LPDs Flashcards

Question

SMZL diagnostic criteria

Answer 1

Essential:  > Small B-cell lymphoma involving BM and/or PB composed of small lymphoid cells with villous processes  > Cells express pan-B markers, IgM and IgD. Negative for BCL6, annexin A1, CD103, cyclin D1, SOX11 and LEF1 .  - exclusion of other splenic and nodal NHL - splenomegaly   Desirable  > CD5 and CD10 negative

Answer 2

30% show hemizygous deletion of 7q31-32 is seen in splenic marginal zone lymphoma, but is virtually absence in all other B-lymphoproliferative disorders   25% associated with trisomies 3 and 18 (seen in all marginal zone entities)  

Answer 3

Pan B-cell antigens (CD19, 20, 22), monotypic SIg, FMC7+, PAX5+, CD38 (dim)  BCL6-, annexin A1-, CD103-, cyclin D1-, SOX11-, LEF1-  A small subset express CD11c, CD123, CD5 (usually weak) or CD43  Rare cases are CD10+  CD25 is positive in 30-50% 

Answer 4

Del(7q31-32) is the sole biomarker specifically associated with SMZL  NOTCH2 and KLF2 can occur in both SMZL and nodal MZL, but are rare in other small B-cell lymphomas 

Answer 5

A splenic B-cell neoplasm with some morphologic/immunophenotypic features which overlap with HCL  lacks BRAF mutation and is resistant to conventional HCL therapy  Cells have a characteristic single large nucleolus  RARE elderly patients PB: Leucocytosis +/-Thrombocytopenia NO monocytopenia Morph: medium cells, prominent nucleolus and some degree of fine villious projectiosn BUT NOT circumferentrial INTERSTITIAL No BRAF More aggressive than HCL.

Answer 6

Essential  > medium lymphoid cells with prominent nucleoli or convoluted nuclei. > circumferential projections are absent.  > CD19+, CD20+, CD79a+ or PAX5+  > Absence of characteristic phenotype of HCL, including expression of CD25, annexin A1, cyclin D1 and TRAP (tartrate-resistant acid phosphatase)   Desirable  > Diffuse involvement of the splenic red pulp with atrophic white pulp (but most cases are diagnosed without a spleen specimen)  > Absence of BRAF mutation

Answer 7

Neoplasm comprising small B lymphocytes; plasmacytoid lymphocytes and plasma cells usually involving the BM, sometimes involving LNs and spleen.   Waldenstrom's Macroglobulinaemia = LPL in BM with an IgM paraprotein  Bing-Neel syndrome = LPL involvement of the CNS   Non-IgM type LPL (5%) - IgG or IgA - non secretory - IgM LPL without BM involvement

Answer 8

Essential:  - BM infiltration by > 10% small lymphocytes with plasmacytoid and/or plasma cell differentiation   - immunophenotype of LPL cells: IgM+, CD19+, CD20+, CD22+, CD25+, CD10-, CD23-, CD103-, CD138+/-  Desirable:  - MYD88  - CXCR4 somatic mutation.  - Serum electrophoresis and immunofixation showing presence of monoclonal IgM 

Answer 9

Fatigue and constitutional symptoms most common  LN/hepatosplenomegaly in <25% at diagnosis, 50-60% at relapse   30% hyperviscosity syndrome with blurred vision, headache, epistaxis and shortness of breath  > More common if IgM >60 g/L   Type II cryoglobulinaemia -> vasculitis, skin lesions, renal complications and neuropathy   Neuropathy in 20% due to anti-MAG in majority:   Gradually worsening distal sensory loss, ataxic gait and tremor  - Demyelinating pattern on EMG  

Answer 10

95% MYD88 p.L265P -> leads to constitutive activation of the NF-kB pathway   - IgM MGUS = higher risk of progression to LPL - NGS may lead to false negatives in up to 1/3rd of cases   40% CXCR4  - unique to LPL, assoc with   High serum IgM   Hyperviscosity   Acquired vWF disease  Earlier time to treatment   Resistance to ibrutinib therapy   40-50% deletions in chr 6p   - Exclusive to CXCR4 mutations in treatment naïve patients  

Answer 11

WM-IPSS score  >65   age Hb <115  Platelet <100  B2M >3mg/L  IgM paraprotein >70g/L 

Answer 12

2nd most common indolent lymphoma, 7% of NHL    Indolent B-cell lymphomas with overlapping histopathological features:   > CD5-/10- in majority   Often show plasmacytic differentiation  > Associated reactive follicles are frequent   Types:   EMZL (MALT) = 70%  Splenic MZL = 20%  Nodal MZL= 10%   Primary cutaneous MZL**   New entity in the 5th edition of the WHO, comprises 30-40% of cutaneous B-cell lymphomas

Answer 13

Prognosis -> MZL-IPI > LDH > Anaemia > Thrombocytopenia > Lymphopenia > MZL type (nodal or disseminated)

Answer 14

- extranodal marginal zone lymphoma of MALT Indolent with architectural features reminiscent of Peyer's patches   Associated with chronic inflammatory disorders/infection --> dysregulated immune response and somatic genetic changes.   Essential:  - Lymphoma arising in an extranodal site.  - Atypical small/medium-sized lymphoid cell proliferation mimicking reactive MALT and showing architectural distortion.  - Expression of B-lineage markers.  - Exclusion of other small B-cell neoplasms   Desirable:  - Demonstration of light chain restriction or clonal immunoglobulin gene rearrangement.  - Lymphoepithelial lesions.  - Remnants of underlying inflammatory background e.g., reactive lymphoid follicles, Hashimoto thyroiditis in thyroid or lymphoepithelial sialadenitis in salivary gland. More common in Asia , F>M H pylori= gastric EMZL  C psittaci= ocular EMZL  Immunophenotype - B cell markers, usually sIgM Aberrant CD43 expression ~40% cases and can help distinguish from reactive process.

Answer 15

monoclonal Ig gene rearrangements may help establishing diagnosis  t(11;18)/BIRC3::MALT1 is seen in 24% of stomach and 40% of lung EMZL.

Answer 16

Essential:  - Morphology consistent with MZL  - Presence of CD5-, CD10- small B cells.  - Demonstration of monotypic plasma cells, monotypic B cells, and/or clonal immunoglobulin gene rearrangement.  - No evidence of extracutaneous disease at the time of diagnosis.  - Exclusion of other cutaneous lymphomas.  Desirable:  - Lesions on trunk or arms  - Reactive lymphoid follicles in lesion  5yr OS >98%   Recurrences are common  Extracutaneous spread is RARE but more commonly occurs in: non-class switched; multifocal form; transformed disease 

Answer 17

Primary nodal zone lymphoma of small mature B cells from marginal zone B cells WITHOUT extranodal or spleen involvement. Essential:  - Proliferation predominantly of small, mature B cells with scant to moderate amount of pale cytoplasm - Architectural distortion in a nodular/follicular, parafollicular, interfollicular, or diffuse growth pattern.  - Absence of markers supporting follicular lymphoma, mantle cell lymphoma or other specific small B-cell lymphomas; Desirable:   - Residual follicles with follicular colonization  - monotypic light chain expression in B cells and/or plasma cells.  - clonal immunoglobulin gene rearrangements IHC: MNDA and IRTA1 in 75% of cases  Can have BM involvement

Answer 18

<2% of childhood NHL   Most common in adolescent males (16yrs)   Most commonly involves head and neck LNs  Follicles are often enlarged with a disrupted CD23+ follicular dendritic meshwork and IgD positive mantle cells extending into the GC resembling progressively transformed germinal centres; most cases are CD43+   Monoclonal rearrangements of IgH or IgK are detected in almost all cases   Cure rates reach 100%  

Answer 19

10-20% of all lymphomas Adults median age in 60s A haematologic neoplasm of germinal centre (GC) B-cells with varying proportions of centrocytes (CC) and centroblasts (CB) or large transformed cells and at least a partially follicular growth pattern.   Subtypes:  > Classic FL  > FL with unusual cytological features  > FL with predominantly diffuse growth pattern  > Follicular large BCL - defined by lack of centrocytes  85% of cases harbour t(14;18)   / IGH:BCL2 rearrangement Grading (1, 2, 3A and 3B) based on number of centroblasts present

Answer 20

Essential:   > B-cell lymphoma - centrocytes (CC) and/or centroblasts (CB)/large transformed cells, with the dominance of CC in the overwhelming majority of cases   Immunophenotype GCB origin: > eg CD10, BCL6   Desirable:   At least partly follicular growth pattern   BCL2 or BCL6 rearrangements and/or lack of IRF4 rearrangement(in equivocal cases)  

Answer 21

SIg and pan B cell marker +  (19/20/22/79a/Pax-5)(  Germinal centre marker positive: CD10+ BCL6+   BCL2+: BCL2 overexpression is the hallmark of FL (85-90% of grade 1-2 FL, and <50% of grade 3 FL)   Negative for IRF4/MUM1  

Answer 22

Predicts overall survival 5 independent risk factors:   Age >60 years   Hb <120g/L   Elevated LDH   An Arbor stage III/IV   >4 involved nodal area

Answer 23

A group of mature B cell neoplasm derived from the mantle zone of lymphoid follicles and typically composed of small to medium sized monomorphic cells expressing CD5, SOX11 and Cyclin D1.  Associated with:  CCND1/IGH translocation in >95% of cases In situ mantle cell neoplasm - confined to mantle zone - Cyclin D1 and SOX11 expression MCL - lymph node effacement - can progress to blastoid or pleomorphic Non-nodal MCL - inv BM, PB and spleen but little or no LAD - arise from IGHV mutated SOX11 neg cell, tp53 - low Ki-67 - CD5 -

Answer 24

Cyclin D1 positive B cells confined to mantle zones of lymphoid follicles Very rare Older pop Indolent, progresses to MCL with frequency <10% Diagnosed on histopath > preservation of lymphoid archiecture Cyclin D1 positive cells Staging negative for over MCL CCND1 rearrangement present CD5 and SOX11 expression can be variable

Answer 25

Mature B cell neoplasm dervied from mantle zone of lymphoid follicles. Small to medium sized monomorphic cells CD5+, SOX11, and cyclin D1 Blastoid:   - Cells resemble lymphoblasts with round nuclei, fine chromatin, inconspicuous nucleoli and a narrow of cytoplasm  Pleomorphic:   - irregular nuclear contours, generally pale cytoplasm, and often prominent nucleoli in at least some of the cells     Small-cell:   - Cells are small, round lymphocytes with more clumped chromatin, round nuclei and a narrow rim of cytoplasm mimicking a small lymphocytic lymphoma   - Can be difficult to distinguish from CLL/SLL   Marginal zone-like:   - Medium sized cells with abundant, pale cytoplasm resembling marginal monocytoid B cells and marginal zone cells 

Answer 26

MCL with PB, BM and splenic involvement, without significant adenopathy (typically peripheral nodes <1-2cm and no enlargement on CT)   Resembles CLL morphologically   Cyclin D1 overexpression from t(11;14)  SOX11 negative, low Ki67 and DBA44 positive (different fro MCL)  IGHV mutated   May be CD5-   May be CD38 negative, and CD200 positive (overlapping with CLL)   Less genomic instability with CCND1 translocation sometimes being the sole abnormality   Associated with better prognosis than classic MCL (median survival 79 months)  

Answer 27

Common: CD5+, CD10-, CD19+, CD20+, CD79a CLL: CD23+, CD200 bright, sIg dim, CD20 DIM, FMC7- MCL: CD23 -, CD200 -, FMC7+, sIg strong/moderate

Answer 28

SOX11 Either cyclin D2 or cyclin D3

Answer 29

Median OS of 3-5 years   Adverse prognostic factors   - Ki67 >30%   - ECOG PS   - LDH level   - WCC   - Blastoid or pleomorphic morphology   - Karyotypic complexity   - TP53 mutation Mantle cell IPI (MIPI)

Answer 30

Irrespectively of the underlying histopathology —> HGT carries inferior prognosis as compared to de novo counterpart   In HGT - process of progressive or parallel acquistion of genetic alteration that confer increased proliferation and aggressive phenotype Hence important to demobstrate clonal relationship between aggressive lymphoma and lo-grade counterpart

LPDs Flashcards

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