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Case  - Discussion

Hematopathology Case


Diagnosis: Chronic Lymphocytic Leukemia

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

The Key Features

  • Small mature lymphocytes, round nuclei, condensed chromatin, smudge cells, prolymphocytes

  • Positive: CD5 and CD23

  • Weak: CD20, CD22, CD79b, CD11c, surface light chain

  • Negative: CD10, FMC7, Cyclin D1

  • Worse prognosis: germline IgVH, CD38+, ZAP70+, trisomy 12, deletions at 11q22-23

  • Better prognosis: mutated IgVH, deletions at 13q14


  • CLL is the most common leukemia in the Western world and comprises 90% of chronic lymphoid leukemias; SLL/CLL accounts for 6.7% of NHL;

  • Age: most patients>50 years, median 65 years; M:F=2:1;

  • CLL: lymphocyte count in bone marrow and peripheral blood >5109/L, possible <5109/L provided typical morphology and immunoprofile;

  • SLL: absence of bone marrow or blood involvement;

  • Clinical features: most patients asymptomatic, or fatigue, infection, autoimmune hemolytic anemia, hepatosplenomegaly, lymphadenopathy, or extranodal involvement.


  • Lymph node and spleen

    • Architecture: effacement of the lymph node with a  pseudofollicular pattern; occasionally intrafollicular infiltrate; In the spleen, white pulp is often prominently involved and also red pulp;

    • Pseudofollicles: pale areas containing a continuum of small, medium and larger cells in dark background of small cells; prolymphocytes: medium size, nuclei with dispersed chromatin and small nucleoli; para-immunoblasts: medium to large size, round to oval nuclei with dispersed chromatin and central eosinophilic nucleoli and slightly basophilic cytoplasm. The pseudofollicles are MUM1 positive. In ~20% of CLL/SLL cases, the proliferative centers can be BCL1+, but lack t(11;14) and expression of SOX11 (Am J Clin Pathol. 2012, 138(1):132-9)

    • Cytology: predominantly small cells, slightly larger than normal lymphocytes; round nuclei with clumped chromatin and occasional a small nucleolus; low mitotic activity; in some cases, the small lymphoid cells show moderated nuclear irregularity, resembling MCL; occasionally, tumor cells may present plasmacytoid differentiation.

  • Bone marrow and blood

    • Small cells, clumped chromatin, and scant clear to basophilic cytoplasm, nucleoli indistinct or absent, frequent smudge cells and basket cells;

    • Prolymphocytes usually <2%; CLL with increased prolymphocytes, 10%<prolymphocytes<50%;

    • Bone marrow involvement may be nodular, interstitial, diffuse or combined; paratrabecular aggregates are not typical;

  • Some CLL cases may show atypical morphology with variable proportional atypical lymphocytes (cleaved cells, prolymphocytes and large lymphocytes) with characteristic CLL immunophenotype;

  • Richter syndrome: transformation to DLBCL (3.0% of CLL) is characterized by confluent sheets of large cells that paraimmunoblasts or immunoblast-like; or transformation into Hodgkin lymphoma (0.5% of CLL).


  • CLL of naive B-cell origin: 40-50%, no somatic mutations of IgVH;

  • CLL of post-germinal center B-cell origin: 50-60%, with somatic mutation of IgVH, better survival.


sIg + (dim) + + + + +
CD19 + + + + + +
CD20 + (dim) + + + + +
CD22 + + + + +
FMC7 + + + + +
CD79b + + + + +
CD5 + +
CD23 + +/− +/−
CD25 +/− +
CD11c +/− + +/−
CD103 +
CD10 +


  • Positive: weak or dim surface IgM or IgM and IgD, CD5, CD19, CD20 (weak), CD22 (weak), CD79a, CD23, CD43, CD11c (weak);

  • Negative: CD10, cyclin D1, FMC7 and CD79b


  • Del(13q14): >50%, MIR15A and MIR16-1, favorable prognosis

  • Tri 12: < 20%, often associated with atypical morphology

  • Del (11q22-q23): ~ 20%, ATM

  • Del (17p13): 5-10%, TP53, adverse prognosis

  • Prolymphocytoid transformation: progressive increase in prolymphocytes

  • Richter's syndrome: mostly DLBCL, rarely Hodgkin's lymphoma, mostly but not always clonally related, fludarabine therapy → increased transformation and often EBV related


  • Indolent, median survival of CLL 7 years, and median survival of SLL 5 years

  • Favorable: CD38-, ZAP-70-, germline IGH@V, pre-GC

  • Unfavorable: CD38+, ZAP-70+, unmutated IGH@V, post-GC, <55 years old


  • Practical Diagnosis of Hematologic Disorders, Fourth Edition. By Carl R. Kjeldsberg, 2006.
  • Hematopathology, 2011, Jaffe