Functional Engagement of the PD-1/PD-L1 Complex But Not PD-L1 Expression Is Highly Predictive of Patient Response to Immunotherapy in Non-Small-Cell Lung Cancer.

PURPOSE: In many cancers, the expression of immunomodulatory ligands leads to immunoevasion, as exemplified by the interaction of PD-L1 with PD-1 on tumor-infiltrating lymphocytes. Profound advances in cancer treatments have come with the advent of immunotherapies directed at blocking these immuno-suppressive ligand-receptor interactions. However, although there has been success in the use of these immune checkpoint interventions, correct patient stratification for these therapies has been challenging. MATERIALS AND METHODS: To address this issue of patient stratification, we have quantified the intercellular PD-1/PD-L1 interaction in formalin-fixed paraffin-embedded tumor samples from patients with non-small cell lung carcinoma, using a high-throughput automated quantitative imaging platform (quantitative functional proteomics [QF-Pro]). RESULTS: The multisite blinded analysis across a cohort of 188 immune checkpoint inhibitor-treated patients demonstrated the intra- and intertumoral heterogeneity of PD-1/PD-L1 immune checkpoint engagement and notably showed no correlation between the extent of PD-1/PD-L1 interaction and PD-L1 expression. Importantly, PD-L1 expression scores used clinically to stratify patients correlated poorly with overall survival; by contrast, patients showing a high PD-1/PD-L1 interaction had significantly better responses to anti-PD-1/PD-L1 treatments, as evidenced by increased overall survival. This relationship was particularly strong in the setting of first-line treatments. CONCLUSION: The functional readout of PD-1/PD-L1 interaction as a predictive biomarker for the stratification of patients with non-small-cell lung carcinoma, combined with PD-L1 expression, should significantly improve the response rates to immunotherapy. This would both capture patients excluded from checkpoint immunotherapy (high PD-1/PD-L1 interaction but low PD-L1 expression, 24% of patients) and additionally avoid treating patients who despite their high PD-L1 expression do not respond and suffer from side effects.

Pure white cell aplasia an exceptional condition in the immunological conundrum of thymomas: Responses to immunosuppression and literature review.

Thymomas are tumours frequently associated with autoimmune manifestations or immunodeficiencies like Good syndrome. In rare cases, pure white cells aplasia (PWCA) has been described in association with thymomas. PWCA is characterized by agranulocytosis of autoimmune background primary refractory to granulocyte colony-stimulating factor (G-CSF). It is necessary the use of immunosuppressor to allow granulocyte recovery. Without treatment, it could be fatal.

[Paratesticular fibrous pseudotumor]. / Pseudotumor fibroso paratesticular.

OBJECTIVE: Benign testicular proliferative processes are known by the name of pseudotumors, because currently they are not considered real neoplasias. The paratesticular fibrous pseudotumor (PFP) is a rare entity the definition and etiopathogenesis of which is under great confusion. It is a process that misleads the clinical because they simulate neoplasias. This paper aims to help a better knowledge of this non-tumoral process and to avoid diagnostic confusions. METHODS/RESULTS: We review our series of PFP (three cases), which can be considered significant due to its oddity. We analyze the clinical picture, its behavior, imaging diagnostic tests, operative findings and outcomes. CONCLUSIONS: PFP is a rare entity which may misleads the clinical because it may be diagnosed as a neoplasia and lead to aggressive treatment (orchiectomy) which in case of a proper diagnosis could be avoided. The analysis of our series of three cases, with their contribution, and a literature review may help the clinical practice of urologists by recognizing this disease.

Pseudotumor fibroso paratesticular / Paratesticular fibrous pseudotumor

Objetivos: Los procesos proliferativos benignos testiculares se conocen con el nombre de pseudotumors, al no ser considerados en la actualidad verdaderas neoplasias. El Pseudotumor Fibroso Paratesticular (PFP) es una entidad sobre las que existe gran confusión en su definición y etiopatogenia. Se trata de un proceso que confunde al clínico al aparecer simulando neoplasias. La presente comunicación puede ayudar a conocer mejor este proceso no tumoral y evitar confusiones diagnósticas. Métodos/Resultados: Revisamos nuestra serie de PFP (tres casos) sobre esta rara entidad, por lo que dada su rareza puede considerarse significativa. Analizamos su clínica, su comportamiento antes los estudios diagnósticos por imagen, hallazgos operatorios y evolución. Conclusiones: El PFP es una rara entidad que puede confundir al clínico al ser diagnosticado como una neoplasia, y conllevar tratamientos agresivos (orquiectomía) que de realizar un exacto diagnóstico podrían obviarse. El análisis de una serie de tres casos, con sus aportaciones, y la revisión de la literatura efectuada pueden ayudar en la practica clínica al urólogo a reconocer esta enfermedad (AU)

Objective: Benign testicular proliferative processes are known by the name of pseudotumors, because currently they are not considered real neoplasias. The paratesticular fibrous pseudotumor (PFP) is a rare entity, the definition and etiopathogenesis of which is under great confusion. It is a process that misleads the clinical because they simulate neoplasias. This paper aims to help a better knowledge of this non-tumoral process and to avoid diagnostic confusions. Methods/Results: We review our series of PFP (three cases), which can be considered significant due to its oddity. We analyze the clinical picture, its behavior, imaging diagnostic tests, operative findings and outcomes. Conclusions: PFP is a rare entity which may misleads the clinical because it may be diagnosed as a neoplasia and lead to aggressive treatment (orchiectomy) which in case of a proper diagnosis could be avoided. The analysis of our series of three cases, with their contribution, and a literature review may help the clinical practice of urologists by recognizing this disease (AU)

Blastoma pleuropulmonar: un tumor pediátrico infrecuente. A propósito de un caso y revisión de la literatura / Pleuropulmonary blastoma: an unusual pediatric tumor. Case report and review of literature

El blastoma pleuropulmonar (BPP) es un tumor disontogénicopediátrico muy raro y agresivo reconocido comoentidad clínico-patológica desde 1988 y del que se han descritoalrededor de 100 casos en la literatura mundial. Se clasificacomo tipo I, II y III en base a su naturaleza quística osólida. Presentamos un caso de una niña de 3 años con unatumoración que ocupa gran parte del hemitórax izquierdocon colapso del pulmón izquierdo y derrame pleural.Macroscópicamente es una masa sólida con áreas quísticasde 400 g y 15 cm de diámetro. Microscópicamente se tratade una tumoración mesenquimal de diferenciación divergentecon zonas blastematosas y mesenquimales que incluyediferenciación rabdomioblástica, fibroblástica, liposarcomatosay condroblástica-condroide. Su inmunofenotipomuestra positividad para desmina en extensas áreas deltumor, actina estriada en célula aisladas y S-100 en losfocos condroides. Marcadores neuroendocrinos negativos.Queratina positiva únicamente en las células epiteliales ymesoteliales de revestimiento atrapadas en el crecimientotumoral

Pleuropulmonary blastoma is an aggressive and extremelyrare pediatric dysontogenic tumor. It was firstly describedin 1988 and since then only about 100 cases havebeen reported. Based on of cystic or solid predominant features,type I, type II and type III were established. In thispaper a 3 yrs old female case is reported. The tumor massoccupied the main part of left hemithorax, collapsing lungand causing pleural effusion. Surgical specimen was a solidwith cystic areas, 400 g and 15 cm in main diameter mass.Microscopically it was a mesenchymal tumor showing blastematousareas and divergent differentiation with rhabdomyoblastic,fibroblastic, liposarcomatous and chondroblastic/chondroid components. Immunohistochemistry showedpositivity for desmin in wide areas, striated muscle actin inisolated cells and S-100 in chondroid foci. Neuroendocrinemarkers were negative. Cytokeratins were positive only inepithelial and mesothelial cells remaining within the tumor (AU)

Endocarditis fúngica en un paciente portador de prótesis valvular / Fungal endocarditis in a patient bearing a valve prosthesis

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