Evolutionary analysis of indeterminate cytology and risk of malignancy in a thyroid nodule unit.

OBJECTIVE: The objective of this study was to analyze the evolution in the diagnosis and management of indeterminate thyroid nodules over three time periods. METHODS: 3020 patients with thyroid nodules underwent cytological evaluation during three periods (2006-2008, 2012-2014, 2017-2019). Distribution of diagnostic cytologies, risk of malignancy, diagnostic performance indices of FNA, and cytologic-histologic correlation in indeterminate cytologies were analyzed. RESULTS: only 2.2% of cytology tests were insufficient for a diagnosis. 86.9% cytologies were benign, 1.7% malignant, and 11.4% indeterminate. Indeterminate cytology rates were 15.9% (2006-2008), 10.1% (2012-2014), and 10% (2017-2019). Surgery was performed in 13% of benign cytology, result-ing in malignant histology in 2.7%. All malignant and suspicious cytologies underwent surgery: malig-nancy confirmed in 98% and 77% of cases, respectively. All 'indeterminate with atypia' cytologies (2006-2008) and Bethesda IV (2012-2014; 2017-2019) un-derwent surgery, with malignancy confirmed in 19.6%, 43.8%, and 25.7%, respectively. In the 'inde-terminate without atypia' category (2006-2008) and Bethesda III (2012-2014; 2017-2019), diagnostic surgery was performed in 57.7%, 78.6%, and 59.4%, respectively, with malignancy confirmed in 3.3%, 20.5%, and 31.6%. The FNA sensitivity was 91.6% with a negative predictive value greater than 96% in all periods. The specificity exceeded 75% in the last two periods. CONCLUSION: Bethesda system reduces indeterminate cytologies and improves the accuracy of FNA diagnosis. We reported a higher proportion of malignancy than expected in Bethesda III, underscoring the importance of having institution-specific data to guide decision-making. However, there is a need for risk stratification tools that allow for conservative management in low-risk cases.

Pleural empyema secondary to perforated diverticulosis due to biliary neoplasia infiltration.

A long-term female smoker presented to the emergency department with cough, greenish mucus and dyspnoea, without fever. The patient also reported abdominal pain and significant weight loss in recent months. Laboratory tests showed leucocytosis with neutrophilia, lactic acidosis and a faint left lower lobe consolidation on chest X-ray, for which she was admitted to the pneumology department and started on broad-spectrum antibiotherapy. After 3 days of clinical stability, the patient deteriorated rapidly, with worsening of analytical parameters and coma. The patient died a few hours later. Given the rapid and unexplained evolution of the disease, a clinical autopsy was requested, which revealed a left pleural empyema caused by perforated diverticula by neoplastic infiltration of biliary origin.

PD-L1 immunoexpression and molecular characterization of histological subtypes in urothelial carcinoma.

INTRODUCTION: Urothelial carcinoma (UC) has histological subtypes whose phenotype reflects their molecular diversity, behavior and response to conventional therapy. Immune checkpoint inhibitors (ICIs) have improved the management of UC by evaluation of PD-L1. In the case of PD-L1 22C3, the initiation of ICI is considered from a combined positive score (CPS) greater than 10. However, UC subtypes with absent PD-L1 22C3 expression in cases with CPS>10 may not respond to these treatments. This study aims to establish a correlation between the PD-L1 immunoexpression and molecular alterations in divergent differentiation and histological subtypes of UC (UC-s). MATERIAL AND METHODS: Twenty-six samples of UC were detected from a total of 24 patients. Two pathologists performed separately an assessment of UC-s on hematoxylin-eosin as well as PD-L1 expression. Molecular study of each case was performed by next generation sequencing (NGS). A descriptive analysis of the variables included was conducted. RESULTS: Nine cases (34.61%) showed a CPS>10, some with negative PD-L1 immunoexpression in aggressive UC-s. The molecular study revealed alterations in genes belonging to the p53/cell cycle control, RAS, and DNA repair pathways, among others. None of the alterations were exclusive to any histological subtype. DISCUSSION: Special attention should be paid to CPS>10 cases that include histological subtypes of UC with divergent expression for PD-L1 as they may not respond to treatment with ICI. We recommend examining the proportion and PD-L1 status of each subtype, especially if it has aggressive behavior.

PD-L1 immunoexpression and molecular characterization of histological subtypes in urothelial carcinoma / Inmunoexpresión de PD-L1 y caracterización molecular de subtipos histológicos de carcinoma urotelial

Introduction: Urothelial carcinoma (UC) has histological subtypes whose phenotype reflects their molecular diversity, behavior and response to conventional therapy. Immune checkpoint inhibitors (ICIs) have improved the management of UC by evaluation of PD-L1. In the case of PD-L1 22C3, the initiation of ICI is considered from a combined positive score (CPS) greater than 10. However, UC subtypes with absent PD-L1 22C3 expression in cases with CPS>10 may not respond to these treatments. This study aims to establish a correlation between the PD-L1 immunoexpression and molecular alterations in divergent differentiation and histological subtypes of UC (UC-s). Material and methods: Twenty-six samples of UC were detected from a total of 24 patients. Two pathologists performed separately an assessment of UC-s on hematoxylin–eosin as well as PD-L1 expression. Molecular study of each case was performed by next generation sequencing (NGS). A descriptive analysis of the variables included was conducted. Results: Nine cases (34.61%) showed a CPS>10, some with negative PD-L1 immunoexpression in aggressive UC-s. The molecular study revealed alterations in genes belonging to the p53/cell cycle control, RAS, and DNA repair pathways, among others. None of the alterations were exclusive to any histological subtype. Discussion: Special attention should be paid to CPS>10 cases that include histological subtypes of UC with divergent expression for PD-L1 as they may not respond to treatment with ICI. We recommend examining the proportion and PD-L1 status of each subtype, especially if it has aggressive behavior.(AU)

Introducción: El carcinoma urotelial (CU) presenta subtipos histológicos cuyo fenotipo refleja su diversidad molecular, su comportamiento y su respuesta al tratamiento. Los inhibidores de puntos de control inmunitario (ICI) han mejorado el manejo del CU mediante la evaluación de PD-L1. En el caso de PD-L1 22C3, se considera el inicio de ICI a partir de una puntuación positiva combinada (combined positive score [CPS]) mayor de 10. Sin embargo, los subtipos de CU con ausencia de expresión de PD-L1 22C3 en casos con CPS>10 podrían no responder a estos tratamientos. Este estudio pretende establecer una correlación entre la inmunoexpresión de PD-L1 y las alteraciones moleculares en áreas con diferenciación divergente y subtipos histológicos de CU (CU-s). Material y métodos: Se obtuvieron 26 muestras con CU de 24 pacientes. Dos patólogos evaluaron de manera independiente las CU-s en hematoxilina-eosina y la expresión de PD-L1. Se realizó el estudio molecular mediante Next Generation Sequencing (NGS). Se realizó un análisis descriptivo de las variables incluidas. Resultados: Nueve casos (34,61%) mostraron un CPS>10, algunos con PD-L1 negativo en los CU-s de comportamiento agresivo. El estudio molecular reveló alteraciones en genes de las vías de p53/control del ciclo celular, RAS y reparación del ADN, entre otras. Ninguna alteración fue exclusiva de algún CU-s. Discusión: Debe prestarse especial atención a los casos con CPS>10 que incluyan subtipos histológicos con expresión divergente para PD-L1, ya que podrían no responder al tratamiento con ICI. Se recomienda cuantificar la proporción y el estado de PD-L1 de cada subtipo, especialmente si es de comportamiento agresivo.(AU)

Asociación de enteritis quística profunda, ileocolitis de Crohn y endometriosis como causa de obstrucción intestinal / A combination of enteritis cystica profunda, Crohn’s ileocolitis and endometriosis as a cause of intestinal obstruction

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