Uterine diverticulum mimicking endometriotic cyst of the ovary.

Uterine diverticulum is a rare congenital malformation caused by abnormal fusion of the Müllerian ducts. The diagnosis of uterine diverticulum is difficult, and it is often misdiagnosed as a Müllerian duct anomaly, degenerated uterine fibroid, or ovarian cyst. We herein report a case of uterine diverticulum mimicking an ovarian endometriotic cyst. A multiparous woman with a history of normal vaginal delivery underwent magnetic resonance imaging for investigation of lower abdominal pain and fever. A 155-mm cystic lesion was observed on the ventral side of the uterus. The content of the cyst showed high signal intensity on T1- and T2-weighted images with precipitates of low signal intensity on the dorsal side, suggesting an endometriotic cyst of the ovary. Surgical and pathological findings revealed that the cyst was pedunculated from the anterior uterine body and composed of 3 layers: CD10-positive endometrium, a smooth muscle layer, and serosa. A uterine diverticulum was definitively diagnosed.

Standardized Classification of Lung Adenocarcinoma Subtypes and Improvement of Grading Assessment Through Deep Learning.

The histopathologic distinction of lung adenocarcinoma (LADC) subtypes is subject to high interobserver variability, which can compromise the optimal assessment of patient prognosis. Therefore, this study developed convolutional neural networks capable of distinguishing LADC subtypes and predicting disease-specific survival, according to the recently established LADC tumor grades. Consensus LADC histopathologic images were obtained from 17 expert pulmonary pathologists and one pathologist in training. Two deep learning models (AI-1 and AI-2) were trained to predict eight different LADC classes. Furthermore, the trained models were tested on an independent cohort of 133 patients. The models achieved high precision, recall, and F1 scores exceeding 0.90 for most of the LADC classes. Clear stratification of the three LADC grades was reached in predicting the disease-specific survival by the two models, with both Kaplan-Meier curves showing significance (P = 0.0017 and 0.0003). Moreover, both trained models showed high stability in the segmentation of each pair of predicted grades with low variation in the hazard ratio across 200 bootstrapped samples. These findings indicate that the trained convolutional neural networks improve the diagnostic accuracy of the pathologist and refine LADC grade assessment. Thus, the trained models are promising tools that may assist in the routine evaluation of LADC subtypes and grades in clinical practice.

Overcoming the Interobserver Variability in Lung Adenocarcinoma Subtyping: A Clustering Approach to Establish a Ground Truth for Downstream Applications.

CONTEXT.­: The accurate identification of different lung adenocarcinoma histologic subtypes is important for determining prognosis but can be challenging because of overlaps in the diagnostic features, leading to considerable interobserver variability. OBJECTIVE.­: To provide an overview of the diagnostic agreement for lung adenocarcinoma subtypes among pathologists and to create a ground truth using the clustering approach for downstream computational applications. DESIGN.­: Three sets of lung adenocarcinoma histologic images with different evaluation levels (small patches, areas with relatively uniform histology, and whole slide images) were reviewed by 17 international expert lung pathologists and 1 pathologist in training. Each image was classified into one or several lung adenocarcinoma subtypes. RESULTS.­: Among the 4702 patches of the first set, 1742 (37%) had an overall consensus among all pathologists. The overall Fleiss κ score for the agreement of all subtypes was 0.58. Using cluster analysis, pathologists were hierarchically grouped into 2 clusters, with κ scores of 0.588 and 0.563 in clusters 1 and 2, respectively. Similar results were obtained for the second and third sets, with fair-to-moderate agreements. Patches from the first 2 sets that obtained the consensus of the 18 pathologists were retrieved to form consensus patches and were regarded as the ground truth of lung adenocarcinoma subtypes. CONCLUSIONS.­: Our observations highlight discrepancies among experts when assessing lung adenocarcinoma subtypes. However, a subsequent number of consensus patches could be retrieved from each cluster, which can be used as ground truth for the downstream computational pathology applications, with minimal influence from interobserver variability.

A collaborative workflow between pathologists and deep learning for the evaluation of tumour cellularity in lung adenocarcinoma.

AIMS: The reporting of tumour cellularity in cancer samples has become a mandatory task for pathologists. However, the estimation of tumour cellularity is often inaccurate. Therefore, we propose a collaborative workflow between pathologists and artificial intelligence (AI) models to evaluate tumour cellularity in lung cancer samples and propose a protocol to apply it to routine practice. METHODS AND RESULTS: We developed a quantitative model of lung adenocarcinoma that was validated and tested on 50 cases, and a collaborative workflow where pathologists could access the AI results and adjust their original tumour cellularity scores (adjusted-score) that we tested on 151 cases. The adjusted-score was validated by comparing them with a ground truth established by manual annotation of haematoxylin and eosin slides with reference to immunostains with thyroid transcription factor-1 and napsin A. For training, validation, testing the AI and testing the collaborative workflow, we used 40, 10, 50 and 151 whole slide images of lung adenocarcinoma, respectively. The sensitivity and specificity of tumour segmentation were 97 and 87%, respectively, and the accuracy of nuclei recognition was 99%. One pathologist's visually estimated scores were compared to the adjusted-score, and the pathologist's scores were altered in 87% of cases. Comparison with the ground truth revealed that the adjusted-score was more precise than the pathologists' scores (P < 0.05). CONCLUSION: We proposed a collaborative workflow between AI and pathologists as a model to improve daily practice and enhance the prediction of tumour cellularity for genetic tests.

[A case of upper gastrointestinal bleeding due to a ruptured gastric aneurysm caused by arteriosclerosis derived from primary aldosteronism-induced hypertension].

A 77-year-old woman with a history of hypertension underwent upper gastrointestinal endoscopy for hematemesis, and vasodilation with erosion was detected. Contrast-enhanced computed tomography and abdominal angiography revealed a gastric aneurysm penetrating the stomach wall. Endoscopic hemostasis was thought to be not applicable to a ruptured aneurysm. Transcatheter arterial embolization was not performed because of technical difficulties. Therefore, local gastric resection was performed. It was later determined that the cause of the persistent hypertension was primary aldosteronism, which was thought to cause arteriosclerotic obstruction of the celiac, common hepatic, and splenic arteries, resulting in the formation of the gastric arterial aneurysm. In the case of upper gastrointestinal bleeding, keeping primary aldosteronism in mind as a differential diagnosis is important to make a precise diagnosis and suitable treatment selection.

[Ectopic Cervical Thymoma that was Difficult to Differentiate from Thyroid Tumor:Report of a Case].

We report a case of ectopic cervical thymoma that was difficult to differentiate from thyroid tumor. A 69-year-old woman was referred to our hospital with a tumor on the left side of the neck. Fine-needle aspiration cytology could not establish the diagnosis and the surgery was then performed for diagnosis and treatment. Since the intraoperative pathological diagnosis was also inconclusive, thymectomy was performed because of the macroscopic finding suggesting close relation to the thymus. The final pathological diagnosis was type AB thymoma.

Alveolar Epithelial Denudation Is a Major Factor in the Pathogenesis of Pleuroparenchymal Fibroelastosis.

The pathogenesis of pleuroparenchymal fibroelastosis (PPFE), a rare interstitial lung disease, remains unclear. Based on previous reports and our experience, we hypothesized that alveolar epithelial denudation (AED) was involved in the pathogenesis of PPFE. This multicenter retrospective study investigated the percentage of AED and the features of the denudated areas in 26 PPFE cases, 30 idiopathic pulmonary fibrosis (IPF) cases, and 29 controls. PPFE patients had lower forced vital capacities and higher residual volume/total lung capacities in pulmonary function tests compared to IPF and control patients. Histopathologically, subpleural fibroelastosis was observed in PPFE, and AED was observed in 12.01% of cases in the subpleural or interlobular septa regardless of fibroelastosis. The percentage of AED in the PPFE group was significantly higher than that in the IPF group (6.84%; p = 0.03) and the normal group (1.19%; p < 0.001). In the IPF group, the percentage of AED and the presence of PPFE-like lesions in the upper lobes were examined radiologically, but no correlation was found. We showed that AED frequently occurred in PPFE. AED was less frequent in IPF, which, in combination with imaging data, suggests that PPFE may have a different pathogenesis from IPF.

Impact of Mg level on lattice relaxation in a p-AlGaN hole source layer and attempting excimer laser annealing on p-AlGaN HSL of UVB emitters.

Mg-doped p-type semiconducting aluminium-gallium-nitride hole source layer (p-AlGaN HSL) materials are quite promising as a source of hole 'p' carriers for the ultraviolet-B (UVB) light-emitting diodes (LEDs) and laser diodes (LDs). However, the p-AlGaN HSL has a central issue of low hole injection due to poor activation of Mg atoms, and the presence of unwanted impurity contamination and the existence of a localized coherent state. Therefore, first the impact of the Mg level on the crystallinity, Al composition and relaxation conditions in the p-AlGaN HSL were studied. An increasing trend in the lattice-relaxation ratios with increasing Mg concentrations in the p-AlGaN HSL were observed. Ultimately, a 40%-60% relaxed and 1.4 µm thick p-AlGaN HSL structure with total threading dislocation densities (total-TDDs) of approximately ∼8-9 × 108 cm-2 was achieved, which almost matches our previous design of a 4 µm thick and 50% relaxed n-AlGaN electron source layer (ESL) with total-TDDs of approximately ∼7-8 × 108 cm-2. Subsequently, structurally a symmetric p-n junction for UVB emitters was accomplished. Finally, the influence of excimer laser annealing (ELA) on the activation of Mg concentration and on suppression of unwanted impurities as well as on the annihilation of the localized energy state in the p-AlGaN HSL were thoroughly investigated. ELA treatment suggested a reduced Ga-N bonding ratio and increased Ga-O, as well as Ga-Ga bonding ratios in the p-AlGaN HSL. After ELA treatment the localized coherent state was suppressed and, ultimately, the photoluminescence emission efficiency as well as conductivity were drastically improved in the p-AlGaN HSL. By using lightly polarized p-AlGaN HSL assisted by ELA treatment, quite low resistivity in p-type AlGaN HSL at room temperature (hole concentration is ∼2.6 × 1016 cm-3, the hole mobility is ∼9.6 cm2 V1 s-1 and the resistivity is ∼24.39 Ω. cm) were reported. ELA treatment has great potential for localized activation of p-AlGaN HSL as well as n- and p-electrodes on n-AlGaN and p-AlGaN contact layers during the flip-chip (FC) process in low operating UVB emitters, including UVB lasers.

[Experience with Pleural Metastasis from Hepatocellular Carcinoma;Report of a Case].

A 69-year-old man with a ruptured hepatocellular carcinoma(HC) was treated by hepatic transcatheter embolization (TAE) followed by upper segmentectomy of the liver. He developed postoperative intrahepatic recurrence and was treated with transcatheter arterial chemoembolization (TACE) at 6 months and 12 months postoperatively. Furthermore, chest computed tomography (CT) revealed a nodule suspected to be pleural metastasis 12 months postoperatively. Pathological assessment of a CT-guided biopsy of the nodule confirmed pleural metastasis of HC. Surgical resection of the metastatic tumor and adjuvant chemotherapy was performed. Despite developing lung metastasis, the patient has survived for more than 20 months. Early detection and treatment of pleural metastasis of HC might help to prolong survival.

Viral load and inflammatory cytokine dynamics associated with the prognosis of severe fever with thrombocytopenia syndrome virus infection: An autopsy case.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease caused by a novel bunyavirus. The mechanism underlying disease progression remains unknown, and effective treatment strategy for SFTS is yet to be completely established, making its increasing incidence and subsequent mortality a great concern. Here, we present the autopsy case of a patient with rapidly progressed, fatal SFTS infection. Her viral titer and serum cytokines levels were measured daily and compared with the values of a survivor of the infection. Our findings elucidate the clinical features and pathophysiology of SFTS.

Whole-slide imaging at primary pathological diagnosis: Validation of whole-slide imaging-based primary pathological diagnosis at twelve Japanese academic institutes.

Several reports have demonstrated the use of whole-slide imaging (WSI) for primary pathological diagnosis, but no such studies have been published from Asia. We retrospectively collected 1070 WSI specimens from 900 biopsies and small surgeries conducted in nine hospitals. Nine pathologists, who participated in this study, trained for the College of American Pathologists guidelines, reviewed the specimens and made diagnoses based on digitized, 20× or 40× optically magnified images with a WSI scanner. After a washout interval of over 2 weeks, the same observers reviewed conventional glass slides and diagnosed them by light microscopy. Discrepancies between microscopy- and WSI-based diagnoses were evaluated at the individual institutes, and discrepant cases were further reviewed by all pathologists. Nine diagnoses (0.9%) showed major discrepancies with significant clinical differences between the WSI- and microscopy-based diagnoses, and 37 (3.5%) minor discrepancies occurred without a clinical difference. Eight out of nine diagnoses with a major discrepancy were considered concordant with the microscopy-based diagnoses. No association was observed between the level of discrepancy and the organ type, collection method, or digitized optical magnification. Our results indicate the availability of WSI-based primary diagnosis of biopsies and small surgeries in routine daily practice.

Breakdown of lung framework and an increase in pores of Kohn as initial events of emphysema and a cause of reduction in diffusing capacity.

PURPOSE: Pulmonary emphysema is the pathological prototype of chronic obstructive pulmonary disease and is also associated with other lung diseases. We considered that observation with different approaches may provide new insights for the pathogenesis of emphysema. PATIENTS AND METHODS: We reviewed tissue blocks of the lungs of 25 cases with/without emphysema and applied a three-dimensional observation method to the blocks. Based on the three-dimensional characteristics of the alveolar structure, we considered one face of the alveolar polyhedron as a structural unit of alveoli and called it a framework unit (FU). We categorized FUs based on their morphological characteristics and counted their number to evaluate the destructive changes in alveoli. We also evaluated the number and the area of pores of Kohn in FUs. We performed linear regression analysis to estimate the effect of these data on pulmonary function tests. RESULTS: In multivariable regression analysis, a decrease in the number of FUs without an alveolar wall led to a significant decrease in the diffusing capacity of the lung for carbon monoxide (DLCO) and DLCO per unit alveolar volume, and an increase in the area of pores of Kohn had a significant effect on an increase in residual capacity. CONCLUSION: A breakdown in the lung framework and an increase in pores of Kohn are associated with a decrease in DLCO and DLCO per unit alveolar volume with/without emphysema.

Difference of morphology and immunophenotype between central and peripheral squamous cell carcinomas of the lung.

BACKGROUND: Recent agents, that is, pemetrexed and bevacizumab, have shown reproductive negative association between squamous histology. According to these agents' effectiveness, ruling out of the squamous histology is a significant issue for surgical pathologists. Several articles have proposed the distinction of peripheral type from central type of squamous cell carcinoma (SqCC) due to its similarity to adenocarcinoma, although little evidence to support the difference between these two types was published. In this study, we compared the clinicopathologic findings of central and peripheral pulmonary SqCCs. MATERIAL AND METHODS: 15 central and 35 peripheral types of SqCC from 2005 to 2010 were examined. Twelve morphological features were scored based on their intensity in the original H&E slides, and then, tissue microarray holding triplicated cores from 43 cases was immunohistochemically examined for cytokeratin (CK)7, CK14, TTF-1, Napsin A, p63, CK34 ß E12, CK5/6, and p53. RESULT: Most of the histological findings did not separate central and peripheral SqCCs; only the presence of emphysema, interstitial fibrosis, and entrapped pneumocytes inside the tumor showed statistic predominance in peripheral SqCC. This is the first immunophenotypic research in the central and peripheral types of SqCC.

Interstitial pneumonia associated with MPO-ANCA: clinicopathological features of nine patients.

Myeloperoxidase anti-neutrophil cytoplasmic autoantibody (MPO-ANCA) is a well known marker for small vessel vasculitis. Recent reports have demonstrated that interstitial pneumonia (IP) may rarely be associated with serum MPO-ANCA. Yet, little is known about the histological features. We reviewed surgical lung biopsy from nine patients with IP of uncertain etiology with serum MPO-ANCA. There was a male predominance (6:3) with a median age of 62.1. Histologically, eight patients presented with a usual interstitial pneumonia (UIP) pattern of pulmonary fibrosis, frequently accompanied by areas of nonspecific interstitial pneumonia (NSIP) pattern. One patient showed diffuse alveolar damage (DAD), and two patients showed mixture of UIP and DAD reflecting acute exacerbation of UIP. Microscopic honeycomb cysts were common, but fibroblastic foci were inconspicuous. The most frequent additional findings were small airway disease (9/9), and lymphoid follicles (7/9). Neither capillaritis nor vasculitis was seen in any of our cases. Three patients had microscopic hematuria, but none progressed to microscopic polyangiitis during the follow up. Mortality rate was 44% (median follow up 39.1 months). IP associated with MPO-ANCA showed characteristic histology dominated by UIP pattern. Vasculitis was not identified in our cohort, but small airways disease and lymphoid follicles were present in most cases. IP associated with MPO-ANCA may be a histologically distinctive disease from idiopathic pulmonary fibrosis. Mortality was relatively high and life threatening acute exacerbation may occur.