So in focusing on the T follicular helpers, uh, subset of T-cell lymphoma, so this is really the classic angiomunoblastic T cell lymphoma, which has a certain histologic appearance, uh, mixed cell infiltrate, um, usually EBV positive B cells in the mix, um. Uh, and sort of the T cells are in this inflammatory background. And then there's other, um, types of follicular helper T cell lymphoma that have the same, um, sort of genetic underpinnings we think have the same cell of origin, uh, from a germinal center T cell or so called follicular helper T cell, and those are now grouped together, and we think they biologically behave similarly and respond similarly to therapy. I would know that sometimes in T cell lymphoma, uh like B cell lymphoma, we don't talk about cell of origin, but we talk about cell state. So because these um lymphomas develop on a background of um mutations typical in clonal hematopoiesis, we don't really know for sure that it's truly the cell of origin or that the genetics drive the phenotype and therefore it's more of a cell state and that maybe the cell wasn't truly derived or the the original malignant cell wasn't truly uh a germinal center or a T cell, but they tend to develop um uh with those characteristics. Uh, the genetic underpinnings probably really drive the phenotype, and those are usually things like t2 and other epigenetic mutations, uh, often DNMT3A, and then additional mutations, most commonly Roe A or IDH2 that that kind of uh lead to the malignant phenotype, um. Right now though, they're divine immunohistochemically, so, um, they're usually CD4 positive T-cell lymphomas, and then they, uh, should have, uh, two or more follicular helper T cell markers. Uh, so those, if I remember them all, are like CD10 uh can be expressed in T cell, CXCL 13, PD1, uh, ICOS, BCL 6. those are often seen in, in a constellation of those two or more. To define the follicular hyper phenotype. There's usually Epstein-Barr virus that's usually in the in uh in B cells or immunoblasts in the mix. Those usually are not in the T cells, but that's often a part of the microenvironment. And when you see, um, uh, enough of those markers, the pathologist may assign a TFH a diagnosis. It has the full histologic appearance of angioimunoblastic T cell lymphoma with all the inflammatory background and, and, uh, vascularization. And, uh, dendritics on that network, then they would call it AITL and if it has the right phenotype but maybe lacks some of those classic characteristics, they'll call it TFH. And, and how they call that may vary a little bit, uh, between pathologists, but at least our data here we think shows that the TFH and and specifically AITL uh lymphomas are quite similar, behave similar, have similar outcomes, respond similarly, uh, to most of our, our, our therapies.
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