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FCPath(SA)Haem - HaemOnc > Small BLPDs > Flashcards

Small BLPDs Flashcards

1
Q

Immunophenotype of CLL/SLL

A

Matutes Score/Moreau score
* Positive for:
* CD19, CD20, CD22 and CD79b
* Dim surface IgM/IgD
* CD5 and CD43
* Strong positive: CD23 and CD200
* ​​​Negative for:
* CD10 and FMC7 (may be weakly expressed)

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2
Q

What is the atypical immunophenotype that may be seen with CLL/SLL ?

A
  • Negative:
    • CD5 or CD23
  • Positive
    • FMC7
    • Strong surface immunoglobulin
    • or CD79b
  • In these cases, especially CD5 negative, important to exclude:
    • Splenic Marginal Zone Lymphoma

Moreau score of 3%

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3
Q

Can Cyclin D1 be positive in CLL/SLL?

A
  • YES!
  • some positive cells can be seen in proliferation centres in ~30% of cases
    • These cells are SOX11 negative
    • No chromosomal translocations are seen affecting the CCND1 gene

Note: MYC and NOTCH can also be seen in proliferation centres without gene alterations

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4
Q

What is the postulated normal counterpart to the CLL/SLL cell?

A
  • An antigen-experienced mature CD5+ B cell with mutated or unmutated IGHV genes
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5
Q

What are some of the most common cytogenetic abnormalities identified in CLL/SLL?

A
  • No specific genetic markers
  • Most common alterations identified include:
    • del11q -Bad prognosis
    • Trisomy 12 or partial trisomy 12q13 (~20% cases) - Intermediate prognosis
    • del13q (~50% of cases) - Good prognosis
    • del17p (TP53) - Bad prgnosis
  • Chromosomal translocations are uncommon in CLL
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6
Q

What is the name of the clinical staging system used for CLL/SLL?

A

Rai and Binet are used to define disease extent and prognosis:

I. Rai:
0 - Lymphocytosis
1 - + LAD
2 - + organomegaly
3 - Hb < 11
4 - Plt < 100

II. BINET:
A - Hb > 10, Plt > 100, < 3 sites
B - > 3 sites
C - Hb < 10/Plts < 100

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7
Q

True or False:

Patients who have CLL/SLL and have the mutated IGHV genes have a better prognosis that those who do not have the mutated gene.

A

True

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8
Q

The expression of what three markers in CLL/SLL has an adverese prognosis in the disease?

A

ZAP70

CD38

CD49d

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9
Q

Additional adverse predictive factors for CLL/SLL

A
  • Complex karyotype: poor outcome
  • rapid lymphocyte doubling in the blood (<12 months)
  • elevated serum markers of rapid cell turnover:
    • thymidine kinase
    • beta-2 microglobulin
    • > LDH
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10
Q

Risk scores for CLL

A

CLL-IPI and IPSE

CLL-IPI:
1. Age
2. Stage
3. B2-microglobulin
4. IGHV
5. TP53

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11
Q

What are the Tx indications for CLL?

A
  1. Constituational Sx and AI Cx
  2. LAD
  3. Splenomeg and extranodal involvement
  4. Lymphocytosis x2 within 6mo
  5. BMF (Hb < 10 and Plts < 100)
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12
Q

How do the three epigenetic subtypes of CLL/SLL affect the prognosis of the disease?

A
  • IGHV unmutated (Naive-like) cases: have the worst prognosis
  • IGHV mutated (Memory-like) cases: have the best prognosis
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13
Q

What gene abnormalities predict a lack of response to Fludarabine-containing regimes in CLL/SLL?

A
  • TP53 abnormalities:
    • Deletion of 17p13.1
    • TP53 mutations
  • These mutations must be checked before starting any type of therapy in these patients.
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14
Q

What other mutations in CLL have been associated with a poor outcome?

A
  • TP53
  • ATM
  • NOTCH1
  • SF3B1
  • BIRC3
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15
Q

What features of CLL/SLL are suggestive of prolymphocytic progression?

A
  • Prolymphos > 15%
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16
Q

What diseases can CLL transform into and what is the prognosis?

A
  • DLBCL (~2-8% of cases)
  • **Classic Hodgkin Lymphoma **(< 1%)
  • RICHTER Syndrome: cases of DLBCL that are clonally related to the previous CLL
    • Express the same immunoglobulin gene rearrangement and are IGHV-unmutated
  • Clonally unrelated CLL and DLBCL usually occur in IGVH mutated CLL
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17
Q

In what situation does Hodgkin Lymphoma develop in patients with CLL/SLL?

A
  • Mutated CLL
  • Hodgkin lymphoma cases are EBV positive
  • Hodgkin cases are unrelated to the CLL clone
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18
Q

Treatment modalities in CLL

A

I. Chemo-Immunotherapy
* FCR - fit and good prognosis
* BR - unfit

II. Targeted Tx
* BTK Inh (Ibrutinib/Acalabrutinib) in TP53 mutations
* PI3K Inh - Idelalisib in RR CLL
* BCL2 Inh - Venetoclax

III. Mabs
* Ritux (with chemo)
* Obinotuzumab (with Venetoclax)

IV. AlloHSCT (younger/High risk/RR)

V. Supportive
* IVIG

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19
Q

What is the definition of a monoclonal B-cell lymphocytosis (MBL)?

A
  • Monoclonal B-cell count < 5 x 109/L in the peripheral blood
  • NO associated lymphadenopathy, organomegaly, other extramedullary involvement
  • No other features of lymphoproliferative disorder

K:L ratio of > 3 or < 0.3 or > 25% with no sIg

IMP: remember that many small B-cell lymphomas and leukemias have low-level peripheral blood involvement

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20
Q

What are the three categories of Monoclonal B cell lymphocytosis?

A

< 0.5
* Low count MBL

> 0.5
* CLL type MBL
* Non CLL type MBL (MZ like)

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21
Q

3 factors associated with MBL progression?

A
  1. Clonal Bs > 3
  2. unmutated IGHV
  3. sB2-micro > 3.5
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22
Q

Characteristic features of FL?

A
  1. Old white men
  2. Enviromental factors
  3. LAD and Splenomeg
  4. t(8;14)
  5. Nuclear clefts
  6. Paratrabecular
  7. IMPT: Positive for CD20, CD10 (GC), BCL6 (GC), BCL2 and Negative for CD5
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23
Q

Subtypes of FL

A

I. Classical FL (cFL) - Old Gr1, 2, 3a:
* Centrocytes (clefts), Centroblasts (large with marginated nucleoli) with Ts, Macrophages and FDCs.

Previously:
Gr1 - < 5 centroblasts on high power field
Gr2 - > 5
Gr3 - > 15 (a = CC and CBs and b = predom CBs)

II. FLBCL - Old Gr3b

III. FL with uncommon fts (uFL):
* FL with blastoid fts
* FL with predominant diffuse growth pattern (CD23 and No t(14;18)

24
Q

Treatment of FL

A

cFL
AnnArbour
* 1 and 2: RadioTx
* 3 and 4: GELF/FLIPI or Sx
* R
* R+chemo (BR, RCHOP, RCVP)
* R2

FLBCL
* Tx as DLBCL

25
Q

What are the 4 subtypes of splenic lymphomas

A
  1. HCL
  2. SMZL
  3. SDRPL
  4. SBLwPN
26
Q

Features of HCL

A
  1. Hairy cells with kidney/bilobed nucleus
  2. TRAP enzymatic activity
  3. Fried egg appearance in BM
  4. Pancytopenia and Monocytopenia
  5. BRAFV600E
  6. IMPT: Positive for CD20, CD22, CD200 and CyclinD1 with CD11c, CD25, CD103 and CD123
  7. Annexin 1 Positivity
  8. Tx: Purine Analogues - Cladrabine
27
Q

What is the disease defining molecular alteration in Hairy Cell Leukemia?

A
  • BRAF V600E
  • This mutation leads to a constituitive activation of MAPK
  • This mutation is present in 100% of cases
28
Q

What are the fts of SMZL?

A
  1. del7p
  2. Hep C associated
  3. Lymphocytes with short polar villi
  4. Splenomegaly
  5. IMPT: Positive for PanB, IgM and CD25 (1/2 of cases)
  6. Tx: Ritux, HepC and splenectomy
29
Q

True or False:

Plasmacytic differentiation is seen in SMZL?

A

TRUE

  • plasmacytic differentiation can occur
  • RARELY clusters of plasma cells can be seen in the centre of the white pulp nodules
30
Q

What is the differential diagnosis of SMZL?

A
  • CLL
  • Hairy cell leukemia
  • Mantle Cell Lymphoma
  • Follicular lymphoma
  • Lymphoplasmacytic lymphoma
31
Q

What is the immunophenotype of SMZL?

A
  • express surface IgM and usually IgD
  • Positive
    • CD20, CD79a
  • Negative
    • CD5 and CD10
    • CD23 and CD43
    • Annexin 1
    • CD103 and cyclin D1
  • Ki67 usually in a targetoid pattern
    • positive in GC and marginal zone
32
Q

The absence of staining of cyclin D1 and LEF1 in SMZL is helpful in excluding which two entities?

A
  • Cyclin D1: Mantle Cell Lymphoma
  • LEF1: CLL
33
Q

The absence of staining of Annexin 1, CD10 and BCL6 in SMZL helps exclude which entities?

A
  • Annexin 1: Hairy Cell Leukemia
  • CD10 and BCL6: Follicular Lymphoma

IMP: a group of CD5+ SMZL cases has been described and are characterized by a higher lymphocytosis and diffuse bone marrow infiltration.

34
Q

Presence of MYD88 mutations point to which entity instead of SMZL?

A

Lymphoplasmacytic lymphoma

Note: although rarely SMZL can have this mutation.

35
Q

Does SMZL associated with Hepatitis C virus infection respond to antiviral treatment?

A
  • YES
  • Treatment with Interferon gamma with or without Ribavirin has been shown to be effective in treating SMZL
36
Q

Favourable and unfavourable markers in mantle cell lymphoma

A 
the following features are associated with a favourable prognosis in mantle cell lymphoma (MCL):
Non-nodal presentation
Hypermutated IGVH
Lack of genomic complexity
Negative SOX11 expression

A high Ki-67 proliferation index, or p53 mutations and p16 deletions, is closely related to the more aggressive MCL subtypes, such as the blastoid variants.

37
Q

Features of SDRPL

A
  1. Spenomegaly and lymphocytosis
  2. Polar villi and small nucleoli
  3. Intrasinusoidal
  4. IMPT: Positive for PanB and CyclinD3 (**CD200:CD180 **of < 0.5 = SDRPL)
38
Q

Features of SBLwPN (old HCLv and BPLL)

A
  1. Splenomegaly and lymphocytosis
  2. M-L size, fine, circumfirential villi and prominent nucleoli
  3. No BRAFV600F mutation - Resistant to cladrabine
  4. IMPT: Positive for PanB, CD20, CD11c and CD103
39
Q

What is the clinical presentation of Lymphoplasmacytic lymphoma (LPL)

A
  1. Fatigue
  2. Constitutional symptoms
  3. Hyperviscosity (IgM Abs)
  4. Acquired vWD (IgM Abs)
  5. Cryoglobulinaemia (CHAD - IgM Abs precipitate at low Temps)
  6. Neuropathy (AutoAbs to myelin in peripheral n. and IgM tissue deposition)
39
Q

Etiologies of LPL

A
  1. Previous MGUS
  2. HepC
  3. Familial
40
Q

IMPT of LPL

A

Positive for PanB, CD20, Pax5, CD25, CD27 and CD52 ±CD38

40
Q

Mutations associated with LPL

A
  1. MYD88 mutations (Gain of Fx)
  2. CXCR4
41
Q

What is WM?

A

LPL in BM with IgM

42
Q

Treatment of LPL/WM

A
  1. R
  2. BR

Not Ritux if High IgM = IgM flare

43
Q

What are the 4(5) types of MZL?

A
  1. MALT
  2. Primary cutaneous MZL
  3. NMZL
  4. Paediatric NMZL
  5. (SMZL)
44
Q

Different causitive factors in MALT lymphoma?

A
  • Gastric - H.Pylori
    • t(18;14)
    • Treatment = Eradication of H. Pylori (PPI, Clarithromycin, Amoxil/Metronidazole)
    • If they do not respond = RadioTx/Chemo
  • Ocular - Chlamydia
  • Skin - B. Burgdorferi
  • Salivatory glands - Sjogren
  • Thyroid - Hashimotos
45
Q

Features of NMZL

A
  1. LAD of head and neck
  2. IMPT: Positive for PanB, BCL2 and CD43
  3. Tx: Like FL
46
Q

What are the 3 types of MCL?

A
  1. Insitu MCL (confined to LN)
  2. MCL (unmutated IGHV, SOX11+ and Aggressive)
  3. Non-nodal/Leukaemic MCL (mutated IGHV, SOX11- and < aggressive)
47
Q

Characteristics of MCL

A
  1. t(11;14), SOX11, CyclinD1
  2. IMPT: Positive for PanB, CD5 and CD43 (Negative for CD200)
  3. Morphological variants (Blastoid, Pleomorphic, Small Cell and MZ-like)
  4. Prognosis
    • MIPI: Age, PS, WCC and LDH
    • Independant prog fts: >Ki67, TP53 and delCDKN2A
48
Q

Treatment of MCL

A

I. Sx
No = WW
Yes = Fit or Not

II. Fit
No = BR/R
Yes = Age

III. Age
< 65 = RCHOP then AlloSHCT
> 65 = RCVP/BR/RCHOP with R-maintenance

49
Q

DDx for B-cell neoplasms that do not express pan B-markers

2

A
  1. CLL
  2. PBL
50
Q

DDx for CD19/CD10 Positive B-cell neoplasms (CD5-)

6

A
  1. B-ALL
  2. Haematogones
  3. FL
  4. BL
  5. DLBCL
  6. MM
51
Q

DDx for CD19/CD5 Positive B-cell neoplasms (CD10-)

4

A
  1. CLL
  2. MCL
  3. B-PLL (SBLwPN)
  4. 5% of DLBCL
52
Q

DDx for CD19 Positive B-cell neoplasms (CD5 and CD10-)

2

A
  1. HCLv
  2. MZL (SMZL, NMZL, MALT)
53
Q

Cyclin D1 positivity

A

MCL

54
Q

Annexin 1 Positivity

A

HCL

55
Q

DDx for villous lymphocytes

5

A
  1. HCL
  2. SMZL
  3. HCLv
  4. BPLL
  5. SDRPL

FCPath(SA)Haem - HaemOnc (20 decks)

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