Machine learning methods for automated classification of tumors with papillary thyroid carcinoma-like nuclei : A quantitative analysis

When approaching thyroid gland tumor classification, the differentiation between samples with and without “papillary thyroid carcinoma-like” nuclei is a daunting task with high inter-observer variability among pathologists. Thus, there is increasing interest in the use of machine learning approaches to provide pathologists real-time decision support. In this paper, we optimize and quantitatively compare two automated machine learning methods for thyroid gland tumor classification on two datasets to assist pathologists in decision-making regarding these methods and their parameters. The first method is a feature-based classification originating from common image processing and consists of cell nucleus segmentation, feature extraction, and subsequent thyroid gland tumor classification utilizing different classifiers. The second method is a deep learning-based classification which directly classifies the input images with a convolutional neural network without the need for cell nucleus segmentation. On the Tharun and Thompson dataset, the feature-based classification achieves an accuracy of 89.7% (Cohen’s Kappa 0.79), compared to the deep learning-based classification of 89.1% (Cohen’s Kappa 0.78). On the Nikiforov dataset, the feature-based classification achieves an accuracy of 83.5% (Cohen’s Kappa 0.46) compared to the deep learning-based classification 77.4% (Cohen’s Kappa 0.35). Thus, both automated thyroid tumor classification methods can reach the classification level of an expert pathologist. To our knowledge, this is the first study comparing feature-based and deep learning-based classification regarding their ability to classify samples with and without papillary thyroid carcinoma-like nuclei on two large-scale datasets

Histone 3.3 hotspot mutations in conventional osteosarcomas: a comprehensive clinical and molecular characterization of six H3F3A mutated cases

Background: Histone 3.3 (H3.3) hotspot mutations in bone tumors occur in the vast majority of giant cell tumors of bone (GCTBs; 96%), chondroblastomas (95%) and in a few cases of osteosarcomas. However, clinical presentation, histopathological features, and additional molecular characteristics of H3.3 mutant osteosarcomas are largely unknown. Methods: In this multicentre, retrospective study, a total of 106 conventional high-grade osteosarcomas, across all age groups were re-examined for hotspot mutations in the H3.3 coding genes H3F3A and H3F3B. H3.3 mutant osteosarcomas were re-evaluated in a multidisciplinary manner and analyzed for genome-wide DNA-methylation patterns and DNA copy number aberrations alongside H3.3 wild-type osteosarcomas and H3F3A G34W/L mutant GCTBs. Results: Six osteosarcomas (6/106) carried H3F3A hotspot mutations. No mutations were found in H3F3B. All patients with H3F3A mutant osteosarcoma were older than 30 years with a median age of 65 years. Copy number aberrations that are commonly encountered in high-grade osteosarcomas also occurred in H3F3A mutant osteosarcomas. Unlike a single osteosarcoma with a H3F3A K27M mutation, the DNA methylation profiles of H3F3A G34W/R mutant osteosarcomas were clearly different from H3.3 wild-type osteosarcomas, but more closely related to GCTBs. The most differentially methylated promoters between H3F3A G34W/R mutant and H3.3 wild-type osteosarcomas were in KLLN/PTEN (p < 0.00005) and HIST1H2BB (p < 0.0005). Conclusions: H3.3 mutations in osteosarcomas may occur in H3F3A at mutational hotspots. They are overall rare, but become more frequent in osteosarcoma patients older than 30 years. Osteosarcomas carrying H3F3A G34W/R mutations are associated with epigenetic dysregulation of KLLN/PTEN and HIST1H2BB

Expression of S-locus inhibitor gene (Sli) in various diploid potatoes

Current guidelines recommend immunosuppressive treatment (IT) in patients with primary sclerosing cholangitis (PSC) and elevated aminotransferase levels more than five times the upper limit of normal and elevated serum IgG-levels above twice the upper limit of normal. Since there is no evidence to support this recommendation, we aimed to assess the criteria that guided clinicians in clinical practice to initiate IT in patients with previously diagnosed PSC.This is a retrospective analysis of 196 PSC patients from seven German hepatology centers, of whom 36 patients had received IT solely for their liver disease during the course of PSC. Analyses were carried out using methods for competing risks.A simplified autoimmune hepatitis (AIH) score >5 (HR of 36, p5 and a mHAI score >3, suggesting concomitant features of AIH, influenced the decision to introduce IT during the course of PSC. In German clinical practice, the cutoffs used to guide IT may be lower than recommended by current guidelines

Role of pathologists with respect to therapy decisions for gastric cancer

The role of pathologists in gastric cancer management is expanding to tumor subtyping analogous to recent genetic findings and the detection of biomarkers to reveal additional therapeutic options. The purpose of this article is to provide an overview of the current role of pathologists in gastric cancer and particularly with respect to guiding therapeutic decisions. This article is based on a selective literature review using PubMed database and World Health Organization (WHO) publications in particular on the clinically relevant problems in gastric cancer which pathologists are currently confronted with. New sequencing techniques recently allowed a molecular-based classification of gastric carcinoma. The results underline the overlap between morphologically and molecularly defined subtypes which can provide guidelines for biomarker exploration aimed at disclosing new therapeutic options

First case report of a curative wedge resection in epithelial-myoepithelial carcinoma of the lung

Epithelial-myoepithelial carcinoma is a well differentiated malignant neoplasm, which originates from the salivary glands. The primary pulmonary manifestation is rare-about 30 cases have been reported worldwide. In the literature, anatomical resection has been described as the standard surgical approach. In the presented case, a wedge resection was performed, with no evidence for tumor relapse in the follow-up reevaluation after 24 months. This is the first case report of a primary pulmonary epithelial-myoepithelial carcinoma that has been treated with a non-anatomical wedge resection and lymph node dissection as a curative approach

Prognostic impact of perineural, blood and lymph vessel invasion for esophageal cancer

Background: With a median survival of <22 months esophageal cancer is one of the most aggressive tumors, up to 20% of node negative patients develop systemic relapse. Studies investigating the prognostic impact of tumor-micro-invasion in blood (AI) and lymphatic vessels (LVI) as well as perineural invasion (PNI) have shown inconsistent results. The aim of the present study was to investigate the prognostic value of the aforementioned factors in a large homogenously treated cohort of patients with esophageal cancer. Methods: Data from 695 patients with surgically treated esophageal cancer were analyzed. AI, LVI and PNI were determined and data were statistically correlated with clinico-pathological parameters and survival of the patients. Results: Thirteen percent of all specimens showed an AI, 35% a LVI and 5% a PNI. The invasion factors were mostly significantly correlated with the established prognostic parameter, including bone marrow micrometastases. Kaplan-Meier analysis revealed a prognostic impact for LVI in both cancer subtypes, while AI and PNI were significant factors in adenocarcinoma only. In multivariate analysis, none showed statistical significance. However, sub-analysis of completely resected, node negative and non-metastasized patients showed a significant prognostic impact of LVI. Conclusion: The prognostic significance of AI, LVI and PNI seems to be limited compared to the established prognostic parameters of the UICC staging system. In completely resected, node negative and nonmetastasized patients, LVI is an independent prognostic parameter for a worse outcome. Those patients might benfit from additional treatment or more intensive follow up

Lymphangioma of the fetal neck within the PIK3CA‐related‐overgrowth spectrum (PROS): A case report

Abstract The delineation of the prenatal diagnostic key features of PIK3CA‐related overgrowth spectrum disorders will assume a crucial part in future and a prenatal diagnosis of the causing mutations would provide physicians with a simplified interdisciplinary perinatal management