Mammographic calcifications undergoing percutaneous biopsy: outcome in women with and without a personal history of breast cancer.

PURPOSE: To compare the positive predictive values (PPVs) of BI-RADS categories used to assess pure mammographic calcifications in women with and without a previous history of breast cancer (PHBC). MATERIALS AND METHODS: In this retrospective study, all consecutive pure mammographic calcifications (n = 320) undergoing a stereotactic biopsy between 2016 and 2018 were identified. Mammograms were evaluated in consensus by two radiologists according to BI-RADS and blinded to patient history and pathology results. Final pathologic results were used as the standard of reference. PPV of BI-RADS categories were compared between the two groups. Data were evaluated using standard statistics, Mann-Whitney U tests and Chi-square tests. RESULTS: Two hundred sixty-eight patients (274 lesions, median age 54 years, inter-quartile range, 50-65 years) with a PHBC (n = 46) and without a PHBC (n = 222) were included. Overall PPVs were the following: BI-RADS 2, 0% (0 of 56); BI-RADS 3, 9.1% (1 of 11); BI-RADS 4a, 16.2% (6 of 37); BI-RADS 4b, 37.5% (48 of 128); BI-RADS 4c, 47.3% (18 of 38) and BI-RADS 5, 100% (4 of 4). The PPV of BI-RADS categories was similar in patients with and without a PHBC (P = .715). Calcifications were more often malignant in patients with a PHBC older than 10 years (47.3%, 9 of 19) compared to 1-2 years (25%, 1 of 4), 2-5 years (20%, 2 of 10) and 5-10 years (0%, of 13) from the first breast cancer (P = .005). CONCLUSION: PPV of mammographic calcifications is similar in women with or without PHBC when BI-RADS classification is strictly applied. A higher risk of malignancy was observed in patients with a PHBC longer than 10 years.

Artificial Intelligence in Toxicological Pathology: Quantitative Evaluation of Compound-Induced Follicular Cell Hypertrophy in Rat Thyroid Gland Using Deep Learning Models.

Digital pathology has recently been more broadly deployed, fueling artificial intelligence (AI) application development and more systematic use of image analysis. Here, two different AI models were developed to evaluate follicular cell hypertrophy in hematoxylin and eosin-stained whole-slide-images of rat thyroid gland, using commercial AI-based-software. In the first, mean cytoplasmic area measuring approach (MCA approach), mean cytoplasmic area was calculated via several sequential deep learning (DL)-based algorithms including segmentation in microanatomical structures (separation of colloid and stroma from thyroid follicular epithelium), nuclear detection, and area measurements. With our additional second, hypertrophy area fraction predicting approach (HAF approach), we present for the first time DL-based direct detection of the histopathological change follicular cell hypertrophy in the thyroid gland with similar results. For multiple studies, increased output parameters (mean cytoplasmic area and hypertrophic area fraction) were shown in groups given different hypertrophy-inducing reference compounds in comparison to control groups. Quantitative results correlated with the gold standard of board-certified veterinary pathologists' diagnoses and gradings as well as thyroid hormone dependent gene expressions. Accuracy and repeatability of diagnoses and grading by pathologists are expected to be improved by additional evaluation of mean cytoplasmic area or direct detection of hypertrophy, combined with standard histopathological observations.

A pathogenic HEXA missense variant in wild boars with Tay-Sachs disease.

Gangliosidoses are inherited lysosomal storage disorders caused by reduced or absent activity of either a lysosomal enzyme involved in ganglioside catabolism, or an activator protein required for the proper activity of a ganglioside hydrolase, which results in the intra-lysosomal accumulation of undegraded metabolites. We hereby describe morphological, ultrastructural, biochemical and genetic features of GM2 gangliosidosis in three captive bred wild boar littermates. The piglets were kept in a partially-free range farm and presented progressive neurological signs, starting at 6 months of age. Animals were euthanized at approximately one year of age due to their poor conditions. Neuropathogens were excluded as a possible cause of the signs. Gross examination showed a reduction of cerebral and cerebellar consistency. Central (CNS) and peripheral (PNS) nervous system neurons were enlarged and foamy, with severe and diffuse cytoplasmic vacuolization. Transmission electron microscopy (TEM) of CNS neurons demonstrated numerous lysosomes, filled by parallel or concentric layers of membranous electron-dense material, defined as membranous cytoplasmic bodies (MCB). Biochemical composition of gangliosides analysis from CNS revealed accumulation of GM2 ganglioside; furthermore, Hex A enzyme activity was less than 1% compared to control animals. These data confirmed the diagnosis of GM2 gangliosidosis. Genetic analysis identified, at a homozygous level, the presence of a missense nucleotide variant c.1495C > T (p Arg499Cys) in the hexosaminidase subunit alpha gene (HEXA), located within the GH20 hexosaminidase superfamily domain of the encoded protein. This specific HEXA variant is known to be pathogenic and associated with Tay-Sachs disease in humans, but has never been identified in other animal species. This is the first report of a HEXA gene associated Tay-Sachs disease in wild boars and provides a comprehensive description of a novel spontaneous animal model for this lysosomal storage disease.

Artificial Intelligence in Toxicologic Pathology: Quantitative Evaluation of Compound-Induced Hepatocellular Hypertrophy in Rats.

Digital pathology evolved rapidly, enabling more systematic usage of image analysis and development of artificial intelligence (AI) applications. Here, combined AI models were developed to evaluate hepatocellular hypertrophy in rat liver, using commercial AI-based software on hematoxylin and eosin-stained whole slide images. In a first approach, deep learning-based identification of critical tissue zones (centrilobular, midzonal, and periportal) enabled evaluation of region-specific cell size. Mean cytoplasmic area of hepatocytes was calculated via several sequential algorithms including segmentation in microanatomical structures (separation of sinusoids and vessels from hepatocytes), nuclear detection, and area measurements. An increase in mean cytoplasmic area could be shown in groups given phenobarbital, known to induce hepatocellular hypertrophy when compared to control groups, in multiple studies. Quantitative results correlated with the gold standard: observation and grading performed by board-certified veterinary pathologists, liver weights, and gene expression. Furthermore, as a second approach, we introduce for the first time deep learning-based direct detection of hepatocellular hypertrophy with similar results. Cell hypertrophy is challenging to pick up, particularly in milder cases. Additional evaluation of mean cytoplasmic area or direct detection of hypertrophy, combined with histopathological observations and liver weights, is expected to increase accuracy and repeatability of diagnoses and grading by pathologists.

Quantification of Lung Fibrosis in IPF-Like Mouse Model and Pharmacological Response to Treatment by Micro-Computed Tomography.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive degenerative lung disease leading to respiratory failure and death. Although anti-fibrotic drugs are now available for treating IPF, their clinical efficacy is limited and lung transplantation remains the only modality to prolong survival of IPF patients. Despite its limitations, the bleomycin (BLM) animal model remains the best characterized experimental tool for studying disease pathogenesis and assessing efficacy of novel potential drugs. In the present study, the effects of oropharyngeal (OA) and intratracheal (IT) administration of BLM were compared in C57BL/6 mice. The development of lung fibrosis was followed in vivo for 28 days after BLM administration by micro-computed tomography and ex vivo by histological analyses (bronchoalveolar lavage, histology in the left lung to stage fibrosis severity and hydroxyproline determination in the right lung). In a separate study, the antifibrotic effect of Nintedanib was investigated after oral administration (60 mg/kg for two weeks) in the OA BLM model. Lung fibrosis severity and duration after BLM OA and IT administration was comparable. However, a more homogeneous distribution of fibrotic lesions among lung lobes was apparent after OA administration. Quantification of fibrosis by micro-CT based on % of poorly aerated tissue revealed that this readout correlated significantly with the standard histological methods in the OA model. These findings were further confirmed in a second study in the OA model, evaluating Nintedanib anti-fibrotic effects. Indeed, compared to the BLM group, Nintedanib inhibited significantly the increase in % of poorly aerated areas (26%) and reduced ex vivo histological lesions and hydroxyproline levels by 49 and 41%, respectively. This study indicated that micro-computed tomography is a valuable in vivo technology for lung fibrosis quantification, which will be very helpful in the future to better evaluate new anti-fibrotic drug candidates.

Atypical ductal hyperplasia: breast DCE-MRI can be used to reduce unnecessary open surgical excision.

PURPOSE: To evaluate the diagnostic performance of dynamic contrast-enhanced (DCE)-MRI in predicting malignancy after percutaneous biopsy diagnosis of atypical ductal hyperplasia (ADH). METHODS AND MATERIALS: In this retrospective study, 68 lesions (66 women) with percutaneous biopsy diagnosis of ADH and pre-operative breast DCE-MRI performed between January 2016 and December 2017 were included. Two radiologists reviewed in consensus mammography, ultrasound, and MR images. The final diagnosis after surgical excision was used as standard of reference. Clinical and imaging features were compared in patients with and without upgrade to malignancy after surgery. The diagnostic performance of DCE-MRI in predicting malignant upgrade was evaluated. RESULTS: A 9-gauge vacuum-assisted biopsy was performed in 40 (58.8%) cases and a 14-gauge core needle biopsy in 28 (41.2%) cases. Upgrade to malignancy was observed in 17/68 (25%) lesions, including 4/17 (23.5%) cases of invasive cancer and 13/17 (76.5%) cases of ductal carcinoma in situ (DCIS). In 16/17 (94.1%) malignant and 20/51 (39.2%) benign lesions, a suspicious enhancement could be recognized in DCE-MRI. The malignant lesion without suspicious enhancement was a low-grade DCIS (4 mm size). Sensitivity, specificity, positive predictive value, and negative predictive value of DCE-MRI on predicting malignancy were respectively 94.1%, 60.7%, 44.4%, and 96.8%. No other clinical or imaging features were significantly different in patients with and without upgrade to malignancy. CONCLUSION: After a percutaneous biopsy diagnosis of ADH, malignancy can be ruled out in most of the cases, if no suspicious enhancement is present in the biopsy area at DCE-MRI. Breast DCE-MRI may be used to avoid surgery in more than half of the patients with final benign diagnosis. KEY POINTS: • Breast DCE-MRI can safely rule out malignancy if no suspicious enhancement is present in the biopsy area after a percutaneous biopsy diagnosis of ADH. • All cases of upgrade to high-grade DCIS and invasive cancers can be identified at breast DCE-MRI after a percutaneous biopsy diagnosis of ADH. • Breast DCE-MRI may be used to avoid surgery in more than half of the patients with final benign diagnosis.

Phenotypic characterization of a highly pathogenic Italian porcine reproductive and respiratory syndrome virus (PRRSV) type 1 subtype 1 isolate in experimentally infected pigs.

Highly pathogenic (HP) isolates of the PRRS virus started emerging in North America and Asia in the late 1990s. More recently, they have emerged in Europe. These isolates are characterized by high viral loads, severe general clinical signs and high mortality, in sows, weaners and growers. Their genome shows a discontinuous aminoacids deletion in the non-structural protein 2 (NSP2). The present study was aimed at characterizing the clinical, pathological and immunological features of a highly pathogenetic, Italian PRRSV-1 subtype 1 isolate (PRRSV1_PR40/2014), following experimental infection in conventional 4-weeks-old pigs. The PRRSV1_PR40/2014 infected group showed severe clinical signs (high fever and dispnoea). Pathological lesions, including severe lymphocytopenia in bronchial lymph-nodes and thymus were also recorded. Higher serum PRRSV genome copies and lower virus neutralizing antibody titer were observed in the PR40 group, when compared to the group infected with a conventional PRRSV strain. The genetic analysis of the strain, and the phenotypic features observed in the field and reproduced in the experimental study, confirmed the high pathogenicity of the Italian PRRSV-1 subtype 1 PR40 isolate.

A Clinical Case of an SRY-Positive Intersex/Hermaphrodite Holstein Cattle.

A single-born, 15-month-old Holstein cattle, diagnosed as hermaphrodite, was investigated for estrous cycle, hormonal profiles, karyotype, presence of SRY, as well as anatomopathological and histological aspects. Normal continuous estrous cycles and basal testosterone levels were reported. Necropsy showed the presence of a female genital tract that mismatched a vulvar opening and a male pelvic urethra continued within a penis. Moreover, we observed islands of seminiferous tubules with the presence of germline cells, 2 pampiniform plexi, the corpus cavernosum, the penile urethra, the corpus spongiosum and the glans. Cytogenetic analyses of the blood cells showed an XX karyotype, while the molecular analyses revealed the presence of the SRY gene in several tissues, including blood. This is the first report in the scientific literature of an SRY-positive hermaphrodite Holstein cattle with continuous ovarian cycles.