Differential Expression of RORγt and T-bet in ALK-Negative Anaplastic Large Cell Lymphoma: Implications for Biological Heterogeneity and Differential Diagnosis.

Authors

Aya Muramatsu, Daisuke Yamashita, Yuta Tsuyuki, Akira Satou, Naoko Asano, Waki Hosoda, Kennosuke Karube, Shigeo Nakamura, Seiichi Kato

Published in

The American journal of surgical pathology. Sep 03, 2026. Epub Sep 03, 2026.

Abstract

ALK-negative anaplastic large cell lymphoma (ALK-negative ALCL) frequently expresses cytotoxic molecules, which may complicate its distinction from peripheral T-cell lymphoma NOS (PTCL-NOS), particularly in cytotoxic molecule-positive cases. Among these, nodal EBV-negative cytotoxic T-cell lymphoma (CTL) represents an important diagnostic consideration. We evaluated the clinicopathological features of ALK-negative ALCL in comparison with nodal EBV-negative CTL and ALK-positive ALCL, with a focus on the immunohistochemical expression of master transcription factors (RORγt, T-bet, and GATA3). RORγt expression was significantly more frequent in ALK-negative ALCL than in nodal EBV-negative CTL (11/21 [52%] vs. 2/25 [8%]; P=0.001), and was uniformly present in ALK-positive ALCL (10/10 [100%]; P=0.012 vs. ALK-negative ALCL). In contrast, T-bet expression was less frequent in ALK-negative ALCL (2/21 [10%]) than in nodal EBV-negative CTL (9/25 [36%]; P=0.045), and was absent in all ALK-positive ALCL cases. RORγt and T-bet expression were largely mutually exclusive across the cohort, with only one overlapping case. GATA3 expression was absent in all evaluable cases of nodal EBV-negative CTL and ALK-positive ALCL, and was detected in only 2 of 19 ALK-negative ALCL cases (11%). These findings suggest that ALK-negative ALCL shows a distinct transcription factor profile characterized by frequent RORγt expression and infrequent T-bet expression, in contrast to nodal EBV-negative CTL. Assessment of these markers may provide a useful adjunct in the differential diagnosis of cytotoxic T-cell lymphomas, particularly in diagnostically challenging cases.

PMID:
42687744
Bibliographic data and abstract were imported from PubMed on 03 Sep 2026.

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