Molecular and Pathological Features of Paediatric High-Grade Gliomas.

Paediatric high-grade gliomas are among the most common malignancies found in children. Despite morphological similarities to their adult counterparts, there are profound biological and molecular differences. Furthermore, and thanks to molecular biology, the diagnostic pathology of paediatric high-grade gliomas has experimented a dramatic shift towards molecular classification, with important prognostic implications, as is appropriately reflected in both the current WHO Classification of Tumours of the Central Nervous System and the WHO Classification of Paediatric Tumours. Emphasis is placed on histone 3, IDH1, and IDH2 alterations, and on Receptor of Tyrosine Kinase fusions. In this review we present the current diagnostic categories from the diagnostic pathology perspective including molecular features.

Cytological features of diffuse and circumscribed gliomas.

The current World Health Organization classification of gliomas is based on morphological, genetic, and molecular parameters. In this review, we intend to present the most relevant cytological features of these tumours, with a particular focus on their analysis during intraoperative studies. Rapid diagnosis is required in this context, and at present it is not possible to evaluate the genetic or molecular profile of a tumour intraoperatively. New terminology and diagnostic parameters have been introduced, but the essence of intraoperative recognition remains the same. The main challenge in astrocytoma IDH-mutant, grade 2 is recognising the tissue as neoplastic. Since glioma grades 3 and 4 are assigned based on histological and genetic variables that are not necessarily measurable on cytology, the term high-grade glioma is often used for intraoperative diagnosis. Oligodendroglioma, IDH-mutant and 1p/19q-codeleted shows peculiar cytological findings as well as the common subtypes of glioblastoma IDH-wildtype (giant cell, epithelioid, gliosarcoma and small cell). Many of the paediatric-type-diffuse gliomas have been described very recently and there are no cytological reports of proven cases. Finally, pilocytic astrocytoma, pleomorphic xanthoastrocytoma, subependymal giant cell astrocytoma, chordoid glioma, and astroblastoma MN1-altered constitute the group of circumscribed astrocytic gliomas. They are remarkable entities that the pathologist must be able to recognise since most are low-grade neoplasms that can show atypical morphological features.

A tree-based machine learning model to approach morphologic assessment of malignant salivary gland tumors.

Malignant salivary gland tumors represent a challenge for pathologists due to their low frequency and morphologic overlap. In recent years machine learning techniques have been applied to the field of pathology to improve diagnostic performance. In the present work, we fitted a machine learning algorithm to approach the diagnosis of malignant salivary gland tumors. Twelve morphologic variables were scored across 115 samples representing the most commonly encountered malignant salivary gland tumors. The sample was randomly split into a discovery and validation set. A recursive partitioning algorithm was used to systematically screen and organize candidate variables into a classification tree using the discovery set. A cross-validation strategy was used to tune the algorithm hyperparameters. Inter-observer concordance was calculated by independent evaluation of 26 randomly selected cases. The five-tiered tree built, required the evaluation of 6 morphological variables. Basaloid appearance, presence of mucous cells, necrosis, cribriform pattern, clear cells and keratinization were selected by the algorithm to build the tree. This diagnostic tool correctly classified 89.9% and 84.6% of the samples in the discovery and validation sets respectively. Misclassification pattern was consistent between both sets. Misclassified tumors belonged to one of three histologic types: epithelial-myoepithelial, polymorphous and mucoepidermoid carcinomas. Other histotypes demonstrated perfect recall in both the discovery and validation sets. Overall inter-observer concordance was good, with median kappa scores between the expert evaluator and training pathologists being 0.81. Overall, our classification tool developed using a recursive partitioning algorithm can effectively guide the morphological approach to malignant salivary gland tumors.

Maternal and perinatal outcomes and placental pathologic examination of 29 SARS-CoV-2 infected patients in the third trimester of gestation.

AIM: On December 31, 2019, an unknown outbreak of pulmonary disease was reported in China. The novel coronavirus SARS-CoV-2 was the etiologic agent of this disease, and responsible of the current pandemic of COVID-19. Accumulated evidence on placental features is based most on case-reports and small case-series, with differing results. METHODS: We gathered a cohort of 29 infected pregnant mothers who delivered 32 newborns, and had placentas available for pathologic examination. Placentas were compared with a control group. RESULTS: Of the 29 mothers, clinical and radiological features were similar to what was already described in COVID-19. Pregnancy modified some analytical parameters. One of the mothers succumbed to the disease. Of the 32 newborns, 1 developed an early infection, with positive reverse-transcriptase polymerase chain reaction (RT-PCR) at 48 h of life, with an initial RT-PCR negative. SARS-CoV-2 presence was assessed on placental tissue with immunohistochemistry and RT-PCR, both were negative. All newborns had good clinical outcomes. No differences in morphological placental findings were found among both groups. CONCLUSION: Lack of statistically significant differences among case and control groups suggest that placentas from SARS-CoV-2 infected mothers represent a cohort of normal placentas only submitted because of maternal SARS-CoV-2 status. To the best of our knowledge, no irrefutable cases of vertical transmission have been yet described. Other authors have failed to demonstrate presence of viral RNA in placental tissue. Accumulated knowledge suggests that if vertical transmission is possible, it is a rare event.

Diagnostic role of DOG-1, GFAP and B-catenin in Basal cell Adenoma and Cellular Pleomorphic Adenoma of the Salivary Gland.

BACKGROUND: Pleomorphic Adenoma (PA) and Basal cell adenoma (BCA) are benign salivary gland tumors that may pose a diagnostic challenge if typical features are not present. Due to the increased relapse and malignant transformation rate of the former, a correct diagnosis carries relevant prognostic information. Even though immunohistochemistry (IHC) plays a limited role in the diagnosis of these tumors, the use of IHC panels could increase diagnostic accuracy. In the present work, we aimed to demonstrate that the use of an IHC panel consisting of Glial Fibrillary Acid Protein (GFAP), B-Catenin and Discovered On GIST 1 (DOG-1) can aid in the differential diagnosis between PA and BCA. METHODS: We analyzed 18 cases of benign salivary gland tumors (Pleomorphic adenomas and Basal cell adenomas) with overlapping histologic features. First, a head and neck pathologist diagnosed the cases relying on morphology alone. Afterwards, cases were re-evaluated considering the IHC panel results. Inter-observer IHC scoring concordance was evaluated with pre-defined marker cut-off points using Cohen's Kappa scores. RESULTS: Based on morphology alone, 9 cases were classified as PA while the remaining tumors were considered to be BCA. Five out of nine BCA cases showed GFAP staining and absent nuclear B-catenin and DOG-1 positivity. Conversely, 2 PA cases showed absent GFAP and positive nuclear B-catenin with concurrent DOG-1 expression. Therefore, after IHC evaluation, up to 40% of morphologic diagnoses were reconsidered. Overall, the inter-observer concordance for IHC evaluation was good (resulting Kappa Scores between 0.78 and 1). CONCLUSION: Our work supports the use of a concise IHC panel to improve the diagnostic accuracy of benign salivary gland tumors with overlapping histologic features.