Cytomorphologic spectrum of small lymphocytic lymphoma in patients with an accelerated clinical course

Cancer. 2003 Oct 25;99(5):293-300. doi: 10.1002/cncr.11441.


Background: Patients with transformed large cell lymphoma (TLCL), or Richter syndrome, and patients with small lymphocytic lymphoma/leukemia (SLL) in accelerated phase (SLL-AP) frequently undergo fine-needle aspiration (FNA) to elucidate the cause of massive lymphadenopathy and a worsening clinical condition. It is well known that patients with Richter syndrome have poor clinical outcomes as a result of the biologic aggressiveness of the transformed large cells that often are refractory to therapy. The objective of this study was to evaluate reliable criteria for recognizing SLL-AP and SLL in transformation that are needed to determine the appropriate clinical management of individual patients.

Methods: FNA specimens from 20 patients with SLL, 26 patients with SLL-AP, and 13 patients with TLCL or Richter syndrome were identified based on the reported diagnosis. Patients were included only if they had histologically confirmed SLL that also satisfied the immunophenotypic criteria of CD5/CD23 coexpression with negative CD10 and < 55% prolymphocytes. On the basis of an initial blind review of routinely stained slides from the FNA specimens, the authors defined four groups based on a consensus review diagnosis: Group 1: typical SLL; Group 2: low-grade SLL-AP; Group 3: high-grade SLL-AP; and Group 4: TLCL. Cytomorphologic features, including the proportion of intermediate-to-large cells with prominent nucleoli and intermediate-sized plasmacytoid lymphoid cells, increased numbers of mitotic figures, the presence of apoptotic bodies and necrosis, and a myxoid/dirty background, were considered features that indicated an accelerated phase. Specimens that had more than two grades of diagnostic discrepancy compared with the original reported diagnosis were reexamined using a Ki-67 immunostaining labeling index to reach a final review diagnosis.

Results: On the basis of the review diagnosis, the specimens were recategorized as follows: Group 1: 20 patients with typical SLL; Group 2: 13 patients with low-grade-SLL-AP; Group 3: 16 patients with high-grade SLL-AP; and Group 4: 10 patients with TLCL. The mean Ki-67 labeling index (%) was correlated with the morphologic progression of SLL as follows: Group 1: 11%; Group 2: 16%; Group 3: 34%; and Group 4: 48%. The follow-up by subsequent FNA or biopsy demonstrated large cell transformation in 25% of patients in Group 1, 25% of patients in Group 2, and 100% of patients in Group 3. Among the clinical parameters, increased value of serum beta2-microglobulin and lactic dehydrogenase (LDH) levels were found to be well correlated with the cytomorphologic progression of SLL/chronic lymphocytic leukemia.

Conclusions: Aspirates from patients who had signs and symptoms clinically suspicious for SLL-AP demonstrated a spectrum of cytomorphologic features, ranging from low-grade SLL-AP and high-grade SLL-AP to TLCL. The results showed that the Ki-67 labeling index, as determined by immunohistochemical studies in FNA specimens, and the levels of serum beta2-microglobulin and LDH are valuable diagnostic adjuncts for recognizing a subset of patients with SLL-AP or SLL in transformation who may require more aggressive therapy.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Biopsy, Needle
  • Cell Transformation, Neoplastic
  • Cohort Studies
  • Cytodiagnosis / methods
  • Diagnosis, Differential
  • Disease Progression
  • Female
  • Humans
  • Immunohistochemistry
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology*
  • Lymphoma, Large B-Cell, Diffuse / pathology*
  • Lymphoma, Non-Hodgkin / pathology
  • Male
  • Middle Aged
  • Prognosis
  • Retrospective Studies
  • Risk Assessment
  • Sensitivity and Specificity