Lymphoma - CLL / Chronic lymphocytic leukemia

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Lymphoma - B cell neoplasms

B cell lymphoma subtypes

Chronic lymphocytic leukemia - features that differ from SLL

Reviewer: Nikhil Sangle, M.D., University of Utah and ARUP Laboratories (see Reviewers page)
Revised: 20 September 2012, last major update February 2011
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.

See also SLL (small lymphocytic lymphoma)

Terminology
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● Leukemic disorder of CD5+ CD23+ tumor cells, usually B cell, that are small, round, low grade, with soccer ball appearance

Terminology
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● Called CLL/chronic lymphocytic leukemia if leukemic involvement at diagnosis (5K or more of monoclonal B cell lymphocytosis per microliter)
● Less than 5K per microliter is termed monoclonal B lymphocytosis or possibly low stage CLL
● CLL with increased prolymphocytes (CLL/prolymphocytic leukemia): 10-55% prolymphocytes
● Prolymphocytic leukemia: >55% prolymphocytes

Clinical features
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● Most common adult leukemia in Western countries, less common in Japan/Asia
● Almost always a B cell disorder, only rarely of T cell origin
● Usually associated with lymphadenopathy or hepatosplenomegaly

Transformation of CLL
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● Often transforms to high grade neoplasm via prolymphocytic transformation or Richter’s syndrome
● 5% have prolymphocytoid transformation with prolymphocytes (moderate basophilic cytoplasm, coarse chromatin, prominent single nucleoli) and paraimmunoblasts (larger cells with more abundant cytoplasm, disbursed chromatin, single prominent eosinophilic nuclei); causes death within median 2 years
● Richter syndrome is transformation from B-CLL or other low grade B cell lymphoproliferative disorder to a pleomorphic lymphoma, such as diffuse large cell lymphoma; appears to be due to transformation of previously well differentiated tumor cells; retains CLL phenotype (Am J Clin Path 2001;115:385), but causes death within median 5 months (22 months for digestive tract Richter’s syndrome, Mod Pathol 2001;14:452); symptoms are abrupt onset of fever, weight loss, adenopathy, rapid clinical deterioration; peripheral blood smear usually normal
● Richter syndrome cases with EBV+ Hodgkin’s lymphoma features may have distinct clonal origin (Am J Surg Pathol 2004;28:679)
● Rarely transforms to aggressive T cell or NK cell lymphoma with cytotoxic immunophenotype (Am J Surg Pathol 2004;28:849)
● Cases with serum IgM paraprotein (3% of total) are otherwise similar (Am J Clin Path 2005;123:594)
● ZAP-70 positivity is associated with IGHV unmutated status (Blood 2003;101:4944)

CD5 negative cases
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● Probably do NOT represent CLL
● Have adhesion molecular profiles resembling leukemic non-Hodgkin lymphoma but different from CD5+ B-cell CLL (Hum Pathol 2001;32:66)
● Patients are older with more advanced disease and lower absolute lymphocyte counts than CD5+ B-cell CLL (Am J Clin Path 1999;111:477)

Staging of CLL
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Rai staging of CLL:

0: lymphocytosis in blood (>15,000 per mm3) and marrow
I: lymphocytosis and lymphadenopathy
II: lymphocytosis and hepatomegaly or splenomegaly
III: lymphocytosis and anemia (hemoglobin < 11g/dL)
IV: lymphocytosis and thrombocytopenia (<100,000/mm3)

Binet staging of CLL:

A: no anemia, no thrombocytopenia, fewer than 3 lymphoid areas enlarged (cervical, axillary and inguinal lymphadenopathy, spleen, liver)
B: no anemia, no thrombocytopenia, 3 or more lymphoid areas enlarged
C: anemia or thrombocytopenia

Reference: US National Cancer Institute

Poor prognostic factors
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● High stage, high CD38 expression (particularly >30% CD38 positive population in peripheral blood, Blood 2001;98:181, Blood 2003;101:1262), p53 expression, lack of somatic mutations of immunoglobulin variable region (pre-germinal cell phenotype)

Case reports
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● CLL with composite prolymphocytoid and Hodgkin’s transformation (Arch Pathol Lab Med 2000;124:907)
● CLL with composite thymoma (Arch Pathol Lab Med 2003;127:E76)
● CLL with systemic mastocytosis (J Clin Pathol 2006;59:264), filamentous cytoplasm inclusions in peripheral blood due to dilated cisternae of rough endoplasmic reticulum containing IgG (Arch Pathol Lab Med 2003;127:618), cases with t(14;18) (Arch Pathol Lab Med 2002;126:1543), CLL with meningeal infiltration

Micro description
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● CLL cases with marrow involvement usually have interstitial, interstitial/focal or diffuse patterns; paratrabecular pattern is not seen

Micro images
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Increased numbers of mature lymphocytes in peripheral blood

1-small cells with scant pale cytoplasm and condensed chromatin; 2-atypical CLL with lymphoplasmacytoid cells; 3-atypical CLL with irregular or clefted nuclei; 4-CD79b+ by flow cytometry

A-CLL with intracytoplasmic filamentous inclusion; B-anti-IgG lambda fluorescence; C/D-EM shows dilated rough ER; pseudofollicular growth

Positive stains
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● CD5, CD19, CD23; weak (low density) CD20 staining
● Light chain restriction
● Variable CD38, surface immunoglobulin, FMC7 (Am J Surg Pathol 2002;26:624)

Molecular
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● 17p- (poor survival)
● 17p13 and 11q22-23 (associated with advanced disease)
● 12q trisomy, 13q14, 13q- (longest survival)

End of Lymphoma - B cell neoplasms > B cell lymphoma subtypes > Chronic lymphocytic leukemia

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