B cell LPD Flashcards
GCB immunophenotype
CD10+
CD10-/BCL6+/MUM1-
ABC immunophenotype
CD10-/BCL6+/MUM1+
CD10-/BCL6-
(2 pos or 2 neg)
IPI for DLBCL
(SLOPE) Stage III or IV LDH Old age > 60 Performance status 2 or more Extranodal sites > 1
Immunophenotype of Burkitt lymphoma
Include Endemic subtype and pertinent negative IHC
- Moderate to strong membrane IgM with light chain restriction
- B cell antigens - CD19, CD20, CD79a and PAX5
- Germinal centre markers are positive: BCL6 and CD10
- Ki67 approaches 100% (unless apoptosis causes it to be falsely low)
Negative = TdT, CD5, CD23, CD30, CD138, BCL2
Endemic: almost all are EBV positive and CD21+ (receptor for EBV)
Subtypes of Burkitt lymphoma
Endemic (African) - facial/jaw bone; EBV driven
Sporadic - abdominal mass and ascites
Immunodeficiency - lymphadenopathy
Features of Burkitt lymphoma
Highly aggressive B cell lymphoma Rapidly enlarging mass Very high LDH Spontaneous tumour lysis Characterised by MYC translocations
Cytogenetics and molecular findings of BL
- Hallmark is translocation of MYC at 8q24:
t(8;14) = IgH (80%)
t(2;8) = kappa (15%)
t(8;22) = lambda (5%) - 70% have TCF3 or its negative regulator ID3 mutations which activate the BCR signalling pathway.
Morphology and immunophenotype of ALK+ large B cell lymphoma
Immunoblastic or plasmablastic
Plasma cell phenotype.
ALK+, EMA+, Pan-B negative, CD138+, cIg+, light chain restriction, often CD45-
CD30-
Plasmablastic lymphoma
CD30+
CD138+, CD38+, CD20-
cIg with light chain restriction
CD56+/-
Presentation of Hairy Cell Leukaemia
Splenomegaly, B symptoms
Pancytopenia with monocytopenia
Opportunistic infections
Pathogenesis of HCL?
Post GC B cell
BRAF mutation = constitutive action of MAPK
Prolonged cell survival is mediated by BRAF and BCL2 over-expression (anti-apoptosis)
Hairy cells secrete FGF = reticulin fibrosis
Hairy cells secrete TGF-beta = inhibits normal haematopoiesis
Immunophenotype of HCL?
CD19, CD20, CD22, CD11c and sIg (all bright)
CD25, CD103 and CD123, CD200
Annexin A1, BRAF
Morphology of HCL
Intermediate sized lymphocytes
Oval or kidney shaped nuclei
Spongy, homogenous nuclear chromatin pattern with ABSENT NUCLEOLI
Abundant cytoplasm, grey blue hairy projections
TRAP positive.
Trephine = Fried egg appearance due to widely spaced lymphocytes with abundant cytoplasm and prominent cell borders.
Compare and contrast HCLv with HCL
Clinical: HCLv = leukocytosis, normal monocyte count
Morphology: HCLv = int. lymphocytes with hairy projections but prominent nucleoli and less spongy appearance of chromatin. BM may show intrasinusoidal or subtle interstitial infiltrate, no fried egg appearance
Immunophenotype: HCLv = CD11c and CD103 positive but BRAF, CD25 and CD123 negative. DBA.44 is positive.
Management: Splenectomy or R-chemo, resistant to cladribine.
Clinical features of LPL/Waldenstrom’s
Anaemia Cold agglutinin disease Cryoglobulinaemia Hyperviscosity Amyloidosis Coagulopathy Neuropathy (MAG antibodies) Bing Neel syndrome (CNS involvement)
Causes of coagulopathy in Waldenstrom’s
- Impaired platelet function - paraprotein non-specifically binds to platelets
- Paraprotein interferes with fibrin clot formation
- Acquired VWD
- Acquired factor VIII deficiency
- Amyloidosis causing acquired factor X deficiency
Manifestations of hyperviscosity syndrome?
Triad:
- Mucosal bleeding (epistaxis, gum bleeding)
- Visual - retinal haemorrhages
- Neurological - headaches, dizziness, rarely can get coma
What are cryoglobulins?
Immunoglobulins that precipitate on cooling (and redissolve on re-warming)
Describe how you would test for cryoglobulins
Take blood into pre-warmed syringe and put into pre-warmed test tube free of anti-coagulant
Allow to clot at 37 degrees
Centrifuge at 37 degrees and collect serum
Cool serum to 4 degrees and store for 7 days
Measure amount of ppt compared to original volume of serum.
N.B. pre-warming is essential to avoid false negatives - otherwise cryoglobulins may ppt into clotted blood.
Morphologic findings in LPL?
Small mature lymphocytes + plasmacytoid lymphocytes + plasma cells (may be dispersed or seen in clusters)
Interstitial, nodular, diffuse +/- paratrabecular infiltrate
Immunophenotype of LPL?
- Include B lymphocytes and plasma cells
CD19+, CD20+, CD22+, CD79b positive, sIg+
CD5- and CD10-
Plasma cells - CD138+, CD19+ (unlike MM) and often CD45+
Morphologic variants in Mantle cell lymphoma
Classic = fish mouth Small cell Marginal zone like Blastic (resembles ALL) Pleomorphic
Prognostic factors in Mantle cell lymphoma (MIPI + 2 more)
WBCs > 10 ECOG 2-4 Age >60 Ki67 >30% LDH >ULN Pleomorphic and blastic morphology 17p deletion
What is leukaemic non-nodal MCL?
More indolent form of MCL
PB, BM +/- splenic involvement but not nodal.
CCND1+ but SOX11 negative
IgHV hypermutated (goes through germinal centre)
Can progress to more aggressive form upon acquisition of TP53 mutation.
