Spleen
Hematogenous neoplasms
Small lymphocytic lymphoma / chronic lymphocytic leukemia (SLL / CLL)

Author: Jaleh Mansouri, M.D. (see Authors page)

Revised: 7 March 2018, last major update February 2014

Copyright: (c) 2003-2018, PathologyOutlines.com, Inc.

PubMed Search: Small lymphocytic lymphoma[TIAB] chronic lymphocytic leukemia[TIAB] spleen

See also: CLL and SLL
Cite this page: Mansouri, J. Small lymphocytic lymphoma / chronic lymphocytic leukemia (SLL / CLL). PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/spleensllcll.html. Accessed August 17th, 2018.
Definition / general
  • CLL / SLL:
    • Lymphoid neoplasm of mature cells with > 5 x 109/L monoclonal B lymphocytes, present in peripheral blood (if no extramedullary involvement seen), usually showing CD5 and CD23 coexpression
    • Lymphocytosis must be present for at least 3 months
    • May have lower WBC if cytopenias or extramedullary involvement present
  • SLL:
    • Nonleukemic, extramedullary involvement of tissue with lymphocytes having morphological and immunophenotypic characteristics of CLL, with accompanying lymphadenopathy
    • No cytopenias from bone marrow involvement
    • < 5 x 109/L CLL lymphocytes in peripheral blood
Terminology
  • Atypical CLL:
    • Refers to subtype of CLL with B cells having nuclei with deep clefts or folds and less condensed chromatin, high WBC, increased CD23 expression (compared to typical CLL) and more aggressive clinical course
    • Associated with trisomy 12
    • Not part of current WHO classification scheme
  • CLL / PLL:
Epidemiology
  • Most common leukemia of adults in Western world (incidence 12.8/100,000 at 65 years of age; M:F ratio 1.5 - 2.1)
  • Rare in Far East
  • Hematologic neoplasm with strongest genetic (familial) predisposition
Sites
  • Peripheral blood, bone marrow, lymph nodes, liver, spleen
Pathophysiology
  • Postulated abnormalities in interaction between B cell receptor (BCR) and microenvironment
  • Many potential new investigational therapies (e.g. ibrutinib) target elements in BCR signaling pathway (e.g. tyrosine kinase) (Clin Cancer Res 2014;20:548)
Etiology
  • Postulated to be autoantigenic stimulation of precursor B cells with clonal evolution
Clinical features
  • Many patients asymptomatic, may present with fatigue, infection, anemia, lymphadenopathy, hepatosplenomegaly
Diagnosis
  • Peripheral blood and bone marrow morphologic examination, immunohistochemistry, flow cytometry, cytogenetics (CLL / SLL)
  • Lymph node morphologic examination, immunohistochemistry, flow cytometry, cytogenetics (SLL)
Laboratory
  • Marked lymphocytosis (usually > 5 x 109/L)
  • Thrombocytopenia, autohemolytic anemia, M component may also be present
Prognostic factors
  • Favorable: mutated status, isolated del 13q14.3, low clinical stage (Rai and Binet clinical staging)
  • Adverse: unmutated status, del 11q22-23, del 17p, del 6q, increased CD38 and ZAP70 expression, elevated β-2 microglobulin, high clinical stage
Case reports
Treatment
  • Splenectomy, chemotherapy, monoclonal antibody therapy (e.g. rituximab)
  • Obinutuzumab (type 2 anti-CD20 monoclonal antibody) recently approved for use with chlorambucil in treatment of CLL / SLL (N Engl J Med 2014;370:1101)
Gross description
  • Millimeter sized asymmetric nodules throughout spleen (miliary pattern)
Microscopic (histologic) description
  • Primarily white pulp involvement
  • Prominent enlargement and coalescence of follicles, marked expansion of mantle zone, absent germinal centers
  • Proliferation centers sometimes present, clusters of small round lymphoid cells protruding beneath endothelium of trabecular veins
  • Extensive granulomas may mask underlying lymphoma
  • Findings may be subtle in small spleens or spleens removed incidentally
  • May have prolymphocytes and paraimmunoblasts in white pulp but without atypia
  • Nuclear contours of lymphocytes sometimes irregular
Microscopic (histologic) images

Images hosted on other servers:

Chronic lymphocytic leukemia - bone marrow aspirate

Peripheral smear images

Images hosted on other servers:

Heterogeneity

Characteristic "cobblestone" pattern

Lymphocytes as well as "smudge" cells

Positive stains
Negative stains
Flow cytometry description
  • Positive for surface IgM / IgD (dim), CD19, CD20, CD22, CD79a, CD5, CD23, CD43, CD11c (weak)
  • Negative for CD10, FMC7, CD79b (may have weak expression)
  • Aberrant immunophenotypes exist (e.g. CD5- or CD23-; FMC7+, CD11c+ or CD79b+)
Molecular / cytogenetics description
  • Molecular:
    • Rearrangement of IG genes, unmutated or somatically hypermutated subtypes
    • ZAP70 expression often associated with unmutated IGHV subtype (80%)
  • Cytogenetics:
    • Del 13q14.3 (50% of cases, micro-RNA genes miR-16-1 and miR-15a), trisomy 12 (20% of cases), deletions of 11q22-23 (ATM gene), 17p13 (p53) and 6q21
Differential diagnosis