The document discusses lymphoma of the gastrointestinal tract. It notes that extranodal lymphomas can arise in any tissue, most commonly the GI tract, and are often misdiagnosed due to nonspecific symptoms. Biopsies may miss the diagnosis, and larger biopsies or endoscopic ultrasound may be needed. Primary gastric lymphomas make up 5-10% of gastric cancers and are usually non-Hodgkin B-cell lymphomas. Microscopically, they are classified as low or high grade. Low grade lymphomas involve MALT and can be associated with H. pylori infection. High grade lymphomas are more aggressive and have a poorer prognosis.

1. Lymphoma of GI
tract
Dr. Umme Kulsum Munmun
Lecturer, Department of Pathology
Dhaka Medical College

2.  Extranodal lymphomas can arise virtually in any tissue, most
commonly in the GI tract
 easily misdiagnosed due to its nonspecific GI symptoms
 Moreover, conventional pinch biopsies may miss the
diagnosis
 often infiltrate the submucosa without affecting the mucosa

3.  most likely to occur when no obvious mass is present
 larger biopsy forceps, endoscopic ultrasound guided
biopsy, endoscopic submucosal resection may be required
to obtain adequate tissue for diagnosis
 repeated biopsy may also be required

4. Gastric lymphoma
 5-10% of all gastric malignancies are primary lymphoma
 Nearly all of the cases are of Non-Hodgkin type
 Large majority are of B-cell lymphoma

5.  They can be divided into two large categories
- Low-grade lymphomas, composed of small
lymphoid cells
- High grade lymphomas, composed of large cells
- Mixed small cell - large cell lymphomas also occur
 Often referred to as lymphomas of mucosa associated
lymphoid tissue (MALT) or MALTomas

7.  MALTomas /extranodal marginal zone B-cell lymphomas
arise at sites of chronic inflammation
 Can originate at the pre-existing MALT ; Peyer patches of
small intestine
 In the stomach, MALT is induced as a result of H. pylori
gastritis and is associated with most cases of gastric
MALTomas
 H. pylori eradication often results in durable remisions

8.  Three translocations are associated with gastric MALTomas
 t(11,18) – most common; creates a chimeric API2-MLT fusion
gene
 t(1,14) and t(14,18) – less common
 Net effect of these translocations are the constitutive
activation of NF- kB
 NF- kB is a transcription factor that promote B-cell growth
and survival

10.  Several endoscopic findings have been reported
 thickened gastric folds, mass lesions and nodules
 There may be mucosal - submucosal or transmural
involvement
 Common in distal half of the stomach, rarely affects the
antrum
 Indolent clinical course

13. Microscopy
Low grade lymphoma:
 Majority are ‘MALT type’ / extranodal marginal zone
lymphoma
 Dense infiltrate of small lymphoid cells, accompanied by
scattered reactive lymphoid follicles
 Various admixture of small lymphocytes, centrocyte-like
cells and monocytoid cells

14.  Neoplastic lymphocytes often infiltrate the gastric glands
to create diagnostic ‘lymphoepithelial lesions’
 Focal or extensive plasmacytoid differentiation
 Dutcher bodies (intranuclear eosinophilic inclusions made
up of immunoglobulin) are of diagnostic significance

15.  Adjacent mucosa has epithelial erosion, intestinal
metaplasia, H. pylori, lymphoid follicles, atrophy, atypical
regenerative changes, dysplasia
 Signet ring epithelial cells are present in one third cases in
superficial lamina propria associated with lymphoid areas

16. MALT lymphoma
monocytoid B-cells, centrocyte-like cells, small
lymphocytes, plasma cells, Dutcher bodies

17. MALT lymphoma
LEL

18. Grading system indicating the degree of certainty in diagnosis of
MALToma (Wotherspoon AC et al)
Score Diagnosis Histological features
0 Normal Scattered plasma cells in
lamina propria. No lymphoid
follicles
1 Chronic active gastritis Small clusters of lymphocytes
in lamina propria. No
lymphoid follicles. No
lymphoepithelial lesions
2 Chronic active gastritis with
florid lymphoid follicle
formation
Prominent lymphoid follicles
with surrounding mantle
zone and plasma cells. No
lymphoepithelial lesions
3 Suspicious lymphoid
infiltrate, probably reactive
Lymphoid follicles
surrounded by small
lymphocytes that infiltrate
diffusely in lamina propria
and occasionally into
epithelium
4 Suspicious lymphoid
infiltrate, probably
lymphoma
Lymphoid follicles
surrounded by centrocyte-
like cells that infiltrate
diffusely in lamina propria
and into epithelium in small
groups
5 MALT lymphoma Presence of dense infiltrate
of centrocyte-like cells in
lamina propria with
prominent lymphoepithelial
lesions

19. IHC
 Positive stains :
B cell markers: (CD19 , CD20, CD79a), CD43 (25%)
Monoclonal light chain restriction
 Negative stain:
CD5, CD10, CD23, BCL6, cyclinD1
 Molecular analysis:
to identify translcations
to demonstrate clonality

20. Differential diagnosis
 H. pylori gastritis
Features favoring MALToma:
 dense lymphoid infiltrate
 prominent LEL
 Dutcher bodies
 infiltration of muscularis mucosae
 atypia of lymphoid cells
 B - cell monoclonality
 Other low grade lymphomas
 Lymphoid hyperplasia (pseudolymphoma)
 Plasma cell granuloma

21.  A small proportion of gastric lymphomas are of follicular type,
composed of small cleaved cells and follicular pattern of
growth
 Mantle cell lymphomas may also occur, presents as multiple
lymphomatous polyposis of the GI tract

22. High grade (large cell) lymphoma:
 May be transformed MALToma cases - additional genetic
changes; inactivation of tumor suppressor genes that
encode p53 and p16
 Or arise de novo
 In the setting of immunosuppression (transplant recipients)
or inflammatory bowel disease – EBV positive

23.  Clinically resembles carcinoma, but better prognosis
 Grossly presents with large lobulated mass, superficial or deep
ulceration is common
 Gross or radiographic distinction from carcinoma may be very
difficult
 Advanced cases show full thickness invasion of the gastric
wall, direct extension to adjacent organs and involvement of
regional and retroperitoneal nodes

24.  Microscopically identical to diffuse large B-cell lymphoma
 composed of large non-cleaved cells (centroblasts) with
slightly more abundant cytoplasm
 Plasmablastic or immunoblastic appearance
 Multinucleated cell forms resembling Reed-Sternberg cells

25. Large B-cell lymphoma of stomach

26. Differential Diagnosis:
Undifferentiated carcinoma
Features favoring high-grade lymphoma:
- lack of continuity between epithelium and tumor cells
- lack of acinar patten
- preservation of muscularis mucosae fibres

27. IHC
 Positive stains :
Leukocye common antigen (LCA)
B cell markers: CD19 , CD20, CD79a
CD 10, BCL6
 Negative stain:
Epithelial markers: cytokeratin

28.  Favorable prognosis:
- small tumor size
- superficial mural invasion
- presence of low-grade MALT-type areas
- absence of regional lymph node involvement
 Poor prognosis:
- tumors located in lesser curvature

29. Rare types of lymphoma:
 Anaplastic large cell lymphoma
 Peripheral T-cell lymphoma
 Hodgkin lymphoma

30. Intestinal lymphoma
Factors to be considered :
 Patient’s age
 Site of involvement
 Primary versus systemic nature of disease
 Cell lineage (B, T or NK cell)
 Presence and type of an associated and/or predisposing
condition

31.  Most of the cases occur in middle aged people, ileocecal
region is the common site of involvement
 60-80% primary intestinal lymphoma – B cell type
 Burkitt lymphoma - usually in children
 Patients with celiac disease- proximal jejunum

32. T-cell malignant lymphomas
 Mostly arises as a complication of long standing celiac sprue or
related malabsorption syndrome
 Referred to as enteropathy associated T-cell lymphomas
 Clinical course - aggressive
 Cell of origin- intestinal intraepithelial lymphocytes
 Grossly, tend to involve the small bowel in a widespread, patchy
fashion causing ulceration, stricture formation and perforation
 Microscopically, the process is gradual

33.  Begins as a mixed cell infiltrate in the lamina propria with
increasing numbers of atypical large lymphoid cells
 Ends as a large cell lymphoma
 abundant intraepithelial T cells, often infiltrating the individual
crypt epithelium; villous atrophy may be present
 Atypical binucleated or multinucleated cells may be present,
may lead to a mistaken diagnosis of Hodgkin lymphoma
 Admixed eosinophils and histiocytes are common

34. Enteropathy associated T-cell lymphoma

35. Enteropathy associated T-cell lymphoma

36.  Typically express
- CD3
- CD103 (marker of intraepithelial lymphocyte)
- but not CD5

37. Two forms of enteropathy associated T-cell lymphoma are
recognized
• type I (classical): shows the morphologic features
described above, exhibits CD4-, CD8- and CD56
immunophenotype
• type II (monomorphic): no clinical evidence of celiac
disease, monotonous infiltrate of small to medium
sized cells with few admixed inflammatory cells,
exhibits CD4-, CD8+, CD56+

38.  Some T-cell lymphomas of the small bowel are analogous to
the NK/T-cell lymphomas of the sinonasal region
 These tumors have angiocentric qualities
 Associated with EBV
 Tumour cells are CD56 positive

39. B-cell malignant lymphoma
 Large majority arise from mucosa associated lymphoid
tissue
MALToma:
 Low-grade marginal zone B-cell lymphoma of ‘MALT’ type is
not so common in intestine as in stomach
 Its gross, microscopic and immunohistochemical features
are similar to those of its gastric counterpart

40. Immunoproliferative small intestinal disease (IPSID):
 Distinct type of B-cell lymphoma of small bowel
 Special form of MALT lymphoma
 Also known as Mediterranean lymphoma and Middle Estern
lymphoma
 Patients may have a short history of diarrhea and
malabsorption, but the mucosa is not completely flat in most
cases
 Initially responds to tetracyclin
 Two forms: low grade and high grade

41.  In low grade forms, biopsies of small bowel and lymph nodes
show a heavy lymphoplasmacytic infiltration
 Cells appear mature or only slightly immature
 Presence of monoclonal alpha heavy chains of
immunoglobulin in their cytoplasm, as well as in the serum
and urine
 Also called ‘heavy chain disease’

42.  The high grade form of the disease is usually preceded and
accompanied by the low-grade form
 Grossly, presents as diffuse thickened folds with small
nodules or discrete tumor growths
 Microscopically appears as a highly pleomorphic large cell
lymphoma with immunoblastic and plasmacellular features

43. Follicular lymphoma:
 Common in terminal ileum
 Grossly, presents as innumerable small polypoid masses
throughout the bowel, a condition known as ‘lymphomatoid
polyposis’
 Histologically, confined to mucosa and/or submucosa, low
histologic grade with BCL2 expression

44. Diffuse large B-cell lymphoma:
 Common in ileum, followed by the jejunum and
duodenum
 Grossly, they can show a diffusely infiltrating mass
with a garden hose appearance, a bulky tumour mass
with extensive ulceration, or a predominantly
polypoid mass
 Regional lymph nodes are involved in approximately
half of the patients
 Most cases have a germinal center phenotype

45. Mantle cell lymphoma:
 Uncommonly occurs as a primary tumour
 Intestine is infiltrated as part of systemic involvement
 Multiple lymphomatous polyps similar to that of
follicular lymphoma

46. Other rare types:
 Burkitt lymphoma
 Hodgkin lymphoma
 Anaplastic large cell lymphoma
 Post-transplant lymphoproliferative disorders
 Lymphoid hyperplasia