Wbc Lecture 5 Chronic Lymphoproliferative/Lymphoma Multiple Myeloma/ Plasma Cell Disorders

- Chronic lymphocytic leukemia
- B cell prolymphocytic leukemia (B cell PLL)
- Hairy cell leukemia (HCL)
- Waldenström’s macroglobulinemia (WM)
- Monoclonal gammopathy of undetermined significance (MGUS)
- Plasma cell myeloma (aka MM)
- Follicular lymphoma
- Mantle cell lymphoma
- Burkitt lymphoma

- Adult T cell leukemia/lymphoma
- Mycosis fungoides
- Sézary syndrome

Hodgkin Lymphoma

Normal lymphocyte count or automated diff, WHICH does not exclude lymphoid neoplasm

Flow cytometry

(karyotyping) and fluorescent in situ hybridization (FISH)

Serum Cr,
uric acid,
SPE,
retic count, DAT and haptoglobin in CLL presenting with anemia, LDH and β2-MG as indicators of tumor load,
ESR in Hodgkin lymphoma (high ESR predictive of early relapse and decreased survival)

Peripheral blood is easy
but less informative, biopsy from lymph nodes more informative

Excisional biopsy (gold standard),
but fine needle aspiration (FNA) has become popular due to the ease with which specimens can be obtained

Imaging studies may be needed (CT scan)

Chronic lymphocytic leukemia (CLL): 13q14 del

Prolymphocytic leukemia (PLL): t(8;14), MYC

Hairy cell leukemia (HCL): BRAF V(600)E

Chronic lymphocytic leukemia (CLL),
Prolymphocytic leukemia (PLL),
Hairy cell leukemia (HCL),
Large granular lymphocytic (LGL) leukemia

Chronic lymphocytic leukemia (CLL)

B cell disorder

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More than 85%

In typical CLL: >85% of the lymphocytes appear as small and mature with scant cytoplasm and a dense nucleus with a condensed chromatin pattern without a defined nucleolus (“cobblestone” or soccer balll appearance)

80% cases are typical CLL, and 20% atypical CLL

Smudge cells are very important cells that must be counted as lymphocytes

Diagnosis of Chronic Lymphocytic Leukemia (CLL)

Score 1 point for each of following:
- Weak expression of surface immunoglobulin
- Expression of CD5
- Expression of CD23

- No expression of FMC7
- Absent or weak expression of CD79b or CD22

Low scores of 1 or 2 suggest Non-Hodgkin lymphoma (NHL)

An intermediate score of 3 remains problematic,
and
these cases may require biopsy of a node or molecular data to establish the diagnosis

Del(17p) and TP53 are the worst prognostic indicators

Mutational status of the heavy chain immunoglobulin gene (IGHV) is a strong prognostic factor.
No mutation is associated with pre-germinal center type of CLL and more aggressive clinical course.
Mutated IGHV indicates better prognosis and better response to drug treatment.

Testing for ZAP70 and CD38: correlated with IGHV mutational status.

A rare and very aggressive leukemia with a unique clinical course

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More than 75%

Very aggressive, massive splenomegaly, marked absolute lymphocytosis (>100 × 10⁹/L)

A rapidly rising white blood cell (WBC) count may be a clue that the diagnosis is not CLL!!!

Medium to large lymphocytes with ample cytoplasm, a more open chromatin pattern, and a prominent nucleolus

CD7 is positive, and inv(14) is present in approximately 70% of patients (using FISH)

Increased WBC, increased lymphocytes, but blast or atypical/variant lymph flag, PBS exam is a must!

An indolent disease of B cell lineage most commonly found in middle age (median age, 50 years), mostly in males

In the spleen, blood, and bone marrow with splenomegaly and cytopenias

Characteristic hairy cells have round to ovoid nuclei, lack nucleoli, and have relatively abundant cytoplasm with ragged projections that extend circumferentially around the entire cell

Fibrotic bone marrow due to fibrosis, requiring a biopsy

Monoclonal anti-CD20 and Annexin A (specific to HCL) using Immunohistochemistry

A rare disease characterized by an increase in large granular lymphocytes (>2 × 10⁹/L)

Older adults with a median age of 60 years

Variant or atypical lymphocyte flag or blast flag on the hematology analyzer

CD3, CD8, and CD57 (clonal expansion of cytotoxic T cells)

CD3 negative but CD56 positive

Associated with retroviral infection by the human T lymphotropic virus type 1 (HTLV-1)

HTLV-1 is endemic in Japan, the Caribbean islands, Africa, South America, the Middle East, and northern Oceania

The virus is transmitted via placental circulation, breastfeeding, blood transfusion, or sex.

Approximately 2.5% (women) to 5% (men) over a latency period of 55 to 70 years

Marked leukocytosis in the leukemic phase of ATLL

ATLL cells are medium to large in size and have accentuated, convoluted nuclei, coarsely clumped chromatin, and deeply basophilic cytoplasm (aka “flower cell”)

Generally consistent with T helper cells;
CD3 and CD4 are expressed,

whereas CD7 and CD8 are absent

The soluble form of interleukin 2 (IL-2R) has prognostic significance and can be used as a tumor marker for assessing disease status.

Three subtypes — endemic form, sporadic form, and HIV form

The endemic form is found primarily in childhood in equatorial Africa.

Extranodal involvement is common, with the orbits and mandible as typical

the EBV genome has been found to be present in the neoplastic cells.

sporadic BL presents mostly as an abdominal disease, extranodal involvement is not uncommon.

Profound immunosuppression with blood and bone marrow as primary sites of disease

Medium to large in size, finely clumped chromatin, deeply basophilic cytoplasm with distinct vacuoles

Both bone marrow and lymph node biopsies may show a classic “starry sky” appearance, which results from the interspersed tingible body macrophages suspended in a “sea” of malignant cells.

BL cells are positive for sIgG, CD10, and negative for CD34 and Tdt

A neoplastic disorder of germinal B cells accounting for approximately 12% of NHL cases

Generally, a disease of middle to older age groups.

Indolent, but most often incurable with current therapies

Most patients are asymptomatic, sometimes present with painless lymphadenopathy

10%

circulating FL cells have a condensed chromatin pattern and distinct nuclear clefts

Yes, bone marrow biopsy may reveal FL cells

Approximately 3% to 6% of NHL cases

Median age 68, with male predominance

Clinically aggressive with extensive lymphadenopathy

Diagnosis based on morphology is challenging:
- The small cell form of MCL can easily be mistaken for CLL
- A blastoid variant of MCL can be confused with ALL.
- In some cases, circulating mantle cells exhibit morphologic changes that can be confused with hairy cells, or prolymphocytes.

Demonstration of either t(11;14) via FISH or overexpression of cyclin D1 by immunohistochemistry

Mycosis Fungoides (MF) and Sézary Syndrome (SS)

Elderly individuals, with male predominance

Mycosis Fungoides, accounting for 70% of cases and confined to the skin

Malignant T cells in MF and SS have an abnormal appearance with scant cytoplasm and a cerebriform, folded nucleus, variably condensed chromatin, and inconspicuous nucleoli

CD4+ T helper cells

Psoriatic-like skin lesions requiring a skin biopsy

Erythroderma, generalized lymphadenopathy, and presence of clonal T cells in skin, lymph nodes, peripheral blood and severe pruritus

Neoplasms of terminally differentiated B cells

Multiple myeloma (plasma cell myeloma), median age 69

The precursor state of multiple myeloma; M spike in SPE helps predict the risk for MM transformation

Confined to the bone marrow; plasma cell leukemia (PCL) is rare (>20% plasma cells in peripheral blood)

Paraprotein in plasma

By immunohistochemistry (IHC) with CD138 or kappa and lambda clonality

CD38 and CD138, and CD56 (aberrant)

A low-grade lymphoplasmacytic lymphoma associated with aberrant secretion of IgM

Hyperviscosity syndrome requiring emergent plasmapheresis to alleviate symptoms

Extramedullary involvement includes nodal disease and hepatosplenomegaly.

Somatic mutation in myeloid differentiation factor 88 (MYD88) gene

A nodal-based lymphoma

Classic and lymphocyte-predominant

Always based on node biopsy

More than 85% of cases, usually in young adults

Responds well to chemotherapy

Characterized by Reed-Sternberg (RS) cells (binucleated or multinucleated with abundant cytoplasm and distinct nuclei)

Of B cell origin (but do not express most B cell markers); CD30 and CD15 positive; never seen in peripheral blood

No RS cells; the malignant cell is a lymphocytic histiocytic (L&H) cell, also known as “popcorn” cells because of their distinct morphology.