Publication

Molecular and immunohistochemical characterization of B-cell lymphoma-2-negative follicular lymphomas

Journal Paper/Review - Aug 19, 2011

Units
PubMed
Doi

Citation
Hoeller S, Tzankov A, Hirschmann P, Foerster A, Went P, Zettl A, Ponzoni M, Cogliatti S, Zihler D, Bihl M, Dirnhofer S. Molecular and immunohistochemical characterization of B-cell lymphoma-2-negative follicular lymphomas. Hum Pathol 2011; 43:405-12.
Type
Journal Paper/Review (English)
Journal
Hum Pathol 2011; 43
Publication Date
Aug 19, 2011
Issn Electronic
1532-8392
Pages
405-12
Brief description/objective

Aberrant expression of the antiapoptotic protein BCL (B-cell lymphoma)-2 in neoplastic germinal centers is one of the diagnostic hallmarks of follicular lymphoma. If BCL-2 cannot be detected by immunohistochemistry, the distinction between florid follicular hyperplasia and follicular lymphoma might become a diagnostic challenge. Most of those cases also lack the typical t(14;18), and the underlying pathophysiologic conditions of follicular lymphoma that lack BCL-2 protein expression are largely unknown. Here, we collected 18 BCL-2-negative follicular lymphoma cases from 5 different institutions. After restaining, 9 cases proved to be truly BCL-2 negative (6 follicular lymphoma grade 2, 2 follicular lymphoma grade 3a, and 1 follicular lymphoma grade 3b). In 4 additional cases, BCL-2 was very faint (all grade 2). Of the 9 BCL-2-negative follicular lymphoma cases, 2 were negative for CD10 (22%); all showed expression of BCL-6. Apoptotic level as determined by caspase 3 was the lowest in the BCL-2-positive follicular lymphoma group (15 ± 8 mm(2)), the highest in the normal/reactive group (n = 7, 60 ± 12 mm(2)) and very similar in the BCL-2 low follicular lymphoma and BCL-2-negative follicular lymphoma groups (25 ± 13 and 33 ± 19 mm(2), respectively), assuming an intermediate position between reactive follicles and BCL-2-positive neoplastic follicles (P < .001 [Kruskal-Wallis]). Also noted was a difference in proliferation fractions between the BCL-2-positive follicular lymphoma (27% ± 15%), the BCL-2 low follicular lymphoma (30% ± 20%) and the BCL-2-negative follicular lymphoma groups (30% ± 22%). Regarding the network of follicular dendritic cells, 8 (89%) of 9 cases from the BCL-2-negative subgroup showed disrupted, weakly developed networks, whereas all of the follicular lymphoma BCL-2 low-expression cases showed a well-defined and strongly developed follicular dendritic cell network. Among BCL-2-negative follicular lymphoma, BCL-2 and BCL-6 breaks were found in 1 case each, whereas in the follicular lymphoma BCL-2 low group, only 1 case with a BCL-6 break was recorded. No statistically significant result was achieved upon assessment of BCL-2α or BCL-2β RNA or the ratio of α/β isolated by real-time-polymerase chain reaction. Taken together, BCL-2-negative follicular lymphoma did not show a BCL-2 break on the genetic level and showed both increased apoptotic and proliferation rates compared with BCL-2-positive follicular lymphoma. In our series, BCL-6 breaks were infrequent in BCL-2-negative follicular lymphoma.