Lymphoma & related disorders
Mature B cell neoplasms
Small B cell lymphomas with a circulating component
CLL
Author: Nikhil Sangle, M.D.
Topic Completed: 1 February 2011
Minor changes: 5 July 2020
Copyright: 2001-2020, PathologyOutlines.com, Inc.
PubMed Search: chronic lymphocytic leukemia b cell lymphoma
See also SLL (small lymphocytic lymphoma)
Table of Contents
Definition / general | Terminology | Clinical features | Transformation of CLL | CD5 Negative Cases | Staging / staging classifications | Prognostic factors | Case reports | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Molecular / cytogenetics descriptionCite this page: Sangle N. CLL. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/lymphomaCLL.html. Accessed August 6th, 2020.
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:
Binet staging of CLL:
Reference: U.S. National Cancer Institute
- 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
Molecular / cytogenetics description
- 17p- (poor survival)
- 17p13 and 11q22-23 (associated with advanced disease)
- 12q trisomy, 13q14, 13q- (longest survival)
