Nakadaira Katia Sakimi, Saito Kelly Cristina, Fuziwara Cesar Seigi, Magalhães Patricia Künzle Ribeiro, Ramalho Leandra Naira Zambelli, Ricarte-Filho Julio C, Maciel Lea Maria Zanini, Kimura Edna Teruko
Departamento de Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brasil.
Divisão de Endocrinologia, Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
Arch Endocrinol Metab. 2025 Sep 26;69(5):e250103. doi: 10.20945/2359-4292-2025-0103.
This study aimed to investigate the presence of tertiary lymphoid structures (TLSs) and tumor-infiltrating B cells within the germinal centers of TLSs in the tumor microenvironment of thyroid cancer, utilizing a morphological approach.
Histological samples from patients with papillary thyroid carcinoma (PTC) (n = 112) stained with hematoxylin and eosin were examined. The presence of lymphoid neogenesis in PTC was determined based on morphological features and classified according to TLS location and maturation status. Immunofluorescence staining was performed on selected cases to identify B cells within mature TLSs. Additionally, 499 scanned slides from the PTC cohort in The Cancer Genome Atlas - Thyroid Carcinoma (TCGA-THCA) dataset were accessed via cBioPortal to assess the presence of TLSs and compare the clinical and molecular characteristics of PTC cases with and without TLSs.
Tertiary lymphoid structures, resembling ectopic lymph nodes, were identified in 41% (46/112) of the histological PTC samples. Among these, 63% (29/46) were located in peritumoral regions, while 13% (6/46) were found within the intratumoral area. Mature TLSs containing germinal centers, in which B cells were detected, were observed in 15% (7/46) of cases. Immature TLSs were detected in 52% (24/46) of PTC cases with TLSs. Analysis of PTC scanned images from cBioPortal revealed TLSs in 8.4% of cases, of which 62% harbored the BRAFV600E mutation, along with upregulation of immune cell markers and SLC5A5 (NIS) expression.
The identification of TLSs across multiple malignancies underscores their functional significance in modulating tumor-immune interactions with clinical implications. Therefore, the identification and morphological characterization of TLSs in PTC may provide valuable insights into their potential as immunobiomarkers in thyroid cancer.
本研究旨在采用形态学方法，调查甲状腺癌肿瘤微环境中三级淋巴结构（TLSs）的存在情况以及TLS生发中心内肿瘤浸润性B细胞的情况。
检查了112例经苏木精和伊红染色的甲状腺乳头状癌（PTC）患者的组织学样本。根据形态学特征确定PTC中淋巴新生的存在情况，并根据TLS位置和成熟状态进行分类。对选定病例进行免疫荧光染色，以识别成熟TLS内的B细胞。此外，通过cBioPortal访问了癌症基因组图谱 - 甲状腺癌（TCGA-THCA）数据集中PTC队列的499张扫描玻片，以评估TLS的存在情况，并比较有和没有TLS的PTC病例的临床和分子特征。
在41%（46/112）的组织学PTC样本中发现了类似异位淋巴结的三级淋巴结构。其中，63%（29/46）位于肿瘤周围区域，而13%（6/46）位于肿瘤内区域。在15%（7/46）的病例中观察到含有生发中心的成熟TLS，其中检测到了B细胞。在52%（24/46）有TLS的PTC病例中检测到未成熟TLS。对来自cBioPortal的PTC扫描图像分析显示，8.4%的病例中有TLS，其中62%携带BRAFV600E突变，同时免疫细胞标志物和SLC5A5（NIS）表达上调。
在多种恶性肿瘤中识别出TLS突出了它们在调节肿瘤 - 免疫相互作用方面的功能意义及其临床意义。因此，PTC中TLS的识别和形态学特征分析可能为它们作为甲状腺癌免疫生物标志物的潜力提供有价值的见解。
