Chronic Lymphocytic Thyroiditis with Oncocytic Metaplasia Influences PD-L1 Expression in Papillary Thyroid Carcinoma.

BACKGROUND: Despite the increasing recognition of PD-L1 as predictor of immunotherapeutic response in various malignancies, its role and prognostic significance in thyroid cancer remain underexplored and subject to debate. This study begins to address this gap by comprehensively analyzing PD-L1 expression in papillary thyroid carcinoma (PTC) and investigating its correlation with key clinicopathological variables. METHODS: We conducted immunohistochemistry (IHC) to assess PD-L1 expression in whole-tissue sections from 121 primary papillary thyroid carcinoma (PTC) cases. We then analyzed the correlations between PD-L1 expression and various clinicopathological variables. RESULTS: PD-L1 expression was detected in 33.1% of papillary thyroid carcinomas (PTCs), predominantly exhibiting weak to moderate intensity. Notably, this study found no significant correlation between PD-L1 expression and various clinicopathological variables. The lack of association with traditional factors such as age, sex, histological subtype, and tumor size suggests the complex and multifaceted nature of PD-L1 regulation in PTC. Multivariate logistic regression analysis identified chronic lymphocytic thyroiditis with oncocytic metaplasia as the sole independent predictor of PD-L1 expression (P = 0.014), underlining the potential influence of the tumor microenvironment on immune checkpoint expression in PTC. CONCLUSIONS: Our study underscores the intricate interplay between chronic lymphocytic thyroiditis with oncocytic metaplasia and PD-L1 expression in papillary thyroid carcinoma. The observed link suggests a potential avenue for therapeutic intervention using anti-PD-1/PD-L1 therapies in surgery-refractory PTC. Understanding the dynamics of immune checkpoint regulation in the context of the tumor microenvironment is crucial for devising effective treatment strategies. Future research endeavors should delve deeper into the molecular mechanisms underlying this interaction and explore its implications for patient outcomes. As the field of immunotherapy continues to evolve, our findings contribute valuable insights into the complex immunological landscape of thyroid cancer.

Asociación entre tiroiditis linfocítica crónica y carcinoma papilar de tiroides: Revisión sistemática y metaanálisis de estudios en especímenes quirúrgicos / Association between chronic lymphocityc thyroiditis and papillary thyroid carcinoma: Systematic review and meta-analysis of studieson surgical specimens

Introducción. Existen resultados inconsistentes con relación al planteamiento de la hipótesis que sugiere una mayor probabilidad de documentar un carcinoma papilar de tiroides en especímenes quirúrgicos con cambios compatibles con tiroiditis linfocítica crónica. En los metaanálisis existentes se han incluido estudios no comparables metodológicamente y no se proponen claras fuentes de sesgo, justificación para la realización del presente metaanálisis. Métodos. Se realizó una búsqueda bibliográfica en Pubmed y Embase. Fueron obtenidos estudios retrospectivos donde se comparaba la prevalencia de carcinoma papilar de tiroides en especímenes con y sin cambios por tiroiditis linfocítica crónica. La evidencia recolectada fue sintetizada estadísticamente. Resultados. Un total de 22 artículos fueron incluidos. La población estuvo conformada por 63.548 especímenes. El OR combinado fue 1,81 (IC95%: 1,51-2,21). Hubo heterogeneidad entre la distribución de las razones de oportunidad entre los estudios (I2= 91 %; p>0,00001). La forma del gráfico en embudo de los estudios incluidos en el análisis parece estar simétrica, lo que indica la ausencia del sesgo atribuible a los estudios pequeños. Conclusiones. La literatura actual sugiere que existe un mayor riesgo de documentar un carcinoma papilar de tiroides en especímenes quirúrgicos en los que se observan cambios compatibles con tiroiditis linfocítica crónica; sin embargo, existen fuentes de sesgo que no será posible controlar en estudios retrospectivos, por lo que recomendamos estudiar la hipótesis que sugiere una mayor probabilidad de diagnosticar un carcinoma papilar de tiroides en especímenes con cambios compatibles con tiroiditis linfocítica crónica mediante metodologías prospectivas

Introduction. Inconsistent results exist in the literature regarding the hypothesis statement suggesting an increased likelihood of documenting papillary thyroid carcinoma (PTC) in surgical specimens with changes compatible with chronic lymphocytic thyroiditis. Existing meta-analyses have included studies that are not methodologically comparable and do not propose clear sources of bias, thus, this is justification for the present meta-analysis. Methods. A literature search in Pubmed and Embase was performed from January 1, 1950 to December 31, 2020. Retrospective studies comparing the prevalence of papillary thyroid carcinoma in specimens with and without chronic lymphocytic thyroiditis changes were obtained. The collected evidence was statistically analyzed. Results. A total of 22 articles were included. The study population consisted of 63,548 surgical specimens. The pooled OR, based on the studies, was 1.81 (95% CI: 1.51-2.21). There was heterogeneity between the distribution of prevalence ratios and opportunity ratios across studies (I²= 91%; p>0.00001). The funnel plot shape of the studies included in the analysis appears to be symmetrical, indicating the absence of bias attributable to small studies. Conclusions. The current literature suggests that there is an increased risk of documenting papillary thyroid carcinoma in surgical specimens in which chronic lymphocytic thyroiditis-compatible changes are observed; however, there are sources of bias that will not be possible to control for in retrospective studies, so we recommend studying the hypothesis suggesting an increased likelihood of diagnosing PTC in specimens with chronic lymphocytic thyroiditis-compatible changes using prospective methodologies

Influence of chronic lymphocytic thyroiditis on the risk of persistent and recurrent disease in patients with papillary thyroid carcinoma and elevated antithyroglobulin antibodies after initial therapy / Influência da tireoidite linfocítica crônica sobre o risco de doença persistente e recorrente em pacientes com carcinoma papilífero de tireoide e anticorpos antitireoglobulina elevados após a terapia inicial

Abstract Introduction In patients with papillary thyroid carcinoma who have negative serum thyroglobulin after initial therapy, the risk of structural disease is higher among those with elevated antithyroglobulin antibodies compared to patients without antithyroglobulin antibodies. Other studies suggest that the presence of chronic lymphocytic thyroiditis is associated with a lower risk of persistence/recurrence of papillary thyroid carcinoma. Objective This prospective study evaluated the influence of chronic lymphocytic thyroiditis on the risk of persistence and recurrence of papillary thyroid carcinoma in patients with negative thyroglobulin but elevated antithyroglobulin antibodies after initial therapy. Methods This was a prospective study. Patients with clinical examination showing no anomalies, basal Tg < 1 ng/mL, and elevated antithyroglobulin antibodies 8-12 months after ablation were selected. The patients were divided into two groups: Group A, with chronic lymphocytic thyroiditis on histology; Group B, without histological chronic lymphocytic thyroiditis. Results The time of follow-up ranged from 60 to 140 months. Persistent disease was detected in 3 patients of Group A (6.6%) and in 6 of Group B (8.8%) (p = 1.0). During follow-up, recurrences were diagnosed in 2 patients of Group A (4.7%) and in 5 of Group B (8%) (p = 0.7). Considering both persistent and recurrent disease, structural disease was detected in 5 patients of Group A (11.1%) and in 11 of Group B (16.1%) (p = 0.58). There was no case of death related to the disease. Conclusion Our results do not support the hypothesis that chronic lymphocytic thyroiditis is associated with a lower risk of persistent or recurrent disease, at least in patients with persistently elevated antithyroglobulin antibodies after initial therapy for papillary thyroid carcinoma.

Resumo Introdução Em pacientes com carcinoma papilífero de tireoide e com tireoglobulina sérica negativa após a terapia inicial, o risco de doença estrutural é maior entre aqueles com anticorpos antitireoglobulina elevados em comparação com pacientes sem anticorpos antitireoglobulina. Outros estudos sugerem que a presença de tireoidite linfocítica crônica está associada a um menor risco de persistência/recorrência do carcinoma papilífero de teireoide. Objetivo Este estudo prospectivo avaliou a influência da tireoidite linfocítica crônica sobre o risco de persistência e recorrência do carcinoma papilífero de tireoide em pacientes com tireoglobulina negativa, mas com anticorpos antitireoglobulinas elevados após a terapia inicial. Método Esse foi um estudo prospectivo, no qual foram selecionados pacientes com exame clínico sem anomalias; tireoglobulina basal < 1 ng/mL e anticorpos antitireoglobulina elevados 8-12 meses após ablação. Os pacientes foram divididos em dois grupos: Grupo A, com tireoidite linfocítica crônica no exame histológico; Grupo B, histologicamente sem tireoidite linfocítica crônica. Resultados O tempo de seguimento variou de 60 a 140 meses. Doença persistente foi detectada em 3 pacientes do Grupo A (6,6%) e em 6 do Grupo B (8,8%) (p = 1,0). Durante o seguimento, as recidivas foram diagnosticadas em 2 pacientes do Grupo A (4,7%) e em 5 do Grupo B (8%) (p = 0,7). Considerando tanto a doença persistente quanto a recorrente, doença estrutural foi detectada em 5 pacientes do Grupo A (11,1%) e em 11 do Grupo B (16,1%) (p = 0,58). Não houve nenhum caso de óbito relacionado à doença. Conclusão Nossos resultados não apoiam a hipótese de que a tireoidite linfocítica crônica esteja associada a um menor risco de doença persistente ou recorrente, pelo menos em pacientes com anticorpos antitireoglobulina persistentemente elevados após a terapia inicial do carcinoma papilífero de tireoide.

Influence of chronic lymphocytic thyroiditis on the risk of persistent and recurrent disease in patients with papillary thyroid carcinoma and elevated antithyroglobulin antibodies after initial therapy.

INTRODUCTION: In patients with papillary thyroid carcinoma who have negative serum thyroglobulin after initial therapy, the risk of structural disease is higher among those with elevated antithyroglobulin antibodies compared to patients without antithyroglobulin antibodies. Other studies suggest that the presence of chronic lymphocytic thyroiditis is associated with a lower risk of persistence/recurrence of papillary thyroid carcinoma. OBJECTIVE: This prospective study evaluated the influence of chronic lymphocytic thyroiditis on the risk of persistence and recurrence of papillary thyroid carcinoma in patients with negative thyroglobulin but elevated antithyroglobulin antibodies after initial therapy. METHODS: This was a prospective study. Patients with clinical examination showing no anomalies, basal Tg<1ng/mL, and elevated antithyroglobulin antibodies 8-12 months after ablation were selected. The patients were divided into two groups: Group A, with chronic lymphocytic thyroiditis on histology; Group B, without histological chronic lymphocytic thyroiditis. RESULTS: The time of follow-up ranged from 60 to 140 months. Persistent disease was detected in 3 patients of Group A (6.6%) and in 6 of Group B (8.8%) (p=1.0). During follow-up, recurrences were diagnosed in 2 patients of Group A (4.7%) and in 5 of Group B (8%) (p=0.7). Considering both persistent and recurrent disease, structural disease was detected in 5 patients of Group A (11.1%) and in 11 of Group B (16.1%) (p=0.58). There was no case of death related to the disease. CONCLUSION: Our results do not support the hypothesis that chronic lymphocytic thyroiditis is associated with a lower risk of persistent or recurrent disease, at least in patients with persistently elevated antithyroglobulin antibodies after initial therapy for papillary thyroid carcinoma.

Chronic lymphocytic thyroiditis does not influence the risk of recurrence in patients with papillary thyroid carcinoma and excellent response to initial therapy.

BACKGROUND: This study evaluated the recurrence in patients with papillary thyroid cancer and an excellent response to initial therapy, comparing those with and without chronic lymphocytic thyroiditis. METHODS: This was a prospective study. Patients who met the following criteria were selected: diagnosis of papillary thyroid cancer; submitted to total thyroidectomy followed or not by ablation with 131I; and neck ultrasonography without abnormalities, nonstimulated thyroglobulina (Tg) ≤0.2 ng/ml, and undetectable antithyroglobulin antibodies (TgAb) 12-18 months after initial therapy. The patients were divided into two groups: group A, with chronic lymphocytic thyroiditis on histology; group B, without chronic lymphocytic thyroiditis on histology. RESULTS: Groups A and B were similar in terms of sex and age of the patients, characteristics of the tumor, tumor-node-metastase stage and risk category. The time of follow-up ranged from 24 to 120 months (median 66 months). During follow-up, 5 patients of group A (2.6 %) and 9 patients of group B (2 %) developed recurrence (p = 0.77). Patients with chronic lymphocytic thyroiditis were more likely to progress to persistently borderline TgAb. No patient had positive TgAb (above the reference value) during follow-up. Recurrences occurred in 12/588 patients (2 %) with undetectable TgAb in all measurements, in 1/32 (3.1 %) with detectable TgAb on some occasion but that returned to undetectable spontaneously, and in 1/13 (7.7 %) with persistently borderline TgAb. These rates did not differ significantly (p = 0.25). CONCLUSION: The results of the present study showed the absence of an association between chronic lymphocytic thyroiditis and recurrence risk at least in patients with an excellent response to initial therapy.

Interleukin-10 but not interleukin-18 may be associated with the immune response against well-differentiated thyroid cancer

OBJECTIVES: The aim of this study was to investigate the role of the interleukin-18 +105A/C and interleukin-10 -1082A/G germline polymorphisms in the development and outcome of differentiated thyroid carcinoma associated or not with concurrent thyroiditis. METHODS: We studied 346 patients with differentiated thyroid carcinomas, comprising 292 papillary carcinomas and 54 follicular carcinomas, who were followed up for 12-298 months (mean 76.10 ± 68.23 months) according to a standard protocol. We genotyped 200 patients and 144 control individuals for the interleukin-18 +105A/C polymorphism, and we genotyped 183 patients and 137 controls for the interleukin-10 -1082A/G polymorphism. RESULTS: Interleukin-18 polymorphisms were not associated with chronic lymphocytic thyroiditis or any clinical or pathological feature of tumor aggressiveness. However, there was an association between the presence of interleukin-10 variants and chronic lymphocytic thyroiditis. Chronic lymphocytic thyroiditis was present in 21.74 percent of differentiated thyroid carcinoma patients, most frequently affecting women previously diagnosed with Hashimoto's thyroiditis who had received a lower 131I cumulative dose and did not present lymph node metastases. CONCLUSIONS: We conclude that the inheritance of a G allele at the interleukin-10 -1082A/G polymorphism may favor a concurrent thyroid autoimmunity in differentiated thyroid carcinoma patients, and this autoimmunity may favor a better prognosis for these patients.

Influencia de la tiroiditis linfocitaria crónica en el pronóstico de pacientes con carcinoma papilar de tiroides / Influence of chronic lymphocytic thyroiditis on the prognostic outcome of patients with papillary thyroid carcinoma

Introducción: Algunos estudios atribuyen a la tiroiditis linfocitaria crónica (TLC) asociada al carcinoma papilar de tiroides (CPT) un efecto protector o de buen pronóstico; otros sugieren que sería un factor de riesgo para el desarrollo de recurrencias. Objetivo: Determinar la influencia de la TLC en el pronóstico de pacientes con CPT. Métodos: De un total de 406 CPT operados por un mismo cirujano (JLN), se seleccionaron 140 CPT que cumplieron los siguientes criterios de inclusión: pacientes operados con tiroidectomía total con criterio curativo y diagnóstico histológico de CPT variedad usual, sin tratamientos quirúrgicos previos y con seguimiento mínimo de 5 años. El diagnóstico de CPT y TLC lo realizó un mismo anatomopatólogo. Se definieron como factores de mal pronóstico, la edad ?45 años, el sexo masculino, los tumores grandes (>40 mm), los ganglios metastásicos al momento del diagnóstico de CPT, la multifocalidad tumoral y la invasión extratiroidea. Resultados: Se diagnosticaron histológicamente 51 (36.4%) CPT asociados con TLC y 89 (63.6%) sin TLC. Ninguno de los factores considerados mostró diferencias estadísticamente significativas entre los pacientes con y sin TLC (P=NS). Las tasas de recurrencia (3.6%) y muerte (2.1%) también fueron similares en ambos grupos (P=NS). Conclusión: La coexistencia de CPT y TLC es elevada y concordante con algunas publicaciones, pero la TLC no produjo ningún impacto sobre el pronóstico (recurrencia) de los pacientes. Aquellos que recurrieron y fallecieron presentaron 3 o más factores de mal pronóstico, sin que la TLC fuese un factor determinante del pronóstico.

Introduction: Some articles attribute a protect effect of chronic lymphocytic thyroiditis (CLT) on the prognostic outcome of patients with papillary thyroid carcinoma (PTC); others suggest it as a risk factor of PTC recurrences. Objective: To determine the influence of CLT on the prognostic outcome of patients with PTC. Methods: From 406 PTC patients surgically treated by a same surgeon (JLN), which received radioactive iodine ablative dosis, 140 PTC patients were selected that followed the following criteria: patients who underwent a total thyroidectomy for curative purpose, with histological diagnosis of pure PTC, without previous related surgeries, with a minimal 5-year follow-up. PTC and CLT histological diagnosis were performed by a same pathologist. Bad prognosis factors were defined: ?45 years old, male sex, big tumors (>40 mm), metastatic nodes at PTC diagnosis, multifocality and extrathyroideal extension. Results: 51 (36.4%) were found associated with CLT and 89 (63.6%) showed only pure PTC. No factors showed significantly statistical differences between patients with and without CLT (P=NS). Recurrence (3.6%) and death (2.1%) rates were similar in both groups, too (P=NS). Conclusion: Coexistence of CLT and PTC is high and it coincides with other experiences, but CLT did not cause any impact on the prognostic outcome (recurrence and/or death) of patients with PTC. Patients who had recurrence or died showed at least three risk factors, but CLT did not a bad prognosis factor.