How I Diagnose Angioimmunoblastic T-Cell Lymphoma

Yi Xie, MD, PhD; Elaine S. Jaffe, MD


Am J Clin Pathol. 2021;156(1):1-14. 

In This Article

Skin and Bone Marrow Involvement

In addition to lymph nodes, skin and bone marrow involvement by AITL is also frequent. The histologic findings of AITL involving skin are subtle histologically.[54] Skin biopsy specimens often show mild perivascular or periadnexal lymphoid infiltrates that may be difficult to differentiate from inflammatory conditions. Characteristic features of nodal AITLs, such as clear cells, vascular hyperplasia, and EBV-positive cells, are seen in only a minority of cases.[55] Immunohistochemistry for TFH markers may be helpful to identify the neoplastic cells, and PCR studies have identified a monoclonal T-cell population in more than 80% of cases.[54,56] However, it is important to note that a TFH immunophenotype is not entirely specific for AITL, and it can also be seen in primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder and other cutaneous T-cell lymphomas.[54] Correlation with clinical history and lymph node pathology is essential in these cases, as the skin biopsy specimen alone is usually not definitive.

In bone marrow, AITL usually shows single or multiple loose nodular lymphoid infiltrates with a paratrabecular or interstitial distribution pattern.[19,51,57] The infiltrate is often polymorphic, composed of many small or scattered larger lymphocytes, histiocytes, variable eosinophils, and, occasionally, aggregates of clear cells. Various secondary changes such as trilineage hematopoietic hyperplasia, polyclonal plasmacytosis, and myelofibrosis may be present. Immunohistochemical studies have shown a more subtle expression of the TFH markers in the bone marrow than lymph node. Nevertheless, immunohistochemical staining of the TFH markers, such as PD1, BCL6, and CXCL13, can still be helpful for detecting lymphomatous infiltrates. In addition, it has been recognized that most cases of AITL display a unique sCD3(–/dim)/CD4+/CD10 variable phenotype by flow cytometry.[34,58,59] Thus, flow cytometry is an effective tool in identifying small populations of aberrant T cells and can assist in diagnosis and monitoring of AITL, particularly in fluid specimens such as peripheral blood and bone marrow.[34,58]