Lecture 11 Flashcards
What is leukemia
-neoplasm characterized by BM involving peripheral blood - Hem investigation with BM and PB
What is a lymphoma
-Neoplastic lesions of lymphoid tissue
-investigated by Histology - Lymph nodes with cells that can return to BM and PB
What is part of a lymphoma classification
morphologic, immunophenotypic, molecular & clinical characteristics
-lymphomas and lymphocyctic leukemia affect older ppl
-except Hodgkin lymphoma and Burkitts lymphoma/Leukemia
What are the parts of a lymph node and where can lymphoma originate
cortex - primary and secondary follicle
paracortex
medullary sinus /cords
lymphoma originates anywhere in these compartments
What do the primary follicles of the cortex contain
microscopic aggregates of small naive B lymphs
CD19, CD20, CD5
What do the secondary follicles of the cortex contain
Germinal center - where naive B cells are present with AG and turn into pre plasma cells
Mantle Zone - where naive B cells are pushed into periphery of the follicle
What does the paracortex contain
T lymphs
CD 4 and 8
B imunoblasts
What does the Medulla contain
Plasma cells
What do the sinuses contain
Macrophages
how are lymph nodes processed
- sent to histo unfixed
-transport in sterile container on gauze with saline or tissue media
-gross examination done by pathologist
how are the lymph nodes processed
Touch prep - Wrights stain
-thin sections in formalin and fixed in B5 to give better cellular detail
-paraffined sections are used in immunohistrochemistry
how does WHO classify Mature B cell
lymphoid neoplasms
CLL/CLL
Hairy cell Leukemia
PLL
Plasma cell myeloma
Heavy chain diease
Burkitt Lymphoma/Leukemia
What can lymphadenopathy cause when benign/reactive cause
Follicular hyperplasia - most common , infections (tonsillitis), autoimmune
paracortical expansion - viral expansions (IM) and chronic skin disease
sinusoidal
histiocytes & monocytoid B cells
Infections - toxoplasma & HIV
how does WHO classify Mature T cell
lymphoid neoplasms
Cutaneous - Mycosis fungoides / Sezary syndrome
PLL T-cell type
How is CLL/SLL diagnosed
what is its immunophenotype
- characterized by failed apoptosis
-acculumation of recirculating B cells
-origin of CLL/SLL not known likely naive B or memory B cells from marginal zone of follicles
What is CLL/SLL
what do they present like as per WHO
- affects 72 yr old males
-Asymp
-smll lymphoid cell accumulate in PB , BM and lymphoid organs
as per WHO
CLL - mostly in PB and BM
SLL - involves lymph nodes and lymph organs
what is the immunophenotype of CLL/SLL
CD 19, CD20, CD 23, Abnormal CD 5
IgM and IgD on surface
Kappa or Lambda - monoclonal
What 2ndary conditions is CLL/SLL associated with
Hypogammaglobulinemia due to lack of normal B cells - increased risk of infection
-Autoimmune hemolytic anemia due to altered immune function of abnormal B cell clones
Richter’s syndrome - diffuse large cell lymphoma
how would CLL look like in PB
-Small lymphs
-high n:c ratio
-clumped and coarse chromatin
-inconspicuous nucleoli
-high WBC count >100 x10^9
-Lymphocytosis in PB and BM
->10 X10^9 absolute lymphs
>90% lymphs and smudge cells
BM will be similar
55% prolymphs
large with central nucleoli
What will be the most seen cell on the peripheral blood smear
Smudge cells
-need to be counted WITHIN the differential of 100 cells
-the lymph’s will be immature and abnormal but still count them as lymphs in CLL
How is CLL/SLL treated
chemo
-radiation therapy - enlarged lymphs and spleen
- splenectomy for AIHA
-IV gammaglobulin
-BM and SCT for those under 50
What different types of mature B cell lymphomas
Prolymphocytic Leukemia or PLL
Mantle cell Lymphoma
Hairy cell Leukemia
(Follicular Lymphoma – not in PB)
How are the other types of mature B cell lymphomas separated
- by distinct morphology
- CD markers
-Source and location in lymph node
-histology of LN and IHC stains for CD markers
What is prolymphocytic leukemia
-Rare and mature leukemia - T or B cell
-invovles the PB, Spleen and BM with >55% of PB lymphs having prolymphocyte morph
What will a B Cell PLL look like
Medium round nuc
-abundant cytoplasm
-PUNCHED OUT NUCLEOLUS
mantle cell lymphoma
where is it found ]
what does it look like
-what translocation is most associated with it
- found in LN
-involves BM, PB and GI
-t(11:14) associated with it
-has medium lymphs with IRREGULAR NUCLEAR OUTLINES
-come from follicular mantle zone B cells
-LN shows decreased germinal center
How does hairy cell leukemia occur
What will the cells look like
what will patients present as
-when cells infiltrate BM and RED PULP OF SPLEEN
-rare for the LN to be involved
-cells will produce fibrogenic cytokines which INCREASE RETICULIN FIBRES IN BM AND SPLEEN
-if a BM aspirate is done it will be dry due to the fibrosis
Patients present with pancytopenia, splenomegaly , THICK ITCHY SKIN
-mostly in middle aged men
How will Hairy cell leukemia look like in a PB
-will have HAIR like projections
-abundant light grey blue cytoplasm
-nucleoli are rare
-round/oval nuc
-VARYING % IN PB
how is Hairy Cell leukemia diagnosed
-IMMUNOPHENOTYPING BY FC & IHC with AB used for both
-strong positive for B cell markers 19, 20, 22
-marker CD 123 and annexin A1 is the MOST SPECIFIC FOR HCL
-you will see diagnostic TRAP cytochemical stain which is now replaced by immunophenotyping
What are the plasma cell dyscrasias
Multiple Myeloma
Plasma Cell Leukemia
Waldenstrom Macroglobulinemia
What does a plasma cell look like
where is it seen
-found in LN and BM not seen in PB of normal people
-round/oval nucleus
-eccentric
-dense chromatin no nucleoli CLOCK FACE PATTERN
Cytoplasm
-moderate
-blue/grey
-paranuclear halo (HOF) which is the site of Golgi zone and production of IgG
What is plasma cell multiple myeloma
-when malignant plasma cells in the BM present like lytic bone lesions
a monoclonal IgG is produced by neoplastic cells
seen in
serum
urine
both
What is the morphology and immunophenotype of Plasma cell myeloma
- characterized by marked bone marrow plasmacytosis
-seen with large aggregates and sheets of plasma cells with >30% marrow cellularity
What is the term plasma cell leukemia reserved for
> 20% circulating plasma cells or plasma cells over 2 x 10^9/L
who does MM mostly affect and what is it seen as
> 70 years old
the proliferation of neoplastic plasma cells will cause
-bone destruction
-fractures
-hypercalcemia
-renal insufficiency
-cytopenia
-infection
-coagulopathies
What is the immunophenotype that will be seen with MM
NORMAL and ATYPICAL markers
CB138, CD38
IgG or IgA
Abnormal markers
CD 56 and myeloid markers
What are chemistry lab tests that will be done for MM
-SPE
-IFE
-Quantitative IgG
-Enzymes - LD
-Urea and Creatinine
-Ca
-Bence Jones in urine
What are the Hematology tests are done for MM and what will be seen
CBC
N/N Anemia that turns into pancytopenia
Smear
-Rouleaux and background staining
-plasma cells will be seen in later stages
ESR
-increased due to protein that is made by abnormal clone of plasma cells
Where does Burkitt Lymphoma originate
what does present as
What are its 3 variants
-B cell with a germinate center origin
-presents as Burkitt leukemia with malignant cells in the PB and BM
-EBV will be seen
WHO suggests 3 variants:
Endemic (mostly in Africa)
Sporadic
Immunodeficiency associated (often with HIV+)
how to treat MM
Chemotherapy to reduce the IgG
Allogenic BM transplant for younger patients
most will die of infection or kidney failure
What is heavy chain disease
-excess production of heavy chain portion in an AB
how to diagnose Heavy chain disease
Immunofixation
free monoclonal heavy chain fragments in IgG in serum and urine
-BM biopsy in lymph node biopsy
how is WM diagnosed in the lab
Increased ESR with Rouleaux on PBS
SPE- monoclonal IgM protein
-light chains and bence jones protein in urine
-presence of CRYOGLOBULINS (precipitates in cold temps which can interfere with WBC counts- be sure to pre warm before testing)
What is Waldenström’s Macroglobulinemia
Monoclonal IgM over production
-hyper viscosity syndrome = high protein
-bleeding problems due to thrombocytopenia , abnormal platelets
less bone involvement then Plasma cell myeloma
How does burkitt lymphoma present as
Endemic
Sporadic
Endemic
-childhood cancer found in areas with high prevalence of malaria
-100% EBV+
-aggressive but treatable
-affects jaw bone and seen as a jaw bone mass
Sporadic
-In children and adults
-GIT, abdominal lymph nodes and CNS involved
What do the cells look like in Burkitt Lymphoma
-mature heterogenous B cells
-the nuclear chromatin is stippled and homogenous
-Nucleus is regular/round/oval
-1 or more PROMINENT nucleolii
the Cytoplasm
MODERATLY ABUNDANT; BASOPHILIC
PROMINENT VACUOLIZATION
can do a BM touch prep to see the medium sized cells
What do you look for with Immunophenotype & Cytogenetics to diagnose
-B cell marker variation
-translocation related to genes for Ig heavy or light or MYC gene
t(8;14), t(2;8), t(8;22)
CD19, CD20, CD10, and BCL6
Examples of Mature T cell lymphomas
Mycosis Fungoides and Sezary Syndrome
Sezary Syndrome
T-cell, cutaneous lymphoma
-stage of disease progression, LN infiltration , PB infiltration liver, spleen and lung involvement
What is mycosis fungoides
T-cell, cutaneous lymphoma
disease stage when lymphocytes infiltrate the epidermis - can exist for years
What do the cells in Sézary Syndrome look like
-T cells that enter the peripheral blood
-BM not invovled
-S/M lymphs
-dark and clumped nuclear pattern with irregular nuclear outline - cerebriform
What do pts with Classical Hodgkin’s Lymphoma present with
- can be associated with EBV
-non painful swollen LN
-weight loss
-night sweats
15-35 or >50
1/3 of all lymphoproliferative disorders
What type of cells will you see in Classical Hodgkin Lymphoma
Reed-Sternberg’ cells
-giant, multinucleated cell with acidophilic cytoplasm found in lymph node biopsy
-need biopsy to diagnose as lymphocytes infiltrate the LN
No peripheral blood abnormalities except possible lymphocytopenia in late stages**
For what stain is Classical Hodgkin Lymphoma positive for
Immunoperoxidase positive
What is the immunophenotye for Classical Hodgkin Lymphoma
CD30 (+) Reed-Sternberg cells
two nuclear lobes and distinct nucleoli
What is seen in Non-Hodgkin Lymphoma and what are their classification
No Reed-Sternberg cells
common neoplasm in 20-40
Small lymphocytic lymphoma (like CLL)
Burkitt’s lymphoma (like ALL L3)
B-cell vs. T-cell
Benign vs. malignant, low grade – high grade
