Peripheral T-cell lymphomas correlate with TFH-like featuresC84.4

Inactivating mutations of the ten-eleven translocation 2 (TET2) gene were first detected in myeloid malignancies. Later, they were also indexed in PTCL-NOS, a heterogeneous group of lymphomas that probably originate from Th follicular (T(FH)) cells similar to AITL, in about 40% of cases (Lemonnier Fet al. 2012). In this T-cell variant, TET2 mutations were more frequently detectable when these lymphomas expressed T(FH) markers and/or had features reminiscent of AITL. TET2 mutations were associated with advanced disease stage, thrombocytopenia, and shorter progression-free survival.

Peripheral T-cell lymphomas with a TFH phenotype were previously included in the broad category of PTCL-NOS and now represent their own provisional subgroup in the current WHO classification. TFH cells (TFH is the acronym for "follicular B helper T-cells") form a smaller subpopulation of Th lymphocytes that express CXCR5 on their surface. These cells are found within the B-cell follicles of human tonsils and in the blood.

Immunophenotypically, the neoplastic cells express Pan-T cell antigens(CD2, CD3, and CD5) with frequent deficiency of CD7. Lymphomas of this type are by definition CD4 positive and must express at least 2 (preferably 3) of the TFH markers (PD1, CD10, BCL6, CXCL13, ICOS). Interspersed CD20-positive immunoblasts are often EBV-positive. Hodgkin/Reed-Sternberg-like cells may also have the phenotype of classical Hodgkin lymphoma (CD30+, CD15+, PAX5+, EBV+/-), making lymphocyte-rich classical Hodgkin lymphoma an important differential diagnosis here. It will be seen in the future whether this subgroup represents a separate entity.

It is widely believed that this provisional subset may represent a tumor cell-rich variant of AITL.

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