eccentric nuclei). They are exhibiting cytotological atypia with prominent nucleoli. Foci of apoptotic debris are noted reminiscent of that seen in Burkitt lymphoma (H&E, × 40). The neoplastic cells are negative for CD20, a B-cell marker (b, × 40). They are positive for CD138, a plasma cell marker (c, × 40). They are also positive for c-MYC (d, × 40). H&E: hematoxylin and eosin.

Figure 7. Representative case of an EBV-positive diffuse large B-cell lymphoma subtype of the monomorphic post-transplant lymphoproliferative disorder. The patient had a history of solid organ transplant. (a) Low power view of a small bowel resection showing a transmural, diffuse, and partially nodular proliferation of neoplastic lymphoid cells (H&E, × 0.5). (b) High power view demonstrating large neoplastic cells with predominantly centroblastic morphology seen infiltrating around the intestinal glands. Mitotic figures and apoptotic bodies are present (H&E, × 40). (c) CD20 stain highlights the neoplastic cells, confirming B-cell lineage (× 1). (d) Epstein-Barr virus encoded RNA (EBER) in situ hybridization is positive in the majority of the neoplastic cells (approximately 90%) (× 1). H&E: hematoxylin and eosin.

Table

**Table 1.** Summarized Key Characteristics of Gastrointestinal B-Cell Lymphomas
	Follicular lymphoma	Mantle cell lymphoma	MALT lymphoma	Diffuse large B-cell lymphoma	Burkitt lymphoma	Plasmablastic lymphoma	Post-transplant lymphoproliferative disorder
BTK: Bruton’s tyrosine kinase; CHL: classic Hodgkin lymphoma; EBV: Epstein-Barr virus; GI: gastrointestinal; GCB: germinal center B-cell-like; H. pylori: Helicobacter pylori; HHV-8: human herpesvirus-8; HIV: human immunodeficiency virus; HSCT: hematopoietic stem cell transplant; IHC: immunohistochemistry; MALT: mucosa-associated lymphoid tissue.
Clinical presentation	Typically asymptomatic, incidental	Variable, non-specific	Gastric may be asymptomatic; intestinal may have pain/abnormal bowel habits	Variable, non-specific, high rate of perforation	Rapidly enlarging mass, pain, obstruction, intussusception	Diarrhea, abdominal pain, B symptoms	Variable/non-specific symptoms; history of solid/hematopoietic transplant
Common location	Small intestine, particularly duodenum	Lower GI tract	Stomach	Stomach more common than intestine	Ileocecal region	Any; colon more common in HIV - patients	Stomach and small intestine
Etiological factors/pathogenesis	BCL2 translocation t(14;18)	CCND1 translocation t(11;14)	H. pylori (gastric), t(11;18) (gastric), Campylobacter jejuni (small intestinal)	H. pylori in gastric type; EBV in general	EBV; plasmodium falciparum; HIV; MYC translocation t(8;14)	IGHV rearrangements, MYC translocations, PRDM1/Blimp1 mutations, EBV infection (especially in HIV+)	EBV (mainly); additional: hepatitis C and HHV-8 infection
Histopathology	Follicular or nodular pattern, mixed centrocytes and centroblasts	Nodular infiltrate; small-medium cells	Monocytoid lymphocytes, infiltration of reactive follicles	Sheets of atypical large lymphoid cells, usually centroblastic or immunoblastic	Sheets of medium-sized cells, multiple nucleoli, basophilic cytoplasm, “starry-sky” pattern	Sheets of large neoplastic cells, plasmablastic and immunoblastic morphology	Variable; non-destructive, polymorphic, monomorphic, CHL, mucocutaneous ulcer subtypes
IHC	CD10+ CD5- BCL6+ BCL2+	CD5+ Cyclin D1+ SOX11+	CD5- CD10-	Variable based on GCB vs. non-GCB phenotype; high Ki-67	CD10+ BCL6+ MYC+ High Ki-67 CD5- BCL2-	CD38+ CD138+ Kappa/lambda restriction High Ki-67 CD20- Weak B-cell markers	Variable based on subtype
Treatment	Watch and wait mainly; chemotherapy and immunotherapy	Observation in limited disease, chemo-immunotherapy, novel BTK inhibitors, venetoclax and lenalidomide and auto-HSCT; rituximab maintenance in older patients (not eligible for HSCT)	Variable; H. pylori eradication; observation; surgery; radiotherapy; chemotherapy and immunotherapy	Surgery, chemotherapy and immunotherapy, radiotherapy, H. pylori eradication	Multiagent chemotherapy	Palliation, chemotherapy, HSCT	Reduction of immunosuppression, chemotherapy and immunotherapy, EBV-specific T-cell immunity or donor lymphocyte infusions
Prognosis	Generally favorable; better prognosis with duodenal involvement	Intermediate (potentially favorable with newer therapies/HSCT)	Typically indolent	Favorable compared to primary nodal subtypes	Worse in gastric type vs. intestinal; responds well to chemotherapy	Unfavorable, aggressive	Unfavorable