Application of a 5 Marker Panel to the Routine Diagnosis of Peripheral T-Cell Lymphoma With T-Follicular Helper Phenotype

Abstract

The 2017 World Health Organization update introduced a new category of nodal peripheral T-cell lymphoma with T-follicular helper phenotype (PTCL-TFH) defined by expression of at least 2 or 3 TFH markers. Our study assesses the utility of an immunohistochemical panel of 5 TFH markers (CD10, BCL6, PD-1, CXCL13, and ICOS) for identification of TFH phenotype in angioimmunoblastic T-cell lymphoma (AITL) and PTCL not otherwise specified (NOS). Immunohistochemical for the 5 markers was performed on 22 cases of AITL and 29 cases of PTCL-NOS. Cases were reviewed for morphologic features characteristic of AITL. All AITL cases showed expression of ≥2 TFH markers. This panel resulted in reclassification of 41% PTCL-NOS cases to PTCL-TFH. Positive percent agreement for the TFH phenotype is 97% for PD1, 94% for ICOS, 44% for CD10 and CXCL13, and 29% for BCL6. Negative percent agreement for TFH phenotype is 100% for CD10, BCL6, and CXCL13, 82% for ICOS and 71% for PD1. AITL cases were more likely than PTCL-TFH cases to contain expanded CD21-positive follicular dendritic cell meshworks, clear cell cytology and polymorphous inflammatory background; however, there was a significant (P<0.005) Kruskal-Wallis trend in all morphologic variables between the 3 groups suggesting a continuum from PTCL-NOS to PTCL-TFH to AITL. The median number of morphologic features of AITL also correlated significantly with number of TFH markers positive (Spearman coefficient ρ=0.759). In summary, the stain panel chosen will have an impact on cases classified as PTCL-TFH. This entity may exist along a spectrum between PTCL-NOS and AITL.

In Situ Characterization of Follicular Helper CD4 T Cells Using Multiplexed Imaging

“…Interestingly, the majority of CD30 hi Tfh cells were expressing a BCL6 hi phenotype too, indicating a possible role of CD30 in the differentiation process of AITL Tfh cells. Although the WHO criteria specifically state that expression of at least three Tfh markers is required for assignment of a Tfh phenotype (38,95), we detected a high level of heterogeneity concerning six Tfh markers, which were robustly co expressed in the tumor niche, that is to say CD4, PD-1, CXCR5, ICOS, Bcl6, and CXCL13. In a recent study, two AITL cases were analyzed using multiplexed quantitative immunohistochemistry techniques and one panel to simultaneously stain for a collection of relevant markers in lymphoid tissue to determine the expression of marker of interest in malignant cells, such as the CD4, PD-1, and BCL6.…”

The first reported case of primary extranodal counterpart of follicular T‐cell lymphoma of submandibular gland

“…Although the exact frequency of the disease is unknown, Basha et al reported that approximately 40% of the cases diagnosed as PTCL-NOS could be re-classified as nodal PTCL, using the these markers. 10 Proliferation with mainly follicular growth pattern is characteristic to FTCL, and this is its point of differentiation from PTCL-NOS. 1 Primary cutaneous CD4 + small/medium T-cell lymphoproliferative disorder is an excellent prognosis lesion, which often appears as a single skin lesion; its common sites are the face, neck, and upper trunk.…”

Cytological features and immunohistochemical findings related to lymphomatous effusion in an angioimmunoblastic T‐cell lymphoma patient: Case report

“…1 In particular, PD‐1 with high sensitivity and CXCL13 with high specificity were useful immunophenotypic markers of neoplastic T cells in AITL. 1 , 6 In contrast, there were no reports of AITL lymphomatous effusion diagnosed by cell block immunohistochemistry. Our findings related to atypical lymphoid cells immunoreactivity for TFH‐cell markers on the cell block sections, and our cytologic findings, were useful for the definitive diagnosis of lymphomatous effusion caused by AITL.…”