UNIT 7: MATURE LYMPHOID NEOPLASMS & PLASMA CELL NEOPLASMS

Leukemia

Primary site is the blood or bone marrow

Lymphoma

• Localization of disease in the lymph nodes and spleen.

• Lymphadenopathy is present in approx 40% of cases

Leukemic phase

Phase of lymphona in which the malignant cells are found in the peripheral blood

Plasma cell neoplasm/ Plasma cell myeloma

Increased number of plasma cells, bone marrow-based

• Chronic Lymphocytic Leukemia

• Small Lymphocytic Lymphoma

• Leukocytosis with increased number of mature lymphocytes - B cells

• Most patients are asymptomatic

• Indolent, slow-growing B-cell neoplasm

• Male > Female

• Chronic Lymphocytic Leukemia

• Small Lymphocytic Lymphoma

Composed of mature small B lymphocytes

• Chronic Lymphocytic Leukemia

• Small Lymphocytic Lymphoma

• Disease is often detected by an abnormality in routine CBC

• Confirmed by flow cytometry immunophenotyping

Chronic Lymphocytic Leukemia

Used for non leukemic patients with the tissue morphology and immunophenotype of CL

Small Lymphocytic Leukemia

Lymphoma phase of CLL

Small Lymphocytic Leukemia

• Most common form of leukemia in older adults

• The median age of onset 65-72 years old

Absolute lymphocytosis

Common initial finding for CLL

Lymphadenopathy

common initial finding for SLL

Diagnosis of CLL

> or = to 5×10⁹/L circulating B lymphocytes for 3 months

SLL in nodal form

Blood lymphocyte count may be <5 × 10⁹/L

80-90% small lymphocytes (overmature (well differentiated) with hypercondensed nuclear chromatin

Describe its PBS

• Chronic Lymphocytic Leukemia

• Small Lymphocytic Lymphoma

homogenous, small, hyperclumped lymphocytes

Describe its lymphocytes

• Chronic Lymphocytic Leukemia

• Small Lymphocytic Lymphoma

• Scant cytoplasma and dense nucleus with condensed chromatin without a defined nucleolus

• High N:C ratio

Cobbleston or soccer ball

Chromatin pattern

Smudge Cells/ Basket Cell

Smudge cells/ Basket cell

Remnant of cells that lack any identifiable cytoplasmic membrane or nuclear structure

Smudge cells/ Basket cell

Increased amount because associated with abnormally fragile lymphocytes

Atypical CLL

Associated wiht biologic markers indicating more aggressive disease

• CLL/PLL

• Mixed type/ Atypical CLL

Two Variant subtypes of Atypical CLL

CLL/PLL

What Atypical CLL variant subtype has:

>10% but <55% prolymphocytes

Mixed type/ Atypical CLL

What Atypical CLL variant subtype has:

>15% large atypucal lymphoid cells that exhbit nuclear indentation/ clefts

CD19, CD20, CD23

B cell markers of Atypical CLL

Atypical CLL

Co-express the T cell antigen CD5

Atypical CLL

Weak surface Ig and dim CD20 expression

Atypical CLL

Cyclin D1 and Tdt negative, CD200+ LEF1+

Atypical CLL

CD19+, CD20+, CD 23+, CD5+, weak surface Ig, CD10-, FMC7-

CD10 (CALLA)

Common/intermediate in B cell ALL

Catovsky-matutes scoring for CLL

• weak expression of surface immunoglobulin

• expression of CD5

• expression of CD23

• No expression of FMC7

• Absent or weak expression of CD79b or CD22

Rai and BInet staging systems

Staging for Chronic Lymphocytic Leukemia

Low Risk

RAI classificiation (revised):

Lymphocytosis >5×10⁹/L

Intermediate Risk

RAI classificiation (revised):

Lymphocytosis >5×10⁹/L and (lymphadenopathy + splenomegaly) or hepatomegaly or both

High Risk

RAI classificiation (revised):

Lymphocytosis >5×10⁹/L and hemoglobin <11g/dL

Stage A

Binet Classification

Hemoglobin ≥ 10g/dL and platelets ≥ 100×10⁹/L and < 3 enlarged nodal areas

Stage B

Binet Classification

Hemoglobin ≥ 10g/dL and platelets ≥ 100×10⁹/L and ≥ 3 enlarged nodal areas

Stage C

Binet Classification

Hemoglobin <10 g/dL or platelets < 100×10⁹/L and any number of enlarged nodal areas

Atypical CLL

Del(13q14)

Deletion of 13q

the most ocmmon cytogenetic abnormality in CLL

Del(13q14)

Loss of a segment on the long arm of chromosome 13 that contains tumor suppressor elements

Del(13q14)

Confers a favorable prognosis, associated with the most indolent disease course

Del (17p) and TP23 abnormalites

• Worst prognostic indicators

• <10% of patients

• Deletion of tumor suppressor genes

Del (17p) and TP23 abnormalites

P53-mediated apoptosis is impaired

Del (17p) and TP23 abnormalites

Most ominous cytogenetic findings, confer high-risk disease

Unmutated/ less mature form

More aggressive clinical course of mutation of the heavy chain immunoglobulin genes

Mutated/ more mature

Do better with standard chemoimmunotheraphy mutation of the heavy chain immunoglobulin genes

• Rituximab

• Obinutuzumab

Treatment for Atypical CLL

Rituximab

Anti-CD20 monoclonal antibody

Obinutuzumab

New monoclonal antibody and designed to more efficacious