| Autor: |
Siddiqi, Imran N, Friedman, Julia, Barry-Holson, Keegan Q, Ma, Charles, Thodima, Venkata, Kang, Irene, Padmanabhan, Raghavendra, Dias, Lizalynn M, Kelly, Kevin R, Brynes, Russell K, Kamalakaran, Sitharthan, Houldsworth, Jane |
| Zdroj: |
Modern Pathology; June 2016, Vol. 29 Issue: 6 p570-581, 12p |
| Abstrakt: |
A predominantly diffuse growth pattern and CD23 co-expression are uncommon findings in nodal follicular lymphoma and can create diagnostic challenges. A single case series in 2009 (Katzenberger et al) proposed a unique morphologic variant of nodal follicular lymphoma, characterized by a predominantly diffuse architecture, lack of the t(14;18) IGH/BCL2translocation, presence of 1p36 deletion, frequent inguinal lymph node involvement, CD23 co-expression, and low clinical stage. Other studies on CD23+ follicular lymphoma, while associating inguinal location, have not specifically described this architecture. In addition, no follow-up studies have correlated the histopathologic and cytogenetic/molecular features of these cases, and they remain a diagnostic problem. We identified 11 cases of diffuse, CD23+ follicular lymphoma with histopathologic features similar to those described by Katzenberger et al.Along with pertinent clinical information, we detail their histopathology, IGH/BCL2translocation status, lymphoma-associated chromosomal gains/losses, and assessment of mutations in 220 lymphoma-associated genes by massively parallel sequencing. All cases showed a diffuse growth pattern around well- to ill-defined residual germinal centers, uniform CD23 expression, mixed centrocytic/centroblastic cytology, and expression of at least one germinal center marker. Ten of 11 involved inguinal lymph nodes, 5 solely. By fluorescence in situhybridization analysis, the vast majority lacked IGH/BCL2translocation (9/11). Deletion of 1p36 was observed in five cases and included TNFRSF14. Of the six cases lacking 1p36 deletion, TNFRSF14mutations were identified in three, highlighting the strong association of 1p36/TNFRSF14abnormalities with this follicular lymphoma variant. In addition, 9 of the 11 cases tested (82%) had STAT6mutations and nuclear P-STAT6 expression was detectable in the mutated cases by immunohistochemistry. The proportion of STAT6mutations is higher than recently reported in conventional follicular lymphoma (11%). These findings lend support for a clinicopathologic variant of t(14;18) negative nodal follicular lymphoma and suggests importance of the interleukin (IL)-4/JAK/STAT6 pathway in this variant. |
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