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.

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.

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.

[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.

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.

[Adenoma metanephric: Report of 2 cases and bibliographic review.] / Adenoma metanefrico: presentación de 2 casos y revisión de la literatura.

OBJECTIVE: Two cases of metanephric adenoma are presented, a rare benign renal tumor, and a literature review is done under the current WHO classification (2016). METHODS: Standard histopathological study was performed with hematoxylin-eosin and immunohistochemistry to analyze the expression of WT, Vimentin, Racemase, CK7, CD10 and RCC. RESULTS: Neoplasms of 3 and 4.5 cm, histologically, exhibiting tubulopapillary architecture. There was no evidence of significant nuclear atypia and mitotic figures. Immunohistochemical study showed positive immunoreaction for WT1 and Vimentin in tumor cells. CONCLUSIONS: Two new cases of metanephric adenoma are presented and a review of the literature was performed in order to discuss the prognosis and differential diagnosis of metanephric adenoma. This is a rare tumor and its diagnosis lies on its morphology and its immunohistochemical profile.

Expression of dog1 in low-grade fibromyxoid sarcoma: A study of 19 cases and review of the literature.

DOG1 is a highly-sensitive marker often included in the immunohistochemical panel for the diagnosis of gastrointestinal stromal tumors (GISTs). Recent research has shown that DOG1 may also be expressed by low-grade fibromyxoid sarcomas (LGFMSs); this may give rise to diagnostic error when the sarcoma is located in the abdominal cavity. This paper reports on immnohistochemical expression of DOG1 in 19 LGFMSs using two different monoclonal antibodies: K9 (Leica, Novocastra Laboratories, Newcastle upon Tyne, UK) and SP31 (Thermo Scientific, Freemont, USA). All LGFMSs displayed the standard histological pattern of alternating myxoid and fibrous areas, low cellularity and bland spindle-cell morphology. Positive staining for MUC4 was observed in 18/19 cases (94.7%), while there was rearrangement of the FUS gene in 14/19 (73.7%) cases and of the EWR1 gene in 2/19 (10.5%). The sarcoma staining negative for MUC4 displayed FUS gene rearrangement. Whole-section immunohistochemistry revealed positive staining for DOG1 in 8/19 cases (42.1%), though only with clone K9. Cytoplasmic as well as membrane staining was observed in all cases; staining was focal (10-30%) and of varying intensity (1+ to 2+). In conclusion, DOG1 clone K9 exhibited low sensitivity (42.1%) for the diagnosis of LGFMS, although higher than clone SP31. Since the two clones display similar sensitivity and specificity for GIST diagnosis, SP31 would appear to be more specific for this purpose, since no reaction was observed here with LGFMS, a GIST-mimicking lesion.

[Major complications of acquired renal cystic disease: Wünderlich syndrome and papilar carcinoma.] / Complicaciones de la enfermedad renal quística adquirida: síndrome de Wünderlich y carcinoma papilar.

OBJETIVE: We report a case of acquired renal cystic disease associated with renal dialysis and endstage renal disease. The patient suffered the two major complications related with acquired renal cystic disease; hemorrhage and renal carcinoma. METHODS: Our case is a patient with acquired renal cystic disease, single kidney after surgery for renal clear cell carcinoma four years earlier, who developed a Wünderlich syndrome (WS). RESULTS: The histological study of the nephrectomy specimen showed a renal papillary carcinoma in the context of acquired renal cystic disease after surgery for a WS. CONCLUSIONS: Renal hemorrhage is a serious complication that can lead to a fatal outcome. Patients undergoing dialysis should be monitored actively due to the risk of developing acquired renal cystic disease and associated complications.