CHRONIC LYMPOCYTIC LEUKEMIA

CH.VYSHNAVI MSC MLT 1ST YEAR

DEFINITION

Chronic lymphocytic leukaemia \small lymphocytic lymphoma is a neoplasm composed of monomorphic small, round to slightly irregular B lymphocytes in the peripheral blood ,bone marrow ,spleen and lymph nodes, admixed with prolymphocytes and paraimmunoblasts forming proliferation centres in tissue infiltrates

SITE OF INVOLVEMENT

Peripheral blood and bone marrow are usually involved

Lymph nodes, liver and spleen are also typically infiltrated , and other extra nodal sites may occasionally be involved

CLINICAL FEATURES

Clinical features are very variable including presentation, course and out come

Most of the patients are asymptomatic , but some present with fatigue, autoimmune haemolytic anaemia, infection, splenomegaly, heptomegaly , lymphadenopathy or extra nodal infiltrates

MONOCLONAL B –CELL LYMPHOCYTOSIS Healthy individuals may show monoclonal or

oligoclonal B-cell expansion with the characteristic phenotype with the characteristic phenotype of CLL

Monoclonal B-cell lymphocytosis with a non-CLL phenotype may correspond to similar phenomena in other B-cell neoplasms

Whether MBL is a predisposin condition or even a precursor of overt CLLhas to be elucidated

MORPHOLOGY

LYMPH NODES AND SPLEEN

Enlarged lymph nodes in patients with CLL\SLL show effacement of the architecture, with s pseudofollicular pattern of regular-distributed pale areas corresponding to proliferation centres containg larger cells in a dark background of small cells

The predominant cell is a small lymphocyte, which may be slightly larger than a normal lymphocyte, with clumped chromatin ,usually a round nucleus, and occasionally a small nucleolus

Mitotic activity is usually very slow

Proliferation centres contain a continuum of small , medium and large cells

Prolymphocytes are small to medium sized cells with relatively clumped chromatin and small nucleoli

Paraimmunoblasts are larger cells with round to oval nuclei ,dispersed chromatin , central eosinophilic nucleoli and slightly basophilic cytoplasm

BONE MARROW AND BLOODOn BM and PB smears , CLL cells are

small lymphocytes with clumped chromatin and scanty cytoplasm

Smudge or basket cells are typically seenn in pb smear

The proportion of prolymphocytes in

pb is usually <2%

CLL IN THE PHERIPHERAL BLOOD, THE CLL LYMPHOCYTES ARE SMALL,ROUND ,WITH DISTINCT CLUMPED CHROMATIN. SMUDGE CELLS ARE COMMONLY SEEN

More than 55% prolymphocytes , however, would favour the diagnosis of B-cell prolymphocytic leukaemia [B-PLL]

Atypical CLL shows less condensed nuclear chromatin and nuclear irregularities in PB lymphocytes

Bone marrow involvement as seen in trephine biopsies may be interstitial, nodular or diffuse; proliferation centres are less common in the BM than in lymphnodes

The definition of minimal BM involvement required to diagnose CLL\SLL in the absence of other defining features is not established, although >30% lymphoid cells as “characteristically” present

IMMUNOPHENOTYPE Using flow cytometry, the tumor cells

express dim surface IgM\IgD, CD20, CD22, CD5, CD19, CD79a, CD23, CD43 and CD11c[week]

CD10 is negative and FMC7 and CD79b are usually negative or weekly expressed in typical CLL

The immunophenotype of PB lymphocytes has been integrated into scoring system that helps in the differential diagnosis between CLL and other B-cell leukaemias

PROGNOSIS AND PREDICTIVE FACTOR

New biological prognosis factor have become increasingly important especially in early stagee CLL

Expression of ZAP-70 and CD38 are both associated with an adverse prognosis

PROGRESSION AND TRANSFORMATION OF CLL TO HIGH GRADE LYMPHOMAOver time, CLL may show an

increase in cell size and proliferative activity as well as confluence of proliferation centres in lymph nodes an BM

This may correlate with increase in prolumphocytes in the PB

Progression of CLL to B-PLL is extremely rare

2-8% of patients with CLLdevelop diffuse large B-cell lymphoma[DLBCL] and <1% develop classical Hodgkin lymphoms

The majority of the DLBCL have been reported to be clonally related to the previous CLL and are unmutated, whereas the clonally unrelated cases of DLBCL usually occurred in mutated CLL