Flashcards in WBC Hematopathology Part 1 Deck (223):
What technologies were needed to establish flow cytometry?
2. Computer processing
3. Monoclonal antibodies
What outbreak accelerated accpetance of lfow cytometry?
Solution of cells that can be ran through flow cytometry include? 3
1. Peripheral blood
2. bone marrow
3. Solid tumor
How can WBC populations and subpopulations be characterized in flow cytometry?
Number and type of cell surface antigens
CD1-8 is antigen for what cells?
CD 19-20 are antigens for what cells?
CD15 and 56 are antigens for what cells?
CD45 is an antigen for what cells?
What is measured in flow cytometry?
Intensity of scattered light signals from each cell
In flow cytometry, what are the cells labeled with?
How should flow cytometry be used clinically? 2
1. Supplementary to confirm diagnoses made by conventional morphologic studies
2. Provide prognostic information
Flow cytometry is best used how?
Technique to answer specific clinical questions
What should you do before flow cytometry?
Know what information is actually needed
What is immunophenotyping?
Identification and classificaiton of cells by determining the presence of specific cell surface antigens
Antibodies with a similar antigenic reactivity were assigned to what?
HLA-DR antibody is seen where?
In immature cells
Two purposes of analyzing DNA in tumor cells?
1. Identify and quantitate the cell's DNA content
2. Determine the distribution of cells within different phases of cell cycle
How is abnormal DNA content defined in cancer cells
What does aneuploidy reflect?
Chromosomal aberrations or mutations
S-phase analysis examines what?
Proliferative capacity of neoplastic cells
What makes an image of the cell cycle?
What do you call not enough white blood cells?
What do you call too many WBC's?
Two types of leukocytosis?
WBC cancers cause what % of deaths in adults?
9% in adults
40% in kids
Two types of leukopenia?
Main cause of reactive leukocytosis?
Three causes of reactive lymphadenitis?
1. Acute nonspecific lymphadenitis
2. Chronic nonspecific lymphadenitis
3. Cat scratch disease
What is the most common WBC cytopenia
Two ways to get lymphocytopenia?
1. Congenital immunodeficiency disease
2. Acquired (HIV, steroids, drugs, autoimmune, malnutritions, viruses)
Neutropenia has a total neutrophil count of what?
Less than a 1000/uL
What problem does having neutropenia cause?
Increased susceptibility to infection
3 categories of etiologies of neutropenia?
Which is most common
1. Inadequate/ineffective granulopoiesis
2. Accelerated removal of neutrophils
3. Drug toxicity (most common cause)
What would cause inadequate/ineffective granulopoiesis? (3)
1. Suppression of myeloid stem cells (aplastic anemia, leukemia)
2. Suppression of granulocyte precursors by drugs or chemo
3. Ineffective granulopoiesis due to megaloblastic anemia or myelodysplasia
Causes of accelerated removal/destruction of neturophils? 3
1. Immune mediated
2. Used up peripherally to fight infection
3. Splenic sequestration (hypersplenism)
Drug toxicity is related to what 3 drugs?
How does neutropenia present?
How serious can neutropenia get?
Fatal in hours if drops below 500/mm
Major complication of neutropenia?
Treatment for neutropenia? (3)
1. Recombinant hematopoietic growth factors (G-CSF, neupogen)
3. Supportive care
Reactive leukocytosis is a common reaction to what?
Reactive leukocytosis is classified how?
What particular white cell line is affected
What might reactive leukocytosis mimic?
Neutrophils are distributed in what five pools?
1. Precursor pool
2. Storage pool
3. Marginating pool
4. Circulating pool
5. Tissue pool
Bone marrow pool is comparable to peripheral blood pool how for neutrophils?
50X peripheral blood pool
Circulating pool of neutrophils is measured by what?
Glucocorticoids have what effect on neutrophils?
How is this detected?
Decrease extravasation into tissues
Increased WBC count
Neutrophilic leukocytosis causes (7)
1. Acute bacterial infections
2. Sterile inflammation by tissue necrosis
3. Myeloproliferative disorders
4. Malignancy in marrow
5. Physiologic response to stress
Eosinophilic leukocytosis causes? (5)
1. Allergic disorders like asthma
2. Skin diseases (dermatitis)
4. Drug reactions
5. Hodgkin/Non-hodgkin lymphomas
Basophilic leukocytosis cause? 1
Indicates myseloproliferative disease
Monocytosis cause? 3
1. Chronic infections (TB, endocarditis, rickettsia, malaria
2. Collagen vascular disease (SLE)
3. Inflamatory bowel disease
Lymphocytosis causes? 3
1. With monocytosis in chronic immune disease
2. Viral infections
3. Bordatella pertussis
Leukoerythroblastosis means what?
Presence of nucleated RBC's and left shift of the neutrophils (immature neutrophils in blood)
Toxic change in PMN's in neutrophilia? 3
Infectious mononucleosis is seen in what population?
Adolescents and young adults
Cause of infectious mono? 2
B-cell lymphocytotropic EBV
Symptoms of EBV? (7)
2. Sore throat
3. Generalized lymphadenitis
4. Atypical lymphocytes in peripheral blood
5. Lymph node changes
Reactive lymphocytosis may resemble what other disease?
Lymph node changes in infectious mono may mimic what?
Diagnosis of infectious mono? (3)
1. Lymphocytosis with atypical cells
2. Positive monospot test
3. Specific antibodies for EBV
How long does infectious mono last?
Reactive lymphadenitis is defined how?
Immune response against foreign antigens with lymph node enlargement
Acute nonspecific lymphadenitis may be localized where?
Or generalized why?
Local = Focal infection
Generalized = Systemic viral infection or bacteremia
Usual etiology of acute non-spec lymphadenitis?
Leads to what histologic change?
Follicular hyperplasia with large germinal centers
Main symptom of acute nonspecific lymphadenitis?
Nodes affected are enlarged and painful with abscess penetrating to the skin
Two special kinds of acute nonspecific lymphadenitis?
What are bubos?
Enlarged lymph nodes most often associated with bubonic plague
What is scrofula?
Cervical lymphadenitis caused by mycobacteria
Adult cause of scrofula?
Adult = M. tuberculosis
Kids = Atypical tuberculosis
Chronic nonspecific lymphadenitis has what three forms?
1. Follicular hyperplasia
2. Paracortical hyperplasia
3. Sinus histiocytosis
Causes of paracortical hyperplasia? (3)
1. Virus like mono
2. Post vaccination
Are lymph nodes painful in chronic nonspecific lymphadenitis?
Where are the main sites?
Inguinal and axillary
Cat scratch fever is caused by what?
Symptoms of cat scratch fever (2)?
1. Regional lymphadenopathy
2. Stellate necrotizing granulomas
Diagnosis of cat scratch fever? 3
1. Exposure to cats
2. Clinical findings
3. Positive skin test
Lymphoid neoplasms are derived from what?
Lynphocytes and their precursors
4 types of lymphoid neoplasms?
1. Acute leukemias (immature lymphocytes ALL)
2. Chronic leukemias (mature lymphocytes CLL)
3. Plasma cell dyscrasias (multiple myeloma)
4. Lymphomas (H and Non-H)
Myeloid neoplasms are derived from what?
Stem cell that gives rise to granulocytes, RBC's, platelets
2 types o fmyeloid neoplasms?
1. Acute leukemias (AML)
2. Chronic disorders
Histiocytic neoplasms are proliferations of what?
Histiocytes (macrophages) and dendritic cells
Main histiocytic neoplasm?
Langerhans cell histiocytosis
6 causes of neoplastic disorders?
1. Chromosomal tranlocations/Oncogenes
2. Inherited genetic factors
4. Localized chronic immune stimulation
5. Iatrogenic factors
How does the mutation of proto-oncogenes occur
Errors in lymphoid cells during antigen receptor gene rearrangement and diversification/antibody development
Oncoproteins have what 2 effects?
1. Block normal maturation
2. Give inappropriate proliferative signals
Development of neoplasia requires what?
Combination of multiple genetic lesions
Inherited genetic factors are seen in what two neoplastic disorders? 2
Down's syndrome (ALL)
3 viruses and the WBC neoplasm they cause
1. HTLV-1 --> Adult T-cell leukemia/lymphoma
2. EBV: Burkitt, Hodgkin, B-cell lymphomas
3. KSHV/HHV8: B-cell primary effusion lymphoma
Environmental factors that cause WBC neoplasms? 2
1. H. pylori --> Gastric B cell lymphoma
2. Gluten sensitive enteropathy --> Intestinal T-cell lymphomas
Iatrogenic factors include what? (2)
Smoking increases what neoplasm?
What is common of cells in a lymphoid neoplasm? (2)
1. Arrested at particular stage
2. Reside in lymph nodes, peripheral blood, BM, or a combination
If a neoplasm is defined to tissue masses it is called? (Outside marrow)
If a neoplasm is confined to peripheral blood and/or bone marrow is it called? (In Marrow)
What do most incurable lymphomas evolve into?
Tumors identical to leukemia sometimes arise as what?
Soft tissue masses with NO BM involvement
Hodgkin lymphoma is different for what main histologic difference?
Plasma cell neoplasms (dyscriasis) are commonly found in lymph nodes and peripheral blood?
What is their pathology related to?
Main thing they cause?
No they are not. Rarely
Lytic bone lesions
What dictates clinical presentation of lymphoid neoplasms?
Anatomic distribution of disease
What proportion of lymph neoplasm is nodal?
What proportion is etranodal?
Presentation of each
2/3 nodal: No pain lymphadenopathy
1/2 extranodal: Tissue masses
What is required for diagnosis of lymphoid neoplasm?
Histologic examination of lymph nodes or tissues
What do all lymphoid neoplasms demostrate?
What does this mean?
How can this be determined?
Why does this work?
Derived from single transformed cell = Monoclonal
Analysis of antigen receptor proteins
Gene rearrangement produces unique DNA sequence (monoclonal will have same)
80-85% of lymphoid neoplasms are of what origin?
What are the rest?
Rest are T cell, a few rare NK
What is a follicular lymphoma?
If the B-cell lymphoma recapitulate the follicular growth pattern of normal B cells
What is diffuse lymphoma?
B and T-cell neoplasms spread diffusely in the lymph node
If you have an effaced lymph node, how does that help your diagnosis?
Tumors of immune system will have what effect?
How does this present (2)
Disruption of normal immune regulatory mechanisms
In terms of location, how are Non-Hodgkin lymphomas described?
Is staging important?
Present as particular tissue site, but actually widely disseminated and systemic
Staging not very important
How do you generally treat NHL's?
Hodgkin lymphomas are described how in terms of location?
Is staging important?
Present in single site and spread to contiguous lymph node groups.
Yes staging is important
What might cure hodgkin lymphoma?
Excision and local radiation
What is the progression of B cells with locations
Bone marrow: HSC --> CLP --> Pro B --> Pre B
Peripheral blood: Mature B --> Plasmacytoid B cell
Lymph nodes bone marrow: Plasma cell
What is progression of T cells with locations
Bone marrow: HSC --> CLP --> T/NK
Thymus: Pro-T --> Pre-T --> Intrathymic DP -->
1. Posthymic SP --> Peripheral Blood Th
2. Postthymic SP --> Peripheral blood Tc
Myeloid CD's? (3)
In acute leukemias what happens in differentiation?
There is a block so that the bad blasts have a prolonged generation time
What causes accumulation of blasts in marrow? 2
What is this associated with?
1. Clonal expansion
2. Failure of maturation
Suppression of normal hematopoiesis
How does acute leukemia generally present?
Abrupt stormy onset
1. Anemia --> Fatigue
2. Leukopenia --> Fever and infection
3. Thrombocytopenia --> Bruising/bleeding
4. Bone pain and tenderness
What are some acute leukemia symptoms seen mainly in ALL? 5
3. Testicular involvement
4. Compression of BV's and airways
5. CNS manifestations
CNS manifestations are seen mainly in what demographic?
Lab findings of acute leukemias? 4
3. WBC's greater than 100,000
4. Blasts in peripheral blood and bone marrow
What is the diagnostic feature of AL?
20-100% of cells in peripheral blood and bone marrow being blasts
Aleukemic leukemia presents how?
Pancytopenia with rare blasts in peripheral blood
Why is it important to differentiate ALL from AML?
Precursor B- and T- cell leukemia/lymphoma is composed of what cells?
What age group?
Children and young adults
Pre-B lymphoblastc tumors present in what form?
With what involvement?
Bone marrow and peripheral blood
Pre-T lymphoblastic tumors commonly present how?
Progress to what?
Mediastinal masses involving thymus
B and T cell tumors usually appear as what at some time in their course?
Acute Lymphoblastic Leukemia
ALL is the most common cancer of what?
Pre-B ALL peaks at what age?
Pre-T cell tumors are more common with who?
Pre-B cell tumors have what antigens? 2
CD19 and CD10
Pre-T cell tumors have what antigens? 4
Later which ones (3)
CD1, CD2, CD5, CD7
CD3, CD4, CD8
What enzyme is present in both Pre-B and Pre-T?
90% of precursor T and B tumors have what genetic change?
More common with which one?
Nonrandom karyotypic abnormalities
B cell (hyperdiploidy)
Which is more severe, nonrandom karyotypic abnormalities or other?
Who has the best prognosis of all precursor T and B cell tumors?
Children 2-10 with pre-B cell tumor
What % of kids get complete remission of Pre-B cell tumor?
11 Peripheral B-cell neoplasms
1. Small lymphocytic lymphoma/chronic lymphocytic leukemia
2. Follicular lymphoma
3. diffuse large B-cell lymphoma
4. Burkitt lymphoma/leukemia
5. mantle cell lymphoma
6. Marginal zone lymphoma
7. Hairy Cell leukemia
8. Plasma cell neoplasia
9. Lymphoplasmacytic lymphoma
10. Heav-chain disease
11. Primary/Immunocyte associated amyloidosis
Small lymphocytic lymphoma and chronic lymphocytic leukemia are related how?
CLL is circulating SLL
Special title of Small lymphocytic lymphoma/chronic lymphocytic leukemia?
Most common leukemia in Western world
Small lymphocytic lymphoma/chronic lymphocytic leukemia Age?
Males more common
Small lymphocytic lymphoma/chronic lymphocytic leukemia appears how in peripheral blood?
Absolute lymphocytosis with smudge cells
Immunophenotype of Small lymphocytic lymphoma/chronic lymphocytic leukemia?
1. Pan-B markers (CD19 and 20)
2. Monoclonal kappa or delta light chains
CD23 appears in Small lymphocytic lymphoma or chronic lymphocytic leukemia
Status of B cells in Small lymphocytic lymphoma/chronic lymphocytic leukemia
Long lived, but nonfunctional B cells infiltrate BM, LN's, peripheral blood due to apoptosis defects
Clinical features of Small lymphocytic lymphoma/chronic lymphocytic leukemia? (2)
1. Asymptomatic at diagnosis
2. Autoimmune hemolytic anemia/thrombocytopenia
Survival length of Small lymphocytic lymphoma/chronic lymphocytic leukemia?
What does CLL/SLL transform into over time?
Aggressive tumors such as diffuse large B-cell lymphoma (Richter) or prolymphocytic leukemia
Key histopathic finding in SLL/CLL?
1. Smudge cells
Follicular lymphoma makes up what % of adult NHL's?
FL arises from what?
Germinal center B cell
Markers for FL? (5)
1. Pan B markers (CD19,CD20)
5. No CD5
Folicular lymphoma age?
How does FL present? (4)
2. Generalized lymphadenopathy
3. Bone marrow involved
4. t(14,18) --> Overexpress BCL2
Prognosis of FL?
Some progress to?
Diffuse large B-cell lymphoma
What is most common form of Large B-cell lymphoma?
Diffuse Large B-cell lymphoma
3 characteristics of Diffuse Large B-cell lymphoma?
1. Diffuse growth pattern
3. Heterogeneous in terms of pathogenesis
Markers for Diffuse Large B-cell lymphoma? 2
1. Pan B (CD19, CD20)
2. Variable after that due to different subtypes
Diffuse Large B-cell lymphoma age?
60 median age
How does Diffuse Large B-cell lymphoma present? (3)
1. Rapidly enlarging mass at single node or extranodal site
2. Spleen, liver involved
3. Bone marrow not involved initially
Result of Diffuse Large B-cell lymphoma if not treated?
What % can be cured?
Complete remission in 60-80%
50% can be cured
Burkitt lymphoma/leukemia (B-cell leukemia) has what special title?
Fastest growing human neoplasm
Burkitt lymphoma/leukemia (B-cell leukemia) histologic pattern?
Where are most Burkitt lymphoma/leukemia (B-cell leukemia) located?
Burkitt lymphoma/leukemia (B-cell leukemia) age?
Main involvement location in US?
30% of childhood NHL's
Visceral (GI and sinus)
Burkitt lymphoma/leukemia (B-cell leukemia) markers? 5
5. Translocations of c-MYC gene on Ch 8
Three translocations possible of c-MYC gene?
What is the other gene involved
1. t(8:14) and Ig Heavy chain (Most common)
2. t(2:8) and Ig light chain
3. t(8:22) and Ig light chain
All endemic Burkitt lymphoma/leukemia (B-cell leukemia) tumors are infected with what?
Majority of Burkitt lymphoma/leukemia (B-cell leukemia) can be cured via what?
Mantle Cell lymphoma is seen in what age group?
Middle aged males
Mantle Cell lymphomas are composed of what?
B cells resembling those in mantle zone surrounding normal lymphoid follicles
Majority of Mantle Cell lymphoma patients have what at diagnosis?
What else is typically involved
Extranodal sites: BM, spleen, liver, GI
Markers for Mantle Cell lymphoma?
3. CD23 negative
4. Overexpression of cyclin D1
How to differentiate between Mantle Cell lymphoma and SLL/CLL?
CD23 positive in SLL/CLL
CD23 negative in mantle cell lymphoma
Most Mantle Cell lymphoma have what translocation?
t(11;14): IgH locus on 14 and cyclin D1 locus on 11
Increases cyclin D1 --> Promote G1 to S progression
Most Mantle Cell lymphoma present how?
Mantle cell lymphoma has what prognosis?
Aggressive and incurable with survival of 3-4 yeras
Marginal zone lymphoma arises where? 3
MALT (salivary glands, intestines, thyroid)
What bacteria commonly accompanies marginal zone lymphoma?
Extra-nodal marginal zone lymphoma is seen with what 3 associations?
2. Hashimoto thyroiditis
3. H. pylori
Extra-nodal marginal zone lymphoma occurs where?
Extra-nodal marginal zone lymphoma may regress if what happens?
Inciting agent removed
Extra-nodal marginal zone lymphoma may transition between what?
Reactive lymphoid hyperplasia and B-cell lymphoma
How to differentiate between acute leukemia and chronic?
Acute = 20% blasts
Chronic = <20% blasts
Hair cell leukemia is most commonly seen in who?
Middle-aged caucasian males
Peripheral blood leukemic cells have fine hair-like cytoplasmic projections
Hairy cell leukemia markers? (5)
Hairy cell leukemia triad of symptoms?
3. Dry tap on bone marrow aspiration
What treatment is Hairy cell leukemia really sensitive to?
Prognosis if treated?
Excellent with possible curable relapses
Hairy cell leukemia stains best with what stain?
TRAP (tartrate resistant acid phosphatase)
Plasma cell neoplasms are defined how?
Another name for this (2)
B-cell neoplasms of single clone of immunoglobin-secreting cells
Increase in serum levels of a single homogeneous Ig or its fragments (M component or monoclonal spike)
Monoclonal gammopathy or paraproteinemia
Neoplastic plasma cells have what main finding?
Bence-Jones proteinuria due to a poorly balanced synthesis of heavy and light chain. BJ is light chains in urine
When are the M components of plasma cell neoplasms normally seen in healthy people?
What is this called?
Monoclonal gammopathy of undetermined significance (MGUS)
3 forms of plasma cell neoplasms to know?
1. Plasma cell myeloma/Multiple myeloma
2. Solitary plasmacytoma
Plasma cell myeloma has what special title?
Most common plasma cell dyscrasias
Prognosis of plasma cell myeloma?
What proliferates in plasma cell myeloma?
Neoplastic plasma cells in BM
What physical finding is associated with plasma cell myeloma?
How does this present (2)?
Multifocal lytic lesions of axial skeleton
The M component of plasma cell myeloma is made up of what two Ig's mainly?
What % is Kappa or light chains?
What are these called in urine?
What % have both M component and Bence-Jones?
Half IgG and a quarter IgA
20% is light chains
Age of plasma cell myeloma?
Clnical features of plasma cell myeloma occur for what reasons (3)
1. Effects of infiltration of organs and bones by the bad plasma cells
2. Production of excessive Ig's
3. Suppression of normal immunity
4 main findings of plasma cell myeloma?
1. Bone resoprtion
2. Renal insufficiency (BJ proteinuria is damaging)
3. Amyloidosis (Due to BJ)
What is the mnemonic to remember for organs involved in plasma cell myeloma?
plasma cell myeloma peripheral blood finding? 2
Mott Cells with Russell bodies
Prognosis of plasma cell myeloma?
Remission but survival doesn't change
Localized plasmacytoma has what definition?
presence of a single lesion in skeleton or soft tissues
Most Localized plasmacytoma patients develop what?
Disseminated disease (myeloma)
What type of Localized plasmacytomas spread less commonly and can be cured locally?
MGUS is seen with what age group?
Diagnosis of MGUS should be made after what?
Excluding all other specific monoclonal gammopathies
How do you care for MGUS patient?
Keep assessing M component and Bence Jones levels
Lymphoplasmacytic lymphoma is defined how?
Mixed proliferation of B cells from small round lymphocytes to plasmacytoid lymphocytes to plasma cells
What is the M component of Lymphoplasmacytic lymphoma usually?
What happens if this gets high?
Hyperviscosity syndrome called Waldenstrom Macroglobulinemia (WM)
Lymphoplasmacytic lymphoma resembles other B-cell lymphomas in what presentations (4)
1. Diffuse infiltration of BM
2. Diffuse infiltration of LN's
3. Diffuse infiltration of liver and spleen
4. Autoimmune hemolysis via cold agglutinins
Prognosis for Lymphoplasmacytic lymphoma?
Incurable and progressive
Hyperviscosity syndrome is due to what?
Increased monoclonal IgM
4 manifestations of hyperviscosity syndrome?
1. Visual impairment
2. Neurologic problems
Heavy-chain disease definition?
Only heavy chains produced of IgG, IgA, or IgM
How does IgG Heavy-chain disease present?
Diffuse lymphadenopathy with hepatosplenomegaly
How does IgA heavy-chain disease present?
Goes for the MALT
Primary or immunocyte-assicated amyloidosis is defined how?
Form of amyloidosis where monoclonal plasma cells produce excessive amounts of light chains
The amyloid deposits in Primary or immunocyte-assicated amyloidosis consist of what?
Partially degraded light chains --> Beta pleated sheets --> Amyloid