Expanding the Morphologic Spectrum of Follicular Lymphoma In Situ: 13 Examples Including In Situ Grade 3 and BCL2-Negative Cases
Rajeev Bala, Roger A Warnke, Yasodha Natkunam. Stanford Hospital, Stanford, CA
Background: To date, the definition of follicular lymphoma in situ (FLIS) has included CD10 and BCL2 brightly positive centrocytes involving select follicles of otherwise-normal lymph nodes. Our understanding of the significance of this finding, its association with follicular lymphoma (FL), and the criteria for diagnosis are still evolving. We report a series of 13 cases from patients with and without FL, including 6 cases that exhibit Grade 3 morphology and lack BCL2 expression.
Design: Review of our pathology files yielded 13 cases from patients ranging in age from 6-71 years that displayed either abnormal BCL2+ follicles or isolated Grade 3 follicles in otherwise normal nodes. Histologic features were assessed and immunohistochemistry (IHC) for CD20, CD3, CD10, BCL2 and HGAL, FISH for BCL2, and B-cell clonality were performed in cases with sufficient tissue. Additional concurrent or subsequent lymph node or bone marrow material was available in 5 cases.
Results: Of the 13 cases, 7 showed grade 1-2 morphology in involved follicles of which 6 showed intense staining for CD10 and BCL2 (higher than background T-cells). In 3 of these cases, FL was seen either in an adjacent node or partially involving the same node. The fully developed FL in these 3 cases showed markedly reduced intensity of CD10 and BCL2. Another patient subsequently developed marrow and lymph node involvement by FL. Of the 6 cases with grade 3 morphology (1 3A and 5 3B), 5 were discovered incidentally and contained <10 follicles each that were partially or completely replaced by atypical centroblasts; 3 showed clonal light chains within involved follicles although all cases tested lacked BCL2 by IHC and FISH. The case of grade 3A showed strong CD10 and BCL2 staining and was found to have paratrabecular lymphoid aggregates in the bone marrow.
Conclusions: Our results suggest that FLIS may demonstrate a wider spectrum of histologic and immunoarchitectural features than has been previously described. In the cases where a concurrent FL was diagnosed, the areas of typical FL showed a reverse pattern of CD10 and BCL2 intensity. Of particular interest are the cases with grade 3B morphology in isolated follicles within otherwise normal nodes. Since grade 3B FL is managed similarly to DLBCL, these cases raise the possibility that this pattern may be associated with an aggressive B-cell lymphoma. Recognizing this grade 3 in situ pattern will be the first step in understanding its biologic signficance and relationship to B-cell neoplasia.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 217, Monday Morning