1List examples of leukemias (lymphoid neoplasms)
Chronic Lymphocytic Leukemia (CLL)
Prolymphocytic leukemia (PLL)
Hairy Cell Luekemia (HCL)
Large granular lymphocytic leukemia(LGL)
2List the lymphomas in lymphoid neoplasms
1. adult T cell leukemia/ lymphoma
2. Burkitt's (sporadic/ HIV related)
3. Lymphoplasmacytic (Waldenstroms)
4. Sezary Syndrome/ adv mycosis fungoides
5. Plasma cell neoplasms
3What kind of disorder is chronic lymphocytic leukemia (CLL)?
B cell disorder
4What ages are affected by CLL?
older age, around 72
5What is the diagnostic criteria according to IWCLL of CLL?
>5 x 109 cells/ L
clonality using flow cytometry
6What are the cell features of CLL?
>85% small, mature lymph, dense chromatin (cobblestone or soccer ball)
7What are the lymphs for atypical CLL/ PLL?
>10% Pls (<55% total lymphs)
8What are the lymph counts for mixed-type/ atypical CLL?
>15% atypical lymphs
(nuclear clefts/ indentations)
9What type of CLL is more aggressive?
atypical CLL
(flagged by analyzer)
10What markers are seen in CLL cells?
CDD19+ CD23+ CD20+ CD5+ (aberrant expression)
CD200+ sIg(dim) CD10-
11What kind of scoring system is used for CLL?
Catovsky-Matutes Scoring for CLL dx
(because the antigen expression is variable)
12What does the Catovsky-Matutes scoring grade consist of for CLL diagnosis?
weak expression of surface immunoglobulins (sIg)
expression of CD5, CD23
No expression of FMC7
Absent or wk expression of CD79b or CD22
13What score can indicate CLL? (from catovsky)
more than or equal to 4 = CLL
14What does Catovsky Matutes score of 1-2 indicate?
non Hodgkin's lymphoma (NHL)
15What does Catovsky Matutes score of 3 (or <1?) indicate?
problematic
requires biopsy from lymph nodes and molecular testing
16What chromosomal changes lead to CLL?
Del (p17) and TP53 mutation
(worst prognosis and resistance to chemo and immunomodulatory drugs
17What is the best prognostic marker of CLL?
mutational status of IGHv gene
18What can unmutated IGHv gene in CLL indicate?
pre-germinal B cell phenotype, more aggressive
19What can mutated IGHv gene in CLL indicate?
better response to chemo immunomodulatory drugs
20What is the RAi classification of CLL staging (general)?
Low risk
intermediate risk
high risk
21What is low risk CLL? (Rai classification)
lymphocytosis > 5 x109/ L
22What is intermediate risk CLL?
lymphocytes >5 x109/ L
lymphadenopathy and splenomegaly
or hepatomegaly (or both)
23What is considered high risk CLL?
lymphocytes >5 x109/ L
Hb <11 g/ dL (anemic)
24What is the Binet classification of CLL (general)?
Stage A
Stage B
Stage C
25What does PLL stand for?
prolymphocytic leukemia (PLL)
26What age groups become affected by PLL?
elderly
27Describe PLL
rare (1-2% lymphoid leukemia)
aggressive
high lymph count (100 x109/ L)
(rapidly rising WBC ct)
could be both T & B Cells
28What cells are affected by PLL?
both T and B cells
29Describe B-PLL
cells larger than normal lymphocyte, ample cytoplasm, open chromatin,
one prominent nucleolus
30Describe T-PLL
difficult to distinguish from mature T cell malignancies
cells are smaller, nucleolus may not be seen
(genetic studies and FC may be req)
31What markers are involved in B-PLL?
CD19+ CD22+ (bright), sIg (bright), FMC7+,
CD5 +/ - CD10-
32What markers are involved in T-PLL (T cell prolymphocytic leukemia)?
CD4+ or CD4+/ CD8+ (dual)
TCL1+ CD2+ CD3+ CD7+ CD52+ Tdt-
**Inv(14) in 70% of T-PLL patients <-- specific
33What kind of neoplasm is hairy cell leukemia (HCL)?
B cell neoplasm
34What population does HCL affect?
middle aged people
35Describe HCL
indolent (slowly growing??)
prominent cytopenia
splenomegaly
mature B cell, ample cytoplasm, hair projections round/ oval nucleus, no nucleolus
36What markers are associated with HCL?
IHC with anti-CD20
37What is specific to HCL? What does it do?
Annexin-A
differentiates from splenic marginal zone lymphoma
38What special stain does HCL use?
TRAP+
39What is large granular lymphocytic (LGL) leukemia defined by?
LGLs 15% of circulating lymphs
(normally 0.6 x10^9/ L)
older adults (~60yrs): LGL >2 x 10^9/ L
40Where are HIGH LGLs often found?
in autoimmune disorders,
after chemotherapy and BM transplantation
41What is the immunophenotype of T-cell LGL (cytotoxic)?
CD3+ CD8+ CD57+ CD56-
42What is the immunophenotype of NK-cell LGL?
CD3- CD56+
43What virus is adult T cell leukemia/ lymphoma (ATLL) associated with?
HTLV-1
44What is the main feature of ATLL?
marked leukocytosis
45Describe ATLL cells
deeply basophilic cytoplasm
convoluted nucleus
clumped chromatin
flower cells
46What is the immunophenotype of ATLL?
Th markers: CD4+ CD3+ CD7- CD8- CD25 CCR4 (strongly positive)
soluble form of IL-2: diagnostic
47What kind of malignancy is Burkitt Leukemia/ Lymphoma?
aggressive B cell malignancy: fulminant clinical pictures
48What are the 3 subtypes of Burkitt's?
Endemic
sporadic
HIV relation
49What is endemic Burkitt's?
EBV-related, African children,
extra nodal involvement (mandible, orbits)
50What is sporadic Burkitt's?
mostly abdominal, extra-nodal involvement
(BM and CNS)
51What is HIV-related Burkitt's?
profound immunosuppression,
Blood and BM primary sites
52Describe BL cells (Burkitt's)
medium size, deeply basophilic cytoplasm, vacuoles, starry sky
53What cell is involved in mycosis fungoides (MF) / Sezary syndrome (SS)?
cutaneous T cell lymphoma
Th (CD4+) cells
54What population is affected by MF/ SS?
elderly
55What does MF/ SS involve?
skin involvement and dissemination to blood
LNs
56Describe MF/ SS cells
cerebriform nuclei
nucleoli not obvious
mostly dense chromatin
57What organ is Hodgkin lymphoma based on?
lymph nodes
(NHL involves LNs)
58What are the 2 forms of HL?
classic and lymphocyte predominant
59What is classic HL (>95% cases)?
a disease of young adults
one of the first tumor types cured with combination of tumor therapy
60What are the cellular features of classic HL?
Reed-Sternberg (RS) cells
61What are RS cells?
binucleated or multinucleated and have abundant cytoplasm and distinct nuclei
RS cells are B cells and express CD15 and CD30
62How is classic HL diff from lymphocyte-predom HL?
lymphocyte-predominant HL : no RS cells, CD15 and CD30 negative
63What are plasma cell neoplasms (PCNs)?
malignant disorders of terminally differentiated B cells
2nd most common hematologic malig
prototype MM (multiple myeloma)
64What are the sites of involvement for PCNs?
BM
65What are the cellular features of PCNs?
plasma cells accumulate in BM
66What are the ranges for PCNs?
ranges from relatively benign condition such as MGUS to clinically aggressive plasma cell leukemia (PCL)
67What is MGUS?
monoclonal gammopathy of undetermined significance
68What is SMM?
smoldering myeloma
(asymptomatic)
69What is MM?
Multiple (plasma cell) myeloma
70What does WM stand for?
Waldenstrom's macroglobulinemia
71What does HCD stand for?
heavy chain disease
72List mature B cell lymphomas ~ plasma related
PCNs (Plasma cell neoplasms)
MGUS (Monoclonal gammopathy of undetermined significance)
SMM (Smoldering "asymptomatic" myeloma)
MM (Multiple myeloma)
WM (Waldenstrom's macroglobulienmia)
HCD (heavy chain disease)
73What is the MM (multiple myeloma) culprit?
monoclonal Igs
74What are the complications of MM (multiple myeloma)?
CRAB (hypercalcemia, renal failure, anemia, bone lesions)
75What happens when there is PB involvement for MM?
secondary PCL
76What markers are present in MM (multiple myeloma)?
CD38+ CD138+ CD56 (NCAM)+ weakly positive for CD45
77How is WM (Waldenström macroglobulinemia) characterized?
high IgM!!! (snow flake)
&
very viscous plasma (hyperviscosity syndrome)
78What treatment is required in WM (Waldenström macroglobulinemia)?
plasmapheresis
79What mutation causes WM (Waldenström macroglobulinemia)?
MYD88 gene mutation
80What type of process is Multiple Myeloma?
Multistep process
81What is the progression like in MM?
MGUS -> overt MM -> PCL (rare cases)
82What is present at similar rate at MGUS and MM?
Hyperdiploidy and t(11;14)
83What is commonly found in active myeloma? (cellular level)
MYC secondary rearrangments
Deletion 13(p)
1q+
RAS MUTATIONS
84PCL shows what?
distinct abnormalities including PTEN loss and p14 promoter methylation. (END STAGE DISEASE)
85Deletions of chromosome 17p involving the TP53 locus are rare in?
Newly diganosed myeloma
5-10%
86Deletions of chromosome 17p involving the TP53 locus are common in?
Relapsed and refractory cases
20-40%
87What kind of prognosis are Deletions of chromosome 17p involving the TP53 locus?
Negative
Causes early relapse in patients treated with or without autologous stem cell transplantation (SCT).
88How are myeloma patients divided?
hyperdiploid
nonhyperdiploid
89What is hyperdiploid in myeloma patients?
>46 but <76 chromosomes
34-60% of myeloma
90What type of immunoglobulin is in hyperdiploid patients?
IgG kappa type
91What is involved in hyperdiploid myeloma patients?
Bone involvement
Show gains of odd-numbered chromosomes
Trisomies of chromosomes 15, 9, 5, 19, 3, 11, 7, and 21 (ordered by decreasing frequency)
FAVORABLE PROGNOSIS
92wHAT IS NONHYPERDIPLOID IN MYELOMA PATIENTS?
hypodiploid (UP TO 44-45 CHROMOSOMES)
pseudodiploid (44/45 or 46/47 chromosomes with gains or losses)
Near-tetraploid karyotype <- bad prognosis
93what is the most frequent translocation (20% cases) in myeloma patients?
t(11;14)
94What does t(11;14) lead to?
Upregulation of cyclin D1, a crucial promoter of G1-S transition (cell division)
95What is seen in the peripheral blood of MM?
Anemia, thrombocytopenia, ROULEAUX
Chemistry: M-spike on SPE, clonal Ig on IEF
Coagulopathy (aquired factor deficiency)
96what are mott cells? (seen in MM)
Plasma cells that have multiple cytoplasmic globules with immunoglobulins
aka grape cell or morula cell
ONE globule = Russel body
97What are flame cells in MM?
Plasma cels with a distinctive pinkish hue on the outer rim bc of precipitated immunoglobulin.
98Where are flame cells found?
Plasma cell dyscrasias
chronic infection or inflammation