(F) L2.3 Myelodysplastic syndrome Flashcards
(73 cards)
1
Q
- A group of acquired clonal hematologic disorders characterized by progressive cytopenias (low blood cell counts) in the peripheral blood.
- Reflects defects in the maturation of erythroid (red blood cells), myeloid (white blood cells), and/or megakaryocytic (platelets) cell lines.
- Previously known as refractory anemia, smoldering leukemia, oligoblastic leukemia, or preleukemia.
A
myelodysplastic syndrome
2
Q
familiarize the WHO 2016 revision on myelodysplastic syndrome subtypes
A
- refractory cytopenias with unilineage dysplasia
- refractory anemia with ring sideroblasts (RARS)
- Refractory cytopenia with multilineage dysplasia (RCMD)
- Refractory Anemia with Excess of Blasts (RAEB-1 and RAEB-2)
- MDS Associated with Isolated del(5q)
- Childhood MDS
- Myelodysplastic Syndrome—Unclassified (MDS-U
- Idiopathic Cytopenia of Undetermined Significance (ICUS)
3
Q
WHO recommends that at least 10% of cells within a lineage must show dysplasia for it to be significant for the diagnosis of MDS.
A
Dysplasia Threshold
4
Q
What are the three dyspoises
A
- Dyseruthroiesis
- Dysmyelopoiesis
- Dysmegakaryopoiesis
5
Q
myelodysplastic syndrome (MDS)
a. Bone marrow
b. peripheral blood
- oval macrocytes
- hypochromic microcytes
- erythrocytic hyperplasia
- dimorphic RBC
- megaloblastoid development
- Ring sideroblasts
- poikilocytosis
- Abnormal cytoplasmic features
- internuclear bridging
- nuclear fragments
- Basophilic stippling
- multinucleated RBC precursors
A
- B
- B
- A
- B
- A
- A
- B
- A
- A
- A
- B
- A
6
Q
myelodysplastic syndrome (MDS)
DYSERYTHROPOIESIS
a. Bone marrow
b. peripheral blood
- poikilocytosis
- Abnormal cytoplasmic features
- internuclear bridging
- nuclear fragments
- Basophilic stippling
- multinucleated RBC precursors
A
- B
- A
- A
- A
- B
- A
7
Q
Myelodysplastic syndrome (MDS)
DYSMYELOPOIESIS
a. Bone marrow
b. peripheral blood
- Nuclear-cytoplasmic asynchrony
- Basophilia in cytoplasm
- Abnormal Granulation
- Nuclear anomalies
- Agranular bands
A
- A
- B
- A&B
4.A
5.B
8
Q
Myelodysplastic syndrome (MDS)
DYSMYELOPOIESIS
a. Bone marrow
b. peripheral blood
- Abnormal nuclear features
- Granulocytic hypoplasia or hyperplasia
- monocytic hyperplasia
- abnormal localization of immature precursors
A
- B
- A
- A
- A
9
Q
Myelodysplastic syndrome (MDS)
DYSMEGAKARYOPOIESIS
a. Bone marrow
b. peripheral blood
- abnormal megakaryocytes
- Nuclear abnormalities
- Giant platelets
- abnormal platelet granulation
- Circulating micromegakaryocytes
A
- A
- A
- B
- B
- B
10
Q
Myeloid neoplasms with features of both myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN).
Characteristics: Presence of both cytopenias (low blood cell counts) and cytoses (high blood cell counts).
Clonal Disorder: Characterized by persistent monocytosis of more than 1.0 monocyte x 109/L (monocyte count >0.5 × 10^9/L and >10% in peripheral blood).
Absence of the BCR/ABL1 fusion gene
Blasts and Promonocytes: Less than 20% in peripheral blood and bone marrow.
Exclusion Criteria: Does not meet diagnostic criteria for other myeloproliferative neoplasms or myeloid/lymphoid neoplasms with eosinophilia and specific gene rearrangements (PDGFRA, PDGFRB, FGFR1, or JAK2).
A
Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN)
11
Q
CMML
- PB – 2% blasts; BM – less than 5% Blasts
- PB – 2-4% blasts; BM – less than 5-9% Blasts
- PB – 5-19% blasts; BM – 10-19% Blasts
A. CMML-0
B. CMML-1
C. CMML-2
A
ABC
12
Q
CMML subtypes
- White blood cell (WBC) count <13 × 10^9/L.
- WBC count ≥13 × 10^9/L.
a. myeloproliferative CMML
b. myelodysplastic CMML
A
BA
13
Q
CMML
what are the common cytogenetic abnormalities in CMML?
A
trisomy 8
loss of all or part of chromosome 7
14
Q
Leukocytosis with dysplastic neutrophils and their precursors.
Basophilia may be present but is not prominent.
Multilineage dysplasia is common.
BCR::ABL1 fusion gene is absent.
Karyotype abnormalities in about one-third of patients.
Nearly a
A
MDS/MPN with SF3B1 Mutation and Thrombocytosis (MDS/MPN-SF3B1-T)
aka
atypical chronic myeloid leukemia
15
Q
CMML
Pseudo-Pelger-Huët cells.
Hypogranularity.
Bizarre segmentation
A
MDS / MPN with neutrophilia
neutrophil dysplasia
16
Q
- Characteristics:
15% or more ring sideroblasts. - Anemia and dysplasia in at least the erythroid lineage.
- Platelet count persistently elevated (≥450 × 10^9/L).
- Common mutations: SF3B1 and JAK2 p.V617F, among others.
- Prognosis: Most favorable among MDS/MPN, with a median overall survival of 76 to 128 months.
A
MDS/MPN with SF3B1 Mutation and Thrombocytosis (MDS/MPN-SF3B1-T)
17
Q
Used for cases that meet the criteria for MDS/MPN but do not fit into the specific subcategories.
Diagnosis: Based on time of diagnosis, clinical history, and detection of molecular aberrations.
A
MDS/MPN, Not Otherwise Specified (NOS)
18
Q
A childhood disorder characterized by the proliferation of granulocytic (a type of white blood cell) and monocytic (another type of white blood cell) lineages.
Affects children from 1 month to 14 years of age
A
Juvenile Myelomonocytic Leukemia (JMML)
19
Q
A diverse group of diseases with varying clinical presentations and natural histories, identified by their lineage.
Neoplastic Transformation: Results in abnormal changes in growth and differentiation patterns, leading to lymphoma.
A
mature lymphoid neoplasms
20
Q
MLN
Common diseases under MLN
A
- Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL):
- Mantle Cell Lymphoma (MCL)
- Plasma Cell Neoplasms (PCNs):
21
Q
MLN
helps define disorders according to cell differentiation
a. immunophenotyping by flow cytometry
b. immunohistochemistry
A
a
22
Q
Prevalence: Most common leukemia in adults, about 1% of all new cancer cases in the U.S. annually.
Nature: Malignancy of B lymphocytes; earlier T-cell varieties reclassified among mature T-cell neoplasms.
Demographics: Typically affects older adults, median diagnosis age ~69 years, slight male preponderance.
Incidence: Approximately 4.6 cases per 100,000 persons annually in the U.S.
Detection: Often asymptomatic; detected via abnormal CBC during routine screening or noted lymphadenopathy/splenomegaly.
Diagnosis Criteria: Requires ≥5 × 10^9/L circulating B lymphocytes with clonality confirmed by flow cytometry
A
Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
23
Q
CLL/SLL
scoring system
1-2 =
3 =
A
1-2 =Non-hodgkin lymphoma
3= further testing such as lymph node biopsy or molecular tests
24
Q
T or F
Peripheral blood anaylsis is enough for CLL / SLL
A
f (not enough)
25
# CLL / SLL
how is the chromatin pattern described?
cobbleston / pepperoni pizza
26
# CLL / SLL
T or F
low concentrations of smudge cells are linked to better prognosis
F (higher >30 is linked to better prognosis)
27
# CLL / SLL
a. Del (17p) and TP53
b. Unmutated IGHV
c. Mutated IGHV
1. Worst prognostic indicators, predict resistance to standard treatments.
2. More aggressive disease, often with additional unfavorable genetic changes
3. Better outcomes, respond well to standard treatments.
ABC
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# CLL / SLL
Staging systems
a. Rai and Binet systems
b. Risk categories
c. autoimmune phenomena
1. Reflects the degree fo oranomegaly / lymphadenopathy or marrow function compromise
2. Affect up to 25% of patients; important to rule out autoimmune causes of anemia or thrombocytopenia to avoid incorrect staging.
3. sed to categorize patients based on organ involvement and marrow function
BCA
29
# CLL / SLL
Cell markers
a. CD49d, CD38, ZAP70
b. CD49d
c. CD38
d. ZAP70
e. NOTCH1, SF3B, BIRC3
1. Higher proliferative capacity, potential for progression.
2. Incorporated into standard panels; significant cutoff established.
3. Testing variability; methylation states more reproducible but limited to research labs.
4. Indicators of unfavorable prognosis.
5. Negative prognostic value, not yet routine in clinical practice.
BCDAE
30
# CLL / SLL
a. BITK inhibitors
b. P13K inhibitors
c. BCL2 inhibitos
d. New Monoclonal antibodies
1. Obinutuzumab, gradually replacing rituximab.
2. Idelalisib.
3. Venetoclax
4. Ibrutinib, acalabrutinib
DBCA
31
# CLL / SLL
Preferred as initial ("upfront") therapy due to greater clinical benefits.
BTK and Venetoclax-Based Regimens
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Classification:
Historically subclassified as B-cell PLL (B-PLL) and T-cell PLL (T-PLL).
The 2022 WHO classification no longer recognizes B-PLL as a distinct entity.
B-PLL cases are now classified as:
MCL positive for the IGH::CCND1 fusion gene.
CLL/SLL with prolymphocytic progression.
Splenic B-cell lymphoma/leukemia with prominent nucleoli.
PROLYMPHOCYTIC LEUKEMIA (PLL)
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Size: Smaller than B prolymphocytes, less distinct nucleolus.
Nucleus: Round, oval, or irregular with a cerebriform appearance.
Cytoplasm: Often shows protrusions or blebbing.
T-Prolymphocytic Leukemia (T-PLL)
34
Characteristics
Prolymphocytes: Large number in peripheral blood with immature features.
Nucleus: Round with a distinct "punched-out" nucleolus.
Cytoplasm: Moderately abundant.
Leukocyte Count: Greater than 100 × 10^9/L.
Prolymphocytes: Must exceed 55% of lymphoid cells in peripheral blood.
B-Prolymphocytic Leukemia (B-PLL)
35
# PLL treatments
a. B-PLL
b. T-PLL
1. Alemtuzumab
2. Allogenic Bone Marrow Transplantation
3. Idelalisib
4. Hematopoietic Stem Cell Transplantation
5. Ibrutinib
BAABA
36
Presence of a monoclonal B-cell population in the peripheral blood.
Criteria:
Fewer than 5 × 10^9/L circulating B lymphocytes.
Does not meet IWCLL criteria for CLL/SLL diagnosis.
Symptoms: Asymptomatic, no lymphadenopathy, organomegaly, cytopenias, or systemic symptoms.
Risk of Progression: 1% to 2% per year to CLL.
Monoclonal B-Cell Lymphocytosis (MBL)
37
Criteria:
Fewer than 5 × 10^9/L circulating monoclonal B lymphocytes.
Evidence of disease elsewhere (e.g., adenopathy, organomegaly).
Diagnosis: May require histologic confirmation via lymph node or tissue biopsy.
Clinical Management: Similar to that used in CLL.
Small Lymphocytic Lymphoma (SLL)
38
Abundant pale blue cytoplasm with medium to large azurophilic granules.
Represent up to 15% of circulating lymphocytes or less than 0.6 × 10^9/L in healthy adults.
Counted with normal lymphocytes in WBC differential; comment added if increased.
Large Granular Lymphocytes (LGLs):
39
Characterized by >2 × 10^9/L circulating LGLs.
Disease of older adults (median age 60 years).
Patients may be asymptomatic or present with cytopenias (neutropenia or anemia).
Increased LGLs may trigger a morphology flag on automated analyzers.
Important to document persistence of LGLs for >6 months and rule out other conditions
LGL Leukemia
40
Clonal plasma cells secrete monoclonal protein (M-protein).
Nonsecretory form of MM is less than 1% of cases.
Monoclonal protein can cause detrimental effects across multiple organ systems.
M-protein serves as a surrogate marker for disease burden (observed as M spike in protein electrophoresis).
Monoclonal Protein
41
Monoclonal Gammopathy of Undetermined Significance (MGUS): Presence of monoclonal protein in asymptomatic individuals.
Multiple Myeloma (MM): Clinically aggressive, with tumor infiltration and monoclonal protein excess causing systemic complications.
Plasma Cell Leukemia: Severe form with significant morbidity and mortality.
Spectrum of Disease
42
Nature: Bone marrow-based disease with potential extramedullary extension to bone or soft tissue.
Diagnosis Criteria:
Tumor Burden: Percentage of plasma cells in the bone marrow.
Monoclonal Protein: Quantity in serum or urine.
Systemic Manifestations: Assessed using CRAB criteria:
C: Hypercalcemia.
R: Renal failure.
A: Anemia.
B: Osteolytic bone lesions.
Plasma Cell (Multiple) Myeloma (MM)
43
Common complications of plama cell neoplasms
extramedullary spread
imaging studies
44
Marked by ≥5% plasma cells in peripheral blood; poor response to treatment and poor prognosis.
Plasma Cell Leukemia
45
CD138: Used to identify plasma cells.
Kappa/Lambda Clonal Excess: Helps distinguish malignant from reactive plasma cells.
mmunohistochemical Stains:
46
High levels of CD38 and CD138.
Low expression of CD45.
May express CD56 (NK cell-associated marker).
Malignant Plasma Cells:
47
Increasingly used for MM diagnosis and to quantify minimal residual disease post-therapy.
mmunophenotyping
48
Nature: Benign monoclonal (premalignant stage) proliferation of plasma cells in the bone marrow.
Relation to PCNs: Considered a precursor state for Multiple Myeloma (MM).
Detection: Usually found during routine lab tests when elevated serum protein is detected.
Diagnostic Criteria: Specific criteria used to diagnose MGUS (not detailed here).
Risk of Progression:
Conversion Rate: About 1% per year to overt MM.
High-Risk Subset: Patients with adverse risk factors have over a 60% chance of progression over 20 years.
Risk Assessment: Serum M protein concentration, serum free light-chain ratio, and other markers help assess the risk of conversion to MM or other PCNs.
Monoclonal Gammopathy of Undetermined Significance (MGUS)
49
Nature: Localized form of Plasma Cell Neoplasm (PCN).
Monoclonal Protein: No accompanying monoclonal protein in serum or urine.
Diagnosis:
Requires testing to confirm the plasmacytoma is localized to a single area.
Ensures it is not part of an underlying systemic disease.
Therapeutic Implications:
Generally treated with radiation therapy.
Plasmacytoma – SOLITARY PLASMOCYTOMA
50
Nature: Low-grade lymphoplasmacytic lymphoma (LPL).
Secretory Product: Aberrant secretion of IgM.
Waldenström Macroglobulinemia (WM)
51
Complications of Waldenström Macroglobulinemia (WM)
* hyperviscosity syndrome
* Extramedullary involvement
52
Genetic marker of Waldenström Macroglobulinemia (WM)
MYD88 Mutation
53
nature: Lymphoplasmacytic neoplasm.
Symptoms: Depend on the type of immunoglobulin heavy chain involved.
Complications: Monoclonal protein can cause significant organ damage, such as to the kidneys.
Heavy Chain Disease
54
Nature: Aggressive malignancy of mature B cells with rapid tumor growth and often-fulminant clinical presentation
BURKITT LYMPHOMA (BL)
55
# burkitt lymphoma
a. endemic BL
b. sporadic BL
c. Immunodeficiency-associated BL
Associated with HIV, post-transplantation, and congenital immunodeficiency.
Blood and bone marrow are primary sites of disease.
c
56
# burkitt lymphoma
a. endemic BL
b. sporadic BL
c. Immunodeficiency-associated BL
Found primarily in children in equatorial Africa.
Geographic distribution similar to malaria.
Common sites: Orbits and mandible.
Nearly all cases have Epstein-Barr virus (EBV) genome in neoplastic cells.
a
57
# burkitt lymphoma
a. endemic BL
b. sporadic BL
c. Immunodeficiency-associated BL
Seen in the United States and Western Europe.
Mostly manifests as abdominal disease.
Extranodal involvement common; various tissues can be involved.
Bone marrow infiltration in up to 70% of cases.
CNS disease found in about one-third of patients.
b
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Nature: Most familiar forms of cutaneous T-cell lymphoma.
Differences:
Cell of Origin and Clinical Characteristics: Different for MF and SS, hence considered separate entities.
Demographics:
Diseases of the elderly.
Slight male preponderance
t-cell neoplasm: mycosis fungoides and Sézary Syndrome
59
Prevalence: More common, making up 60% to 70% of cutaneous T-cell lymphoma cases.
Disease Course: Generally indolent with a slow, progressive course.
Involvement: Largely confined to the skin; later stages may involve lymph nodes, organs, and peripheral blood.
small to medium sized lymphoma cells with cerebriform nuclei
Early diagnosis can be difficult; may present with psoriatic-like skin lesions requiring repeated biopsies.
Mycosis Fungoides (MF)
60
Nature: Aggressive systemic disorder.
Involvement: Peripheral blood involvement.
Prognosis: Worse than MF.
Characterized by erythroderma, generalized lymphadenopathy, and clonal T cells in skin, lymph nodes, and peripheral blood.
Sézary Syndrome (SS
61
Nature: Neoplastic disorder of germinal B cells; second most common form of Non-Hodgkin Lymphoma (NHL).
Demographics: Typically affects middle-aged to older adults.
Course: Indolent but generally incurable with current therapies; characterized by serial responses to treatment followed by relapse.
Presentation: Most patients present with painless lymphadenopathy and are otherwise asymptomatic.
Follicular Lymphoma (FL)
62
Nature: Most common form of Non-Hodgkin Lymphoma (NHL), representing about 30% of cases.
Demographics: Generally affects the elderly but can occur in younger patients.
Origins: Can arise de novo or from transformation of more indolent lymphomas (e.g., SLL, FL, MZL).
Course: Aggressive but curable in approximately two-thirds of patients with combination chemoimmunotherapy.
Presentation: Rapidly expanding painless lymphadenopathy in one or more sites.
Extranodal Involvement: Common in GI tract, testis, or bone.
Diffuse Large B-Cell Lymphoma (DLBCL)
63
# Diffuse Large B-Cell Lymphoma (DLBCL)
a. BCL6
b.BCL2
c. MYC
1. In 20% to 30% of cases.
2. In about 30% of cases.
3. Rearranged in about 10% of cases; often concurrent with BCL2 and/or BCL6 abnormalities ("double- or triple-hit" lymphoma).
BAC
64
Prevalence: MCL makes up about 6% of Non-Hodgkin Lymphoma (NHL) cases.
Demographics: The median age at diagnosis is 68 years, and it affects males more often than females.
Clinical Aggressiveness: Generally aggressive, but an indolent type exists.
Presentation: Most patients have extensive lymphadenopathy. Extranodal disease, especially in the GI tract, is common.
Indolent Form: Often restricted to blood, bone marrow, and spleen.
Mantle Cell Lymphoma (MCL)
65
an indolent B-cell lymphoma.
Association: Typically linked with chronic antigen stimulation due to infection or autoimmunity.
Marginal Zone Lymphoma (MZL)
66
# Marginal Zone Lymphoma (MZL)
A. Extranodal Marginal Zone Lymphoma (MALT)
B. Splenic Marginal Zone Lymphoma (SMZL)
C. Nodal Marginal Zone Lymphoma (NMZL)
1. Involves mucosa-associated lymphoid tissue.
2. Primarily affects the spleen.
3. Involves lymph nodes
ABC
67
Prevalence: Most common subtype of Marginal Zone Lymphoma (MZL), representing 7% to 8% of B-cell lymphomas.
Demographics: Median age at diagnosis is 61 years.
Association: Typically linked with organs lacking obvious lymphoid tissue but subjected to chronic inflammation.
Common Sites:
Stomach (most often involved, closely associated with Helicobacter pylori infection).
Other sites: salivary gland, ocular adnexa, thyroid, skin, small intestine (associated with different infectious stimuli).
Variant: Immunoproliferative small intestine disease, seen in the Middle East, Africa, and the Mediterranean, associated with severe malabsorption.
MALT Lymphoma
68
Prevalence: Accounts for less than 1% of Non-Hodgkin Lymphoma (NHL) cases.
Demographics: Most common in adults over 50 years.
Areas of Involvement:
White pulp of the spleen
Splenic lymph nodes
Bone marrow
Peripheral blood
Clinical Presentation:
Massive splenomegaly
Absolute lymphocytosis in peripheral blood
Presence of villous
Splenic Marginal Zone Lymphoma (SMZL)
69
Accounts for 1% of Non-Hodgkin Lymphoma (NHL) cases.
Demographics: Most common in adults over 50 years of age.
Localization: Primarily localized to the lymph nodes, but bone marrow involvement can occur.
Cell Behavior: NMZL cells extend from the mantle-marginal zone interface, disrupting the interfollicular region.
Diagnosis
Represents a generic term for disorders that resemble other low-grade B-cell malignancies but lack specific distinguishing characteristics (e.g., cyclin D1 expression, BCL2 abnormalities).
associated with hepa C
Nodal Marginal Zone Lymphoma (NMZL)
70
Nature: Primarily a nodal-based disease, distinct from nodal Non-Hodgkin Lymphoma (NHL), but can also involve extranodal sites.
Incidence: Relatively rare, with an estimated US incidence of 2.6 cases per 100,000 persons per year.
Unique Features:
Associated with unique biological and clinical features.
One of the first cancers to be cured with combination chemotherapy, serving as a model for modern oncology therapeutics.
Relapse and Cure: Patients who relapse can still be cured with current therapies, which is uncommon in oncology.
Survival Rate
Approximately 86% of HL patients are alive 5 years after diagnosis.
Patient Demographics
Often affects a younger patient cohort, making long-term survival data important for understanding the effects of chemotherapy and cancer therapy toxicity.
Hodgkin Lymphoma (HL)
71
# Hodgkin Lymphoma (HL)
Age Distribution: Bimodal peaks in the 30s and after age 50.
Reed-Sternberg (RS) Cells: Large binucleated/multinucleated cells with abundant cytoplasm and distinct nuclei.
Immunophenotyping: RS cells primarily express CD30 and often coexpress CD15.
Histologic Subtypes: Nodular sclerosis, mixed cellularity, lymphocyte rich, and lymphocyte depleted.
Cell Origin: RS cells are of B cell origin but lack most B cell markers.
Cervical/supraclavicular and mediastinal adenopathy, spreads contiguously, B symptoms more common.
CHL CHARACTERISTICS
72
# Hodgkin Lymphoma (HL)
Malignant Cells: Lymphocytic histiocytic (L&H) variants, also known as "popcorn" cells.
Immunophenotyping: L&H cells are negative for CD15 and CD30, about 50% express epithelial membrane antigen (EMA).
Background: Nodular background composed primarily of small lymphocytes.
Peripheral lymphadenopathy, mediastinal adenopathy uncommon, non-contiguous nodal involvement, rare extranodal involvement.
NLPHL Characteristics
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