Hematological Diseases Flashcards
1
Q
AML with normal cytogenetics
A
- Normal Cytogenetics
- Any non-lymphatic cell lineage can be affected
- DNA sequencing to see if pts will respond to treatment
- Presentation: any age; pediatric AML is uncommon, but happens Gingival Hypertrophy
- All AML: bruising, fatigue, bleed, infection, bone pain
- Immunophenotype: CD34+, + lineage-specific markers
- Morphology: Undifferentiated
- Monocytic/monoblastic
- Vacuoles
2
Q
AML, t(8;21)
A
- Translocation forming ETO-AML1 [RUNX1-RUNX1t1]
- Two common ways translocations cause malignancy:
- Bind to DNA as co-repressor: inhibit transcription needed for differentiation
- Constitutively active pro-proliferation system
- Inhibits Myeloid Differentiation
- Presentation: young adults (age associated) and kids; pancytopenia symptoms (fatigue, infection, bleeding).
- Immunophenoptye: CD13+, CD33+ (Maturing myeloid), CD34+ (Blasts)
-
Morphology: Auer Rods
1. Crystalized azurophilic granules (MPO); only AML
2. Large blasts with smooth/smudgy chromatin
3
Q
Acute promyelocytic leukemia, t(15;17), M3
A
- Fusion protein of transcription factor and retinoic acid receptor: PML-RARA
- Inhibits granulocyte differentiation
- Presentation: thrombocytopenia, DIC, leukocytosis
- Immunophenotype: CD34-, HLA-DR- (Low Blasts, normal for APL), CD13+, CD33+
- Morphology: big blasts
- *1. AuerRod Stacks
2. Heart-shaped/bat-wing nuclei, Butterfly Nuclei** - Best situation is remission –> NO CURE
4
Q
Acute myelomonocitic leukemia, inv or t(16;16)
A
- Fusion protein of transcription factors: CBFB-MYH11
- Inhibits myeloid maturation
- AKA “Core-Binding Factor” Leukemia
- FISH diagnosis for inversions is backwards. Normally, fusion signals bad, but for inversions they’re normal.
- Presentation: Kids, adults
- Immunophenotype: CD34+, CD117+ = blasts, CD13+, CD33+ = maturing granulo, CD14+, CD11b+ = monocyte
-
Morphology:
1. Mixed granulocyte-monocyte (myelomonocytic)
2. Eosinophilia - Prognosis: POOR, chemo improves
5
Q
CML, t(9;22)
A
- p210 BCR-ABL1 (Philly chrom): INC TK activity
- Pluripotent stem cell affected (myeloid + lymphoid) If granulocyte/monocyte –> Chronic Myelomonocytic Leukemia (CMML)
- Blast Criss (4-5 years): Chronic Phase -> Accelerated -> Blast Phase -> Leukemia (blasts, but NO Auer rods)
- Presentation: 30-60 years (age related), asymptomatic PE: Hepatosplenomegaly (chronic disease); exposure: ionizing radiation + benzene
- Morphology: BM Hypercellular, no blasts (pre blast crisis), and unexplained basophilia in PS
- DDx:
- RT-PCR of BCR-ABL1
- Low LAP b/c non-functional leukocytes (vs. Leukemoid Rxn)
*Leukomoid reaction: normal leukocytosis–> left shift; has high LAP
6
Q
Mastocytosis
A
- C-KIT mutation
-
PDGF-RA via F1P1 translocation
- Increased tyrosine kinase activity: mast cells
- Usually presents outside the bone marrow/lymph nodes
- Similar to Chronic Eosinophilic Leukemia
- Presentation: variable, confusing
- Immunophenotype:
1. Tryptase+ (mast cell granule)
- CD117+ (Blast CKIT, SCF-receptor), CD25+
- Morphology: Bland looking cells, possible eosinophilia
- Treatment: Imatinib
7
Q
Primary myelofibrosis
A
- Jak2 Mutation on Ch. 9 Short arm - increased TK signaling via J/K pathway
- Abnormal megs secrete cytokines –> deposition of Type 3 Collagen –> Marrow Fibrosis + Extra-medullary Hematopoiesis (EMH)
- EMH –> Fibrohematopoietic Extra-Med. Tumors
- Presentation: >50 year olds w/splenomegaly, portal hypertension, osteosclerosis/bone pain, cytokine-like symptoms (muscle wasting), and thrombosis
- Morphology:
- BM - Full of Type 3 collagen
- Peripheral Blood - bizarre megs, abnormal platelets, tear drop RBC, nucleated RBC
- DDx: Reticulin Stains for Fibers
- Treatment: Supportive care (blood transfusion)
8
Q
Polycythemia vera
A
- Jak2 Mutation on Ch. 9 short arm - increased effect of growth factors (95%)
- Erythroid lineage primarily affected > megs > others
- INC RBC/HCT –> sludgy RBC movement –> bad
- Presentation: thrombosis, CNS symptoms, itchiness after hot bath, facies, blurred vision (retinal distention), splenogmegaly
- Labs: DECREASED EPO (best to rule out reactive polycythemia)
- Morphology: erythroid hyperplasia (BM) Increased RBC (PS)
- Treatment: Phlebotomy, deplete iron, aspirin, myelosuppressive
- Prognosis: Progress to MDS, AML, Myelofibrosis
9
Q
Essential thrombocythemia
A
- Jak2 Mutations (50% of cases)
- Excess of dysplastic/abnormally functioning platelets from Megs
- Have to differentiate ET from Secondary Thrombocythemia; Bleeding, inflammation, iron deficiency or asplenia will cause secondary thrombocythemia. Platelet count will not extremely high. TPO will be high.
- Pharmacology/Treatment: Hydroxyurea
- Presentation: thrombosis OR bleeding (GI), splenomegaly
-
Morphology:
1. Increased megs, large/abnormal megs, clustering megs
2. Bizarre platelets = Meg Fragment - DDx:
1. Extremely elevated platelets
2. Normal TPO
- Prognosis: 10 yr survival, but can progress to myelofibrosis, MDS, acute leukemia
10
Q
Refractory cytopenia with unilateral dysplasia
A
- Clonally expanded acquired mutation of stem cell for one lineage
- Monosomies/trisomies may be present
- Diagnosis made on morphological findings
- Presentation: unexplained cytopenia(s) in elderly population (>65 years)
- Immunophenotype: Abnormal markers
- Morphology: Weird looking precursors; binucleation or irregular nuclei; can show fibrosis, high or low cellularity, megaloblastoid features
- Prognosis: Survival normal for age (rarely progress to AML)
11
Q
Refractory anemia with ring sideroblasts
A
- Clonally expanded acquired mutation in erythroid cell line
- Monosomies/trisomies may be present
- Dx via morphological findings + IRON STUDIES
- Presentation: unexplained cytopenia(s) in elderly pop (>65 years); anemia + associated symptoms
- Immunophenotype: Abnormal markers
- Morphology: Ring sideroblasts with dyspoietic features in red cells only
- Prognosis: Survival normal for age (rarely -> AML)
12
Q
MDS with isolated deletion 5q
A
- Loss of large arm of chromosome 5 (CYTOGENETICS)
- ALL megas fail to divide nuclei –> mononuclear megs
- 10% progress to AML
- Presentation: Anemia (severe), elderly (>65), women
- Morphology: ALL megs are mononucleated
- Prognosis: Good survival, treat with lenalidomide
- NOTE: Morphologic/cytologic features usually make dx failry easy
13
Q
Refractory cytopenia with multilineage dysplasia
A
- BAD PLAYER, CLINICALLY -> little to offer pts.
- Clonally expanded acquired mutation in MULTIPLE cell lineages
- 50% show non-specific cytogenic abnormalities
- Morphology: based on linages affected; if granulocytic, abnormal granules; if erythroid, expect nRBC, etc.
- Presentation: Anemia (severe), elderly (>65), women
- Immunophenotype: Abnormal markers
- Morphology: Granulocytes lacking normal granules; abnormal lobulation
- Prognosis: Median survival 30 months; 10% progress to AML in 2 years
14
Q
Refractory anemia with excess blasts
A
- BAD PLAYERS -> used to be called “pre-leukemia
- RAEB-1: 5-9% morphological blasts
- RAEB-2: 10-19% morphological blast
- >20% — Acute Leukemia
- 50% show nonspecific abnormal cytogenics
- How is this different from Acute Leukemia? AMLs devo blasts from translocated mut that halts differentiation. Here, mut occurs that is clonally expanded and takes over as a cell line. This is more like a TRUE malignancy
- Presentation: cytopenia in elderly patient (65+ yrs)
- Immunophenotype: Blast Population: CD34+, CD117+
- Morphology: Blasts and dyspoeitic maturation
- Prognosis: RAEB-1 progression to AML (25%) RAEB-2 progression to AML (33%)
15
Q
B-Cell ALL, t(9;22)
A
- Fusion protein of BCR-ABL1
1. Fusion protein of serine-threonine kinase (BCR) to TK (ABL1) -> INC proliferation — Class I mutation
2. IKZF1 transcription factor INH (differentiation inhibited) — Class II mutation - Different than CML t(9;22); diff break in oncogene; DIFFERENT FUSION PROTEIN
- Presentation: kids and older adults
- Immunophenotype: (early B cell): CD 10+, 19+, TdT+
- Morphology: Big, agranular blasts
- POOR PROGNOSIS
- Treatment: Imatinib is also an option
16
Q
B-Cell ALL, t(11;19)
A
- Rearranged MLL
1. Fusion of transcription regulator (histone methyl transferase) to many chromosomes (Class II)
2. FLT3 mutations (Class II) -> INC proliferation - MLL becomes transcriptional repressor –> decrease differentiation
- Presentation: Kids <1year; most common form in very young children
- Immunophenotype (early B cell): CD10- (differentiate between t(9;22) ALL), CD19+, TdT+
- POOR PROGNOSIS
- Morphology: Big agranular blasts
17
Q
B-Cell ALL, t(12;21)
A
- Fusion protein of TEL-AML1 [ETV6-RUNX1]
1. Dominant negative transcription factor (Class II) 2. Pax5 mut inhibits differentiation (Class II) - GOOD RESULTS - 90% CURE
- Presentation: Kids - 25% of all pediatric B-ALL
- Immunophenotype: CD34+, CD20-, TdT+, CD34+
- Morphology: big agranular blasts
18
Q
Hairy cell leukemia
A
- BRAF V600F mutation
- Only leukemia WITHOUT lymphadenopathy
- Key diagnostis: resistant to Tartrate-resistant acid phosphatase (TRAP)
- Presentation: thrombocytopenia, splenomegaly, dry bone marrow *Common in middle aged men
- Morphology: “hairy cell”; fried egg
- Immunophenotype: CD19, CD20
- Treatment: Rituximab, IFN alpha
19
Q
T-Cell ALL
A
- Oncogene translocated to Ig or TCR promoter (any of the 3 TCR loci in the genome)
1. Example: t(14;10) (TCR-alpha;HOX11) - Prognosis -> High Risk (but if treated correctly, their prognosis can be just as good as lother patients)
- Presentation: kids - 25% of all pediatric, thymic, lymph mass, splenomegaly (where T cells go)
- Immunophenotype: CD3+, 5+ (T cell markers), TdT+ (marker of T/B cell precursors), B-cell/myeloid CDs/Ags
- Morphology: big agranular blasts
20
Q
Classical Hodgkin’s lymphoma
A
- Etiology:
- No Ig expression
- Anti-apoptosis (via NFkB or EBV)
- Genetically unstable, more mutations
- Affected Cell: B-Lymphocyte –> R-S Cell
-
Four Types:
1. Nodular lymphocyte predominant (best prognosis)
- Nodular sclerosing (women > men)
- Mixed cellularity (most associated with EBV)
- Leukocyte Depleted (worst prognosis)
- Presentation: Older men (except nodular sclerosing) w/cervical adenopathy, B- like symptoms, rare extra-nodal involvement, EBV infection
- Immunophenotype: (different in lymphocyte dominant HL): CD15/30+ = RS Cells, CD20+, Pax5+
- Morphology: RS Cells over diverse cellular backdrop
21
Q
Nodular lymphocyte dominant Hodgkin’s
A
- Etiology:
- Ig is EXPRESSED
- Anti-apoptosis (NFkB, EBV)
- Genetically unstable, more mutations
- Affected Cell: B-cell —> Lympho-histocytic (L/H Variant) BEST PROGNOSIS
- Presentation: older men w/cervical adenopathy, B- like symptoms, rare extranodal involvement, EBV infection
- Immunophenotype: CD15/CD30- (fewRScells), CD20+, Pax5+
- Morphology: RS cells with collar of T-lymphocytes; popcorn cell
22
Q
CLL
A
- Strom Etiologies:
- Deletion in Chromosome 13 (good prognosis)
- Deletion in Chromsome 17 (p53 - bad prognosis)
- Big Complication: Hypogammaglobulinemia - look for recurrent infections
- CLL and SLL are similar: CLL high peripheral lymphos; SLL is LYMPHoma and CLL is leukemia (blood’s territory)
- Affected Cell: Memory Cell
- Presentation: older men w/recurrent infections (hypo-gammaglobulinemia), warm hemolytic anemia
- Immunophenotype: light chain restricted (clonal), CD 20+ (weak), CD 5 + (odd, but characteristic phenotype of CLL/SLL)
***ZAP-70 expression is BAD
***CD38 expression is BAD
- Lymph Node: effaced lymph node = pseuodofollicular
- Peripheral smear: small lymphocytes, SMUDGE CELLS
23
Q
Mantle cell lymphoma
A
-
t(11,14) - CyclinD1-IgH
1. Cyclin D1 expression pushes cells: G1—>S - Affected Cell: B cell in (pregerminal center) mantle zone or memory cell in periphery
- Presentation: similar to CLL, but worse prognosis (older men w/recurrent infection, warm hemo anemia)
- Immunophenotype: Light chain restricted, CD20+ (strong), CD5+, K1g7+ = marker for fast growth
- Lymph Node: effacement = Starry Sky
- PS: SMUDGE CELLS
- Treatment: combination (Fludrabine + Rituximab; CVP, CHOP, CHOP-R)
25
Q
Follilcular lymphoma
A
-
t(14;18) IgH-BCL-2
1. Grade 1: lots of centrocytes –> least aggressive
2. Grade 2: mixture of centrocytes/centroblasts
3. Grade 3: lots of centroblasts —> aggressive - Presentation: older, w/painless lymphadenopathy (if painful = reactive (flu))
- Lymph Node: follicular hyperplasia, effacement of architecture, slow mitosis +, few tingible body macros (indolent, slow growing)
- Immunophenotype: CD 19, CD 20+ (B Cell), CD 10+ (Germinal Center), BCL-2
- DDx: immunohistochemistry + immunophenopyting (BCL-2 stain)
- Prognosis: see grade; progress to diffuse large B cell lymphoma
26
Q
Diffuse large B-cell lymphoma
A
- T(V; 3) - BCL-6, t(14;18) - BCL2-IgH
- Most common NHL in Adults; poorly defined group
- Differs from Follicular Lymphoma: 1. Extranodal involvement, 2. RAPID DIVISION
- Presentation: older patients (few pediatric cases)
- Immunophenotype: CD19+, CD20+, CD10+, BCL-6/BCL-2+
- Lymph Node: Immature (large B) cells w/high mitotic rate
- Treatment: CHOP + R-CHOP
27
Q
Burkitt lymphoma
A
- t(8;14), t(2;8), t(8;22)
- MYC gene + IgH, IgL, IgK
- African Burkitts - malaria belt, EBV
- Sporadic - everywhere else, NOT EBV associated
- Presentation: Endemic: Jaw Lesions; Sporadic: pelvic lesions or abdomen
- Immunophenotype: CD19+, 20+, 22+, 79+, Ki-67+
- Morphology: starry Sky appearance with sheets of lymphocytes/blasts containing empty spaces of tingible body macrophages
- Treatment: usually curable in children; long term cure not likely
29
Q
Peripheral T-cell lymphoma, not otherwise specified
A
- Poorly defined group of AGGRESSIVE T-Cell lymphoma
- Aggressive; survival <5 years
- Presentation: Lymphadenopathy, paraneoplastic syndromes (hemolytic anemia); B-type symptoms
- General Immunophenotype: T-cell markers + abnormal markers (B-cell, random)
- Lymph Node: cells too uniform for the lymph node
- Expanded paracortex
- Effacement of architecture
- Paracaortical Epitheliold Histocytes
30
Q
Mycosis fungoides and sezary syndrome
A
- Both involve Neoplastic CD4 T Cells
- Sezary syndrome is mycosis fungiodes w/leukemic phase - circulating cells are called Sezary cells
- Presentation: skin rash, pruritis, psoriasis; neoplastic cells in epidermis are called Pautrier’s microabscesses
31
Q
Aplastic anemia
A
- Reduction or deletion of hematopoietic stem cells b/c:
1. Cells are damaged
2. Immunosuppression of hematopoiesis
3. Bad BM environment - Congenital: Faconi’s + Familial Aplastic
- Acquired: Benzene, ionizing radiation, infections, PNH
- Important point: aplastic anemia is not malignancy
- Of all the causes, autoimmune destruction of stem cells is the PRIMARY CAUSE OF APLASTIC ANEMIA
- Presentation: variable, anemic (normocytic), bleeding, infections, PERIPHERAL CYTOPENIA, HYPOCELLULAR MARROW
- Labs: pancytopenia; maybe luekocytosis (relative), decreased reticulocyte count (BM failure)
- Morphology (BM): hypocellular, yellow marrow (fat; note image on front of card)
- Treatment: Remove causing agent, supportive care, Immunosupressive, HSCT
32
Q
Multiple myeloma
A
- Abnormal plasma cell clonal expansion leading to multiple lytic bone lesions
- Bone lesions caused by myeloma cell production of DKK1 —> IL6 —> RANK-L –> stimulates osteoclasts, inhibits osteoblasts
- IgG > IgA > IgM (Waldenstrom’s Syndrome)
- NOT Monoclonal Gammopathy of Uncertain Significance (MGUS; benign myeloma), Smoldering Myeloma
- Stage1 - Normal Bence Jones; Hg, few lesions
- Stage2 - not 1 or 3
- Stage3 - Lots of Bence Jones, multiple lesions, anemic
- Presentation: old, AA, arthritis, pain; CRAB, cytopenia (plasma cell infiltration), low Ig_ levels (other than IgG)
- DDx: Serum Plasma E-Phoresis –> Immunofixation, M-Spike (monoclonal protein)
- Immunophenotype: CD38, CD138 (Plasma Cell) CD19-, CD20-
- Peripheral Smear: Rouleax formation in blood
- BM: holes in bones; packed with irregular plasma cells
- Deletion of Ch. 17 is key genetic (negative) predictor
- Treatment: Bortezumib (protesomes), lanilomide (mmunomodulator), HSCT
33
Q
Waldenstrom’s hypogammaglobulinemia
A
- Lymphoma producing excess IgM paraprotein caused by maturation arrest b/t mature B-cell and plasma cell
- Act like myeloma, but as a mass they are lymphoma
- Presentation: hyperviscoscity syndrome because of pentameric IgM, NO BONY DESTRUCTION
- DDx: SPEP, Immunofixation
- Treatment: Rituximab, Borezamib, lanalidomide
34
Q
Amyloidosis
A
- Abnormal protein caused by light chain build up
- Associated with chronic inflammation, familial (transtyretin), secondary to myeloma
- Presentation: any organ affected by amyloid – Heart, liver, kidney, macroglossitis (swollen tongue), and
neuropathies - DDx: CONGO RED STAIN–> APPLE RED BIREFRINGENCE
-
Treatment: borizamib, lanilomide
*if familial (transthyretin) –> bone marrow transplant
