Case 8 - Discussion

Uploaded: 2007-06-09, Updated: 2008-01-04


Diagnosis: Chronic Lymphocytic Leukemia

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

The Key Features

  • Small cells with pseudofollicles;

  • Positive: CD5 and CD23

  • Negative or weak: CD20, CD22, CD79b, CD11c

  • Negative: CD10, FMC7, Cyclin D1

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

  • Better prognosis: mutated IgVH, deletions at 13q14

CLINICAL FEATURES

  • 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.

MICROSCOPIC FINDINGS

  • 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;

    • Pseudofollicules: 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;

    • 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).

SUBTYPES

  • 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.

DIFFERENTIAL DIAGNOSES

  CLL/SLL B-PLL HCL SMZL FL MCL
sIg + (dim) + + + + +
CD19 + + + + + +
CD20 + (dim) + + + + +
CD22 + + + + +
FMC7 + + + + +
CD79b + + + + +
CD5 + +
CD23 + +/− +/−
CD25 +/− +
CD11c +/− + +/−
CD103 +
CD10 +

IMMUNOHISTOCHEMISTRY AND SPECIAL STAINS

  • 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

CYTOGENETIC STUDIES

  • Trisomy 12: 20%, aggressive clinical course;

  • Deletions at 13q14: 50%, long survival;

  • Deletions at 11q22-23: 20%, poor survival

TREATMENT AND PROGNOSIS

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

  • CD38+ and/or ZAP70+ cases, worse prognosis;

REFERENCES

  • Practical Diagnosis of Hematologic Disorders, Fourth Edition. By Carl R. Kjeldsberg, 2006.
  • Jaffe ES, Harris NL, Stein H, Vardiman JW, editors. Pathology and genetics of tumours of haematopoietic and lymphoid tissues. World Health Organization classification of tumours. Lyon (France): IARC Press; 2001.