Term
B-ALL
majority of ALL's are pre-B |
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Definition
Bone marrow precursor B cell
mainly kids
sx relating to marrow replacement and pancytopenia
aggressive
+TdT, CD19, PAX5, CD10 (CALLA)
(in very immature B-ALLs, CD10 is -)
+/- CD20 (mature B-ALLs express CD20, as well as IgM heavy or mu chain)
Hyperdiploidy and hypodiploidy |
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Term
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Definition
Precursor T cell (often thymic origin)
NOTCH1 mutations (50-70%)
Mainly adolescent males
Thymic masses and variable BM involvement
Aggressive
+TdT, CD1, CD2, CD5, CD7
(-) CD10
"late" T-ALLs: + CD3, CD4, CD8 |
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Term
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Definition
Germinal center B cell
Translocation involving c-MYC and Ig loci, usually t(8;14)
subset EBV-associated
Adolescents or young adults with extranodal masses, rapidly proliferating
Uncommonly presents as "leukemia"
Aggressive
+IgM, CD19, CD20, CD10, BCL6 (indicates germinal center origin)
(-) BCL2
*all forms have translocations of c-MYC gene on csome 8*
starry sky: neoplastic B cells and reactive histiocytes with phagocytic debris |
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Term
| Diffuse large B-cell lymphoma |
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Definition
Germinal-center or post-germinal-center B cell
Diverse rearrangements:
- BCL6 (30%)
- BCL2 (10%)
- c-MYC (5%)
All ages, but MC in adults
Often appears as rapidly growing mass
30% extranodal
Aggressive
+ CD19, CD20
subtypes:
immune-def-assoc: EBV
malignant effusion: KSHV/HHV-8 |
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Term
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Definition
Memory B cell
in between reactive lymphoid hyperplasia and lymphoma - polyclonal to monoclonal transition during lymphomagenesis
t(11:18) - MALT1-IAP2
t(1:14) - BCL 10-IgH
t(14:18) - MALT1-IgH
Arises at extranodal sites in adults with chronic inflammatory diseases
May remain localized
Indolent
May regress if inciting agent is removed
H. pylori, salivary gland (Sjogren), thyroid (Hashimoto's) |
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Term
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Definition
Germinal center B cell
*t(14:18) BCL2-IgH*
Older adults with generalized lymphadenopathy and marrow involvement
Indolent
+CD19, CD20, CD10, surface Ig, BCL6
**(-) CD5!**
centrocytes & centroblasts
effaced lymph nodes |
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Term
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Definition
Memory B cell
*the only leukemia w/o lymphadenopathy*
Older males with pancytopenia and splenomegaly, 1/3 present with infxns
Indolent
+CD19, CD20, Ig, CD11c, CD25, CD103
reticulin fibers, dry tap
+TRAP stain |
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Term
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Definition
Naive B cell
*t(11:14) CyclinD1-IgH*
Older males with disseminated disease
Moderately aggressive
*high cyclinD1*, +CD19, CD20, CD5
(-) CD23 (diff from CLL)
(-)CD10, CD23 |
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Term
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Definition
Post-germinal-center bone marrow homing plasma cell
Diverse rearrangements involving IgH
13q deletions
Older adults with lytic bone lesions, pathologic fractures, hypercalcemia, and renal failure
Moderately aggressive |
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Term
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Definition
Naive B cell or memory B cell
Older adults with bone marrow, lymph node, spleen, and liver disease
Hypogammaglobulinemia (neoplastic B cells don't form plasma cells)
Smudge cells
Increased incidence of immune hemolytic anemia (both warm and cold types)
Indolent
proliferation centers (have mitotically active cells) = pathognomonic
+CD19, CD20, *CD23, CD5*
low-level expression of surface Ig
tends to transform to more aggressive tumors!
-prolymphocytic
-Richter syndrome (diffuse large B cell lymphoma) |
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Term
| Adult T-cell leukemia/lymphoma |
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Definition
Helper T cell
HTLV-1
Adults with cutaneous lesions, marrow involvement, and hypercalcemia
Mainly in Japan, West Africa, and the Caribbean
Aggressive
CD4+, TdT(-) |
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Term
| Peripheral T-cell lymphoma |
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Definition
Helper or cytotoxic T cell
No specific chromosomal abnormality
Mainly older adults
Usually presents with lymphadenopathy
Aggressive
diffuse effacement of LN, pleomorphic mix of different size malignant T cells
reactive cell infiltrate
worse prognosis than mature B cell neoplasms
+CD2, CD3, CD5, TCR
+/- CD4 or CD8 |
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Term
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Definition
NK-cell (common) or cytotoxic T cell (rare)
EBV-associated
Adults with destructive extranodal masses
Most commonly sinonasal
Aggressive |
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Term
| Mycosis fungoides/Sezary syndrome |
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Definition
Helper T cell
no specific chromosomal abnormality
Adult patients with cutaneous patches, plaques, nodules, or generalized erythema; indolent
CD4+
tumor cells expression CLA, CCR4, CCR10 - help home CD4+ T cells to skin |
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Term
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Definition
BCR-abl fusion gene, Philadelphia chromosome
CML
myeloproliferative disorder, increased basophils
hepatosplenomegaly & generalized painless lymphadenopathy due to EMH & metastasis
Blast crisis - progresses to AML (70% of cases) or ALL (30% of cases)
- blasts DON'T contain Auer rods
PBS may look like BM aspirate
increased M:E
platelets normal or i/c in most patients early in disease
decreased LAP score
tx = imatinib |
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Term
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Definition
a tyrosine kinase
PCV
Essential thrombocytosis/thrombocytopenia (also MPL)
primary myelofibrosis (also MPL)
MPL - normally activated by thrombopoietin |
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Term
| Langerhans cell histiocytosis |
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Definition
| expresses both CCR6 and CCR7 - chemokine receptors that allow neoplastic cells to migrate into tissues: skin and bone, lymphoid organs |
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Term
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Definition
| Directly inhibits Gp IIb/IIIa, thereby inhibiting platelet aggregation |
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Term
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Definition
| inhibits epoxide reductase |
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Term
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Definition
inhibits II, VII, IX, X, XI
activated by heparin |
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Term
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Definition
| asplenia, liver disease, thalassemia |
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Term
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Definition
| triad of iron deficiency anemia, esophageal web, and atrophic glossitis |
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Term
| drugs that cause folate deficiency |
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Definition
methotrexate
trimethoprim
decrease purine synthesis |
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Term
drugs that bring on crisis in G6PD def
when do you do the assay? |
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Definition
sulfa drugs
primaquine
decreased glutathione (in pentose phosphate pathway) increases RBC susceptibility to oxidant stress
cross-linking of sulfhydryl groups
NOT when they're hemolyzing! Do it before tx, or after they're done with hemolysis. G6PD levels are lowest in old RBCs. |
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Term
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Definition
negative direct Coombs
defects in akyrin, band 3.1, spectrin
*increased* MCHC, RDW
B19 infxn --> aplastic crisis
calcium bilirubinate gallstones |
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Term
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Definition
ITP: anti-Gp IIb/IIIa antibodies cause platelet destruction. See i/c megakaryocytes in labs
TTP: deficiency in ADAMTS13 (a vWF metalloprotease) causes decreased degradation of vWF multimers
big vWF multimers cause increased platelet aggregation & thrombosis
labs: schistocytes, i/c LDH
pentad: neurologic, renal, fever, thrombocytopenia, microangiopathic hemolytic anemia |
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Term
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Definition
acute phase reactant in response to inflammation (IL-6)
enters mac's in bone marrow
prevents release of iron to transferrin (inhibits ferriportin) |
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Term
| why is increased HbF in sickle cell anemia good? |
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Definition
causes left shift of O2 binding curve, increased affinity of RBCs for O2
a right shift in the O2 binding curve (acidosis) causes release of O2 from RBCs, causing sickling |
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Term
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Definition
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Term
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Definition
i/c unconj bilirubin, jaundice, i/c LDH (that also happens in intravascular hemolysis)
sickle cell, spherocytes; IgG mediated hemolysis |
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Term
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Definition
d/c haptoglobin; hemosidenuria; hemoglobinuria; possible iron deficiency
mechanical damage; G6PD def; IgM-med hemolysis; PNH |
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Term
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Definition
| Sickle cell disease (complication of) |
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Term
| Calcium bilirubinate gallstones |
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Definition
d/t increased conjugated bilirubin in bile from chronic hemolysis
HbS, HbAS
hereditary spherocytosis |
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Term
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Definition
40-45% HbS
normal PBS
isosthenuria over time
microhematuria (d/t necrosis of renal papillae) |
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Term
| Protective against P. falciparum? |
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Definition
Beta thalassemia
G6PD deficiency |
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Term
| Drug-induced (warm) autoimmune hemolytic anemia |
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Definition
Pencillin, cephalosporin (IgG Ab against drug attached to RBC membrane)
Quinidine (immunocomplex)
alpha-methyldopa (autoantibody induction against Rh antigens) |
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Term
Malaria: (P. falciparum)
proteins that cause rosette formation
protein that causes sequestration
what causes cerebral malaria? |
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Definition
ICAM-1, CD36
pfEMP1 (induced by increased NO, which causes tissue damage)
ischemia d/t poor perfusion |
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Term
Protection against malaria:
HbS
HbC
G6PD deficiency
Duffy antigen (P. vivax)
people living in endemic regions... |
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Definition
HbS decreases low O2 concentration
HbC reduces parasite proliferation
G6PD deficiency reduces lifespan of RBCs
Blacks often lack the Fy Ag on RBCs, which is the binding site for P. vivax
...often show immune-mediated resistance (Ab and T lymphocytes) |
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Term
leukoerythroblastic rxn
dry tap |
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Definition
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Term
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Definition
burning, throbbing of hands and feet
occurs in myeloproliferative disorders (PCV, ET)
due to arteriolar occlusion by platelets |
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Term
| myelodysplastic syndromes |
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Definition
neoplastic myeloid disorders (same category as MPS)
BM is replaced by clonal cells that can differentiate, but do so in a disordered fashion --> abnormal myeloid cells that stay in the BM, severe pancytopenias
refractory anemia, ringed sideroblasts
frequent transformation to AML
*pseudo Pelger-Huet cells* (2-lobed nucleus)
megaloblastoid cells
fragmentation, nuclear budding
giant platelets, pawn ball megakaryocytes
myeloblasts <20% (if >20%, progressing to AML) |
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Term
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Definition
acute promyelocytic leukemia (M3)
lots of Auer rods
DIC
lots of granules
tx = ATRA (antagonizes fusion protein) |
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Term
| Hand-Schuller-Christian triad |
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Definition
Form of Histiocytosis X
lytic lesion in skull
diabetes insipidus
exophthalmos
(also get fever and localized rash on scalp and in ear canals) |
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Term
| why do you get rouleaux formation? |
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Definition
in MM, the high level of M protein causes the RBCs to stick together.
seen in conditions in which Ig levels are elevated |
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Term
| Lymphoplasmacytic lymphoma |
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Definition
Waldenstrom's macroglobulinemia
Tumor B cells differentiate --> plasma cells that secrete *IgM*
behaves like CLL/SLL
generalized lymphadenopathy
hyperviscosity syndrome: retinal hemorrhages, HA, neuro, cryoglobulinemia, platelet aggregation defects |
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Term
| in DIC, which coagulation factors are consumed? |
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Definition
| I, II, V, VIII (these are what are required to make thrombi); also platelets |
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Term
| Prolonged PTT that doesn't correct with mixing studies |
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Definition
Antiphospholipid syndrome (an acquired thrombosis syndrome)
highest assoc w/ SLE (also RA, Sjogren's HIV)
antiphospholipid Abs, anticardiolipi Ab, lupus anticoagulant
False + syphilis serologic test if anticardiolipin Ab are present |
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Term
| no prolongation of PTT after administering heparin? |
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Definition
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Term
| ABO determination (forward/backward type) |
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Definition
forward type: identifies the blood group Antigen - patient RBCs are added to test tubes
Blood group A RBCs will agglutinate with anti-A test serum but not anti-B test serum |
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