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The term T follicular helper (TFH) lymphoma encompasses three lymphomas that arise from TFH cells: angioimmunoblastic T-cell lymphoma (AITL), follicular T-cell lymphoma and nodal peripheral T-cell lymphoma with TFH phenotype. A TFH phenotype is defined by the expression of at least two, preferably three, of the T follicular markers: CD10, BCL6, PD1, CXCR5, ICOS, SAP and MAF. These three lymphomas are considered as definitive entities in the revised WHO classification [1,2]. Cutaneous T-cell lymphomas with a TFH phenotype are excluded from this category.

The prototype of these lymphomas is AITL, which has distinct clinical and histological features and a TFH gene signature with the majority of cases showing expression of most if not all of the TFH-associated genes.

Clinical features

These lymphomas affect middle-aged and elderly patients and often manifest with B symptoms and advanced stage disease. Lymphadenopathy, hepatosplenomegaly and skin involvement are common in AITL and follicular T-cell lymphoma [3]. Clinical features of nodal peripheral T-cell lymphoma with TFH phenotype are similar to those of peripheral T-cell lymphoma, not otherwise specified.

Haematological and pathological features

Involvement of the peripheral blood is very rare. Polyclonal hypergammaglobulinaemia is frequent. Immune abnormalities such as circulating immune complexes, cryoglobulinaemia, positive rheumatoid factor, other autoantibodies and a Coombs-positive haemolytic anaemia can be seen in both AITL and follicular T-cell lymphomas.

The lymph node architecture is completely or partially effaced in AITL (Figure 22.1). The neoplastic cells often cluster adjacent to endothelial venules and are admixed with an inflammatory background. Three patterns have been described. Pattern 1 is characterized by the presence of hyperplastic follicles surrounded by neoplastic cells; this pattern is difficult to distinguish from reactive follicular hyperplasia. In pattern 2 there are only remnants of follicles and pattern 3 is characterized by the presence of few remnants of follicles in the outer cortex displaced by an expanded paracortex. Other characteristic features of AITL are the proliferation of follicular dendritic cells and the presence of large B immunoblasts or Reed–Sternberg-like cells that are often Epstein–Barr virus (EBV) positive (Figure 22.2). This B-cell component can expand further and progress to an EBV-positive diffuse large B-cell lymphoma. The bone marrow is involved in about two thirds of cases. The bone marrow infiltrate is pleomorphic with increased inflammatory cells (reactive lymphocytes, immunoblasts, macrophages and often eosinophils, neutrophils, fibroblasts and plasma cells).

Figure 22.1

Lymph node section in angioimmunoblastic T-cell lymphoma (AITL) showing effacement of the architecture by a population that includes intermediate sized neoplastic cells associated with prominent high endothelial venules. Haematoxylin and eosin stain (H&E) stain, ×20 objective.

Figure 22.2

Lymph node section in AITL (same case as Figure 22.1) showing scattered Epstein–Barr virus (EBV)-positive cells. In situ hybridization ...

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