Peripheral B Cell malignancies Flashcards
Most common leukemia of adults in western world
Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic LTerminology & Epidemiology
Same morphology and immunophenotype of malignant cells but with two different clinical presentations
CLL if initially presents with >5000 abnormal B cells/uL blood
Same features but count < 5000 = monoclonal B-cell lymphocytosis
SLL if presents initially as malignant lymphadenopathy
ymphoma (SLL)
Small Lymphocytic Lymphoma
Diffusely effaced lymph node architecture
- Proliferation centers -prominent mitotically active foci with prolymphocytes
- Pathognomonic for SLL
Small (6-12 micron) lymphocytes with irregular nuclear chromatin
Variable numbers of prolymphocytes & rare large immunoblasts
Chronic Lymphocytic Leukemia
- Irregular nuclear chromatin
- Smudge cells
Peripheral blood and bone marrow lymphocytosis with small lymphocytes
Hemolytic anemia and/or thrombocytopenia in some patients
soccer ball/ petoskey stone/ turtle shell pattern
small lymphocytic lymphoma
CBC reveals anemia with anisocytosis, spherocytes, doublets, schistocytes, a mildly elevated WBC count due to lymphocytosis with lymphocytes with irregular lymph chromatin and an elevated erythrocyte sedimentation rate.
Follow up reveals a low serum haptoglobin level.
What is this?
Chronic lymphocytic leukemia (CLL)
Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma Immunophenotype
+ for CD19 and CD20
Classic finding is presence of T-cell marker CD5 on cells and also expresses CD23
Some CD38+
Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma Cytogenetics/Molecular Genetics
Chromosomal translocations are rare but can have
Poor prognosis- trisomy 12q and deletions of 11q, 12q,17p
Good prognosis- deletion 13q (LUCKY 13)
Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma Clinical Features
Onset > age 50 (median age 60)
Male predominance 2:1 Often asymptomatic May have hypogammaglobulinemia (↑bacterial infections) May have small monoclonal Ig peak by electrophoresis CLL/SLL disrupts normal immune function (infections)
*** 10-15% patients have autoantibodies produced by non-neoplastic cells to red cells and/or platelets
Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma Prognosis
50-60% have mutated IGVH* (memory-post GC)
– live >24 years
ZAP 70-, CD38-
40-50% have unmutated IGVH* (naive-pre GC)
– live mean of 7 years
ZAP 70+, CD38+
Indolent clinical course
Responds poorly to treatment
Diffuse involvement of marrow and/or high serum Beta-2 microglobulin - worse prognosis
- Immununoglobulin variable region heavy chain
Prolymphocytic Transformation (Leukemia) (CLL/ SLL)
a rare transformation with worsening of cytopenias
Richter Transformation (Syndrome) (CLL/ SLL)
into Diffuse Large B-cell Lymphoma (3%) or EVB+ Hodgkin Lymphoma (0.5%) with more aggressive course
Follicular Lymphoma frequency
“most common form of indolent lymphoma” = most common of the lymphomas that will not kill you quickly
Follicular Lymphoma Two cell types:
and grading
Centrocytes - small cleaved
Centroblasts - Larger cell with open nuclear chromatin & ↑cytoplasm
Grade given based on number of centroblasts (grade 3: >15 centroblasts/HPF)
Follicular Lymphoma Immunophenotype:
+ for CD19, CD20, CD10 (CALLA) and sIg
+ for BCL2 (apoptosis antagonist), BCL6
Follicular Lymphoma Clinical Features/Prognosis
extranodal sites uncommon
Median survival 7 – 9 years (incurable)
Transformation occurs in 30-50% of patients
Usually to Diffuse Large B-Cell Lymphoma
Following transformation, survival under 1 year
Diffuse Large B-cell Lymphoma Morphology
Large size neoplastic lymphocyte
Diffuse pattern of growth
Tumor cells have large nuclei, open chromatin, and prominent nucleoli
Diffuse Large B-cell Lymphoma Immunophenotype
and Cytogenetics/ molecular genetics
+ for CD19, CD20, sIg
Variable expression germinal center markers (CD10, BCL6)
** dysregulation BCL6, a DNA-binding zinc-finger
transcriptional regulator inhibits expression of factors that regulate differentiation
inhibits p53 activity
Diffuse Large B-cell Lymphoma Clinical Features
Typically present with rapidly enlarging often symptomatic mass at a single nodal or extranodal site
Oropharynx (Waldeyer ring, tonsils, adenoids) common site
Diffuse Large B-cell Lymphoma Important Clinical Subtypes and prognosis
Mediastinal large B-cell lymphoma- young women with involvement of viscera and CNS
Immunodeficiency-associated large B-cell lymphoma – occurs in end-stage HIV infection or bone marrow transplantation plus Epstein-Barr Virus
Body cavity large cell lymphoma (Primary effusion lymphoma): associated with KSHV/HHV-8 in HIV patients
Prognosis: 60-80% remission (~50% of these cured)
Burkitt Lymphoma Three types
(different demographics - same histologic findings)
African
- EBV positive
- Jaw and viscera involvement
Sporadic US (nonendemic)
- Most EBV negative
- Abdominal masses (ileocecal involvement most frequent)
- Bilateral breast, ovaries
Immunodifficiency-associated
- In association with HIV infection
- May be initial manifestation of AIDS
- Highly aggressive lymphoma
Burkitt Lymphoma Morphology
** “Starry Sky”
Involved tissues effaced by diffuse infiltrate neoplastic lymphocytes
Intermediate-sized lymphocytes (10-25 micron in diameter) and moderate amount of amphophilic or basophilic cytoplasm
High mitotic rate (Warburg effect with aerobic glycolysis and high biosynthesis)
Apoptotic tumor cell death (“Starry Sky” pattern)
Marrow and blood rarely involved
Burkitt Lymphoma Immunophenotype
Hypermutated mature follicular center B-cells with surface IgM, kappa or lambda light chains and + for IgM, BCL6, CD19, CD20 and CD10
Mantle Cell Lymphoma morphology
Onset 5th to 6th decade
Morphology: Homogenous population small cleaved lymphocytes resembling the normal mantle B-cells that surround the follicular center
Mantle Cell Lymphoma Cytogenetics and Molecular Genetics and immunophenotype:
t(11:14) translocation involving the Cyclin D1 (cell cycle regulator promoting G1→S phase) locus on 11 and IgH locus on chromosome 14
Classical nodal (90%) Leukemic nonnodal (10%) - Hypermutated cell
Immunophenotype: * Cyclin D1, * CD5,
(CD19, CD20, BCL2, and moderately high levels of surface immunoglobulin (IgM or IgD), but CD23-, CD10-)
Mantle Cell Lymphoma Clinical Features
Presents with painless lymphadenopathy +/- peripheral blood involvement
Signs/symptoms of splenomegaly
Extranodal GI involvement commonly seen
Sometimes presents as ***lymphomatoid polyposis
Prognosis: Aggressive, Median survival only 3-4 years
Marginal Zone Lymphoma terminology, location, pathogenesis
(MALT Lymphoma when in GI Tract, BALT when in bronchial tissue)
Terminology: Initially recognized in mucosal sites and referred to as MALTomas or mucosal-associated lymphoid tissue lymphomas
Body Location and Morphology: Extranodal (GI & Spleen) and/or lymph nodes
Remain localized for long periods, spreading systemically only late in course
If gastric, may regress if inciting agent (H. pylori) is removed
Marginal Zone Lymphoma Immunophenotype
[nothing here really helps us]
Positive CD19, CD79a, BCL2
Negative CD5, CD10, CD23, cyclin D1
Marginal Zone Lymphoma genetics and prognosis
No translocations initially but later can develop;
t(11;18) MALT1; BIRC2 (API2);
Prognosis
Excellent if inciting agent removed (80% 15 year survival)
If translocations occur then tumor does not regress with antibiotic treatment
May transform into diffuse large B-cell lymphoma
Hairy Cell Leukemia Immunophenotype
CD25, PAX5, CD11c , CD103
**TRAP (tartrate resistant acid phosphatase)
[CD19, CD20, CD79a, sIg, CD22, ]
also CD123, HC2, FMC7 and annexin A1
Hairy Cell Leukemia Clinical Features and prognosis
Massive * splenomegaly common
- Pancytopenia with increased susceptibility to infection
Increased atypical mycobacterial infections
Prognosis:
Indolent course
Tumor cells **“exceptionally sensitive” to chemotherapy
Long-lasting remission in majority of patients
