1. MANTLE CELL Lymphoma (WITH EMPHASIS ON THE gi TRACT)
Scott R. Owens, M.D.

2. Unique to GI Or at least things that make it interesting….
Our “gross” is often the endoscopist’s description
We are often (usually) dealing with very small pieces of tissue
The GI tract is rife with inflammatory conditions that can result in lymphoproliferative disorders… and confound our diagnosis of them
The GI tract is also rife with normal populations of lymphoid tissue that can give rise to lymphoproliferative disorders…and confound our diagnosis of them!

3. Why lymphoma?
Primary GI lymphoproliferative disorders are fairly uncommon
About 1-4% of GI tumors
But…the GI tract is the most common extranodal site of lymphoma
4-20% of non-Hodgkin lymphoma
B-cell lymphoma most common
And…the development of lymphoma can complicate other disorders

4. GI Lymphoma Facts Distribution Stomach Small intestine Large intestine
Primary site in 55-65%
1-7% of all gastric malignancies
Small intestine
Primary site in 20-35%
About 25% of small intestinal malignancies
Large intestine
Primary site in 7-20%
About 0.5% of colonic malignancies
Other sites
Liver
Appendix

5. Distribution of GI Lymphoma
55-65%
20-35%
7-20%
Courtesy of Dr. Alyssa Krasinskas

6. Mantle Cell Lymphoma Definition
Monomorphous small/medium-sized lymphocytes
Resemble centrocytes (small follicle center cells)
Often with angular (not cleaved) nuclear contours
Centroblasts and paraimmunoblasts (prolymphocytes) are absent

7. Measuring Mantle Epidemiology Sites of involvement
Accounts for 3-10% of all non-Hodgkin lymphoma
Occurs in middle-aged and older individuals
Median age ~60 years
Males > females (about 2:1)
Sites of involvement
Most commonly affects lymph nodes
Extranodal sites
Commonly disseminates to spleen and bone marrow
GI tract is most common extranodal site (involved in up to 30% of MCL patients)
Many (but not all!) cases of lymphomatous polyposis are MCL
Waldeyer’s ring

8. Mantle Manifestations
Clinical manifestations
Most present at advanced stage (stage III or IV)
>50% have massive splenomegaly, marrow positivity

9. Mantle Morphology Morphology
Pattern can be diffuse, nodular, “mantle zone”
Mantle zone pattern has central follicle with neoplastic cells around it
Cells with irregular nuclei, often angulated
Resemble centrocytes, but usually not cleaved
Inconspicuous nucleoli
Small, hyalinized vessels are common
Large, epithelioid histiocytes may be scattered throughout (“pink histiocytes”)
May mimic “starry sky” pattern at low power
Non-neoplastic plasma cells may also be admixed

10. More Mantle Morphology
MCL does not transform to large cell lymphoma
Some cases (especially relapsed) can have aggressive features
Larger cells, fine chromatin
Blastoid MCL
Cells resemble lymphoblasts
Very high mitotic rate (usually >20/10 hpf)
Pleomorphic MCL
Cells with large, oval or irregular (possibly cleaved-appearing) nuclei
Prominent nucleoli
Beware diagnosing these as DLBCL!

11. Mantle Markers Immunophenotype Positive: Negative:
Surface IgM and/or IgD
CD19, CD20
CD5, CD43 (usually), FMC-7
bcl-2
Cyclin-D1
47 homing receptor on GI cases
Negative:
CD10, CD23 (usually), bcl-6
Occasionally CD5 (should still be cyclin-D1 positive)

12. Molecular Mantle Genetics Ig genes t(11;14)(q13;q32) Others:
IgH rearranged
Variable regions usually unmutated
Indicates pre-germinal center B-cells
t(11;14)(q13;q32)
Seen by classical cytogenetics in 70-95%
Involves the IgH and cyclin-D1 genes (PRAD1, bcl-1)
Seen in virtually 100% by FISH
Results in over-expression of cyclin-D1 mRNA
Others:
p53, p16, p18 may be mutated
Especially in blastoid variant
13q14 deletion
Total or partial trisomy of chromosome 12
Latter two also seen in CLL/SLL

15. CD20
CD3

16. CD5
Cyclin-D1