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ACP > Lymphoproliferative Neoplasms and Plasma Cell Myeloma > Flashcards

Lymphoproliferative Neoplasms and Plasma Cell Myeloma Flashcards

1
Q

Plasma cell myeloma: definition, epidemiology

A

Neoplastic proliferation of bone marrow plasma cells, characterised by lytic bone lesions, plasma cell accumulation in BM and monoclonal protein in serum and urine

Common malignancy in adult and elderly (90% cases >50), uncommon in <30 yrs old

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2
Q

Clinical presentations of plasma cell myeloma

A

Asymptomatic: Incidental finding of reversed A:G ratio or hyperCa or elevated ESR

End organ damage: CRAB

  • hyperCa due to bone lesions
  • Renal impairment due to cast nephropathy or amyloidosis
  • Anaemia
  • Bone pain/ cord compression due to lytic lesions

Others:

  • bleeding tendency (proteins may interfere with platelet functions and coagulation)
  • recurrent infections due to immuneparesis
  • hyperviscosity in 2% cases with visual impairment, CNS symptoms and heart failure
  • AL amyloidosis (5%)
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3
Q

Plasma cell dyscrasias

A

Spectrum of disorders with proliferation of plasma cells:

Monoclonal gammopathy of undetermined significance (MGUS)
Plasma cell myeloma
Plasmacytoma

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4
Q

MGUS - diagnostic criteria, risk factors for progression

A

Usually asymptomatic

<10% plasma cells in BM
Paraprotein levels <30g/L
No myeloma defining events
Normal Ig and FLC ratio (higher risk of transformation if abnormal FLC)

Risk of transforming to MM at 1% per yr

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5
Q

Plasma cell myeloma - diagnostic criteria

A

Smouldering/ Asymptomatic

  • Paraprotein >30g/L OR Clonal plasma cells in BM >10%
  • No myeloma defining events
  • Reduced Ig, abnormal FLC
  • 10%/yr progress to symptomatic

Symptomatic

  • Paraprotein >30g/L OR Clonal plasma cells in BM >10%
  • 1 or more Myeloma defining events e.g. >1 CRAB feature, BM plasma cells >60%, serum free light chain ratio >100, MRI focal lesion >5mm
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6
Q

Investigations of plasma cell myeloma

A
  1. Identification of monoclonal Ab in serum and/or urine
    - serum protein electrophoresis and immunofixation
    - serum free light chains
    - urine free light chains (Bence Jones proteins) in 2/3 cases
  2. BM study for clonal plasma cells (>10%)
    - plasma cell atypia (large, high N:C, prominent nucleoli)
  3. End organ damage
    - RFT, Ca, Skeletal survey (XR, MRI spine, lytic lesions without surrounding sclerosis), CBC
    - (and blood smear shows rouleaux formation due to hyperproteinaemia!)

Others:

  • elevated beta-macroglobulin and reduced albumin are poor prognostic indicators
  • cytogenetics and FISH for prognostic markers
  • MRI for plasmacytoma of bone
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7
Q

Serum protein electrophoresis and immunofixation - purpose, method, expected results

A

Detect paraproteinaemia due to monoclonal population of plasma cells secreting specific Ig

Method: separate proteins based on size and charge

  • -> abnormal Ig usually create M-spike at gamma-globulin region
  • -> reduced background levels of Ig (immuneparesis)

Further separation of protein subtypes by staining with immunologically active agent to determine Ig type
- IgG in 60% cases

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8
Q

Immunophenotype of plasma cells

A

CD19, 38, *138, 56, light chain restriction

CD20-ve

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9
Q

Prognostic markers in MM

A

Favourable – hyperdiploidy, t(11;14)

Unfavourable – t(4;14), t(14;16), del(17p), gain in chr1

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10
Q

Revised International Staging System (R-ISS) for MM

A

4 features to determine stage:

  • serum albumin (low = poor prognosis)
  • serum beta-2 microglobulin (high = poor prognosis)
  • serum LDH (high = poor prognosis)
  • specific cytogenetic abnormalities with poor prognosis

R-ISS stage I-III

  • stage I 5 yrs OS 82%
  • stage III 40%

Prognosis improving with 7-10 yrs median survival

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11
Q

Treatment of MM

A

Intensive (<70yrs)
- chemotherapy (thalidomide, bortezomib and dexamethasone) and autologous SCT

Non-intensive
- oral alkylating agent melphalan with prednisolone and thalidomide

Supportive

  • renal: hydration, treat hyperCa, hyperUr
  • bone: bisphosphonates
  • anaemia: EPO, transfusion
  • bleeding and hyperviscosity: plasmapheresis
  • infections: prophylactic Ig concentrates
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12
Q

Plasmacytoma - definition, sites, features, prognosis

A

Isolated plasma cell tumour

In bone (solitary plasmacytoma of bone)
- no other lesions, no plasmacytosis of BM, no clinical features of MM
or
Extraosseous (commonly upper respiratory tract, GI tract, LN)

May progress to MM

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13
Q

Lymphoproliferative neoplasms - definition, classical features, possible presentations, relation to lymphoma

A

Clonal proliferation of MATURE lymphoid cells (B/T/NK) that is rare before 40 yrs old

Characterised by persistent lymphocytosis
Blood and BM involvement ++
Chronic fluctuating course, generally incurable

Asymptomatic - Dx on routine checkup
May have lymphadenopathy, hepatosplenomegaly, extra-nodal disease, cytopenia

Overlap with lymphoma as lymphoma cells can present in blood at advanced stage

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14
Q

Lymphoproliferative disease vs Lymphoma

A

Distinction is arbitrary depending of relative amount of cells in blood vs soft tissue masses

Lymphoma

  • proliferation in lymphoid tissue (nodal or extranodal)
  • may involve blood and BM in leukaemic phase

Lymphoproliferative disease

  • proliferation in bone marrow and blood
  • may also involve LN, spleen and liver (lymphoid tissues)
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15
Q

Immunophenotypes of lymphocytes

A 
B cells - CD20
T cells - CD3
-- T helper CD4
-- Cytotoxic T CD8
NK cells - CD56
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16
Q

Investigations of Lymphoproliferative neoplasms

A
  1. CBC and blood film
    - lymphocytosis – morphology
    - cytopenia – Ix causes of anaemia e.g. DCT, LDH, bilirubin, retic %, spherocytes; thrombocytopenia/ neuropenia
  2. BM study – morphology
    - assessment infiltration extent, cause of cytopenia
  3. Immunophenotyping by flow cytometry
    - define lineage
  4. Genetics – identify clonal lymphoid, classification of disease, prognostic factors
    - cytogenetics
    - FISH
    - molecular e.g PCR for IgH/TCR gene rearrangement, RT-PCR for fusion transcripts
  5. Others
    - biopsy of enlarged LNs
    - imaging for stage and extent of disease
    - microbiological (viral related neoplasms)
17
Q

Mature B and T cell neoplasms that preferentially involve PB and BM

A

B-lineage

  • CLL
  • hairy cell leukaemia

T-lineage

  • T cell prolymphocytic leukaemia
  • Adult T cell leukaemia/lymphoma
  • aggressive NK cell leukaemia
18
Q

Chronic Lymphocytic Leukaemia - age group, aetiology, diagnostic criteria, blood film appearance, clinical features, immunophenotype

A

Most common form of LPD, mean age 65 and rare before 40
Unknown aetiology, familial predisposition+
Small lymphocytic lymphoma is counterpart in tissue
Indolent clinical course

Diagnostic criteria

  • > 5x10^9/L monoclonal B lymphocytes in PB for 3 months with characteristic immunophenotype
  • > 30% BM involvement (heavy infiltration of small lymphoid cells with depressed haemopoiesis)

Blood film:

  • small lymphocytes with round nuclei, scanty cytoplasm and indistinct nucleoli
  • smear cells/ SMUDGE cells

Clinical features:

  • incidental finding of lymphocytosis
  • constitutional symptoms
  • anaemic, thrombocytopenic, neutropenic symptoms
  • LN/ hepatosplenomegaly (at later stages)

Immunophenotype

  • CD19, 20, 22 (B cells)
  • CD5 and CD23 (aberrant markers)
  • restricted light chain expression
19
Q

CLL molecular prognostic markers

A

80% cases have abnormalities detected by FISH

Favourable: del(13)
Intermediate: trisomy 12
Unfavourable: del(17), del(11)

20
Q

Staging of CLL

A 
BINET 
- A = 0-2 lymphoid areas
- B = >3 lymphoid areas
- C = Hb <10 or Plt <100
(lymphoid areas = cervical, axillary, inguinal, liver, spleen)

RAI

  • 0 = lymphocytosis only (>5x10^9)
  • I = 0 + LN
  • II = 0 + hepato/splenomegaly +/- LN
  • III = 0 + Hb<10 +/- hepatosplenomegaly +/- LN
  • IV = 0 + Plt<100 +/- hepatosplenomegaly +/- LN

RAI stage 0 = 12 yr survival vs 3 yrs for stage IV

21
Q

Overall prognostic factors for CLL - gender, stage, lymphocytes, BM involvement, serum markers, IgH gene, cytogenetics

A

Low risk

  • female
  • BINET A or RAI 0
  • typical lymphocytes
  • non-diffuse BM involvement (nodular)
  • normal serum beta2-macroglobulin and CD23
  • CD38-ve
  • ZAP70 low
  • IgH gene mutated
  • cytogenetics: del(13) or normal

High risk

  • male
  • BINET C or RAI III/IV
  • atypical lymphocytes
  • diffuse BM involvement
  • elevated beta2 macroglobulin and CD23
  • CD38+ve and ZAP70 high
  • IgH non-mutated
  • cytogenetics: del(11), del(17)
22
Q

Treatment of CLL

A

Difficult to cure, aim for conservative approach and symptom control

Many patients never need Tx (low stage)
Normally give for high stage, troublesome LN, constitutional symptoms

Chemotherapy: rituximab (anti-CD20) + cytotoxic drugs e.g. fludarabine, cyclophosphamide

Supportive:

  • RT for bulky LNs
  • Ig replacement if recurrent infection
23
Q

Hairy cell leukaemia - prevalence, presentation, CBC/blood film/BM findings, immunophenotype, genetics, treatment

A

Uncommon, M>F, 40-60 yrs peak

Presentation:

  • MASSIVE SPLENOMEGALY
  • infection, anaemia

CBC, blood film, BM:

  • pancytopenia
  • MONOCYTOPENIA
  • “hairy cells” with villous cytoplasmic projections on blood film –> +ve staining with TRAP
  • BM: fibrosis and cellular infiltrate

Immunophenotype;

  • CD19, 20, 22
  • CD11c, CD25, CD103
  • light chain restriction

Genetic:
- BRAF mutation

(spleen biopsy shows red pulp involvement by bland tumour cells)

Treatment: effective with relapse-free survival for 16 yrs

  • CDA, DCF (+/- alpha interferon)
    • rituximab for relapsed cases
24
Q

T cell prolymphocytic leukaemia - clonal cells, clinical features, blood film appearance, immunophenotype, cytogenetics

A

Clonal proliferation of post-thymic T cells

Clinical features:

  • lymphocytosis
  • LN, splenomegaly
  • serous effusions (pleural or ascites)

Blood film:

  • small-medium sized cells with round nuclei, prominent nucleoli
  • agranular cytoplasm with BLEBBING

Immunophenotype:

  • CD2, 3 (surface), 5, 7
  • CD 34 and Tdt -ve
  • CD4 (60%), CD8 (15%), both (25%)

Cytogenetics:

  • 8, 11, 14, X most commonly involved
  • inv(14) is distinctive (70% cases), isochr(8)
25
Q

Adult T-cell leukaemia/lymphoma - main aetiology, clinical presentation, blood film, immunophenotype, treatment

A

A/w human T cell leukaemia/lymphoma virus type 1 (HTLV-1) but most infected subjects don’t develop disease

  • endemic in Japan, Caribbean
  • only occurs in adult, poor prognosis

Clinical presentation:

  • can be smouldering, chronic lymphatomatous or acute
  • widespread LN
  • hepatosplenomegaly
  • > 50% with skin involvement
  • hyperCa +/- lytic bone lesions

CBC, blood film, BM:
- convoluted CLOVER LEAF nucleus

Immunophenotype:

  • CD2, 3, 5
  • CD7 -ve!
  • consistent CD4 +ve , CD8 -ve
  • CD25 ++

Treatment: Zidovudine

ACP (27 decks)

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