CLL / Chronic lymphocytic leukemia

Lymphoma and plasma cell neoplasms
B cell lymphoma subtypes
Chronic lymphocytic leukemia - Features that differ from SLL

Author: Nikhil Sangle, M.D. (see Authors page)

Revised: 3 April 2017, last major update February 2011

Copyright: (c) 2001-2017, PathologyOutlines.com, Inc.

PubMed Search: chronic lymphocytic leukemia b cell lymphoma

See also SLL (small lymphocytic lymphoma)

Table of Contents

Cite this page: CLL / Chronic lymphocytic leukemia. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/lymphomaCLL.html. Accessed August 19th, 2018.

Definition / general

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

Terminology

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

CLL with composite prolymphocytoid and Hodgkin 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

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

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

Molecular / cytogenetics description

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