The Revolution of Immunotherapy in Gynecological Cancers: The Lazarus Effect in Endometrial Cancer.

Patients with solid tumors and mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H) are eligible for immunotherapy. Recently, different reports described patients with poor performance status (PS), unrelated to comorbidities, which showed a rapid improvement of their clinical conditions under immunotherapy, which evoked a Lazarus response. Very few data on the efficacy and safety of immunotherapy in patients with gynecological malignancies and poor PS are available.

Automated Analysis of Proliferating Cells Spatial Organisation Predicts Prognosis in Lung Neuroendocrine Neoplasms.

Lung neuroendocrine neoplasms (lung NENs) are categorised by morphology, defining a classification sometimes unable to reflect ultimate clinical outcome. Subjectivity and poor reproducibility characterise diagnosis and prognosis assessment of all NENs. Here, we propose a machine learning framework for tumour prognosis assessment based on a quantitative, automated and repeatable evaluation of the spatial distribution of cells immunohistochemically positive for the proliferation marker Ki-67, performed on the entire extent of high-resolution whole slide images.

Pathology of autoimmune hepatitis.

Autoimmune hepatitis (AIH) is a relatively rare non-resolving chronic liver disease, which mainly affects women. It is characterized by hypergammaglobulinemia, circulating autoantibodies, interface hepatitis on liver histology and a favourable response to immunosuppression. The putative mechanism for the development of autoimmune hepatitis is thought to be the interaction between genetic predisposition, environmental triggers and failure of the native immune system.

Detection of ERBB2 amplification in uterine serous carcinoma by next-generation sequencing: an approach highly concordant with standard assays.

Uterine serous carcinoma is an aggressive subtype of endometrial cancer that accounts for fewer than 10% of endometrial carcinomas but is responsible for about half of deaths. A subset of cases has HER2 overexpression secondary to ERBB2 gene amplification, and these patients may benefit from anti-HER2 therapies, such as trastuzumab. HER2 protein overexpression is currently assessed by immunohistochemistry (IHC) and ERBB2 gene amplification by fluorescence in situ hybridization (FISH).

DNA Methylation of Steroidogenic Enzymes in Benign Adrenocortical Tumors: New Insights in Aldosterone-Producing Adenomas.

Context: DNA methylation has been identified among putative regulatory mechanisms for CYP11B2 expression in primary aldosteronism.

Objective: The objective of this work is to investigate DNA methylation and expression of genes encoding steroidogenic enzymes in benign adrenocortical tumors.

Design And Setting: This cross-sectional study took place at university hospitals.

A Risk Score Based on 5 Clinico-Pathological Variables Predicts Recurrence of Atypical Meningiomas.

The use of adjuvant radiotherapy is controversial in patients with atypical meningiomas treated with gross total resection (GTR). This study aimed to determine whether clinico-pathological features could be helpful to predict the recurrence risk in this group of patients and to identify high-risk ones who could benefit from adjuvant treatment. We collected 200 patients with primary atypical meningiomas treated with GTR but with no adjuvant radiotherapy from 5 different centers.

Tumor budding is an adverse prognostic marker in intestinal-type sinonasal adenocarcinoma and seems to be unrelated to epithelial-mesenchymal transition.

Intestinal-type adenocarcinoma (ITAC) of sinonasal tract is a rare malignant tumor with strong morphological, immunophenotypical, and molecular similarities to colorectal adenocarcinoma (CRC). Tumor budding (TB) is a well-established adverse prognostic marker in CRC and some head and neck tumors, with features of epithelial-mesenchymal transition (EMT). The aim of this study was to assess TB in ITAC and to evaluate its possible association with EMT markers in this setting.

RAS, Cellular Plasticity, and Tumor Budding in Colorectal Cancer.

The high morbidity and mortality of colorectal cancer (CRC) remain a worldwide challenge, despite the advances in prevention, diagnosis, and treatment. RAS alterations have a central role in the pathogenesis of CRC universally recognized both in the canonical mutation-based classification and in the recent transcriptome-based classification. About 40% of CRCs are mutated, 5% mutated, and only rare cases are mutated.

Sudden death with massive hemoptysis from aortobronchial fistula.

Aortobronchial fistula is an uncommon clinical entity, with unpredictable clinical course and significant mortality. Here, we describe a case of fistulous tract between a descending aortic graft and a branch of the left upper lobar bronchus leading to massive hemoptysis causing death for hemorrhagic shock in a 72-year-old man.

Loss of BAP1 in Pheochromocytomas and Paragangliomas Seems Unrelated to Genetic Mutations.

Breast cancer-associated protein 1 (BAP1) gene is a broad-spectrum tumor suppressor. Indeed, its loss of expression, due to biallelic inactivating mutations or deletions, has been described in several types of tumors including melanoma, malignant mesothelioma, renal cell carcinoma, and others. There are so far only two reports of BAP1-mutated paraganglioma, suggesting the possible involvement of this gene in paraganglioma (PGL) and pheochromocytoma (PCC) pathogenesis.

HER2 status in sinonasal intestinal-type adenocarcinoma.

Given that the prognosis of patients with sinonasal intestinal-type adenocarcinoma (ITAC) has not significantly changed recently, there is a desire for new therapeutic approaches to improve clinical management. HER2-targeted therapy has remarkably improved the overall survival of patients with HER2 amplified tumors. To date, HER2 assessment has produced contradictory results in ITAC.

Prognostic role of BAP-1 and PBRM-1 expression in intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) has universally poor outcome, mainly due to its late clinical presentation. Identification of specific biomarkers and development of effective treatment are still urgently required. Mutations in PBRM-1 and BAP-1 genes, and the expression of S100P have been related to survival in ICC.

Paradoxical GH Increase During OGTT Is Associated With First-Generation Somatostatin Analog Responsiveness in Acromegaly.

Context: The oral glucose tolerance test (OGTT) is considered the most useful method for diagnosing active acromegaly and for patient follow-up after neurosurgery. Despite its widespread use, only a few small studies have so far focused on patients' clinical features associated with different GH responsiveness to OGTT.

Objective: We aimed to investigate the association between glucose-induced GH response and endocrine profiles, clinical manifestations, and response to therapy in a large cohort of patients with acromegaly.

Histological criteria for age determination of fatal venous thromboembolism.

In clinical and forensic practice, fatal thromboembolism is a major problem, particularly in a patient with no pre-existing risk factors. Out of a recent case, we discuss here the criteria for age determination of venous thrombi in a 46-year-old female with concomitant deep vein thrombosis in the common femoral left vein and in the right heart and fatal pulmonary embolism. At autopsy, histopathology and immunohistochemistry evidenced the different composition of thrombi in different sites and permitted to define the different timing.

Histopathological and genetic characterization of aldosterone-producing adenomas with concurrent subclinical cortisol hypersecretion: a case series.

Purpose: Aldosterone-producing adenomas with concurrent subclinical cortisol hypersecretion are reported in an increasing number of patients. Five aldosterone-producing adenomas from patients with primary aldosteronism and subclinical hypercortisolism were examined.

The Aims Of Our Study Were: (1) to analyze pathological features and immunohistochemical expression of CYP11B1 (11β-hydroxylase) and CYP11B2 (aldosterone synthase) in these tumors; (2) to investigate somatic mutations involved in adrenal steroid hypersecretion and/or tumor growth.

Validation of the prognostic role of the "Helsinki Score" in 225 cases of adrenocortical carcinoma.

Adrenocortical carcinoma patient prognosis is extremely variable and poorly predictable. The newly introduced Helsinki Score is the first so far proposed diagnostic and prognostic system based on the combined evaluation of morphological (mitoses and necrosis) and immunohistochemical (Ki-67) parameters. The aim of the study was to validate the prognostic role of the Helsinki Score for adrenocortical carcinoma characterization.