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GI Lymphoma

Overview

 Lymphoma are solid malignancies of lymphoid system –


Hodgkins(HL) and non hodgkins(NHL)

 HL is rare in GI tract

 Of all GI malignancy lymphomas – 1-4%

 GI tract is most common site of lymphomas after LN

 Majority of the GI lymphomas are B cell lymphoma


Bautista J gastro-onco 2012
Lymphoid cells array

 Lymphoid tissue in gut is near the mucosa and named as Mucosa


Associated Lymphoid Tissue(MALT) e.g. Peyer’s patches

 Germinal center – Ag exposed B cells – somatic mutation center 


become more Ag specific

 Marginal zone –
memory
cells’ residence

 Mantle – Naïve(unexposed) B
cells zone
Family of GI lymphomas
 Gastric –  Other sites
 Marginal Zone B cell lymphoma/ MALToma  Walyder’s ring
 Diffuse large B cell lymphoma(DLBCL)  Esophagus
 Uncommon types  Liver and biliary tree
 Small intestinal  Pancreas
 B-cell  Colon, rectum and anus
 IPSID
 Non-IPSID  Immunodeficiency – related
 MALToma  Post transplant
 DLBCL  HIV associated
 Mantle
 Follicular
 Burkitt’s
 T-cell
 Enteropathy associated T cell lymphoma
Distribution
More than 1 Rectum Diffuse
site 2% colonic
13% 1%

Ilececal
7%

SI
9%
Stomach
68%

Papaxoinis, Leuk Lymphoma


2006
Predisposing factors
 H. pylori infection
 Autoimmune diseases
 Sjogren’s
 RA
 SLE, Wegners in all these immunosuppressive Rx culprit
 Immunodeficiency/suppression
 Wiscot Aldrich
 SCID – severe combined immunodeficiency syndrome
 HIV
 Celiac disease
 Inflammator y bowel disease – controversial
 Nodular lymphoid hyperplasia
Staging

 Ann arbor staging for HL is inadequate for GI lymphoma

 Several alternatives available


 Paris staging
 Lugano

 Paris
 T1-T4 – mucosal to adjacent organ invasion
 N1-N3 – regional to extra abdominal spread
 M – mets non contiguous involvement
 B – bone marrow infiltration
S tag e I - The tumor is confined to the gastrointestinal tract. I t can
be a single primary lesion or multiple, noncontiguous lesions.
Stage l l - The tumor extends into the abdomen . This is further
subdivided based upon the location of nodal involvement:

•Stage I I 1 : Involvement of local nodes (paragastric nodes for


gastric lymphoma or para-intestinal nodes for intestinal
lymphoma)

•Stage I I 2 : Involvement of distant nodes (para-aortic, para


caval, pelvic, or inguinal nodes for most tumors; mesenteric
nodes in the case of intestina l lymphoma)

•Stage liE: The tumor penetrates the serosa to involve adjacent


organs or tissues

Stage m -There is no stage I I I disease in this system.

S ta g e IV -There is disseminated extranodal involvement or


concomitant supra-diaphragmatic nodal involvement.
Gastric lymphomas

 These are 5% of all gastric neoplasms

 Most of these (90%) are either MALToma or DLBCL

 Most common presenting symptoms


 Epigastric pain – 78-93%
 Anorexia – 47%
 Weight loss – 25%
 Nausea and vomiting - 18%
 Occult GI bleeding – 19%
Early satiety
 B symptoms – fever, weight and loss night sweats
 Hematemesis and melena are uncommon
Koch P J Clin Onco 2001
Pathogenesis

Immune response
Hp infection Hp specific T cell
and MALT formation

Somatic
Growth signals to B hypermutation in Ig
B cell proliferation
cells to increase Ag
affinity

Autonomy -
Continued B cell
Accumulation of Independence from
proliferation for
genetic aberrations T cell for growth
prolonged time
factors
Immuno-histochemistry and molecular
tests

 MALToma express pan B antigens


 CD 19, CD 20, CD 79a +ve
 CD 5, CD 10, CD23 cyclin D are absent
 Differentiation from B cells – MALToma are CD 43 +ve

 Molecular test
 PCR assay of immunoglobulin heavy chain assist in
documentation of monoclonality
 But monoclonality may also be seen in gastritis
 Not for practical purposes - reser ved for research
Diagnosis

 Clinical features as described earlier


 Median age 60 years
 Nearly 40 % of gastric lymphomas

 Endoscopy findings
 Er ythema
 Erosions
 Ulcers

 Most common in body, antrum and cardia


Biopsies

 Bx from both suspicious appearing and normal lesion – since lymphoma


can be multifocal with inter vening normal appearing mucosa, including
D2 and OGJ

 Aim for largest biopsy specimen as possible

 Conventional pinch biopsy may miss diagnosis, since lymphoma may


infiltrate s/mucosa without involving mucosa – more so when no
obvious mass

 Jumbo biopsy, snare biopsies, well technique and needle aspiration can
increase yield in suspected cases

 EUS guided Bx increase outcome


Additional work up
 Hp should be tested – HPE, fecal Ag test or breath test

 EUS for depth of infiltration and assessment of perigastric lymphnodes

 Additional staging CT – chest, abdomen and pelvis

 Bone marrow aspiration and Bx

 LDH and B2 microglobulin levels

 PET is not useful since MALToma have low uptake on FDG

 Optional pretreatment test – FISH/PCR for t(11:18)


Treatment

 Large RCTs to prove the best treatment are not available

 Trial of antibiotics for Hp eradication should be offered


to all even advanced disease can show regression

 When early stage disease fails [(or those with t(11:18)] on


antibiotic therapy, CT/ RT should be planned

 Nearly 75% respond over median of 5 months


Locally advanced disease
 T2 disease is a grey area best treatment as to surger y/CT/RT is under
debate

 All should receive antibiotics along with either of the theapies

Modality Cure Comment Event free Overvall


rate survival - survival
7.5y
Surgery – gastrectomy 80% ↓ QOL 52% 80%
Chemotherapy – 80- Acceptable S/E 52% 75%
Cyclophos/chlorambucil 100%
+fludarabine +/-
rituximab
Radiation – 30-40 Gy 90- Preserve gastric 87% 87%
100% function
Avlies, Med 2005
Diffuse large B cell
Lymphoma (DLBCL)
 Most common lymphoma of stomach – nearly 50% of all lymphomas

 Higher in developing countries, mean age 60 y, M>F

 Etiology is poorly understood

 Many large cell tumours(20-40%) are suspected to arise from


MALTomas

 But rest of the DLBCL have no e/o of low grade MALToma tissue

 Role of Hp is thus suggested in few cases


Pathology

 Microscopic examination

 Compact clusters, confluent aggregates or sheets of large cells


(immunoblasts like cells) and centroblasts

 IHC- CD 19,20,22 and CD79a positive and also CD45

 Differentiation from MALToma – BCL2 negative in DLBCL.


Clinical findings

 They may occur as large tumours and


may present with GOO

 Common sites are – antrum and body

 Appear as large ulcers, multiple shallow


ulcers

 May present as adenoca. like features


Other work up

 Hp detected in 35% more often in those which have evolved from


MALToma

 EUS for depth assessment

 Unlike MALToma PET-CT has special role in DLBCL, more sensitive than
BM biopsy

 Sns – 88.7% and Sps – 99.8% for detection of BM involvement

 BM negative - 13% patients detected +ve by PET


Adams, Eur J Nucl Med 2014
Treatment of DLBCL

 Current consensus – chemoimmunotherapy +/- RT

 Traditionally surger y was 1st choice – 70% stage 1 disease free for 5
years but 5% -10% risk mortality

Modality for localized 10 year event free 10 overall survival


dis survival
Surgery 28% 54%
Surgery+RT 23% 53%
Surgery+CT 82% Aviles Ann Surg 2004
92%
Chemotherapy 92% 96%
Chemotherapy DLBCL

 CHOP - R – Cyclophosphamide, Hydroxidoxorubicin, Oncovin,


Prednisone and Rituximab

 Standard regimen – for Lugano I and II for 3-4 cycles.

 For stage IV 6-8 cycles

 With any Hp evidence – antibiotics but alone not as treatment.


Persky J clini Onco 2008

 Previously feared concept of perforation with CT is seen in <5% of


patients.
Vaidya R, Ann Onco, 2013
Other GI sites
 Primar y hepatic lymphoma –
 M>F, median age 50

 Multilobulated mass or single or multiple nodules

 ∆ - Bx, to check Hep C if marginal zone lymphoma – response to Hep C Rx


documented also in splenic lymphoma
Salmon, Clin Lymphoma myeloma 2008

 Long term sur vival – after


surger y

 Chemo if DLBCL
 Primar y pancreatic lymphoma – presentation similar
to adenoca – pain, obs jaundice, chylous ascites
 HPE usually – DLBCL
 Rx – CHOP-R
 When Bil is high, stenting to ease chemo

 Colorectal lymphoma – MC site – cecum, most are


early stages
 Treatment - Resection followed by chemo
Gonzales, Am Surg 2008
Immunodeficency related
lymphoma
 Post transplant lympho-proliferative disease(PTLD)
 Seen in 0.8 – 20% pts. post transplant

 Highest after hear t-lung, also seen in BMTs

 Usually results from EBV transformed B cell proliferation

 HPE – polymorphic/ monomorphic

 May have symptoms like lymphoma depending on site

 Treatment – withdrawal of immunosuppression, CHOP regimen for


nonresponders, RT/Surg for localized disease

 Other modalities – EBV Rx – acyclovir, IFN- α, donor WBC infusions


HIV associated NHL
 Risk of B cell NHL high in HIV

 Presence of lymphoma is AIDS defining condition

 MC - DLBCL, HIV asso. NHL are typically aggressive

 Unusual site presentation – anus and rectum

 With low CD4 count chemo tolerance poor

 Malignant ascites may be due to body cavity lymphoma caused by


HHV-8 – kaposis Sa asso virus
 Disease progression rapid – sur vival few weeks- months
Brimo Cancer 2007
Thank You