L21- WBC Pathology II Flashcards
classify the precursor lymphoid neoplasms (according to WHO)
B-lymphoblastic leukemia/lymphoma, 85%:
- ” “, NOS* (not otherwise specified)
- ” “, w/ recurrent genetic abnormalities
T-lymphoblastic leukemia/lymphoma, 15%
(1)/(2) are the most common childhood malignancy with overlapping presentations. Classification of (1)/(2) is based on (3) and (4). Causes of (1)/(2) are unknown, but it is suspected to be associated with (5).
1/2- ALL, acute lymphoblastic leukemia / lymphoma
3- immunophenotyping (B/T cell differentiation)
4- presence of cytogenic abnormalities
5- ionizing radiation
ALL presents with a (slow/rapid) onset with (mild/severe) symptoms.
- (2) and (3) symptoms are seen in all ALL types
- (4) is seen in T-ALL
- (5) is seen in B-ALL
1- rapid (abrupt), severe onset
2- (related to BM replacement) cytopenias, bone pain
3- lymph node enlargement and or organomegaly (liver, spleen)
4- thymic enlargement
5- testicular enlargement, CNS involvement (HAs, blurred vision, vomiting)
ALL, laboratory diagnostics:
- (1) CBC results
- (2) morphology on peripheral blood smear
1- leukocytosis (possibly >100,000)
2- blasts seen in peripheral blood smear and bone marrow aspirate/biopsy: blasts with scanty (agranular) basophilic cytoplasm, delicate stippled (condensed) chromatin and small nucleoli
ALL, laboratory diagnostics:
- (1) specific histochemical stains
- (2) methods of immunophenotyping
- (3) common results of cytogenetic investigations
1- myeloperoxidase and Sudan black negative // some PAS positivity
2- (important for T-ALL v B-ALL) flow cytometry, immunohistochemistry
3- (90% abnormal) translocations, deletions, hyperdiploidy are possibly present
Flow Cytometry in ALL:
- (1) are expressed on pre-B lymphoblasts and indicate B-ALL
- (2) may also be expressed on mature B-cells
(B-cells)
1- CD10, CD19 (pan-B-cell marker)
2- TdT (terminal deoxynucleotidyl-transferase), CD22
ALL Tx:
- (1) list the phases
- (2) and (3) are the common components of each phase
- (4) include remission and fully cured statistics
- (5) Tx is reserved for relapsed cases
1:
i) remission induction
ii) consolidation therapy
iii) maintenance therapy
2- multi-agent chemotherapy
3- testicular, CNS prophylaxis
4- 90% remission, 65% cured overall (higher in children)
5- BMT (bone marrow transplant)
list and describe the 5 factors that affect the prognosis of ALL
1) age
2) WBC count in peripheral blood smear (lower the better)
3) immunophenotype (T cell worse than B cell)
4) cytogenetics
5) residual disease after chemotherapy
ALL prognosis:
- (1) describe age difference
- (2) describe WBC count in peripheral blood smear
- (3) describe residual disease after chemotherapy
1:
Good- age 2-10 y/o
Bad: <2 y/o, >10y/o
2:
Good- low WBC count
Bad- >100,000
3:
Good- undetectable
Bad- detectable
ALL prognosis:
- (1) describe by immunophenotype
- (2) describe by cytogenetics
1:
Good- B-cell
Bad- T-cell
2:
Good: hyperdiploidy, presence of t(12;21)
Bad: other ploidy, presence of t(9;22)
Non-Hodgkin’s Lymphoma = (1)
provide examples, (2)
= Mature (peripheral) B-cell Neoplasms
Exs:
- B-cell chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL/SLL),
- B-cell prolymphocytic leukemia (B-PLL)
- lymphoplasmacytic lymphoma (LPL)
- marginal zone lymphomas (MZL)
- mantle cell lymphoma (MCL)
- follicular lymphoma (FL)
- hairy cell leukemia (HCL)
- diffuse large B-cell lymphomas (DLBL)
- Burkitt lymphoma (BL)
- plasma cell neoplasms
(1) then (2) are the most common B-cell lymphomas, aka (3)
1- DLBCL (diffuse large B-cell lymphoma)
2- FL (follicular lymphoma)
3- Non-Hodgkin’s lymphoma
(1) is the most common lymphoma in adults, with median age of presentation at (2), although it can occur (3).
1- DLBCL (diffuse large B-cell lymphoma)
2- 60 y/o
3- any age, 15% of childhood lymphomas
DLBCL, (1), is a (HL/NHL) with a(n) (aggressive/passive) history. DLBCL can be caused / classified by (4) or (5).
1- diffuse large B-cell lymphoma
2- non-hodgkin’s lymphoma
3- aggressive
4- primary, de novo
5- secondary, transformation of previous low grade lymphoma (mainly FL, but most small B-cell lymphomas have this capability)
Note- many subtypes with variable prognoses
DLBCL, (1), presents with (2) as the main symptom in (3) or (4) location, and usually presents in (5) stage. Other common symptoms include this triad, (6).
1- diffuse large B-cell lymphoma 2- rapidly enlarging lymphoid mass(es) 3- lymph nodes, 60% 4- extra-nodal mass, 40% 5- stage I, II (w/o Bone Marrow involvement) 6- fever, weight loss, night sweats
DLBCL has a (diffuse/patchy) growth pattern with (small/large) (B/T)-cells. Nuclei are described as (4). Immunophenotyping will look for (5).
(diffuse large B-cell lymphoma)
1- diffuse
2- large, 3-4x normal size
3- B-cells
4- medium/large, round/oval nuclei with dispersed chromatin and several small nucleoli
5- expressed B cell Ags (typically includes CD20)
DLBCL (diffuse large B-cell lymphoma) is a(n) (aggressive/passive) cancer that is always (curable/fatal). Treatment includes (3) and (4). (5) are the typical results from treatment.
1- aggressive
2- fatal if untreated, often curable
3- combination chemotherapy
4- anti-CD20 immunotherapy
5- 60-80% remission –> 50% of which remain cured
(1) lymphoma is derived from germinal center B-cells, mainly affecting (2) age group. (3, describe) is the most common cytogenetic abnormality seen as it results in (4).
1- FL, follicular lymphoma
2- 50-60 y/o
3- (>85%) t(14;18) –> translocation fuses BCL2 gene on chr.18 next to igH locus on chr.14
4- overexpression of BCL2 protein –> major apoptosis inhibitor
FL, (1), is a (rapid/slow) growing tumor. It often presents in (3) stage with (4) involvement.
1- follicular lymphoma
2- slow (indolent) growth
3/4- stage IV; bone marrow involvment (80% cases)
list the 3 main manifestations of FL
(follicular lymphoma)
-painless localized to generalized lymphadenopathy
- 40% have tumor cells in blood (resembling CLL)
- frequently involves spleen/liver –> hepatosplenomegaly
FL, follicular lymphoma, has a (1) or (2) growth pattern. Packed follicles contains the following two types of cells (3) and (4), more increased levels on (3/4) indicate a tumor with more aggressive behavior, likely transformation into (6).
1- nodular, >75% follicular
2- nodular and diffuse, 25-75% follicular
3- small cleaved cells w/o nucleoli –> Centrocytes
4- large cells w/ moderate cytoplasm, multiple nucleoli –> Centroblasts
5- Centroblasts (4)
6- DLBCL
describe using Immunophenotyping to differentiate the causes of enlarged lymph node (lymphadenopathy)
Mark for BCL2 in follicle:
-very little staining in follicle (dark brown BCL2 in mantle cell zone) = Reactive Lymph Node
-dark brown BCL2 staining in follicle = FL
FL diagnosis:
- (1) is necessary
- (2) describe immunophenotyping
- (3) characteristic cytogenic change
1- characteristic lymph node morphology
2- by flow cytometry OR immunohistochemistry for CD19, CD20, CD10
3- t(14;18), 90% of cases
FL prognosis:
- mostly (1) characteristic
- 40% transform into (2)
- (3) is the median survival of (2)
1- incurable (except for cases with large cells / high grade)
2- DLBCL
3- <1 yr
CLL and SLL are mostly identical, but differ in…..
(chronic lymphocytic leukemia, small lymphocytic lymphoma)
peripheral blood involvement
describe characteristics of CLL on PB (in comparison to SLL)
(chronic lymphocytic leukemia on peripheral blood smear)
- lymphocyte count > 5000 cells/µL
- bone marrow involvement
- monoclonal B cell count > 5000 cells/µl
describe characteristics of SLL on PB (in comparison to CLL)
(small lymphocytic lymphoma, non-leukemic cases on peripheral blood smear)
- monoclonal B cell count < 5000 cells/µL
- enlarging lymph nodes
(1) is used to discover CLL/SLL in early diagnosis.
In late diagnosis of CLL/SLL:
- (2) is evident diffusely
- (3) is often observed
- some patient develop (4) autoimmune diseases or increased infections due to (5)
- eventually (6) symptoms are evident due to progressive bone marrow replacement
1- CBC showing leukocytosis
2- generalized lymphadenopathy 3- hepatosplenomegaly, 50-60% 4- autoimmune hemolytic anemia or thrombocytopenia 5- acquired hypogammaglobinemia 6- pancytopenia
CLL/SLL morphology and diagnosis:
- (1) cells are seen on peripheral blood smear
- (2) is noted on bone marrow biopsy
- (3) is noted on lymph node biopsies
- immunophenotyping is completed by (4) for the following CDs, (5)
1- small mature appearing lymphocytes = ‘smudge cells’ (inc fragility)
2- interstitial nodules –> diffuse replacement by small lymphocytes
3- diffuse replacement by small round lymphocytes w/ few larger cells concentrated in pale proliferation centers
4- flow cytometry, immunohistochemical staining
5- CD19, CD20, CD5, CD23, CD43
CLL/SLL is noted to be (1) in treatment. Mean survival rate is (2), and can reach up to (3) if diagnosed early.
1- incurable (although indurant)
2- 4-7 yrs
3- 10 yrs
CLL/SLL can lead to death through the following mechanisms,….
- progressive pancytopenia –> infections, bleeding
- transformation into aggressive neoplasm, PLL (20%, prolymphocytic leukemia) OR DLBCL (5-10%)
Extra-nodal marginal zone lymphoma = (1). It is a (rapid/slow) growing tumor mostly composed of (3) cells commonly in (4) locations. (4) locations lack abundant lymphoid tissue, but acquire it via (5), mostly commonly the (6) site- include cause for (6)
1- MALT lymphoma (MALToma)
2- slow growth, indolent (Note- remains localized for long periods, often recur or spread to other mucosal sites)
3- small mature appearing lymphocytes
4- extra-nodal / mucosal sites
5- chronic infection / autoimmune disease
6- stomach w/ superimposed H. pylori gastritis
(1) infections of (2) area can progress into extra-nodal marginal zone lymphoma. (3) treatment has been shown to regression some early MZL (2) tumors.
Other common sites for MZL are (4) and (5).
1- H. pylori (=> chronic inflammation)
2- stomach
3- antibiotic Tx for H. pylori gastritis
4- salivary glands
5- thyroid glands (autoimmune inflammation via Hashimoto’s thyroiditis)
