Is Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) a Lymphoma of Mantle Zone B-Cells?
Bevan Tandon, Steven H Swerdlow, Robert P Hasserjian, Sarah E Gibson. University of Pittsburgh School of Medicine, Pittsburgh, PA; Massachusetts General Hospital, Boston, MA
Background: CLL/SLL is considered a neoplasm of memory type B-cells not related to any of the follicular B-cell compartments. However, the presence of follicular dendritic cells (FDC) in CLL/SLL is controversial and cases with a perifollicular/follicular growth pattern have been described that may suggest the possibility of a CD5+ marginal zone lymphoma, although LEF-1 positivity can now be used to help exclude that diagnosis.
Design: To study the association of CLL/SLL with follicular structures, 43 lymph nodes, 2 extranodal tissues, and 2 spleens with CLL/SLL, enriched for cases with a non-diffuse growth pattern, were selected. Clinical, morphologic and phenotypic parameters, and the presence and distribution of CD21+ FDC meshworks in relation to the CD5+ CLL cells, were assessed.
Results: All cases had a typical CLL phenotype and were LEF-1+. 7/47 cases showed a perifollicular (PF) growth pattern with some associated CD21+ FDC, 17 were nodular/follicular-appearing (Nod) with CD21+ FDC, and 21 were diffuse-appearing, but with some CD21+ FDC in 9/21. CD21+ FDC were present in proliferation centers in 18 cases, including 11/17 Nod cases. The CD21+ FDC were usually more delicate than those in germinal centers. In cases with a PF/Nod growth pattern, the CLL/SLL sometimes surrounded narrow residual mantle zones (MZ), replaced portions of MZ, appeared to be scattered in MZ/primary follicle-like structures, or showed follicular colonization. Cases with PF/Nod growth patterns had fewer nodal sites of involvement compared to diffuse cases (p=0.02), as did cases that contained FDC compared to those without (p=0.01). No statistically significant differences in age, gender, absolute lymphocyte count, or Rai stage were identified between the groups.
Conclusions: The frequent association of CLL/SLL with CD21+ FDC resembling those seen in normal MZ, cases with a PF growth pattern in the outer MZ, a Nod growth pattern that involves primary follicle-like structures, and a phenotype most like a subset of MZ B-cells, all suggest that at least a subset of CLL/SLL is a neoplasm of MZ B-cells. Unlike mantle cell lymphoma, thought to arise from inner MZ cells, CLL/SLL may arise in or initially home to the outer MZ. The results also suggest that PF/Nod CLL/SLL is not a distinct variant, but is related to at least a subset of typical CLL/SLL. The biologic features that maintain the follicular-oriented growth pattern and are ultimately lost in more widely disseminated disease merit further study.
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 237, Monday Morning