The prognostic value of peritumoural and intratumoural tertiary lymphoid structures in hepatocellular carcinoma
Sarelin, Niklas; Kairaluoma, Valtteri; Saarnio, Juha; Kauppila, Joonas H; Böhm, Jan; Huhta, Heikki; Väyrynen, Juha P; Helminen, Olli (2026-03-21)
Springer
21.03.2026
Sarelin, N., Kairaluoma, V., Saarnio, J. et al. The prognostic value of peritumoural and intratumoural tertiary lymphoid structures in hepatocellular carcinoma. Virchows Arch (2026). https://doi.org/10.1007/s00428-026-04482-6
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© The Author(s) 2026. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
https://creativecommons.org/licenses/by/4.0/
© The Author(s) 2026. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
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Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:oulu-202603232292
https://urn.fi/URN:NBN:fi:oulu-202603232292
Tiivistelmä
Abstract
The prognostic relevance of peritumoural tertiary lymphoid structure (pTLSs) in hepatocellular carcinoma (HCC) remains uncertain. We used three methods to analyse pTLSs and performed a combined analysis incorporating intratumoural TLSs (iTLSs). Of 99 resected HCC cases, 74 evaluable samples were retrospectively analysed. We quantified pTLSs using three methods: (1) pTLS density; (2) pTLS maximum length; and (3) pTLS hotspot count. They were then further classified into three grades based on pTLS measurements and the presence of iTLSs: Grade 1 — low pTLS and iTLS-negative (iTLS-); Grade 2 — low pTLS and iTLS-positive (iTLS +) or high pTLS and iTLS-; and Grade 3 — high pTLS and iTLS + . A high pTLS density (HR 0.32, 95% CI, 0.11–0.99, p = 0.048), maximum length (HR 0.33, 95% CI, 0.13–0.86, p = 0.023) and hotspot count (HR 0.30, 95% CI, 0.11–0.81, p = 0.018) were independent predictors of improved 5-year overall survival in multivariable analysis. A high pTLS density (HR 0.23, 95% CI, 0.06–0.91, p = 0.036) and hotspot count (HR 0.14, 95% CI, 0.04–0.56, p = 0.005) were linked with improved 5-year disease-specific survival. In the combined analysis, having grade 3 compared to grade 1 was associated with better overall and disease-specific survival in multivariable analysis across all evaluation methods. Higher pTLS density and hotspot count are independent predictors of improved survival in resected HCC. Furthermore, integrating pTLS measurements with iTLS presence provides enhanced prognostic stratification.
The prognostic relevance of peritumoural tertiary lymphoid structure (pTLSs) in hepatocellular carcinoma (HCC) remains uncertain. We used three methods to analyse pTLSs and performed a combined analysis incorporating intratumoural TLSs (iTLSs). Of 99 resected HCC cases, 74 evaluable samples were retrospectively analysed. We quantified pTLSs using three methods: (1) pTLS density; (2) pTLS maximum length; and (3) pTLS hotspot count. They were then further classified into three grades based on pTLS measurements and the presence of iTLSs: Grade 1 — low pTLS and iTLS-negative (iTLS-); Grade 2 — low pTLS and iTLS-positive (iTLS +) or high pTLS and iTLS-; and Grade 3 — high pTLS and iTLS + . A high pTLS density (HR 0.32, 95% CI, 0.11–0.99, p = 0.048), maximum length (HR 0.33, 95% CI, 0.13–0.86, p = 0.023) and hotspot count (HR 0.30, 95% CI, 0.11–0.81, p = 0.018) were independent predictors of improved 5-year overall survival in multivariable analysis. A high pTLS density (HR 0.23, 95% CI, 0.06–0.91, p = 0.036) and hotspot count (HR 0.14, 95% CI, 0.04–0.56, p = 0.005) were linked with improved 5-year disease-specific survival. In the combined analysis, having grade 3 compared to grade 1 was associated with better overall and disease-specific survival in multivariable analysis across all evaluation methods. Higher pTLS density and hotspot count are independent predictors of improved survival in resected HCC. Furthermore, integrating pTLS measurements with iTLS presence provides enhanced prognostic stratification.
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