Machine Learning Quantification of Intraepithelial Tumor-Infiltrating Lymphocytes as a Significant Prognostic Factor in High-Grade Serous Ovarian Carcinomas.

The prognostic and predictive role of tumor-infiltrating lymphocytes (TILs) has been demonstrated in various neoplasms. The few publications that have addressed this topic in high-grade serous ovarian carcinoma (HGSOC) have approached TIL quantification from a semiquantitative standpoint. Clinical correlation studies, therefore, need to be conducted based on more accurate TIL quantification. We created a machine learning system based on H&E-stained sections using 76 molecularly and clinically well-characterized advanced HGSOC. This system enabled immune cell classification. These immune parameters were subsequently correlated with overall survival (OS) and progression-free survival (PFI). An intense colonization of the tumor cords by TILs was associated with a better prognosis. Moreover, the multivariate analysis showed that the intraephitelial (ie) TILs concentration was an independent and favorable prognostic factor both for OS (p = 0.02) and PFI (p = 0.001). A synergistic effect between complete surgical cytoreduction and high levels of ieTILs was evidenced, both in terms of OS (p = 0.0005) and PFI (p = 0.0008). We consider that digital analysis with machine learning provided a more accurate TIL quantification in HGSOC. It has been demonstrated that ieTILs quantification in H&E-stained slides is an independent prognostic parameter. It is possible that intraepithelial TIL quantification could help identify candidate patients for immunotherapy.

Metastasis of Uveal Melanoma in Bladder: Presentation of Two Cases and Review of the Literature

Objective: Secondary urinary bladder tumors account for 2% of neoplasms in this location. Melanoma is the neoplasm that mostfrequently produces distant metastases in the bladder. Despite its low prevalence, it should be a possible diagnosis to considerfacing urological symptoms, due to the existence of targeted therapies. Method: We present two cases of uveal melanoma metastasis in the bladder, their characteristics, and a review of the literature. Result: In this paper we present the histological characteristics and complementary techniques for the diagnosis of bladder metastases of melanoma and propose their inclusion among the possible differential diagnoses for bladder neoplasms. Conclusions: Given that there are currently targeted therapies against melanoma, the relevance of their inclusion in the differential diagnosis of bladder tumors stands out. (AU)

Objetivo: La vejiga urinaria no es un órgano frecuente de metastasis a distancia. Sin embargo, se puedever afectada secundariamente en un 2% de todas las neoplasias. Dicha afectación se produce habitualmente por extensión local de otros tumores, aunque, ciertas neoplasias pueden producir metástasis a distancia en la vejiga, como es el caso del melanoma. A pesar de esta baja prevalencia, los antecedentes personales del paciente deben ser tenido sen cuenta en el diagnóstico de la neoplasia vesical. Método: Se presentan dos casos de metástasis de melanoma uveal en vejiga, sus características y una revisiónde la literatura.Resultado: En este trabajo se exponen las características histológicas y las técnicas complementarias para el diagnóstico de las metástasis de melanoma y se resalta su importancia en el diagnóstico de las neoplasias vesicales. Conclusiones: Dado que actualmente existen terapiasdirigidas frente al melanoma, se destaca la relevancia de suinclusión en el diagnóstico diferencial de los tumores de lavejiga. (AU)

Metanephric adenoma: molecular study and review of the literature.

INTRODUCTION: Metanephric adenoma (MA) is an uncommon benign tumor accounting for 0.2-0.7% of adult renal epithelial neoplasms. The clinical course is often indolent, but diagnosis should not be delayed since clinical symptoms (hematuria, fever, palpable abdominal mass, and flank pain) may be non-specific and overlap with those of a malign renal neoplasm. We report on 4 cases of AM, for which morphological and mutational analysis were performed. MATERIAL AND METHODS: Immunohistochemical staining was performed on sections cut from paraffin blocks to assess expression of WT1, vimentin, racemase, CK7, CD10 and RCC. Testing for the BRAF gene mutation V600 was carried out using real-time PCR (Cobas® 4800). RESULTS: In all four cases, tumors were visible as well-circumscribed, non-encapsulated masses located in the renal cortex and extending towards the medulla. At immunohistochemical examination, tumor cells stained negative for CK7, CD10 and RCC and positive for both WT1 (nuclear, intense) and vimentin (cytoplasmic, intense, and diffuse). Molecular analysis revealed the BRAF gene mutation V600E in three cases and wild-type BRAF in the fourth. CONCLUSIONS: BRAF molecular mutation analysis may aid diagnosis in cases with atypical histological features, especially in small incisional biopsies when reassessment of surgical treatment may be considered.

Metastasis of Uveal Melanoma in Bladder: Presentation of Two Cases and Review of the Literature.

OBJECTIVE: Secondary urinary bladder tumors account for 2% of neoplasms in this location. Melanoma is the neoplasm that most frequently produces distant metastases in the bladder. Despite its low prevalence, it should be a possible diagnosis to consider facing urological symptoms, due to the existence of targeted therapies. METHOD: We present two cases of uveal melanoma metastasis in the bladder, their characteristics, and a review of the literature. RESULT: In this paper we present the histological characteristics and complementary techniques for the diagnosis of bladder metastases of melanoma and propose their inclusion among the possible differential diagnoses for bladder neoplasms. CONCLUSIONS: Given that there are currently targeted therapies against melanoma, the relevance of their inclusion in the differential diagnosis of bladder tumors stands out.

Comprehensive NGS Panel Validation for the Identification of Actionable Alterations in Adult Solid Tumors.

The increasing identification of driver oncogenic alterations and progress of targeted therapies addresses the need of comprehensive alternatives to standard molecular methods. The translation into clinical practice of next-generation sequencing (NGS) panels is actually challenged by the compliance of high quality standards for clinical accreditation. Herein, we present the analytical and clinical feasibility study of a hybridization capture-based NGS panel (Action OncoKitDx) for the analysis of somatic mutations, copy number variants (CNVs), fusions, pharmacogenetic SNPs and Microsatellite Instability (MSI) determination in formalin-fixed paraffin-embedded (FFPE) tumor samples. A total of 64 samples were submitted to extensive analytical validation for the identification of previously known variants. An additional set of 166 tumor and patient-matched normal samples were sequenced to assess the clinical utility of the assay across different tumor types. The panel demonstrated good specificity, sensitivity, reproducibility, and repeatability for the identification of all biomarkers analyzed and the 5% limit of detection set was validated. Among the clinical cohorts, the assay revealed pathogenic genomic alterations in 97% of patient cases, and in 82.7%, at least one clinically relevant variant was detected. The validation of accuracy and robustness of this assay supports the Action OncoKitDx's utility in adult solid tumors.

Mitotic count: A need for standardization / Recuento mitótico: una necesidad de estandarización

PURPOSE: The mitotic count (MC), number of mitosis per unit area, is a very important parameter frequently used for classification and grading of some tumors. Traditionally, the MC has been expressed in terms of number of mitoses per high power field. The size of the field of view can vary greatly among different microscopes. In order to avoid under or overestimation of mitotic count, a conversion needs to be made. METHODS: A simple formula based on a simple rule of three has been devised to standardize the mitotic count to the reference area by multiplying the number of mitotic figures by a correction factor which has been calculated for the most frequently used microscopes and various common tumors. RESULTS AND CONCLUSIONS: We propose this simple method, which involves only a single multiplication, to standardize the mitotic count to the reference area

OBJETIVO: El recuento mitótico o número de mitosis por unidad de área, es un parámetro muy importante utilizado frecuentemente para clasificar y estadificar ciertos tumores. Tradicionalmente se ha expresado el recuento mitótico en términos de número de mitosis por campos de alta frecuencia. El tamaño del campo de visión puede variar ampliamente entre los diferentes microscopios. A fin de evitar la infraestimación o sobreestimación del recuento mitótico, debe realizarse una conversión. MÉTODOS: Por medio de una simple regla de tres, se ha obtenido una fórmula simple para estandarizar el recuento mitótico. Multiplicando el número de mitosis por un factor de corrección, se obtiene el recuento mitótico estandarizado al área de referencia. Se han calculado los factores de corrección para los microscopios más habituales y para los diferentes tumores comunes. RESULTADOS Y CONCLUSIONES: Proponemos este método simple (únicamente uno por multiplicación) para estandarizar el recuento mitótico con respecto al área de referencia

Mitotic count: A need for standardization.

PURPOSE: The mitotic count (MC), number of mitosis per unit area, is a very important parameter frequently used for classification and grading of some tumors. Traditionally, the MC has been expressed in terms of number of mitoses per high power field. The size of the field of view can vary greatly among different microscopes. In order to avoid under or overestimation of mitotic count, a conversion needs to be made. METHODS: A simple formula based on a simple rule of three has been devised to standardize the mitotic count to the reference area by multiplying the number of mitotic figures by a correction factor which has been calculated for the most frequently used microscopes and various common tumors. RESULTS AND CONCLUSIONS: We propose this simple method, which involves only a single multiplication, to standardize the mitotic count to the reference area.

Tumor de células gigantes primario de pulmón / Primary Pulmonary Giant Cell Tumor

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Mature Cystic Teratoma of the Lung With a Somatic-Like Malignant Component in a Patient With Testicular Germ-Cell Tumor / Teratoma quístico maduro de pulmón con componente maligno de tipo somático en un paciente con un tumor testicular de células germinales

No disponible

[Nested variant Transitional Cell Carcinoma. Report of two cases and bibliographic review.] / El carcinoma urotelial variante en nidos(NESTED). Presentación de dos casos y revisión de la literatura.

OBJECTIVE: Nested type transitional cell carcinoma of the bladder is a rare histological variant among bladder tumors. Although clinical presentation is similar to the other bladder tumors, its macroscopic appearance may be equivocally benign, with submucosal growing which is difficult to detect on cystoscopy, so that diagnosis may be delayed. METHODS: We present the characteristics of nested type transitional cell carcinoma and review the differential diagnosis for this entity with possible counterfeiters. RESULTS: In this article, we report two cases of nested type transitional cell carcinoma that presents, in one of them, all three growing patterns. CONCLUSIONS: Microscopically nested transitional cell carcinoma is characterized by a cell distribution forming nests and tubules. They generally present low cytologic atypia simulating a low grade urothelial carcinoma, or benign bladder lesions such as von Brunn nests or nefrogenic adenoma.

El carcinoma urotelial variante en nidos (NESTED). Presentación de dos casos y revisión de la literatura / Nested variant Transitional Cell Carcinoma. Report of two cases and bibliographic review

OBJETIVO: El carcinoma urotelial de vejiga tipo "nested" o en nidos es una variante histológica rara dentro de los tumores uroteliales de vejiga. Aunque las manifestaciones clínicas son semejantes a los demás tumores de vejiga, su apariencia macroscópica puede ser equívocamente benigna, con crecimiento submucoso difícil de detectar en la cistoscopia, lo que puede retrasar el diagnóstico. MÉTODO: presentamos las características del carcinoma urotelial variante tipo nested y revisamos los diagnósticos diferenciales de esta entidad con sus posibles imitadores. RESULTADO: En este trabajo presentamos dos casos de carcinoma urotelial tipo nested que presentan, en uno de los casos, los tres patrones de crecimiento. CONCLUSIONES: Microscópicamente el carcinoma urotelial nested se caracteriza por la distribución celular en forma de nidos y túbulos. Generalmente presentan poca atipia citológica que simula un carcinoma urotelial de bajo grado, o lesiones vesicales benignas como los nidos de von Brunn o los adenomas nefrogénicos

OBJECTIVE: Nested type transitional cell carcinoma of the bladder is a rare histological variant among bladder tumors. Although clinical presentation is similar to the other bladder tumors, its macroscopic appearance may be equivocally benign, with submucosal growing which is difficult to detect on cystoscopy, so that diagnosis may be delayed. METHODS: We present the characteristics of nested type transitional cell carcinoma and review the differential diagnosis for this entity with possible counterfeiters. RESULTS: In this article, we report two cases of nested type transitional cell carcinoma that presents, in one of them, all three growing patterns. CONCLUSIONS: Microscopically nested transitional cell carcinoma is characterized by a cell distribution forming nests and tubules. They generally present low cytologic atypia simulating a low grade urothelial carcinoma, or benign bladder lesions such as von Brunn nests or nefrogenic adenoma

Tumor ovárico del seno endodérmico (Yolk Sac). Dolor abdominal en el puerperio inmediato como síntoma diagnóstico / Endodermal sinus ovarian tumor (Yolk Sac). Abdominal pain in the immediate puerperium as a diagnostic symptom

RESUMEN Los tumores del seno endodérmico ovárico (Yolk Sac), son neoplasias malignas de origen germinal, que se caracterizan por su diferenciación embriológica a partir de estructuras del saco vitelino. Son tumoraciones muy infrecuentes, de crecimiento rápido y que suelen desarrollarse en adolescentes y mujeres jóvenes, en edad reproductiva. Su diagnóstico se basa en la combinación de pruebas de imagen asociado a niveles plasmáticos elevados de marcadores tumorales como la alfafetoproteína. El manejo terapéutico es eminentemente quirúrgico (pudiendo ser conservador en pacientes con deseo genésico no cumplido), asociado a pautas de quimioterapia sistémica combinada con bleomicina, etopósido y platino. Exponemos el caso de una paciente que en el puerperio tardío, presenta un cuadro clínico de dolor, distensión abdominal y fiebre, siendo diagnosticada tras el tratamiento quirúrgico y el estudio histológico posterior, de un tumor del seno endodérmico ovárico.

ABSTRACT Ovarian endodermal sinus tumors (Yolk Sac), are malignant neoplasms of germinal origin, which are characterized by their embryological differentiation from yolk sac structures. These tumors are very infrequent, of rapid growth and tend to develop in adolescents and young women of reproductive age. Its diagnosis is based on the combination of imaging tests associated with high plasma levels of tumor markers such as alpha-fetoprotein. The therapeutic management is eminently surgical (with a more conservative approach reserved for patients still considering later pregnancy), associated with patterns of systemic chemotherapy combined with bleomycin, etoposide and platinum. We present the case of a patient who, in the late puerperium, presents symptoms of pain, abdominal distension and fever, being diagnosed after the surgical treatment and the subsequent histological study of a tumor of the endodermal ovarian sinus.

[Small cell bladder carcinoma in age extremes: Report of two cases.] / Carcinoma de célula pequeña de vejiga urinaria en edades extremas: presentación de dos casos.

OBJECTIVE: We report 2 cases of small cell neuroendocrine carcinomas (CCP) of the urinary bladder in patients aged 37 and 80 years. CCP is a malignancy with poor prognosis. We review the literature, under the current WHO classification (2016). METHODS: Paraffin blocks were cut for HE staining and immunohistochemistry to analyze the expression of neuroendocrine differentiation. RESULTS: The main diagnosis was based on histopathologic features, which revealed a diffuse growth pattern of small cells with scant cytoplasm and hyperchromatic nuclei. The result of the additional technical immunoreaction was positive for synaptophysin and CD56. CONCLUSIONS: Our cases have been reviewed with the literature to discuss the evolution and differential diagnosis of small cell carcinoma of the urinary bladder. This is a rare tumor with very aggressive behavior and its diagnosis lies in its morphology, and immunohistochemical profile.

Carcinoma de célula pequeña de vejiga urinaria en edades extremas: presentación de dos casos / Small cell bladder carcinoma in age extremes: Report of two cases

Objetivo: Exponemos 2 casos de carcinomas neuroendocrinos célula pequeña (CCP) de vejiga urinaria en pacientes de 37 y 80 años. CCP es una neoplasia maligna de pronóstico infausto y en este trabajo, realizamos una revisión de la literatura, bajo la clasificación actual de la OMS de 2016. Métodos: Se han realizado cortes de bloques de parafina para tinción con HE y para técnicas inmunohistoquímicas con el fin de analizar la expresión de diferenciación neuroendocrina. Resultados: El diagnóstico principal se basó en las características histopatológicas, observándose un patrón de crecimiento difuso de células pequeñas con escaso citoplasma y núcleo hipercromático. El resultado de las técnicas complementarias reveló inmunorreacción positiva para sinaptofisina y CD56. Conclusiones: Nuestros casos han sido revisados junto con la literatura para discutir la evolución y el diagnóstico diferencial del carcinoma de célula pequeña de vejiga urinaria. Este es un tumor poco frecuente, de comportamiento muy agresivo y su diagnóstico reside en su morfología y perfil inmunohistoquímico (AU)

Objective: We report 2 cases of small cell neuroendocrine carcinomas (CCP) of the urinary bladder in patients aged 37 and 80 years. CCP is a malignancy with poor prognosis. We review the literature, under the current WHO classification (2016). Méthods: Paraffin blocks were cut for HE staining and immunohistochemistry to analyze the expression of neuroendocrine differentiation. Results: The main diagnosis was based on histopathologic features, which revealed a diffuse growth pattern of small cells with scant cytoplasm and hyperchromatic nuclei. The result of the additional technical immunoreaction was positive for synaptophysin and CD56. Conclusions: Our cases have been reviewed with the literature to discuss the evolution and differential diagnosis of small cell carcinoma of the urinary bladder. This is a rare tumor with very aggressive behavior and its diagnosis lies in its morphology, and immunohistochemical profile (AU)