Figure 3.
Description of molecular, pathologic, biologic, and imaging features of 71 AITL/TFH patients in the REVAIL trial. The section “mutations in tumor” describes distribution of mutations in TET2, RHOA, DNMT3A IDH2, CD28, PLCG1, STAT3, and STAT5B. Patients represented in dark blue bore at least 2 TET2 mutations, whereas only 1 TET2 mutation was detected in light blue samples. DNMT3AR882X variants are represented in dark green, whereas samples in light green harbored DNMT3A mutations altering another residue than R882. Sequencing failure, in gray, was because of the absence of enough material for DNA extraction or the presence of degraded DNA. In the section “BM/Blood,” BMI represents the presence of bone marrow involvement, as determined locally by the examination of BM trephine. Flow cytometry positivity means that cells with an aberrant phenotype were detected in blood by flow cytometry before treatment. PCR positive means that a significant (ie, representing at least 10% of the T-cell population) TCR clonal population was detected by denaturing gradient-gel electrophoresis PCR. EBV blood shows patients with a high level of EBV > 3 log, a low level of EBV (<3 log), or the absence of detectable EBV replication in blood. “pathological features and IHC” section describes the pathologic features of AITL biopsy. Blue is used to describe neoplastic cells, whereas the tumor microenvironment is scored in yellow. The percentage of neoplastic T cells was estimated by pathologists after IHC interpretation: >50% in darker blue cases, 30% to 50% in blue cases, and <30% in lighter blue cases. Clear cells with a large cytoplasm were detected in cases in dark blue, absent in cases in white, or unknown in gray. Immunohistochemistry assays for TFH markers (CD10, PD1, CXCL13, BCL6, ICOS) are described in the legend, with score 3 indicating >50% positive tumor cells, score 2 indicating 30% to 50% positive tumor cells, score 1 indicating <30% positive cells, and score 0 indicating no staining on tumor cells. FDC distribution was evaluated by CD21 and/or CD23 immunostaining and was assigned a score of 0 when the signal was restricted to germinal centers; 1 in case of perifollicular expansion; 2 in case of perifollicular and perivascular expansion; or 3 for diffuse expansion. The EBV status in large lymphoid cells was based on counting EBER-positive large cells and scored as follows: negative, absence of large EBV-positive cells; positive, up to 5 large EBV-positive cells per high power field (hpf); strongly positive, more than 5 per hpf or sheets or aggregates of large EBV-positive cells. As indicated in the legend, the sections “others” represent IPI at diagnosis (IPI 4-5 vs 1-3), CMR (CMR vs other response or nonevaluable), and SUVmax and TMTV, both being dichotomized at the median of the cohort.

Description of molecular, pathologic, biologic, and imaging features of 71 AITL/TFH patients in the REVAIL trial. The section “mutations in tumor” describes distribution of mutations in TET2, RHOA, DNMT3A IDH2, CD28, PLCG1, STAT3, and STAT5B. Patients represented in dark blue bore at least 2 TET2 mutations, whereas only 1 TET2 mutation was detected in light blue samples. DNMT3AR882X variants are represented in dark green, whereas samples in light green harbored DNMT3A mutations altering another residue than R882. Sequencing failure, in gray, was because of the absence of enough material for DNA extraction or the presence of degraded DNA. In the section “BM/Blood,” BMI represents the presence of bone marrow involvement, as determined locally by the examination of BM trephine. Flow cytometry positivity means that cells with an aberrant phenotype were detected in blood by flow cytometry before treatment. PCR positive means that a significant (ie, representing at least 10% of the T-cell population) TCR clonal population was detected by denaturing gradient-gel electrophoresis PCR. EBV blood shows patients with a high level of EBV > 3 log, a low level of EBV (<3 log), or the absence of detectable EBV replication in blood. “pathological features and IHC” section describes the pathologic features of AITL biopsy. Blue is used to describe neoplastic cells, whereas the tumor microenvironment is scored in yellow. The percentage of neoplastic T cells was estimated by pathologists after IHC interpretation: >50% in darker blue cases, 30% to 50% in blue cases, and <30% in lighter blue cases. Clear cells with a large cytoplasm were detected in cases in dark blue, absent in cases in white, or unknown in gray. Immunohistochemistry assays for TFH markers (CD10, PD1, CXCL13, BCL6, ICOS) are described in the legend, with score 3 indicating >50% positive tumor cells, score 2 indicating 30% to 50% positive tumor cells, score 1 indicating <30% positive cells, and score 0 indicating no staining on tumor cells. FDC distribution was evaluated by CD21 and/or CD23 immunostaining and was assigned a score of 0 when the signal was restricted to germinal centers; 1 in case of perifollicular expansion; 2 in case of perifollicular and perivascular expansion; or 3 for diffuse expansion. The EBV status in large lymphoid cells was based on counting EBER-positive large cells and scored as follows: negative, absence of large EBV-positive cells; positive, up to 5 large EBV-positive cells per high power field (hpf); strongly positive, more than 5 per hpf or sheets or aggregates of large EBV-positive cells. As indicated in the legend, the sections “others” represent IPI at diagnosis (IPI 4-5 vs 1-3), CMR (CMR vs other response or nonevaluable), and SUVmax and TMTV, both being dichotomized at the median of the cohort.

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