This document discusses primary lymphomas of the gastrointestinal tract. It begins by providing background on lymphomas and noting that the gastrointestinal tract is a common extra-nodal site. The most common subtypes of primary GI lymphomas are then described, including their typical locations and risk factors. Diagnostic workup, staging systems, treatments, and outcomes are outlined for several subtypes affecting different areas of the GI tract, such as diffuse large B-cell lymphoma and MALT lymphoma in the stomach, and immunoproliferative small intestinal disease. Throughout, key points are illustrated with images and tables.

1. PRIMARY
LYMPHOMAS OF
GASTROINTESTINAL
TRACT
Presenter: Dr Harsh Shah
MS, FMAS, DNB, MCh(GI)
Kaizen Hospital
Ahmedabad

2. Abbreviations
DLBCL – Diffuse large B-cell lymphoma
MALT – Mucosa associated lymphoid tissue
MCL- Mantle cell lymphoma
FL – Follicular lymphoma
IPSID – Immunoproliferative small intestinal disease
EATL – Enteropathy associated T-cell lymphoma

3. Lymphoma
Hodgkin
Lymphoma
Non Hodgkin
Lymphoma(NHL)
Extranodal
NHL(33%)
Primary GI Lymphoma
30-45%
Nodal NHL
(67%)

4. Introduction
Usually secondary to widespread nodal disease
Gastrointestinal tract – most common extra-nodal site
Primary gastrointestinal lymphoma
- 1-4% of all GI malignancies
- 10-15% of all lymphomas
- 30-40% of all extra nodal lymphomas
Majority – Non Hodgkins Lymphoma [B cell- 90%]
Most common site – stomach (60-65%)
Rare sites – esophagus, pancreas, liver

5. WHO CLASSIFICATION
Diffuse large B cell lymphoma(50-55%)
Mucosa associated lymphoid tissue(MALT)lymphoma(15-45%)
Burkitt lymphoma(3-10%)
Follicular lymphoma(5-10%)
Mantle cell lymphoma
Enteropathy type T cell lymphoma

6. Preferred sites
MALT lymphoma – stomach
Mantle cell lymphoma – small intestine, colon
Follicular lymphoma – duodenum
EATL – jejunum
MALT lymphoma & follicular lymphoma- may be multifocal

7. Risk Factors
H pylori infection - stomach
C Jejuni – IPSID
EBV- Burkitt Lymphoma
Celiac disease – EATCL
HBV, HTLV-1
HIV, After organ transplantation

8. Diffuse Large B Cell Lymphoma
Most common GI lymphoma
Most common location – stomach, ileo caecal valve
High grade variety with aggressive course
2 subtypes – Germ center B cell & Activated B cell
Germ center type – mutation in anti apoptotic gene bcl-2 gene, t(14,18) –
worse prognosis
Activated B cell type – good long term survival
Treatment – chemotherapy (CHOP-R)

9. MALT lymphoma
Low grade, and mostly associated with H pylori infection (>90%)
Stomach is devoid of lymphoid tissue but is the most commonly affected site
(antrum & body)
Lymphoid follicles – develop due to H pylori associated gastritis
B cells in lymphoid follicle proliferate to develop lymphoma
Hallmark – presence of lymphoid clusters in mucosa
20-40% develop due translocation of t(11,18) – has more aggressive tumour
biology and poor response to H pylori eradication therapy
Treatment for early stage - H pylori eradication therapy

10. Burkitt Lymphoma
Association with EBV
Aggressive tumour with poor
prognosis
Terminal ileal mass in children &
young adult
Increased cellular turnover attracts
macrophages“Starry sky”
appearance - pathognomonic
Treatment – Chemotherapy
Starry-Sky Appearance

11. FOLLICULAR LYMPHOMA:
Mostly systemic disease, rarely involve GIT
Most common site - duodenum around ampulla of Vater
spontaneous regression, Can transform in to DLBCL
Multifocality
MANTLE CELL LYMPHOMA:
MCL does not usually infiltrate
Characteristically presentation - multiple lymphomatous polyposis of the
small and large bowel
Endoscopic resemblance to familial adenomatous polyposis

12. EXPRESSION OF COMMON MARKERS AND TRANSLOACTION IN SUBTYPES OF
GI LYMPHOMAS

13. Work-up
UGIE- multiple biopsies, examination of waldeyer’s ring
Immunohistochemistry for typing of lymphoma
FISH for detection of chromosomal translocations
H. Pylori testing – Breath test, Warthin-starry stain in biopsy specimen
If H pylori negative in biopsy – serology to identify true negativity
Serum LDH and beta-2 microglobulin levels

14. Work-up
CT scan of the chest, abdomen and pelvis
Bone marrow aspirate - involvement of lymphoma cells and monitoring
of treatment response
FDG-PET - significant advantage in staging of DLBCL, follicular
lymphoma and MCL (sensitivity = 80%, specificity =90% )
EUS – locoregional staging & response to therapy - superior to CT scan
for the T stage
Follow up - histological remission precedes the normalization of wall
changes - endoscopic biopsy better than imaging

15. Staging Systems

16. Symptoms
Stomach
N=277 (74%)
%
Small bowel
N=32 (9%)
Ileocecal
N=26(7%)
Pain 78 75 78
Loss of appetite 47 41 23
Weight loss 25 35 15
Bleeding 19 7 11
Diarrhea/constipation 3.6/3.2 12.5/25 19/23
Perforation 1.8% 9.4 -
B symptoms 11.9% 15.6 12
Median time to diagnosis
(days)
93 135 76
Male Sex (%)
M:F ratio
53
1.1
67
1.9
73
2.7
Age ,Median (range) 61.2 (20-88) 62 (16-81) 49 (19-77)
Primary Gastrointestinal Non-Hodgkin’s Lymphoma: Anatomic and Histologic
Distribution, Clinical Features,and Survival Data of 371 Patients Registered in the
German Multicenter Study; journal of Clinical Oncology 2003

17. Gastric Lymphoma
Most common site of extra-nodal primary GI lymphoma(60-65%)
Accounts for only <10% of all gastric malignancies
MC age of presentation – 60-70 years. M>F
MC site – Antrum & body
MC type – DLBCL(55%) followed by MALT lymphoma(40%), Burkitt’s(3%).
H pylori association – 85-90% of MALT lymphomas
H pylori is detected in 35% of DLBCL – indolent MALT component

18. Presentation – non specific – abdominal pain, early satiety, loss of weight.
Bleeding in 10-15% & perforation is rare(1%). B symptoms are less common.
DLBCL – de novo variety or from MALT lymphoma transformation
MALT lymphoma:
- t(11,18), t(1,14), t(14,18)
- t(11,18) – non responders to H pylori eradication
Gastric Lymphoma

19. ENDOSCOPY
Ulceration, thickened gastric folds,
polypoid mass, nodular lesion
Cannot distinguish from
adenocarcinoma
Multiple biopsies may be required
for diagnosis
Gastric Lymphoma

20. Gastric lymphoma Gastric adenocarcinoma
Wall thickening
Very thick (>3cm)
Diffuse or segmental
Less thick (<3cm)
Diffuse or segmental
Perigastric fat
planes
Preserved Lost
Lymphadenopathy
Common
May extend below renal
vein
Bulky nodes
Common
Not below renal vein
Less bulky
Extent
May extend into
duodenum
Never
CT Scan

21. EUS
Assessment of gut wall infiltration
and local lymph-node involvement
In assessing treatment response
Gastric Lymphoma

22. Treatment Of MALT Lymphoma
ERADICATION THERAPY:
H. PYLORI POSITIVE
• Stage I (OMC/OAC) - Eradication of H pylori - complete remission of gastric
MALT lymphoma ( 80%) MALT lymphoma in
• Breath test 3 months after treatment to confirm H. pylori eradication
• Repeat endoscopies with biopsies every 6 months for 2 years and then annually
to document remission of the lymphoma
• stage II – H. Pylori eradication therapy  re-assessment every 3 months
progression or persistent disease at 1 year CHOP-R
H. Pylori Negative or t(11;18) or Stage IV – CHOP-R

23. Treatment of DLBCL
Stage I & II: surgery vs. Chemotherapy vs. XRT : equally effective
Stage IV : Chemotherapy : (CHOP-R) 6-8 cycles + XRT
XRT – 30-40Gy in 20-3- fractions
Role of surgery: D2 gastrectomy
Stage I or II disease
Residual disease after chemotherapy
Complication - perforation

24. Small Intestinal Lymphoma
Primary malignant tumors of the small intestine rare
20%-30% of all primary G I lymphomas.
Presentation as perforation is more common(10-15%)
Sites
• Ileum - 60%-65%
• Jejunum -20%-25%
• Duodenum -6%-8%
Histological Subtypes
•Diffuse large B cell lymphoma-58%
•Low grade marginal zone MALT lymphoma-19%
•Burkitt’lymphoma-5%
•Mantle cell lymphoma-2.7%
•T-cell NHL-15 %
•IPSID-1.2%

25. CT Scan
Circumferential bulky mass in the
intestinal wall
May involve a relatively long Segment of
bowel and may ulcerate and perforate into
the adjacent mesentery
Obstruction uncommon, since tumor does
not elicit a desmoplastic response

26. Small Intestinal Lymphoma
BaMFT Double Balloon Enteroscopy

27. Treatment
Outcome poor compared to gastric lymphoma
DLBCL & MALT lymphoma:
Stage I (low grade) – surgery alone – resection with 10cm margin with
minimum of 12 L
Stage II and above & all high grade – CHOP with or without rituximab.
Surgery for complications and in bulky tumour to prevent perforation after
chemotherapy
H pylori eradication – duodenal MALT lymphoma
MCT, FL – primary modality is chemotherapy. Surgery for complications
Overall 5 year survival rate – 30-45%

28. Immunoproliferative Small Intestinal Disease
(IPSID)
Mediterranean lymphoma
Association with C jejuni
Also known as α-heavy chain disease due to heavy chain of the
immunoglobulin A (IgA) class produced by tumour cells
Affects the mucosa-associated lymphoid tissue (MALT)of the gastrointestinal
tract

29. Immunoproliferative Small Intestinal Disease
(IPSID)
Epidemiology: More commonly seen in
low socioeconomic status, poor sanitation
Young males (second or third decade)
Clinical Features: Illness-months’ to years’ duration
Chronic diarrhea
Malabsorption
Weight loss
Abdominal Pain
Physical examination
Cachecic Look (musle wasting)
Peripheral edema
Abdominal mass

30. IPSID
Campylobacter jejuni – biopsy specimen (2/3rd
)
Alpha heavy chain protein- 40-100%
Low serum Ig & albumin
Anemia, Hypocalcemia, Vitamin deficiencies
Giardia infestation

31. IPSID Vs Non-IPSID Primary Small Intestinal Lymphoma

32. IPSID
Early disease Advanced disease
Tetracycline+
metronidazole
Marked improvement after a
6-month course of antibiotic or
CR within 12 months
YES No
Maintenance antibiotic
CHOP +
Antibiotics
Surgery is usually reserved for a palliation of
obstructing tumor masses

33. Enteropathy-associated T-cell lymphoma
(EATL)
Tumour of intraepithelial T lymphocytes
6th
to 7th
decade; male predominance
Most common complication of celiac disease
Mainly localised in the jejunum, may be multifocal
Diagnosis
History & physical examination
CT/MR enterography, DBE + Biopsy
PET-CT may help

34. Treatment
Pre-op nutritional support
Debulking surgery
Adjuvant chemotherapy (CHOP)
Outcome is very poor with a 2-year survival rate of 15–20%

35. Colorectal Lymphomas
Accounts for 10-20% of all GI lymphomas
M>F ; 6th
decade
Third most common large bowel malignancy after adenocarcinoma and
carcinoid
Risk factors: Inflammatory bowel disease, Immunosuppressed states
DLBCL – most common variety. MALT lymphoma – next common, no
association with H pylori
The caecum is the most frequent location - probably due to the larger amount
of lymphoid tissue
Rectal involvement – 8.5 – 30%

36. Colorectal Lymphomas
Symptoms –
Abdominal pain and weight loss
Altered bowel habits
Lower gastrointestinal bleeding
Obstruction & perforation are rare
Colonoscopy
Large, polypoid lesions
Mucosal ulceration –less common
Lymphomatous polyposis – FL & MCL - can appear similar to familial
adenomatous polyposis

37. Colorectal Lymphomas

38. Colorectal Lymphomas
CT scan
Focal mass that infiltrates through
wall and form pericolic mass
An annular mass that can be
relatively smooth but non-
obstructing

39. Treatment of colorectal
lymphoma
Colonic lymphoma
Stage I – surgery
Stage II – surgery + adjuvant chemotherapy (CHOP-R)
Stage IV – chemotherapy (CHOP-R)
Rectal lymphomas – surgery followed by chemo + RT

40. Esophageal Lymphoma
< 1% of all gastrointestinal lymphomas
Primary esophageal lymphoma is extremely rare - less than 30 cases
reported in the literature
The majority are the DLBCL type of NHL
MC site – distal third of esophagus
dysphagia, odynophagia, weight loss, chest pain
complications such as hemorrhage, obstruction or perforation with a
tracheoesophageal fistula

41. Esophageal Lymphoma
Radiographic pattern - stricture, ulcerated mass, multiple submucosal
nodules, aneurysmal dilatation, and TEF
UGI scopy - nodule, polypoidal, ulcerated or stenotic – false negative rate
of 30% due to submucosal nature of lesion
CT scan/EUS – staging
Treatment – combination of R-CHOP with RT

42. Hepatic Lymphoma
PHL – rare
M>F, 5th
decade
Hepatitis C is found in 40%–60%, HIV, EBV
chronic antigenic stimulation may play a role
DLBCL – most common, followed by MALT lymphoma
Presentation – varies from asymptomatic to FHF
Variety – nodular or diffuse – no prognostic significance

43. Hepatic Lymphoma
Elevated LDH with normal alpha-fetoprotein
Multiple liver lesions > solitary lesions
CECT – hypodense lesion with central necrosis with peripheral rim
enhancement
MRI - hypo-intense T1-weighted images and hyper-intense T2-weighted
images
Liver biopsy remains the most valuable tool for diagnosis
Treatment – Anti-HCV therapy + R-CHOP + Radiotherapy

44. Primary Pancreatic Lymphoma
PPL – accounts for <2% of extra-nodal malignant lymphoma
<0.5% of all pancreatic masses constitutes PPL
Male preponderance M:F – 7:1
Majority are of DLBCL
Presentation – abdominal pain, mass, weight loss, acute pancreatitis
Jaundice – less frequent in PPL than adenocarcinoma
better prognosis and different management strategy in comparison with pancreatic
adenocarcinoma
Present with mass lesion – most common in head of pancreas(80%)

45. Primary Pancreatic
Lymphoma
bulky localised tumor in pancreas
without significant MPD dilatation,
bulky lymph nodes
Image guided FNAC, core biopsy
beta 2 microglobulin LDH level 
CA 19-9 – normal
Early Stage (I) - surgery
Advanced stage – CHOP-R

46. GB & EHBD Lymphomas
Very rare
Most common variety – DLBCL,
followed by MALT lymphoma
commonly associated with
gallstones & regional LN
involvement
FL & MCL – multiple polypoidal
lesions in GB
MC symptoms - cholecystitis
Bile duct lymphomas – Jaundice,
early presentation, good prognosis
Surgical resection f/b chemotherapy

47. International Prognostic Index – IPI
Risk factors
Ann Arbor stage III–IV
>1 extra-nodal site
High LDH
Age>60 years
Performance status >2 (ECOG)
Low risk= 0–1 risk factors
Low intermediate risk= 2 risk factors
High intermediate risk =3 risk factors
High risk =4–5 risk factors
5-year survivals of 73%, 51%, 43%, and 26%, respectively

48. SUMMARY
Gastrointestinal tract - most common extranodal site involved by lymphoma –
majority are NHL B cell type – most common variety is DLBCL
MC site in GIT – stomach, small intestine, colorectum
Non specific symptoms with no pathognomic imaging features
Histopathology & immunohistochemistry clinches diagnosis
In general, primary GI lymphomas are treated with chemotherapy with or
without RT
Surgical role – Early lesions & for complications

49. Thank You