Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

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

A

ZAP70

CD38

CD49d

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Risk scores for CLL

A

CLL-IPI and IPSE

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

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

A
  • TP53
  • ATM
  • NOTCH1
  • SF3B1
  • BIRC3
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

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

A
  • Prolymphos > 15%
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

3 factors associated with MBL progression?

A
  1. Clonal Bs > 3
  2. unmutated IGHV
  3. sB2-micro > 3.5
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
What are the 4 subtypes of splenic lymphomas
1. HCL 2. SMZL 3. SDRPL 4. SBLwPN
26
Features of HCL
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
What is the disease defining molecular alteration in Hairy Cell Leukemia?
* BRAF V600E * This mutation leads to a constituitive activation of MAPK * This mutation is present in 100% of cases
28
What are the fts of SMZL?
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
True or False: Plasmacytic differentiation is seen in SMZL?
TRUE * plasmacytic differentiation can occur * RARELY clusters of plasma cells can be seen in the centre of the white pulp nodules
30
What is the differential diagnosis of SMZL?
* CLL * Hairy cell leukemia * Mantle Cell Lymphoma * Follicular lymphoma * Lymphoplasmacytic lymphoma
31
What is the immunophenotype of SMZL?
* 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
The absence of staining of cyclin D1 and LEF1 in SMZL is helpful in excluding which two entities?
* Cyclin D1: Mantle Cell Lymphoma * LEF1: CLL
33
The absence of staining of Annexin 1, CD10 and BCL6 in SMZL helps exclude which entities?
* 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
Presence of MYD88 mutations point to which entity instead of SMZL?
Lymphoplasmacytic lymphoma Note: although rarely SMZL can have this mutation.
35
Does SMZL associated with Hepatitis C virus infection respond to antiviral treatment?
* YES * Treatment with **Interferon gamma** with or without **Ribavirin** has been shown to be effective in treating SMZL
36
Favourable and unfavourable markers in mantle cell lymphoma
``` 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
Features of SDRPL
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
Features of SBLwPN (old HCLv and BPLL)
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
What is the clinical presentation of Lymphoplasmacytic lymphoma (LPL)
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
Etiologies of LPL
1. Previous MGUS 2. HepC 3. Familial
40
IMPT of LPL
Positive for PanB, CD20, Pax5, CD25, CD27 and CD52 ±CD38
40
Mutations associated with LPL
1. MYD88 mutations (Gain of Fx) 2. CXCR4
41
What is WM?
LPL in BM with IgM
42
Treatment of LPL/WM
1. R 2. BR Not Ritux if High IgM = IgM flare
43
What are the 4(5) types of MZL?
1. MALT 2. Primary cutaneous MZL 3. NMZL 4. Paediatric NMZL 5. (SMZL)
44
Different causitive factors in MALT lymphoma?
* **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
Features of NMZL
1. LAD of head and neck 2. IMPT: Positive for PanB, BCL2 and CD43 3. Tx: Like FL
46
What are the 3 types of MCL?
1. Insitu MCL (confined to LN) 2. MCL (unmutated IGHV, SOX11+ and Aggressive) 3. Non-nodal/Leukaemic MCL (mutated IGHV, SOX11- and < aggressive)
47
Characteristics of MCL
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
Treatment of MCL
**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
DDx for B-cell neoplasms that do not express pan B-markers | 2
1. CLL 2. PBL
50
DDx for CD19/CD10 Positive B-cell neoplasms (CD5-) | 6
1. B-ALL 2. Haematogones 3. FL 4. BL 5. DLBCL 6. MM
51
DDx for CD19/CD5 Positive B-cell neoplasms (CD10-) | 4
1. CLL 2. MCL 3. B-PLL (SBLwPN) 4. 5% of DLBCL
52
DDx for CD19 Positive B-cell neoplasms (CD5 and CD10-) | 2
1. HCLv 2. MZL (SMZL, NMZL, MALT)
53
Cyclin D1 positivity
MCL
54
Annexin 1 Positivity
HCL
55
DDx for villous lymphocytes | 5
1. HCL 2. SMZL 3. HCLv 4. BPLL 5. SDRPL

FCPath(SA)Haem - HaemOnc (19 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions