Pathology of white cell disorders II - Zaloga Flashcards
1
Q
precursor B and T cell neoplasms
A
- immature big blast cells
- usually leukemia, sometimes lymphoma
2
Q
peripheral B and T cell neoplasm
A
- mature cells that go to secondary lymphoid organ
- usually lymphoma
3
Q
Hodgkin lymphoma
A
-Reed-sternburg cells*** and variant cells
4
Q
lymphoid neoplasm
A
- from B or T cell differentiation
- antigen receptor genes/proteins distinguish between reactive (polyclonal) and malignant (monoclonal) tumors
5
Q
what can plasma cells lead to?
A
multiple myeloma
6
Q
what are surface markers used for?**
A
- recognized by antibodies to distinguish between lymphomas and leukemias
- B cells: markers CD10,19,20,21,23,79a
- T cells: markers CD1-8
- Monocyte/macrophage: markers CD11c,13,14,15,33,64
- NK: markers CD16,56
- HSC: marker CD34
- marker on all leukocytes: CD45
7
Q
Acute lymphoblastic leukemia
A
- most common cancer in children**
- B-ALL (most common; in child) and T-ALL (adolescence; thymic lymphoma) –> tDt present in both**
- good regression with chemo
- t(12;21) –> good prognosis**
- antibody test to differentiate from AML
- hypercellular marrow packed with lymphoblasts
8
Q
B-ALL markers**
A
- PAX5, CD 10, 19, 22 (higher numbers)
- loss of function mutations via t(12;21) involving genes ETV6 and RUNX1
- contain tDt
9
Q
T-ALL markers **
A
- CD 1,2,5,7
- gain of function mutations in NOTCH1
- contain tDt
10
Q
chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL)
A
- most common leukemia of adults
- CLL if mature cell count is high in peripheral blood, lymphoma if count is low
- usually proliferation of naive B cells –> won’t make mature Igs
- growth confined to proliferation centers
- translocations rare
- usually asymptomatic in patients
- more mutations can lead to diffuse large B cell lymphoma aka Richter syndrome**
- lymph nodes effaced by small lymphocytes –> won’t see follicles
- infiltrate spleen, portal tracts, marrow interstitium
- SMUDGE cells***
11
Q
CLL/SLL markers
A
- CD5**, 19, 20, 23
- smudge cells on blood smear**
12
Q
follicular lymphoma
A
- most common indolent NHL
- translocations of t(14;18) –> BCL-2 over expression** –> no apoptosis
- more mutations –> can progress to diffuse large B cell lymphoma
- infiltrates spleen and marrow paratrabeculae
- contain centrocytes and centroblasts
13
Q
follicular lymphoma markers**
A
- CD 10,19,20
- BCL-2 positive**
- CD5 negative, unlike mantle cell lymphoma
14
Q
diffuse large B cell lymphoma (DLBCL)
A
- most common form of NHL**
- mutation in t(14;18) is rare –> BCL-2 over expression
- mutation in BLC6** (transcription repressor for normal germinal centers)
- aggressive, enlarged lymph node or extra nodal mass**
- enlarge spleen - risk of rupture
- subtypes: 1. Immunodeficiency-associated large B-cell lymphoma in severe T-cell immunodeficiency 2. Primary effusion lymphoma
15
Q
DLBCL markers**
A
-CD 10, 19, 20, and BCL6**
16
Q
burkitt lymphoma
A
- fastest growing human tumor**
- very aggressive, responds well to chemo
- african (endemic) –> mandible mass**
- sporadic (nonendemic) –> ileocecum or peritoneum mass**
- not in bone marrow
- translocations in MYC gene (chromosome 8) to Ig heavy chain t(8;14)**–> increase MYC expression (cell growth)
- all endemic burkitt lymphoma latently infected with EBV***
17
Q
Burkitt lymphoma markers**
A
- IgM, CD10, 19, 20, BLC6*
- usually fails to express BCL6
- many mitoses and macrophages forming “starry sky”***
18
Q
plasma cell neoplasms
A
- B-cell proliferations with neoplastic plasma cells that secrete monoclonal Ig or Ig fragment (marker for tumors)
- multiple myeloma most common and deadly**
19
Q
multiple myeloma**
A
- most common primary malignancy of bone**
- plasma cell neoplasm with lytic bone lesions, hypercalcemia, renal failure, and acquired immune abnormalities
- destructive plasma cell tumors (plasmacytomas)
- high serum IL-6 (growth factor) –> stimulates plasma cell growth and Ig production
- translocations of IgH, cyclin D1,D3**
- deletions of chromosome 17p (TP53 tumor suppressor)*
- expansion of plasma cells, crowding out other cells –> cytopenias
20
Q
clinical symptoms of multiple myeloma**
A
- bone pain with hypercalcemia –> plasma cells activate RANK on osteoclasts –> bone destruction –> “punched out/lytic skull lesions”, hypercalcemia, risk for fratcture
- elevated serum protein - plasma cells tumors produce Ig –> M spike** due to monoclonal IgG and IgA
- increased risk of infection - monoclonal antibody lacks antigen diversity –> produce exact same antibody (lost diversity)
- rouleaux formation - increasing serum protein decreases charge b/w RBCs
- primary AL amyloidosis - overproduce light chain –> free light chain in serum & tissue deposits –> develop amyloidosis
- light chain –> blood –> amyloidosis
- light chain –> urine –> Bence Jones protein
- light chain –> kidney –> myeloma kidney - proteinuria - light chain excreted in urine as Bence Jones protein and in kidney tubules causing renal failure
21
Q
waldenstrom maroglobulinemia
A
- B cell lymphoma that produces monoclonal IgM
- high IgM, hyperviscosity of blood, and associated with lymphoplasmacytic lymphoma
22
Q
Monoclonal gammopathy of undetermined significance (MGUS)
A
- M components (spike), common in elderly, may transform to symptomatic MGUS
- can develop into multiple myeloma**
23
Q
multiple myeloma markers**
A
- CD 138, often CD56 POS**
- reactive plasmacytosis or MGUS is CD56 NEG**
24
Q
lymphoplasmacytic lymphoma
A
- neoplasm of small lymphocytes, plasma cells, and plasmacytoid lymphocytes
- unlike MM, bone destruction does not occur with secretion of light chains**
- mutations in MYD88, which activated NFkB**
- IgM producing tumor** –> hyperviscosity, visual problems, bleeding, and hemolysis
- alleviated by plasmapheresis
25
lymphoplasmacytic lymphoma markers**
-CD20 and surface IgM**
26
mantle cell lymphoma
- t(11;14) involving IgH locus and cyclinD1** --> over expression of cyclin D (progress from G1 --> S phase)**
- naive B cells surround mantle zone
- poor prognosis, no response to chemo, organ dysfunction
27
mantle cell lymphoma markers**
- high cyclin D1, CD19,20
| - usually CD5 pos and CD23 neg** (CLL is CD23 pos)**
28
hairy cell leukemia (rare)
- activating mutations in serine/threonine kinase BRAF**
- see splenomegaly and pancytopenia --> infections if neutrophils are sequestered***
- bone marrow fibrosed and cells trapped in red pulp
- hairy cytoplasmic projections***
- respond to chemo but relapse
29
hairy cell leukemia markers**
- CD19,20, and Ig
| - also CD11c, 25**
30
peripheral T cell lymphoma
- "wastebasket" diagnosis (hard to categorize)
- markers: CD 2,3,5***; also either alpha/beta or gamma/delta T cell receptors**
- see lymphadenopathy, eosinophilia, pruritus, fever, weight loss
- bad prognosis
31
adult T cell leukemia/lymphoma
- neoplasm of CD4+ T cells**
- adults infected with HTLV-1**
- skin lesions, lymphadenopathy, hepatosplenomegaly
32
large granular lymphocytic leukemia (LGL)
- both T and NK cell neoplasm variants**
- T cell --> lymphocytosis and splenomegaly
- NK cell --> no lymphocytosis or splenomegaly
- mutations in STAT3***
- azurophilic granules in cytoplasm
33
LGL markers**
- T cell markers: CD3+**
| - NK cell markers: CD3-, CD56+**
34
Hodgkin lymphoma
- giant cells called Reed-Sternburg cells** (Owl's eye - bilobed nucleus)
- RS cells release cytokines that attract reactive cells forming B symptoms
- RS cells have B cell genes, but do not express them on surface (not B cell phenotype)***
- associated with EBV (LMP-1 encoded protein from EBV unregulated NFkB); EBV proteins can change B cell into RS cell
- gains in REL porto-oncogenes
- unexplained fever, night weights, unexplained weight loss** further stages the tumor (also seen in NHL)
- orderly node progression (stages I-IV)
- lacunar cells** in nodular sclerosis
- popcorn cells** in lymphohistiocytic variants
35
Hodgkin lymphoma variants
1. nodular sclerosis**: most common ("classical"), enlarged cervical or mediastinal lymph node divided by sclerosis --> lacunar cells**
- markers PAX5,CD15,30; neg for T cell markers and CD45
2. mixed cellularity: cellular infiltrate (predominantly eosinophilia due to IL-5)
3. lymphocyte depletion: least common, most aggressive, seen in HIV and elderly
4. lymphocyte rich: lymphocytes seen most, best prognosis
5. lymphocyte predominance**: uncommon, "nonclassical" variant
- only one that has B cell phenotype**
- popcorn cells** instead of classical RS cells
- markers: CD20, BCL6**, neg for CD15,30**
