A spindle cell variant of diffuse large B-cell lymphoma is characterized by T-cell/myofibrohistio-rich stromal alterations: analysis of 10 cases and a review of the literature.
Spindle-shaped diffuse large B-cell lymphoma (Sp-DLBCL) has been recognized as a rare morphologic variant of DLBCL. However, the biological processes that contribute to the specific features of Sp-DLBCL remain poorly understood. In this study, a combined immunophenotypic and genetic analysis was performed in 10 Sp-DLBCL. First, we investigated several unique markers for anaplasia (CD30, ALK, CD68, and EBER-ISH), mesenchyma (SMA, desmin, and vimentin), and B-cell differentiation (CD10, BCL6, and MUM1). We also performed conventional cytogenetic and fluorescence in situ hybridization studies to look for common chromosomal break points (BCL2, BCL6, and MYC). We found that most Sp-DLBCLs were germinal center B cell-like and that none had any other specific phenotypes or any karyotypic abnormalities. Instead, T cells, CD68-positive macrophages and SMA-positive myofibroblasts were significantly increased in Sp-DLBCL when compared with conventional GCB origin DLBCL cases (n = 10) (P = 0.012, P < 0.001, and P < 0.0001, respectively). To further characterize Sp-DLBCL, we next compared the expression of fibroblast growth factor 2 (FGF2) and transforming growth factor-β1 (TGFβ1) between the two types of DLBCL. Finally, we confirmed that the number of FGF2- and TGFβ1-positive stromal cells was markedly increased in Sp-DLBCL and that the difference between these and conventional GCB origin DLBCLs was significant (P < 0.0001 and P = 0.0017, respectively). Thus, T-cell/myofibrohistio-rich stromal alterations in Sp-DLBCL, especially those mediated by TGFβ1 and FGF2, may play a role in the transition of lymphoma cells into those with spindle-shaped features.
Department of Pathology, School of Medicine, Kurume University, Kurume, Japan. kimura_yoshizou@kurume-u.ac.jp
Yoshizo
Y
Kimura
Fumiko
F
Arakawa
Junichi
J
Kiyasu
Hiroaki
H
Miyoshi
Maki
M
Yoshida
Ayako
A
Ichikawa
Shinji
S
Nakashima
Yukinao
Y
Ishibashi
Daisuke
D
Niino
Yasuo
Y
Sugita
Ken
K
Ishiyama
Masakazu
M
Higuchi
Yumi
Y
Takasaki
Taizo
T
Shimomura
Chisato
C
Koike
Nobuo
N
Kuwahara
Kazuhisa
K
Fujikawa
Koichi
K
Ohshima
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D043283:Chromosome Fragile Sites; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D058628:Myofibroblasts / Q000276:immunology*; D017154:Stromal Cells / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology*