Tumor Microenvironment and Microvascular Density in Follicular Lymphoma.

Roberto Tamma,Tommasina Perrone,Giorgina Specchia,Francesco Gaudio,Domenico Ribatti,Giuseppe Ingravallo,Pellegrino Musto,Tiziana Annese

doi:10.3390/jcm11051257

Roberto Tamma, Tommasina Perrone + Show 6 more

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https://doi.org/10.3390/jcm11051257

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Abstract

Follicular lymphoma (FL) is a slowly progressive disease and constitutes the second most common non-Hodgkin lymphoma. Biological factors, such as the tumor microenvironment and the host response, are determinants in the outcome of FL but the experimental data about microenvironment and tumor cells in FL are variable and contradictory. In this morphometric study, we analyzed by immunohistochemistry the cellular components of the tumor microenvironment and correlated these data with the microvascular vascular density in three different grades of FL lymph node biopsies, comparing the results to healthy lymph node controls. The results indicated a significant increase in the number of CD68+ and CD163+ macrophages in all three analyzed FL grades. Tryptase+ mast cells resulted in an increase only in grade 1. PDL-1+ cells, CD4- and CD8-lymphocytes number results were reduced in FL samples. The higher number of CD34+ microvessels in the FL grades 1 and 2 of samples positively correlated with CD68+ and CD163+ cells, underlining the important angiogenic potential of this subset of macrophages.

Highlights

Follicular lymphoma (FL) is a slowly progressive disease belonging to B-cell non-Hodgkin lymphomas (B-NHLs), constituting the second most common NHL
Regarding tryptase+ mast cells, we observed their significant increase in the grade 1 of FL samples (tryptase: FL1 (6.1 ± 0.8%), FL2 (1.7 ± 0.4%), and FL3 (0.91 ± 0.41%)) as compared to the CTRL group (CTRL: 2.5 ± 1.4%)
Our findings indicate that the tryptase+ mast cell number resulted in an increase only in the grade1 of FL samples, whereas in grades 2 and 3A, their number decreased with respect to the controls

Summary

Introduction

Follicular lymphoma (FL) is a slowly progressive disease belonging to B-cell non-. Hodgkin lymphomas (B-NHLs), constituting the second most common NHL. Usual sites of disease development principally include the lymph nodes, but may involve the spleen, bone marrow, peripheral blood, and gastrointestinal tract [1,2]. Its indolent progression leads to delayed diagnosis and a high percentage of patients present an advanced FL at the initial diagnosis. FL results from the clonal expansion of germinal center (GC) B cells, even if malignant transformation is initiated during early B-cell development in the bone marrow, by aberrant repair failure of V(D)J recombination. The resulting t(14;18) translocation promotes high expression of the anti-apoptotic protein BCL2 [4], providing a survival advantage to B cells during GC reaction, wherein BCL2 is normally actively repressed by the GC-specific transcriptional machinery [5,6]

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