264. Lymphoid Histo, B Cell Lymphoma

Question 1

What are the functional compartments of the lymph node? (5)

Answer 1

1. Follicle: Mantle Zone (where naive B cells meet antigen), Germinal Center (proliferating centroblasts differentiate into antigen-specific B cells - centrocytes)
2. Marginal Zone: Memory B cells
3. Medulla: accumulation of mature B Cells
4. Paracortex: Mainly T cell area; site of entrance of all lymphoid cells and accessory cells - T/B cell interaction
5. Sinus: Macrophage area: “sieve” functions

Question 2

What are the common IHC markers for the following:

• All leukocytes
• B Cells (2)
• T Cells (Helper vs. Cytotoxic)
• Germinal Center B Cells
• Plasma Cells

Answer 2

CD45 - All leukocytes
CD20, Pax5 - B Cells
CD3, CD4/8 - T Cells
CD10 - Germinal Center B Cells
Ig Kappa/Lamda - Plasma Cells (abnormal ratio not 2:1 = monoclonal proliferation)

Question 3

What is the Staging for all B Cell Lymphoma (I - IV) and how does stage influence tx?

Answer 3

I: single LN region (or extranodal site - IE)
II: 2+ LN regions on same side of diaphragm (or extranodal side with 1+ LNs - IIE)
III: LN regions on both sides of diaphragm (or extranodal sites and LNs - IIIE)
IV: additional extranodal site with LNs

Type A: no sx
Type B: sx “B” sx include fatigue, weight loss, night sweats

Stage: IA/IIA - radiotherapy
Stage: IB/IIB/III/IV - chemotherapy

Question 4

Follicular Lymphoma

• cell of origin
• pt demo
• CP
• gene
• morphology
• markers
• prognostic factors

Answer 4

Origin: Germinal Center B Cell (centrocytes admixed with centroblasts)
Demo: Older individuals >50yo (rare younger)
CP: painless generalized lymphadenopathy; marrow involvement 80% at dx
Gene: t(14;18) = IgH-Bcl2 (increased anti-apoptotic expression)
Morph: nodular
IHC: CD20 (B cell), CD10 + BCL6 (Germinal Center B Cell)
Prognosis: worse with more centroblasts on biopsy (more aggressive; 30-40% pts progress to DLBCL

Question 5

Diffuse Large B Cell Lymphoma

• epi
• demo
• CP
• gene
• morphology
• markers
• prognostic factors

Answer 5

MOST COMMON type (35% non-Hodgkin Lymphoma in US)
Demo: Adults >50yo but can affect any age (15% are children)
CP: rapidly enlarging, sx mass at 1+ sites - can arise in ANY organ/tissue!
Gene: many
1. BCL2 (30%) - t(14;18) - some are transformed follicular lymphoma
2. BCL6 (33%) - oncogene
3. MYC (5-10%) - oncogene regulating cell growth
Morph: LARGE neoplastic cells, variable morph
IHC: CD20 (B Cell), variable CD10 (GC B), variable BCL6/BCL2/MYC (depending on mutation)
Prognosis: aggressive and fatal w/o tx; 60-80% remission rate with tx (combo chemo and anti-CD20); Stem cell tx for refractory/relapsed disease

Question 6

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

• difference in naming
• CP
• epi
• genes
• labs
• tumor behavior
• morph
• sites
• markers
• prognosis

Answer 6

CLL: when blood neoplastic cells >5000/uL
SLL: less in blood, more in tissue
CP: asx enlarged LN
Epi: MOST COMMON leukemia of adults in western world
Genes: BCL2 expressed highly, abnormal NFKB increases cell survival
Labs: hypoglobulinemia, autoAb’s (abnormal immune fx)
Behavior: indolent and SLOW GROWING (mutations increase survival, less so more proliferation)
Morph: blood - more small lymphocytes with condensed chromatin
LN - sheets of small lymphocytes
Sites: Marrow, spleen, liver
IHC: CD20 (B cell, variable), CD5 (T Cell marker! abnormal)
Prognosis: indolent, survival >10 years
Worse prognosis with TP53 mutation, small % transform to DLBCL (Richter transformation)

Question 7

Mantle Cell Lymphoma

• cell of origin
• demo
• CP
• genes
• morph
• markers
• prognosis

Answer 7

Origin: Mantle Cell (naive B cell in mantle zone of lymphoid follicles)
Demo: men >50yo
CP: fatigue, lymphadenopathy (with generalized disease involving LN, marrow, spleen, liver, GI tract)
Genes: t(11;14) = CyclinD1-IGH = drives cell growth (progression G1 to S)
Morph: diffuse or nodular; intermediately sized tumors with irregular nuclear contours
Markers: CD20 (B cell), CD5 (T Cell), Cyclin D1!, Ki67 (sign of actively proliferating cells, important prognostic marker - bad)
Prognosis: moderately aggressive, median survival 4-6 years

Question 8

Extranodal Marginal Zone Lymphoma

• CP
• pathogenesis
• cell of origin
• morphology
• markers
• prognosis

Answer 8

CP: swelling of salivary gland, thyroid, orbit or in setting of H. pylori gastritis
Pgen: arises and sustained by chronic inflammation or autoimmune disorder - starts polyclonal but then acquires driver mutations for neoplastic clone
Cell of origin: antigen-stimulated B cells
Morph: clonal B cells infiltrate epithelium of involved tissue - small lymphocytes with abundant cytoplasm/plasma cell differentiation
IHC: CD20 (B cell), CD5-, CD10- (not GC), May have H Pylori!
Prognosis: CURED with H Pylori tx or simple excision and radiotherapy

Question 9

Burkitt Lymphoma

• 3 types with CP
• overall CP
• genetics
• morphology

Answer 9

1. Endemic: Africa; maxillary/mandibular masses; EBV assoc
2. Sporadic: involving bowel, retroperitoneum, ovaries
3. Immunodeficiency related form (HIV, immunosuppression tx)
   CP: rapidly growing mass (FASTEST GROWING TUMOR - doubling time 24 hrs)
   Genes: t(8;11) = MYC!! oncogene causing more cell cycle progression, less apoptosis, more cell transformation
   Morph: intermediate round/oval cells with basophilic cytoplasm and cytoplasmic VACUOLES, admixed with phagocytic macrophages (STARRY SKY pattern)
   IHC: CD20 (B Cell), CD10 + BCL6 (GC B Cell), MYC