L20- WBC Pathology I Flashcards
what are the 2 general WBC disorders, include examples
Leukopenia: lymphopenia, neutropenia
Leukocytosis: reactive leukocytosis, neoplastic leukocytosis
define lymphopenia and provide common examples
-reduced lymphocyte count Ex: -advanced HIV -autoimmune disease -acute viral infections -drug induced (chemotherapy, steroid therapy)
define neutropenia and the 2 general mechanisms that cause it
-reduced neutrophil count
i) reduced / ineffective production (bone marrow issue)
ii) accelerated consumption / destruction (peripheral issue)
list the ways Neutropenia is caused by reduced production (hint- 5)
- myeloid stem cell suppression: eg. aplastic anemia (usually idiopathic)
- committed myeloid precursor suppression (usually drug induced)
- ineffective granulopoiesis: megaloblastic anemia, myelodysplastic syndromes
- marrow infiltration: granulomas, malignancies
- rare inherited disorders: eg. Kostmann syndrome, cyclic neutropenia
list the ways Neutropenia is caused by increased consumption or destruction
- Immune-mediated: auto-immune disease, drugs
- Splenic sequestration of blood cells, as in splenomegaly
- Increased consumption, during overwhelming infection
Complications of Neutropenia:
-(1) is a complication of severe anemia with (2) levels and can lead to (3)
-most severe neutropenia is due to (4), where the effect is defined as either (5) or (6)
1- agranulocytosis
2- <500 cells/µL
3- life-threatening infection
4- drugs
5- predictable: dose-related (chemotherapy)
6- idiosyncratic: many drugs, mostly immune mediated by precursor suppression
Patients with neutropenia will present with (1). Most treatment involves (2). In cases of predictable neutropenia (via dose-related issue), (3) treatment may also be necessary.
1- signs and Sxs of related infections
2- broad spectrum antibiotics
3- G-CSF replacement therapy
list the forms of reactive leukocytosis
- neutrophilic
- eosinophilic
- basophilic
- monocytic
- lymphocytic
neutrophilic leukocytosis (reactive), aka (1), is caused by one of either (2), (3), (4)
1- neutrophilia
2- acute inflammation
3- acute hemorrhage
4- malignancy (extensive, necrotic tumors)
list some examples of how acute inflammation causes reactive neutropenia
- infections: pyogenic bacteria
- following tissue damage: burns, MI, trauma, surgery
- chemical or Ab deposition: gout, RA
what are the 2 main features of neutrophilic leukocytosis (reactive) on peripheral blood smear
- neutrophils contain purple cytoplasmic granules / toxic granulations
- neutrophils contain blue cytoplasmic patches of ER / Dohle bodies
(-inc band cells, less lobulated nuclei)
list the causes of (reactive) eosinophilic leukocytosis (hint: 6, include alternate name)
(eosinophilia)
- allergic disorders (asthma, hay fever)
- skin diseases (pemphigus vulgaris, bullous pemphigoid, dermatitis herpetiformis)
- parasitic infestations
- collagen vascular diseases (vasculitis)
- drug reactions
- malignancies (Hodgkin lymphomas)
Basophilic leukocytosis, aka (1) is a (commonly/rarely) reactive in nature, and will almost always indicate (3).
1- basophilia
2- rarely reactive
3- myeloproliferative neoplasm, like CML
list some causes of reactive monocytosis
- chronic infections: Tb, rickettsiosis, bacterial endocarditis, malaria)
- Collagen vascular disease (SLE)
- IBD (UC)
reactive lymphocytosis is seen in many disorders involving (1), or in (2) or (3) infections
1- chronic immunologic stimulation
2- viral infections (EBV, HepA, CMV)
3- B. pertussis infection
list the features of reactive lymphocytosis on peripheral blood smear (hint- 4 main ones)
(reactive atypical lymphocytes, eg. infectious mononucleosis)
- larger than normal
- more cytoplasmic content
- eccentric large nucleus
- membrane attachment to RBCs
Reactive lymph node:
- (1) is the result of B-cell response
- (2) is the result of T-cell response
- (3) is the result of plasma-cell response
1- follicular hyperplasia (cortical region)
2- parafollicular / interfollicular hyperplasia
3- sinus histiocytosis: dilated sinusoids containing histiocytes OR Medullary expansion
If there is reactive leukocytosis in peripheral blood, what are the differential diagnoses that needed to be compared
i) reactive increase in granulocytes / leukemoid reaction VS CML
ii) reactive lymphocytosis VS chronic lymphocytic leukemia
If there is reactive leukocytosis in lymph nodes, what are the diagnoses that need to be compared
reactive lymph node VS lymphoma
In children, lymphadenopathy is most indicative of (1). Lymph nodes are described as (2). (3) may be an important finding in history.
- (4) is a key rule
- patients must f/u in (5) fashion
1- reactive lymphadenopathy (common; cervical, axillary, inguinal area)
2- tender, but mostly asymptomatic
3- h/o infection / rash
4- no rush to biopsy
5- every 2-3 mos to observe for a dec in size
In adults, lymphadenopathy is less indicative of (1) and more concerning for (2). (3) is the protocol if there is no obvious cause.
(adults >40 y/o)
1- reactive adenopathy
2- malignancy- lymphoma, metastatic CA
3- FNA (fine needle aspiration) or Tissue biopsy
define:
(1) leukemia
(2) lymphoma
Leukemia: neoplasia involves predominately bone marrow (and usually peripheral blood) // affects myeloid and lymphoid progenitors
Lymphoma: neoplasia forms discrete tissue masses in lymph nodes or extranodal areas // affects lymphoid progenitors
describe the difference in presentation of Acute VS Chronic leukemia
Acute- precursor cells predominate (note- not used to describe lymphomas)
Chronic- mature differentiated cells predominate
what are the 5 common sources for WBC malignancy
- chromosomal translocations and oncogenes
- inherited genetic factors (down syndrome)
- environmental agents (viruses, bacteria)
- immune dysregulation
- iatrogenic (radiation, chemotherapy)
list the 3 mutations causing WBC malignancies, provide examples
Pro-growth: TK mutations, MYC translocation
Pro-survival: BCL2 translocation
Increased self-renewal: MLL translocation, PML-RARA fusion gene
what are the 2 classifications of lymphomas
Non-Hodgkin Lymphoma / leukemia including plasma cell neoplasms
Hodgkins Lymphomas
what are the classifications of leukemia
- acute myeloid leukemia
- myelodysplastic syndrome
- chronic myeloproliferative neoplasms
what are the additional classifications of Non-Hodgkin’s Lymphoma / Leukemia (according to WHO)
(note- hodgkin’s has no other sub-classifications)
- precursor lymphoid neoplasms
- mature / peripheral B-cell neoplasm
- mature T/NK cell neoplasm
- 60% of NHL / HL (H- Hodgkins, L-lymphoma) patients will present with (1)
- 40% of NHL are in (2) location and will present with (3)
1- nontender lymph node enlargement
2- extra-nodal (GIT, skin, brain, breast)
3- site related Sxs
the signs and symptoms of leukemia include….
mainly related to bone marrow replacement –> cytopenias
plasma cell neoplasms with result in and present with….
bone destruction => bone pain due to pathological fractures
> 90% of lymphoid neoplasms are composed of (1), therefore (2) stage is very important. Most lymphomas show (3) property, therefore all neoplastic cells share (4), detectable by (5).
1- B-cells 2- stage b-cell differentiation 3- clonality 4- Ag receptor gene arrangement pattern 5- PCR / molecular genetics
B-cell neoplasms will show (1) as an essence of monoclonality and expressing it as (2) or (3) detectable by (4).
1- light chain restriction
2- κ-chains
3- λ-chains
4- flow cytometry or immunohistological stains
Most lymphoid neoplasms have recurrent (1) abnormalities to help aid its diagnosis, which is detected by (2)
1- cytogenic abnormalities / frequent translocations
2- FISH
Pair the recurrent translocation with the NHL type:
1) t(8;14
(2) t(11;14)
(3) t(11;18)
(4) t(14;18)
1- Burkitt lymphoma
2- mantle cell lymphoma
3- MALT lymphoma
4- follicular lymphoma
Pair the type of NHL with the associated recurrent translocation:
(1) Burkitt lymphoma
(2) follicular lymphoma
(3) MALT lymphoma
(4) mantle cell lymphoma
1- t(8;14)
2- t(14;18)
3- t(11;18)
4- t(11;14)
