Intro to Lymphomas

Question 1

lymphomas - general overview

Answer 1

*heterogenous group of disorders
*many (over 90)
*due to multiple stages of normal lymphocyte development
*genetic abnormalities result in uncontrolled proliferation of neoplastic lymphocytes at a particular developmental stage

Question 2

primary lymphoid tissues

Answer 2

*bone marrow
*thymus

Question 3

secondary lymphoid tissues

Answer 3

*lymph nodes
*spleen
*tonsils
*clusters of lymphoid tissue in the GI and pulmonary tracts

Question 4

normal B cell development

Answer 4

*mature in the bone marrow
*enter the peripheral blood circulation and migrate to secondary lymphoid tissues

Question 5

composition of a normal lymph node

Answer 5

*cortex (primary & secondary follicles - B cells)
*paracortex (T cells, APCs, high endothelial venules)
*medulla (plasma cells & medullary sinuses)
*sinuses (macrophages, histiocytes that capture antigen and process it)

Question 6

normal lymph node cortex - primary vs. secondary follicles

Answer 6

*primary follicles contain naive B cells (have not been exposed to antigen yet)

*secondary follicles:
-B cells that are proliferating AFTER encountering an antigen
-naive B cells in secondary follicles get pushed to periphery and form mantle zone
-have germinal centers:
~dark zone: centroblasts
~light zone: centrocytes
~tingible body macrophages: destroy B cells with “wrong” antibodies

Question 7

normal T cell development

Answer 7

*lymphoid stem cells migrate to thymus via peripheral blood circulation (occurs even after puberty)
*thymic cortex: contains thymic epithelial cells that interact with lymphocytes to help them differentiate, leading to rapid proliferation
*thymic medulla: final development of T cells occurs here

Question 8

final destinations of mature T cells (based on alpha/beta vs. gamma/delta)

Answer 8

*if T cell receptor is produced from alpha and beta genes, then T cells primarily stay in the thymus
*if T cell receptor is produced from gamma and delta genes, then T cells primarily migrate to various places in body (GI tract, etc)

Question 9

how to distinguish between leukemia vs. lymphoma

Answer 9

*in both lymphoma and lymphocytic leukemia, the cancerous cell type is a lymphocyte, but:
-in LEUKEMIA, the cancerous cells are circulating in the blood
-in LYMPHOMA, the cancerous cells are only in the lymph nodes and are NOT circulating in the blood

Question 10

examples of non-hodgkin lymphomas

Answer 10

highly aggressive:
*Burkitt’s Lymphoma/Leukemia
*pre-B cell ALL/lymphoma
*T cell ALL/lymphoma

intermediate:
*mantel cell lymphoma

low grade:
*CLL/SLL
*mantle cell lymphoma

Question 11

follicular lymphoma - epidemiology

Answer 11

*most common low-grade non-Hodgkin lymphoma (22% of all new NHL diagnoses)
*incidence increases with age
-median age 60-70 years

Question 12

follicular lymphoma - overview

Answer 12

*“small cleaved cells”!!!
*mature-appearing
*flow cytometry: CD20+, CD10+, bcl-2+, CD5-
*B cell lineage

Question 13

follicular lymphoma - grading

Answer 13

*follicular lymphoma cells consist of centrocytes, the small cleaved cells, and centroblasts, the larger cells that divide more

*the larger the number of centroblasts, the more aggressive the follicular lymphoma (ie. more centroblasts indicate higher grade lymphoma)

Question 14

follicular lymphoma - lymph node appearance

Answer 14

*overall lymph node architecture is recognizable but:
-mantle zone is lost
-follicles start to merge together
-polarization of germinal center is lost
-paracortex is lost

Question 15

follicular lymphoma - genetic abnormality

Answer 15

*commonly associated with t(14;18)
*note, this is not diagnostic though

Question 16

follicular lymphoma - treatment

Answer 16

*not curable but very treatable (responsive to chemotherapy)
*like “mowing the grass”
*no definite standard of care
*treatments may range from watchful waiting to stem cell transplantation

Question 17

diffuse large B cell lymphoma - epidemiology

Answer 17

*most common of the intermediate grade lymphomas
*comprises ~30% of all new NHL diagnoses

Question 18

diffuse large B cell lymphoma - oveview

Answer 18

*CD19+, CD20+
*B cell lineage
*cells are larger than a normal lymphocyte
*no standard cytogenetics
*normal architecture is usually effaced (not preserved)
*often very responsive to chemo

Question 19

diffuse large B cell lymphoma - treatment

Answer 19

R-CHOP:
R = rituximab
C = cyclophosphamide
H = hydroxy-doxorubicin
O = oncovin (vincristine is the generic)
P = prednisone

Question 20

Burkitt’s Lymphoma - aggressiveness

Answer 20

*one of the fastest growing tumors that exist
*doubling time is 24-48 hours (FAST)

Question 21

Burkitt’s Lymphoma - 3 types

Answer 21

1. African (“endemic”) - affects jaw or facial bone
2. “American” (sporadic) - affects lymph nodes in abdomen & GI tract
3. immunodeficiency-associated

Question 22

African Burkitt’s Lymphoma - epidemiology

Answer 22

*usually 4-7 years of age
*male to female 2:1
*incidence is 50 times higher than in US
*involves bones of the jaw and other facial bones; kidneys, GI tract, other extranodal sites
*NOTE - EBV IS ALMOST ALWAYS FOUND

Question 23

sporadic Burkitt’s Lymphoma

Answer 23

*usually what we see in the US
*occurs worldwide, regardless of climate
*accounts for 1-2% of lymphomas in adults and up to 40% of lymphomas in children
*involves the abdomen, ovaries, kidneys, omentum, Waldeyer’s ring, and other extranodal sites
*30% of cases are EBV+

Question 24

immunodeficiency-associated Burkitt’s Lymphoma

Answer 24

*primarily occurs in patients affected with HIV
*also seen in allograft recipients, congenital immunodeficiency states
*accounts for 30-40% of all NHL in HIV+ patients

Question 25

Burkitt’s Lymphoma - diagnosis

Answer 25

*diagnose with tissue
*“starry sky” pattern; sheets of lymphocytes with “tingible body” macrophages
*~100% Ki-67 staining (Ki-67 stains for actively dividing cells)
*B cell malignancy: CD20+, CD10+, CD5-

Question 26

Burkitt’s Lymphoma - cytogenic abnormality

Answer 26

ALL have a cytogenic abnormality involving chromosome 8: c-myc

note - any translocation involving the c-myc gene on chromosome 8

Question 27

Burkitt’s Lymphoma - treatment

Answer 27

*treatment must begin immediately
*tx MUST include CNS PROPHYLAXIS (doses of chemo directly into CSF)
*these patients are at extremely high risk for spontaneous tumor lysis syndrome