Lymphoma & related disorders
Mature B cell neoplasms
Small B cell lymphomas with a circulating component

Topic Completed: 1 February 2011

Minor changes: 6 October 2020

Copyright: 2001-2020,, Inc.

PubMed Search: chronic lymphocytic leukemia b cell lymphoma

See also SLL (small lymphocytic lymphoma)

Nikhil Sangle, M.D.
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Cite this page: Sangle N. CLL. website. Accessed October 26th, 2020.
Definition / general
  • Leukemic disorder of CD5+ CD23+ tumor cells, usually B cell, that are small, round, low grade, with soccer ball appearance
  • 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
  • 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
  • Often transforms to high grade neoplasm via prolymphocytic transformation or Richter 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 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 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
  • 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 Pathol 1999;111:477)
Staging / staging classifications
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: U.S. National Cancer Institute
Prognostic factors
  • 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
Microscopic (histologic) description
  • CLL cases with marrow involvement usually have interstitial, interstitial / focal or diffuse patterns; paratrabecular pattern is not seen
Microscopic (histologic) images

Images hosted on other servers:

Increased numbers
of mature lymphocytes
in peripheral blood

Fig. 1: typical chronic lymphocytic leukemia
Fig. 2: atypical CLL with lymphoplasmacytoid cells
Fig. 3: atypical CLL with irregular or clefted nuclei
Fig. 4: CD79b+ by flow cytometry

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

Positive stains
Molecular / cytogenetics description
  • 17p- (poor survival)
  • 17p13 and 11q22-23 (associated with advanced disease)
  • 12q trisomy, 13q14, 13q- (longest survival)
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