cll
TRANSCRIPT
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CHRONIC LYMPOCYTIC LEUKEMIA
CH.VYSHNAVI MSC MLT 1ST YEAR
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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
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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
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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
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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
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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
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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
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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
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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%
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CLL IN THE PHERIPHERAL BLOOD, THE CLL LYMPHOCYTES ARE SMALL,ROUND ,WITH DISTINCT CLUMPED CHROMATIN. SMUDGE CELLS ARE COMMONLY SEEN
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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
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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
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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
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PROGNOSIS AND PREDICTIVE FACTOR
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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
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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
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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
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