Tumor Sclerosis but Not Cell Proliferation or Malignancy Grade Is a Prognostic Marker in Advanced-Stage Follicular Lymphoma: The German Low Grade Lymphoma Study Group

Klapper, Wolfram; Hoster, Eva; Rölver, Lars; Schrader, Carsten; Janssen, Dirk; Tiemann, Markus; Bernd, Heinz‐Wolfram; Determann, Olaf; Hansmann, Martin‐Leo; Möller, Peter; Feller, Alfred C.; Stein, Harald; Wacker, Hans‐Heinrich; Dreyling, Martin; Unterhalt, Michael; Hiddemann, Wolfgang; Ott, German

doi:10.1200/jco.2006.10.5833

Cited by 55 publications

(42 citation statements)

References 40 publications

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“…1 It had no impact on overall survival in our hands, although a correlation of fibrosis with poor overall survival has been reported and was found to be independent of the FLIPI in advanced-stage follicular lymphoma. 23 Diffuse areas were found in 12% of our cases. In some of these cases, the use of CD23 was of help, confirming that the tumor cells were growing outside of the follicules.…”

Section: Discussionmentioning

confidence: 62%

Follicular lymphoma in young adults: a clinicopathological and molecular study of 200 patients

et al. 2013

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Follicular lymphoma is clinically heterogenous, and therefore necessitates the identification of prognostic markers to stratify risk groups and optimize clinical management. It is relatively rare in patients younger than 40 years, and the clinicopathologic characteristics and biological behavior in this age group are poorly understood. In the current study, samples from a cohort of 200 patients between 19 and 40 years were evaluated retrospectively with respect to clinical, histologic, and genetic features. These were then correlated with clinical outcome. The median age at presentation was 35 years with a slight female prepoderance (56%). Most of the cases are presented with nodal disease (90%). Concomitant follicular lymphoma and diffuse large B-cell lymphoma were observed in 7 (4%) patients. Immunohistologic studies showed the expression of CD10 (91%), BCL6 (97%), BCL2 (95%), MUM1/IRF4 (12%), MDM2 (17%), and CD23 (25%). BCL2 rearrangement was present in 74%, and BCL6 in 20%. The estimated overall survival of patients was 13 years (mean). The presence of anemia, elevated lactose dehydrogenase, bone marrow involvement, and high-risk follicular lymphoma international prognostic index correlated with adverse overall survival. Our findings revealed that follicular lymphoma in young adults demonstrate similarities with that of older adults, including the frequency of presentation at various anatomic sites, grade, and adverse prognostic factors.

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Section: Discussionmentioning

confidence: 62%

Follicular lymphoma in young adults: a clinicopathological and molecular study of 200 patients

et al. 2013

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“…In contrast, in the interfollicular and diffuse areas of follicular lymphoma, the FDCs are absent [34,39]. Such distinction is important because in follicular lymphoma, the follicles are sometimes large, very poorly defined, and do not have any mantle zones surrounding them, and therefore, they are very difficult to recognize, and such follicles appear as diffuse areas (diffuse pattern).…”

Section: Fdcs In Follicular Lymphomamentioning

confidence: 93%

Follicular dendritic cells: origin, function, and different disease-associated patterns

et al. 2013

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Summary Follicular dendritic cells (FDCs) are a specialized type of antigen-presenting dendritic cells that are largely restricted to lymphoid follicles. They form dense three-dimensional meshwork patterns within benign follicles, which maintain the follicular architecture. The FDC function is to bind and retain antigens by linking to complement and immune complexes and then present these antigens to germinal center B cells that start the secondary immune response. FDCs aid in the rescue of bound B cells from apoptosis, and induce the differentiation of B cells into long-term memory B cell clones or plasma cells. We will discuss the different patterns of the FDC meshwork observed in different types of reactive and neoplastic disorders, which may be due to underlying different roles that FDCs may play in these disorders and whether changes in the architecture of the FDC meshwork can be useful in routine diagnostic practice or have a prognostic value.

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“…9,10,32 It is hypothesized that the frequency and distribution of non-malignant cells can in part serve as surrogate markers for the clinically relevant gene expression signatures. This issue has recently been the focus of numerous immunohistochemical studies, including evaluating markers for T-helper, cytotoxic and regulatory cell subsets, [17][18][19][20][21]23,[33][34][35] for stromal cells including macrophages, mast cells and dendritic cells, 15,20,33,[36][37][38][39] and for endothelial cells assessing microvessel density. [40][41][42] The results of these studies are often contradictory, which in part can be explained by the small number of patients and variations in patient selection and treatment protocol.…”

confidence: 99%

The reliability of immunohistochemical analysis of the tumor microenvironment in follicular lymphoma: a validation study from the Lunenburg Lymphoma Biomarker Consortium

et al. 2014

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The cellular microenvironment in follicular lymphoma is of biological and clinical importance. Studies on the clinical significance of non-malignant cell populations have generated conflicting results, which may partly be influenced by poor reproducibility in immunohistochemical marker quantification. In this study, the reproducibility of manual scoring and automated microscopy based on a tissue microarray of 25 follicular lymphomas as compared to flow cytometry is evaluated. The agreement between manual scoring and flow cytometry was moderate for CD3, low for CD4, and moderate to high for CD8, with some laboratories scoring closer to the flow cytometry results. Agreement in manual quantification across the 7 laboratories was low to moderate for CD3, CD4, CD8 and FOXP3 frequencies, moderate for CD21, low for MIB1 and CD68, and high for CD10. Manual scoring of the architectural distribution resulted in moderate agreement for CD3, CD4 and CD8, and low agreement for FOXP3 and CD68. Comparing manual scoring to automated microscopy demonstrated that manual scoring increased the variability in the low and high frequency interval with some laboratories showing a better agreement with automated scores. Manual scoring reliably identified rare architectural patterns of T-cell infiltrates. Automated microscopy analyses for T-cell markers by two different instruments were highly reproducible and provided acceptable agreement with flow cytometry. These validation results provide explanations for the heterogeneous findings on the prognostic value of the microenvironment in follicular lymphoma. We recommend a more objective measurement, such as computer-assisted scoring, in future studies of the prognostic impact of microenvironment in follicular lymphoma patients.

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Tumor Sclerosis but Not Cell Proliferation or Malignancy Grade Is a Prognostic Marker in Advanced-Stage Follicular Lymphoma: The German Low Grade Lymphoma Study Group

Cited by 55 publications

References 40 publications

Follicular lymphoma in young adults: a clinicopathological and molecular study of 200 patients

Follicular lymphoma in young adults: a clinicopathological and molecular study of 200 patients

Follicular dendritic cells: origin, function, and different disease-associated patterns

The reliability of immunohistochemical analysis of the tumor microenvironment in follicular lymphoma: a validation study from the Lunenburg Lymphoma Biomarker Consortium

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