Hemepath Missed Questions Flashcards
What immunophenotype in B-ALL indicates a possible MLL gene rearrangement ?
CD10 negative and CD15 positive
Infantile acute lymphoblastic leukemia
Translocation (4;11) usually
Associated with Topoisomerase inhibitor use
What findings are usually absent in cases of Toxoplasmosis?
Neutrophils, eosinophils and areas of necrosis
What is the most common secondary cytogenetic abnormality in Burkitt lymphoma that may indicate disease progression?
Duplication of 1q
- other abnormalities include trisomies of 7 and 12
Cyclin D1 is what type of gene?
Cell cycle regulator
What monoclonal proteins are more often associated with plasma cell leukemia ?
- light chain only disease
- IgD
- IgE
What immunophenotypic markers are almost never seen in pure myeloid lineage leukemias ?
- CD79a, CD10, CD2, and CD3
- IMP: CD117 is most specific (other than MPO) for myeloid lineage as compared to CD13 and CD33
What immunophenotype hints at a B-ALL with t(1;19) ?
- positive for CD19, CD10 and CD9
- negative for CD34 and CD20
What are the chromosomes involved in the BCL6-IGH gene rearrangement seen in high grade or DLBCL?
- t(3;14)
What is often seen in lymph nodes involved by Rosai Dorfmann disease ?
- plasmacytosis, polyclonal hypergammaglobulinemia, and occasional Russel bodies
- the histiocytes of Rosai Dorfmann often aberrantly express CD31
What type of molecule is CD31 and what cells normally express it ?
- CD31 is a cell adhesion molecule
- often expressed by endothelial cells, platelets, and granulocytes
What clinical features are seen in Pelger-Huet anomaly?
- developmental delay
- epilepsy
- skeletal abnormalities
What clinical features are seen in myelokathexis ?
- bacterial and fungal infections
- very abnormal, hypersegmented neutrophils
What percentage of DLBCL have the BCL2 gene rearrangement [t(14;18)] ?
- 20-30%
- BCL6 aberrations on chromosome 3 are the most common alterations (30% of cases)
- only 10% of DLBCL have cMYC rearranged, while nearly 100% of BL have it
* of note, if MYC is rearranged, other complex cytogenetic findings are seen in DLBCL but not BL
What can typically be seen in the bone marrow of patient’s with plasma cell myeloma?
- extensive fibrosis
- consider myeloma in the d/d of dry tap bone marrows
What immunophenotype can be seen in ALCL ?
- positive for: CD45, CD7, HLA-DR, CD13, CD16/56, CD25, CD30
- negative for: CD43, CD3, TCR a/b, g/d
What T cell lymphomas are most common in the post-transplant setting ?
- PTCL, NOS
- Hepatosplenic T cell lymphoma
- only ~15% of PTLDs and are usually EBV negative
- worse prognosis than a B cell PTLD
The t(14;18) is specific to Follicular lymphoma, true or false ?
- False
- a subset of DLBCL can also harbor the translocation
In primary effusion lymphoma, it is thought that EBV plays what role?
- EBV is a co-infection that occurs but is not the driving cause of the neoplasm
- HHV8 is the driving infection
* PEL can occur in non HIV patients, usually in areas of high infection with HHV8 (Mediterranean)
What is another type of lymphoma that can arise in the setting of HHV8 ?
- Large B cell lymphoma arising from HHV8 positive multicentric Castlemann disease
Which hematopoietic malignancies are associated with hemophagocytosis ?
- T cell lymphomas in particular- subcutaneous panniculitis like T cell lymphoma
What are independent risk
factors for CLL/SLL ?
- >30% of cells expressing CD49d and CD38
- these are independent poor prognostic risk factors
G-6-PD is part of which pathway?
- enzyme in the pentose phosphate pathway
- hexose mannose phosphate shunt
What is the most common enzyme
deficiency in hereditary erythrocyte disorders
of the glycolytic pathway?
- pyruvate kinase
- accounts for 90% of cases
What is the abnormal immunophenotype
for BPDCN ?
- same immunophenotype as normal PDCs CD123, CD4, CD56
- abnormal compared to PDCs
- CD56
- TdT (variable)
- CD43
The presence of what mutation portends
a poor prognosis in AML s with t(8;21) and inv(16)?
- KIT mutations
Note: the gene rearrangement de novo AMLs frequently have a normal karyotype.
Also, note, JAK2 mutations are not seen in de novo AML
What are Dohle bodies composed of and what situations can they be seen in?
- seen in high turnover rates of neutrophils, often more common in progranulocytic stage - composed of endoplasmic reticulum * they contain high RNA content so will be destroyed by ribonucleases - can be seen in normal pregnancy (who knew)
What is a relatively specific sign for infection and/or acute alcohol poisoning on a peripheral smear ?
- neutrophils with cytoplasmic vacuoles
In what situations can you see
myeloid hyperplasia in the bone marrow ?
- lithium therapy (shows maturation)
- chronic infection
- G-CSF therapy
- MPN
Note: corticosteroids do not cause myeloid hyperplasia but rather cause peripheralization of the neutrophils (peripheral blood neutrophilia)
In what situations can marginal zone hyperplasia
be seen in the spleen?
- any time there is a sustained humoral reaction you can see this
- ex: autoimmune disease
- note the differences with marginal zone lymphoma
- effacement of the germinal cener and mantle zone by small B cells
What B cell lymphoma usually
demonstrates Trisomy 18 ?
- MALT lymphoma
t(11;18) is seen in which type of
MALT lymphomas ?
- gastric
- pulmonary
- this is the API2 and MALT1 genes
What abnormalities when present together
can indicate CMML with the right
morphologic context ?
- TET2
- SRSF2
- these mutations are characteristic of CMML
What type of cell is decreased in
anemia of chronic disease ?
- siderocytes are decreased
- these cells are normal erythroids with iron granules within their cytoplasm
- these cells can incorporate iron into hemoglobin, unlike ring sideroblasts which cannot
- note:
- storage iron can be normal or increased
What nonclonal conditions can
cause ring sideroblast formation?
- hereditary sideroblastic anemia
- alcoholism
- lead poisoning
- zinc toxicity
- some antimicrobials such as INH and chloramphenicol therapy
What is the morphology of
splenic peliosis ?
- non-neoplastic blood filled cavities haphazardly scattered throughout the splenic red pulp
- isolated splenic lesions in peliosis are rare
- the blood filled spaces generally lack an endothelial cell lining
What is unique about the immunophenotype
of Littoral cell angiomas ?
- they express both endothelial and histiocytic markers (CD31, CD34, CD68, CD163)
- this is a benign entity
What is the most common tumor of the spleen ?
- Hemangioma
- must rule out angiosarcoma which should be atypical, have mitosis and show infiltrative growth
What immunophenotype supports a lymphangioma
of the spleen ?
- D2-40
- also these can variably express other vascular markers such as CD31, CD34, Factor VIII
What gene can be rearranged in a minority
of cases of MALT lymphoma ?
- BCL10 gene at 1p22
Review morphology of
Infectious mononucleosis
- predominantly paracortical hyperplasia with some follicular hyperplasia
- paracortex is moth eaten
- polymorphous lymphocytic infiltrate is usually seen with scattered immunoblasts, sometimes the immunoblasts can form clusters or sheets and mimic DLBCL
What is basophilic stippling and in what
conditions is it normally seen ?
- denatured ribosomal RNA
- seen in:
- thalassemias
- MDS
- lead poisoning
What are the features of
Congenital Dyserythropoietic Anemia Type I ?
- negative RBC agglutination by anti-i and anti-I
- negative serum acidified test (Ham Test)
- Morphology:
- erythroid precursors have thin chromatin bridges between erythroblasts
- incompletely divided erythroid precursors
What are the features of Congenital Dyserythropoietic Anemia
Type II ?
- positive agglutination test by anti-i and anti-I
- positive acidified serum test (Ham Test)
- HEMPAS is a synonym for this disorder
- Hemolytic anemia with a positive acidified serum acid test
- Morphology
- numerous binucleate and rare multinucleated polychromatic erythroblasts
What are the features of Congenital Dyserythropoietic
Anemia Type III ?
- negative for RBC agglutination with anti-i and anti-I
- negative acidified serum test (Ham Test)
- Morphology
- giant, multinucleated erythroblasts
Note: there are 3 major types of CDA
What is the expression of CD43
in Follicular Lymphoma?
- negative for CD43
IMP: Mantle cell lymphoma, CLL and Marginal zone are often positive for CD43
What is the clinical presentation
of Parvovirus B19?
- called Fifth’s disease or erythrema infectiosum
- viral prodrome with slapped cheek effectn and anemia
- it can be associated with pure red cell aplasia
- will see giant pronormoblasts with viral inclusions in the bone marrow
- Parvovirus spreads:
- respiratory secretions
- transplacental (mom to baby)
- blood transfusions
What clinical features would
suggest Fanconi Anemia ?
- presentation of bone marrow failure
- abnormal skin pigmentation (cafe au lait)
- skeletal abnormalities
- mental retardation
- short stature
- renal abnormalities
- IMP more common in:
- Ashkenazi Jews
- South Africans
What is the genetic defect in
Fanconi anemia and its inheritance pattern?
- disorder in 1 out of 15 genes important for DNA repair
- causes DNA damage in hematopoietic and epithelial cells
- most common inheritance pattern:
- Autosomal recessive
- less likely X-linked recessive
How is Fanconi Anemia diagnosed
and what are these patients at risk for?
- Diagnosis:
- lymphocytes and fibroblasts are hypersensitive to DNA cross-linking agents such as mitomycin
- positive chromosome breakage studies
- At risk for:
- aplastic anemia usually develops by age 10
- if they survive this at risk for MDS, AML and other epithelial malignancies
What are the findings in Wiskott Aldrich Syndrome ?
- eczema
- thrombocytopenia with small platelets
- immune deficiency
What are the findings of WHIM syndrome ?
- Warts
- Hypogammaglobulinemia
- infections
- Myelokathexis
- causes retention of neutrophils in bone marrow
IMP: appears to only affect neutrophils
What are the key findings in
Chediak Higashi Syndrome ?
- microtubule polarization defect (LYST gene)
- anemia, neutropenia, numerous infections (defect in phagocytosis)
- platelet dysfunction (first wave only)
- oculocutaneous albnism and neurologic defects
- abnormally giant granules in granulocytes that range in color from gray to red
What are features of dyskeratosis congenita?
- defects in telomerase maintenance (multiple genes)
- pleiotropic effects mimicking premature aging in multiple different organ systems
- one or more hematopoietic lineages are affected
What is the major feature of
Diamond Blackfan anemia ?
- erythrocyte lineage is affected only
What are the key features
of Schwachman Diamond Syndrome ?
- defect in SBDS gene
- exocrine pancreatic insufficiency
- bone marrow dysfunction
- skeletal abnormalities
- short stature
What are the key features of severe
congenital neutropenia?
- mutations in ELA2 (neutrophil elastase)
- mutations in SCN2 (cyclical neutropenia)
On a CSF specimen how are
Medulloblastoma and ALL differentiated ?
- Medulloblastoma can show nuclear molding while ALL should not
- nucleoli in medulloblastoma can be inconspicuous or prominent
What is the normal counterpart cell
to ALCL ?
- ALK positive is derived from CD4 positive T cells with cytotoxic features
Which lymphoma is characteristically derived
from NK cells or Cytotoxic T cells ?
- Extranodal NK/T cell lymphoma
- usually more NK cells but can be a subset from T cells
- this lymphoma usually involves the nasal cavity but secondary lymph node involvement can be seen
Which lymphoma is from
precursor Thymic T cells ?
- T-ALL
Which lymphoma is derived from gamma delta
T cells ?
- hepatosplenic T cell lymphoma
- certain GI lymphomas
- primary cutaneous gamma delta T cell lymphoma
IMP: none of these lymphomas go to the lymph nodes
