Integration of Pathological Criteria and Immunohistochemical Evaluation for Invasive Lobular Carcinoma Diagnosis: Recommendations From the European Lobular Breast Cancer Consortium.

Invasive lobular carcinoma (ILC) is the second most frequent type of breast cancer (BC) and its peculiar morphology is mainly driven by inactivation of CDH1, the gene coding for E-cadherin cell adhesion protein. ILC-specific therapeutic and disease-monitoring approaches are gaining momentum in the clinic, increasing the importance of accurate ILC diagnosis. Several essential and desirable morphologic diagnostic criteria are currently defined by the World Health Organization, the routine use of immunohistochemistry (IHC) for E-cadherin is not recommended. Disagreement in the diagnosis of ILC has been repeatedly reported, but interpathologist agreement increases with the use of E-cadherin IHC. In this study, we aimed to harmonize the pathological diagnosis of ILC by comparing 5 commonly used E-cadherin antibody clones (NCH-38, EP700Y, Clone 36, NCL-L-E-cad [Clone 36B5], and ECH-6). We determined their biochemical specificity for the E-cadherin protein and IHC staining performance according to type and location of mutation on the CDH1 gene. Western blot analysis on mouse cell lines with conditional E-cadherin expression revealed a reduced specificity of EP700Y and NCL-L-E-cad for E-cadherin, with cross-reactivity of Clone 36 to P-cadherin. The use of IHC improved interpathologist agreement for ILC, lobular carcinoma in situ, and atypical lobular hyperplasia. The E-cadherin IHC staining pattern was associated with variant allele frequency and likelihood of nonsense-mediated RNA decay but not with the type or position of CDH1 mutations. Based on these results, we recommend the indication for E-cadherin staining, choice of antibodies, and their interpretation to standardize ILC diagnosis in current pathology practice.

Prognostic value of micrometric substaging in pT1 bladder cancer patients treated with en-bloc transurethral resection.

AIMS: We aimed to assess the oncological impact of micrometric extent of invasion in patients with pT1 bladder cancer (BCa) who underwent en-bloc resection for bladder tumour (ERBT). METHODS AND RESULTS: We retrospectively analysed the records and specimens of 106 pT1 high-grade BCa patients who underwent ERBT. The extent of invasion, such as depth from basal membrane, number of invasive foci, maximum width of invasive focus, muscularis mucosae invasion and infiltration pattern (pattern A: solid sheet-like, nodular or nested growth, pattern B: trabecular, small cluster or single-cell pattern) were evaluated by a single genitourinary pathologist. The end-points were recurrence-free (RFS) and progression-free survival (PFS). Within a median follow-up of 23 months, overall, 36 patients experienced recurrence and 13 patients experienced disease progression. The 2-year PFS differed significantly depending on depth from basal membrane (< 1.3 mm: 94.8% versus ≧ 1.3 mm: 65.2%, P = 0.005), maximum width of invasive focus (< 4 mm: 91.7% versus ≧ 4 mm: 62.3%, P < 0.001), muscularis mucosae (MM) invasion (above MM = 96.1% versus into or beyond MM = 64.8%, P = 0.002) and infiltration pattern (pattern A: 100% versus pattern B: 83.3%, P = 0.037). In a multivariable analysis, MM invasion [hazard ratio (HR) = 4.54, 95% confidence interval (CI) = 1.25-16.5] and maximum width of invasive focus ≧ 4 mm (HR = 4.79, 95% CI = 1.25-16.5) were independent prognostic factors of progression. CONCLUSIONS: En-bloc resection facilitates the evaluation of pathologic variables that might be useful in predicting disease recurrence and progression. In particular, not only the MM invasion but also the maximum width of invasion focus, reflecting the invasive volume, appear to be reliable prognosticators for disease progression.

Postoperative seizure outcomes and antiseizure medication utilization based on histopathological diagnosis: A retrospective cohort study.

OBJECTIVE: Analyze the association between histopathology, seizure outcomes, and drug load of antiseizure medications (ASMs) 5-8 years after epilepsy surgery to inform preoperative decision-making and consultation. METHODS: In this retrospective, non-interventional, single-center study, patients who visited the epilepsy clinic at West China Hospital, Sichuan University from Jan 1, 2015 to Dec 31, 2020 were assessed. Patients with postoperative histopathology after epilepsy resection were included and categorized into 13 etiological groups. The primary outcomes were achieving Engel class 1 at 1, 2, 3, 5, and 8 years postoperative. Secondary outcomes included the use of ASMs and comparison of postoperative seizure outcomes between adults and children. Univariate and multivariable analyses were conducted to explore the association between clinical characteristics such as histopathology and seizure outcomes. RESULTS: A total of 315 patients were include. Patients with embryonic dysplastic neuroepithelial tumor (DNT) achieved the best seizure outcomes (84.6 % Engel class 1). DNT (odds ratio, OR=0.103, 95 %CI=0.012-0.899), cavernous hemangiomas (OR=0.140, 95 %CI=0.024-0.819) and meningioma (OR=0.137, 95 %CI=0.021-0.910) were independently associated with a higher probability of seizure-free outcome. The results of epileptic seizures in adult and pediatric groups with different pathologies were significantly different, and the preoperative and postoperative ASM dosages were also different among adult patients with various etiologies. Additionally, multivariate analysis showed that early age at onset (adjusted hazard ratio (HR) = 1.754, 95 % CI=1.049-2.934, P=0.032), late surgical age (HR=0.569, 95 %CI=0.339-0.954, P=0.032), and longer duration from seizure onset to surgery (HR=1.735, 95 % CI=1.028-2.928, P=0.039) were independent predictors of unfavorable outcomes in epileptic seizures. CONCLUSIONS: we demonstrated that the seizure outcomes of focal epilepsy have high pathological specificity, with histopathological diagnosis serving as a crucial and independent determinant of seizure outcome. Surgical assessment should be contemplated for all patients with presumed refractory focal epilepsy, irrespective of their age.

Synchronous Computed Tomography-Guided Percutaneous Transthoracic Needle Biopsy and Microwave Ablation for Highly Suspicious Malignant Pulmonary Ground-Glass Nodules.

INTRODUCTION: There is no consensus regarding the most appropriate management of suspected malignant pulmonary ground-glass nodules (GGNs). OBJECTIVE: We aimed to explore the feasibility and safety of synchronous computed tomography-guided percutaneous transthoracic needle biopsy (PTNB) and microwave ablation (MWA) for patients highly suspicious of having malignant GGNs. METHODS: We retrospectively reviewed medical records between July 2020 and April 2023 from our medical center. Eligible patients synchronously underwent PTNB and MWA (either MWA immediately after PTNB [PTNB-first group] or PTNB immediately after MWA [MWA-first group]) at the the physician's discretion. We analyzed the rate of definitive diagnosis and technical success, the length of hospital stay, the postoperative efficacy, and periprocedural complications. RESULTS: Of 65 patients who were enrolled, the rate of definitive diagnosis was 86.2%, which did not differ when stratified by the tumor size, the consolidation-to-tumor ratio, or the sequence of the two procedures (all p > 0.05). The diagnostic rate of malignancy was 83.1%. After the median follow-up duration of 18.5 months, the local control rate was 98.2% and the rate of completed ablation was 48.2%. The rate of perioperative minor and major complications was 44.6% and 6.2%, respectively. The most common adverse events included pain, cough, and mild hemorrhage. Mild hemorrhage took place significantly less frequently in the MWA-first group than in the PTNB-first group (16.7% vs. 45.5%, p < 0.05). CONCLUSION: Synchronous PTNB and MWA are feasible and well tolerated for patients highly suspicious of having malignant GGNs, providing an alternative option for patients who are ineligible for surgical resection.

Deep Learning-Based Classification of Hepatocellular Nodular Lesions on Whole-Slide Histopathologic Images.

BACKGROUND & AIMS: Hepatocellular nodular lesions (HNLs) constitute a heterogeneous group of disorders. Differential diagnosis among these lesions, especially high-grade dysplastic nodules (HGDNs) and well-differentiated hepatocellular carcinoma (WD-HCC), can be challenging, let alone biopsy specimens. We aimed to develop a deep learning system to solve these puzzles, improving the histopathologic diagnosis of HNLs (WD-HCC, HGDN, low-grade DN, focal nodular hyperplasia, hepatocellular adenoma), and background tissues (nodular cirrhosis, normal liver tissue). METHODS: The samples consisting of surgical and biopsy specimens were collected from 6 hospitals. Each specimen was reviewed by 2 to 3 subspecialists. Four deep neural networks (ResNet50, InceptionV3, Xception, and the Ensemble) were used. Their performances were evaluated by confusion matrix, receiver operating characteristic curve, classification map, and heat map. The predictive efficiency of the optimal model was further verified by comparing with that of 9 pathologists. RESULTS: We obtained 213,280 patches from 1115 whole-slide images of 738 patients. An optimal model was finally chosen based on F1 score and area under the curve value, named hepatocellular-nodular artificial intelligence model (HnAIM), with the overall 7-category area under the curve of 0.935 in the independent external validation cohort. For biopsy specimens, the agreement rate with subspecialists' majority opinion was higher for HnAIM than 9 pathologists on both patch level and whole-slide images level. CONCLUSIONS: We first developed a deep learning diagnostic model for HNLs, which performed well and contributed to enhancing the diagnosis rate of early HCC and risk stratification of patients with HNLs. Furthermore, HnAIM had significant advantages in patch-level recognition, with important diagnostic implications for fragmentary or scarce biopsy specimens.

An artificial intelligence model for the pathological diagnosis of invasion depth and histologic grade in bladder cancer.

BACKGROUND: Accurate pathological diagnosis of invasion depth and histologic grade is key for clinical management in patients with bladder cancer (BCa), but it is labour-intensive, experience-dependent and subject to interobserver variability. Here, we aimed to develop a pathological artificial intelligence diagnostic model (PAIDM) for BCa diagnosis. METHODS: A total of 854 whole slide images (WSIs) from 692 patients were included and divided into training and validation sets. The PAIDM was developed using the training set based on the deep learning algorithm ScanNet, and the performance was verified at the patch level in validation set 1 and at the WSI level in validation set 2. An independent validation cohort (validation set 3) was employed to compare the PAIDM and pathologists. Model performance was evaluated using the area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value and negative predictive value. RESULTS: The AUCs of the PAIDM were 0.878 (95% CI 0.875-0.881) at the patch level in validation set 1 and 0.870 (95% CI 0.805-0.923) at the WSI level in validation set 2. In comparing the PAIDM and pathologists, the PAIDM achieved an AUC of 0.847 (95% CI 0.779-0.905), which was non-inferior to the average diagnostic level of pathologists. There was high consistency between the model-predicted and manually annotated areas, improving the PAIDM's interpretability. CONCLUSIONS: We reported an artificial intelligence-based diagnostic model for BCa that performed well in identifying invasion depth and histologic grade. Importantly, the PAIDM performed admirably in patch-level recognition, with a promising application for transurethral resection specimens.

Diagnosis of cholangiocarcinoma from microscopic hyperspectral pathological dataset by deep convolution neural networks.

This paper focuses on automatic Cholangiocarcinoma (CC) diagnosis from microscopic hyperspectral (HSI) pathological dataset with deep learning method. The first benchmark based on the microscopic hyperspectral pathological images is set up. Particularly, 880 scenes of multidimensional hyperspectral Cholangiocarcinoma images are collected and manually labeled each pixel as either tumor or non-tumor for supervised learning. Moreover, each scene from the slide is given a binary label indicating whether it is from a patient or a normal person. Different from traditional RGB images, the HSI acquires pixels in multiple spectral intervals, which is added as an extension on the channel dimension of 3-channel RGB image. This work aims at fully exploiting the spatial-spectral HSI data through a deep Convolution Neural Network (CNN). The whole scene is first divided into several patches. Then they are fed into CNN for the tumor/non-tumor binary prediction and the tumor area regression. The further diagnosis on the scene is made by random forest based on the features from patch prediction. Experiments show that HSI provides a more accurate result than RGB image. Moreover, a spectral interval convolution and normalization scheme are proposed for further mining the spectral information in HSI, which demonstrates the effectiveness of the spatial-spectral data for CC diagnosis.

Diagnostic accuracy of frozen section biopsy for early gastric cancer extent during endoscopic submucosal dissection: a prospective study.

BACKGROUND: Accurate diagnosis of the lateral extent of early gastric cancer during endoscopic submucosal dissection (ESD) is crucial to achieve negative resection margins. Similar to intraoperative consultation with a frozen section in surgery, rapid frozen section diagnosis with endoscopic forceps biopsy may be useful in assessing tumor margins during ESD. This study aimed to evaluate the diagnostic accuracy of frozen section biopsy. METHODS: We prospectively enrolled 32 patients undergoing ESD for early gastric cancer. Biopsy samples for the frozen sections were randomly collected from fresh resected ESD specimens before formalin fixation. Two different pathologists independently diagnosed 130 frozen sections as "neoplasia," "negative for neoplasia," or "indefinite for neoplasia," and the frozen section diagnosis was compared with the final pathological results of the ESD specimens. RESULTS: Among the 130 frozen sections, 35 were from cancerous areas, and 95 were from non-cancerous areas. The diagnostic accuracies of the frozen section biopsies by the two pathologists were 98.5 and 94.6%, respectively. Cohen's kappa coefficient of diagnoses by the two pathologists was 0.851 (95% confidence interval: 0.837-0.864). Incorrect diagnoses resulted from freezing artifacts, a small volume of tissue, inflammation, the presence of well-differentiated adenocarcinoma with mild nuclear atypia, and/or tissue damage during ESD. CONCLUSIONS: Pathological diagnosis of frozen section biopsy is reliable and can be applied as a rapid frozen section diagnosis for evaluating the lateral margins of early gastric cancer during ESD.

Synchronous computed tomography-guided percutaneous biopsy and microwave ablation for highly suspicious malignant lung ground-glass opacities adjacent to mediastinum.

BACKGROUND: This retrospective study aimed to assess the safety and efficacy of synchronous biopsy and microwave ablation (MWA) for highly suspected malignant lung ground-glass opacities (GGOs) adjacent to the mediastinum (distance ≤10 mm). MATERIALS AND METHODS: Ninety patients with 98 GGOs (diameter range, 6-30 mm), located within 10 mm of the mediastinum, underwent synchronous biopsy and MWA at a single institution from 1 May 2020, to 31 October 2021 and were enrolled in this study. Synchronous biopsy and MWA involving the completion of the biopsy and MWA in a single procedure was performed. Safety, technical success rate, and local progression-free survival (LPFS) were evaluated. The risk factors for local progression were calculated using the Mann-Whitney U test. RESULTS: The technical success rate was 97.96% (96/98 patients). The LPFS rates at 3, 6, and 12 months were 95.0%, 90.0%, and 82.0%, respectively. The diagnostic rate of biopsy-proven malignancy was 72.45% (n = 71/98). Invasion of lesions into the mediastinum was a risk factor for local progression (p = 0.0077). The 30-day mortality rate was 0. The major complications were pneumothorax (13.27%), ventricular arrhythmias (3.06%), pleural effusion (1.02%), hemoptysis (1.02%), and infection (1.02%). Minor complications included pneumothorax (30.61%), pleural effusion (24.49%), hemoptysis (18.37%), ventricular arrhythmias (11.22%), structural changes in adjacent organs (3.06%), and infection (3.06%). CONCLUSIONS: Synchronous biopsy and MWA was effective for treating GGOs adjacent to the mediastinum without severe complications (Society of Interventional Radiology classification E or F). Invasion of lesions into the mediastinum was identified as a risk factor for local progression.

Long-term survival in patients with PMP: a single-institutional retrospective study from China.

BACKGROUND: As the standard treatment for pseudomyxoma peritonei (PMP), cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) can significantly prolong the survival of PMP patients, and some patients can even achieve long-term survival (LTS) or clinical cure. The purpose of this study was to analyze the clinicopathological and treatment features of PMP patients with LTS and to explore the survival benefit factors of PMP patients. METHODS: The clinicopathological and prognostic data of PMP patients who received CRS + HIPEC at our center from December 2004 to May 2023 were retrospectively analyzed. PMP patients were divided into LTS group (≥ 10 years) and short-term survival (STS) group (< 5 years) according to the length of natural history. Univariate and multivariate analyses were performed to explore the beneficial factors of PMP patients with LTS. RESULTS: A total of 609 patients with PMP received CRS + HIPEC treatment at our center. Two-hundred one patients with PMP were included in the study after screening, including 39 patients (19.4%) in the LTS group and 162 patients (80.6%) in the STS group. In STS group and LTS group, median overall survival based on natural history was 29.2 (2.4-59.9) vs. 138.9 (120.3-416.7) months. Univariate analysis revealed 8 factors (P < 0.05) with statistically significant differences between the two groups: gender, chemotherapy history, previous surgical score, Karnofsky Performance Status score, pathological diagnosis, lymphatic metastasis, peritoneal cancer index, and completeness of cytoreduction (CC). Multivariate analysis identified only two factors independently associated with LTS of PMP patients: CC and pathological diagnosis. CONCLUSION: Complete CRS and pathological features are two key factors affecting LTS in PMP patients.

Versican core protein aids in the diagnosis and grading of breast phyllodes tumor.

Phyllodes tumors (PTs) are biphasic fibroepithelial lesions that occur in the breast. Diagnosing and grading PTs remains a challenge in a small proportion of cases, due to the lack of reliable specific biomarkers. We screened a potential marker versican core protein (VCAN) through microproteomics analysis, validated its role for the grading of PTs by immunohistochemistry, and analyzed the correlation between VCAN expression and clinicopathological characteristics. Cytoplasmic immunoreactivity for VCAN was identified in all benign PT samples, among which 40 (93.0 %) showed VCAN-positive staining in ≥50 % of tumor cells. Eight (21.6 %) borderline PT samples showed VCAN-positive staining in ≥50 % of the cells with weak to moderate staining intensity, whereas 29 samples (78.4 %) showed VCAN-positive staining in <50 % of the cells. In malignant PTs, 16 (84.2 %) and three (15.8 %) samples showed VCAN-positive staining in <5 % and 5-25 % of stromal cells, respectively. Fibroadenomas showed a similar expression pattern to benign PTs. Fisher's exact test showed that the percentages of positive cells (P < .001) and staining intensities (P < .001) of tumor cells were significantly different between the five groups. VCAN positivity was associated with tumor categories (P < .0001) and CD34 expression (P < .0001). The expression of VCAN gradually decreases as the tumor categories increases, following recurrence. To the best of our knowledge, our results are the first in the literature to reveal that VCAN is useful for diagnosing and grading PTs. The expression level of VCAN appeared to be negatively associated with PT categories, suggesting that dysregulation of VCAN may be involved in the tumor progression of PTs.

Usefulness and limitations of intraoperative pathological diagnosis using frozen sections for spinal cord tumors.

BACKGROUND: Intraoperative pathological diagnosis has a major influence on the intra- and postoperative management of spinal cord tumors. Thus, the aim of this study was to assess the reliability of intraoperative pathological diagnosis for spinal cord lesions by comparing it with the final pathological diagnosis and to determine its usefulness and limitations. METHOD: Three-hundred and three consecutive patients (mean age, 53.9 years) with neoplastic spinal cord lesions who underwent initial surgery between 2000 and 2021 were included. The anatomical locations of the spinal cord tumors and the implementation rate of intraoperative pathological diagnosis in each tumor type were evaluated. As the primary outcome, we determined the concordance rates between the intraoperative pathological diagnosis and the final diagnosis. When the intraoperative pathological diagnosis and final diagnosis were the same, the diagnosis was defined as a "match." Otherwise, the diagnosis was defined as a "mismatch." RESULTS: The overall implementation rate of intraoperative pathological diagnosis was 53%, with implementation rates of 71%, 45%, 47%, and 50% for intramedullary, intradural extramedullary, extradural, and dumbbell tumors, respectively. The overall concordance rate was 87.6%, with concordance rates of 80%, 95%, 75%, and 90% for intramedullary, intradural extramedullary, extradural, and dumbbell tumors, respectively (p < 0.05). The diagnoses of ependymomas, low-grade astrocytomas, and high-grade astrocytomas was occasionally difficult among intramedullary tumors. Among intradural extramedullary tumors, differentiation between grade 1 meningioma and high-grade meningioma was difficult using intraoperative pathological diagnosis. CONCLUSIONS: Surgeons must recognize the lower accuracy of intraoperative pathological diagnosis for intramedullary and extradural lesions and make a final decision by considering the intraoperative gross findings, preoperative clinical course, and imaging.

[Evaluation of accuracy of pathological diagnosis based on thyroid core needle biopsy].

OBJECTIVE: To explore the protocol for diagnosing thyroid nodules based on core needle biopsy (CNB) and study the biomarkers' application in distinguishing indeterminate samples. METHODS: Patients with thyroid nodules treated at Peking University First Hospital from 2015 to 2020 were reviewed. In the study, 598 cases with CNB and matched resected specimens were retrieved. According to "diagnostic categories of thyroid CNB" proposed by the Korean Endocrine Pathology Thyroid Core Needle Biopsy Study Group, the CNB samples were diagnosed as follows: Ⅰ, unsatisfactory; Ⅱ, benign; Ⅲ, indeterminate; Ⅳ, follicular neoplasm; Ⅴ, suspicious for malignancy; and Ⅵ, malignant. The samples of CNB Ⅲ were stained by immunohistochemistry (IHC) using antibodies against CK19, Galectin-3, HBME-1, and CD56, and detected by next-generation sequencing (NGS) using an OncoAim® thyroid cancer multigene assay kit (Singlera Genomics) that detected 26 genes. Taking the resected specimens' classification as the gold standard, the predictive value of CNB for determining the malignancy of thyroid nodules and the biomarkers for distinguishing the samples of CNB Ⅲ was calculated. RESULTS: The study included 598 patients, of which none were CNB Ⅰ, 40 cases were CNB Ⅱ, 40 cases were CNB Ⅲ, 32 cases were CNB Ⅳ, 35 cases were CNB Ⅴ, and 451 cases were CNB Ⅵ. The predictive value of CNB Ⅳ for determining follicular neoplasm was sensitivity (Sen) 100.00% and specificity (Sep) 100.00%, CNB Ⅴ-Ⅵ for determining malignancy was Sen 94.55% and Sep 100.00%, CNB Ⅱ for determining benign lesions was Sen 75.00% and Sep 99.80%. The predictive value of biomarkers for determining malignancy in cases of CNB Ⅲ was Sen 96.30% and Sep 92.31% by NGS, and Sen 81.48% and Sep 92.30% by IHC. CONCLUSION: The Korean "diagnostic categories of thyroid CNB", which considers the histological specificity of CNB samples and the habits of clinicians, have strong operability, high diagnosis rate, and high clinical value. Under this framework, the cases of CNB Ⅵ should be treated with surgical operation, the cases of CNB Ⅴ-Ⅵ are recommended to be treated as malignant neoplasms, and the major cases of CNB Ⅱ could be followed up without worrisome except the one considered malignant by ultrasound. The value of biomarkers in distinguishing the cases of CNB Ⅲ is significant.

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The application of artificial neural network algorithm in pathological diagnosis of gastrointestinal malignant tumors has become a research hotspot. In the previous studies, the algorithm research mainly focused on the model development based on convolutional neural networks, while only a few studies used the combination of convolutional neural networks and recurrent neural networks. The research contents included classical histopathological diagnosis and molecular typing of malignant tumors, and the prediction of patient prognosis by utilizing artificial neural networks. This article reviews the research progress on artificial neural network algorithm in the pathological diagnosis and prognosis prediction of digestive tract malignant tumors.

Invasive Aspergillus outbreak in inhalation injury: a case presentation and literature review.

BACKGROUND: Invasive pulmonary aspergillosis often occurs in patients with poor immune function, who abuse steroids or broad-spectrum antibiotics, or who use intravenous drugs. Among the Aspergillus genus of pulmonary infection, Aspergillus fumigatus is the most important pathogen, followed by Aspergillus flavus, Aspergillus niger, and Aspergillus terreus. Inhalation injury complicated by Aspergillus infection has atypical clinical manifestations. Diagnosis is difficult, and it is easy to make mistakes in treatment. Moreover, there are few cases of burn inhalation injury complicated with pulmonary Aspergillus. CASE PRESENTATION: We report a case of severe burns combined with severe inhalation injury, early pulmonary aspergillosis, and severe respiratory failure due to treatment discontinuation. Through analyzing the processes of diagnosis and treatment in the present case and performing a literature review, we explore feasible diagnosis and treatment plans. CONCLUSIONS: Early application of a variety of diagnostic measures can be used to identify Aspergillus infection, and targeted anti-infection treatment is likely to reverse a severe adverse prognosis.

Clinicopathological discordance in biopsy-proven nephrosclerosis: a nationwide cross-sectional study of the Japan Renal Biopsy Registry (J-RBR).

BACKGROUND: Patients with nephrosclerosis display heterogenous clinical phenotypes, often leading to a clinical diagnosis discordant with pathological nephrosclerosis diagnosis. However, little is known about clinical factors associated with clinicopathological discordance of biopsy-proven nephrosclerosis. METHODS: In a cross-sectional study of 891 patients with biopsy-proven nephrosclerosis registered in the Japan Renal Biopsy Registry (J-RBR) between July 2007 and June 2016, we examined clinical characteristics associated with a pre-biopsy clinical diagnosis discordant with pathological nephrosclerosis diagnosis using multivariable logistic regression with adjustment for relevant clinical characteristics. RESULTS: Overall, the mean (SD) age was 58.6 (13.7) years; 67.6% of patients were male; and 63.2% were on antihypertensive drugs. The median estimated glomerular filtration rate (eGFR) was 43.8 mL/min/1.73 m2 and the median proteinuria was 0.5 g/day. Of the 891 patients, 497 (55.8%) had a clinical diagnosis discordant with pathological nephrosclerosis diagnosis, with chronic nephritic syndrome being the most common (> 75%) discordant clinical diagnosis. After multivariable adjustment, age (odds ratio 1.34, [95% confidence interval, 1.16-1.55], per 10 years increase), eGFR (1.10 [1.00-1.21], per 10 mL/min/1.73 m2 increase), and proteinuria (1.20 [1.03-2.16], per 1 g/day decrease) were found to be significantly associated with the clinicopathological discordance. CONCLUSIONS: Patients with older age, higher eGFR, and lower proteinuria had significantly higher likelihood of being clinically diagnosed with other glomerular disease in patients with biopsy-proven nephrosclerosis. Our findings highlight the heterogeneous clinical phenotypes of nephrosclerosis and suggest the need for continuous improvement of clinical diagnostic accuracy as well as for wider kidney biopsy indications for nephrosclerosis.

Clinical features and difficulty in diagnosis of Langerhans cell histiocytosis in the hypothalamic-pituitary region.

Langerhans cell histiocytosis (LCH) is a multi-organ disorder that rarely involves the hypothalamic-pituitary region (HPR). HPR-LCH presents with severe progressive pituitary dysfunction and its prognosis is poor. The definitive diagnosis of LCH is considerably difficult and complicated owing to the occurrence of several diseases with similar manifestations in the HPR and its location in the deepest portion of the anterior skull base, in close proximity to important normal structures, severely limiting the size of the biopsy specimen. Chemotherapy is the established treatment modality for LCH; hence, timely and accurate diagnosis of LCH is essential for early therapeutic intervention. We retrospectively reviewed clinical features and biopsy procedures in four patients with HPR-LCH (all female, 28-44 years old) from 2009 to 2020. Maximum diameter of supra-sellar lesions was 23-35 mm and 2 cases had skip lesions. All patients demonstrated central diabetes insipidus, hyper-prolactinemia, and severe anterior pituitary dysfunction. Two of the patients had progressive disease. Furthermore, four patients presented body weight gain, two visual disturbance, and two impaired consciousness. The duration from onset to diagnosis of LCH was 3 to 10 (average 7.25) years. In total, eight operations were performed until final diagnosis. The percentage of correct diagnosis by biopsy was 50% (4/8). Clinical features of HPR-LCH are very similar to those of other HPR diseases, and their symptoms are progressive and irreversible. Clinicians should consider repeated biopsy with a more aggressive approach if the lesion is refractory to steroid therapy, in order to ensure accurate diagnosis and appropriate treatment.

Pathological diagnosis of general rules for the description of thyroid cancer by Japanese Society of Thyroid Pathology and Japan Association of Endocrine Surgery.

The Japanese Society of Thyroid Pathology and the Japan Association of Endocrine Surgeons developed the eighth edition of the General Rules for the Description of Thyroid Cancer (GRDTC) in December 2019. This article describes the pathological diagnosis of the GRDTC, which has been improved through repeated revisions based on the experience of Japanese pathologists and translated into English to introduce the Japanese diagnostic standard to foreign countries. In this edition of the GRDTC, the histopathological classification and descriptions differ in some respects from those of the fourth edition of the World Health Organization (WHO) classification as revised in 2017. For example, the GRDTC does not adopt the concept of borderline lesions (FT-UMP, WDT-UMP, and NIFTP) of the WHO, taking into consideration the popular histological criteria accepted by Japanese pathologists. The cytological reporting system of the GRDTC was partly modified from the Bethesda system in 2015. It has an additional cyst fluid category separated from the unsatisfactory category that has been demonstrated to be useful in Japan. This translated edition makes it easy to submit Japanese clinicopathological studies of thyroid tumors in an international journal. We also wish to contribute to the improvement, standardization, and globalization of the pathological diagnosis of thyroid tumors.

[Retrospective Analysis of Pathological Diagnosis of Central Nervous System Diseases in Tibet].

Objective To analyze the disease spectrum and clinicopathological characteristics of central nervous system(CNS)diseases diagnosed based on pathological findings in Tibet. Methods We collected the data of all the cases with CNS lesions in Tibet Autonomous Region People's Hospital from January 2013 to December 2020.The clinicopathological features were analyzed via light microscopy,immunohistochemical staining,and special staining. Results A total of 383 CNS cases confirmed by pathological diagnosis were enrolled in this study,with a male-to-female ratio of 188∶195 and an average age of(40.03±17.39)years(0-74 years).Among them,127(33.2%)cases had non-neoplastic diseases,with a male-to-female ratio of 82∶45 and an average age of(31.99±19.29)years;256(66.8%)cases had neoplastic diseases,with a male-to-female ratio of 106∶150 and an average age of(44.01±14.87)years.The main non-neoplastic diseases were nervous system infectious diseases,cerebral vascular diseases,meningocele,cerebral cyst,and brain trauma.Among the infectious diseases,brain abscess,granulomatous inflammation,cysticercosis,and hydatidosis were common.The main neoplastic diseases included meningioma,pituitary adenoma,neuroepithelial tumor,schwannoma,metastatic tumor,and hemangioblastoma.The meningioma cases consisted of 95.4%(103/108)cases of grade Ⅰ,3.7%(4/108)cases of grade Ⅱ,and only 1(1/108,0.9%)case of grade Ⅲ.Among the neuroepithelial tumor cases,the top three were glioblastoma,grade Ⅲ diffuse glioma,and ependymoma. Conclusions There are diverse CNS diseases confirmed by pathological diagnosis in Tibet,among which non-neoplastic diseases account for 1/3 of all the cases.Infectious and vascular diseases are the most common non-neoplastic diseases in Tibet,and tuberculosis and parasitic infections are relatively common.The types and proportion of brain tumors in Tibet are different from those in other regions of China,and meningioma is the most common in Tibet,with higher proportion than neuroepithelial tumor.

[Updates in the pathological diagnosis of Pleural Malignant Mesothelioma in the WHO classification of thoracic tumors (5(th) edition)].

The WHO Classification of Thoracic Tumors (5(th) edition) mainly has the following changes in the chapter of pleural malignant mesothelioma. (1) The concept of mesothelioma in situ and its diagnostic method have been established for the first time; (2) The tumour grading of pleural malignant mesothelioma was added, it was divided into low grade and high grade according to the cellular atypia, mitotic activity and presence of necrosis. (3) The morphological features of pleural malignant mesothelioma was classified into architectural pattern, cellular and stromal features, the correlation between histological features and prognosis was refined, and some of the controversial cellular types have been reclassified. In this review, we introduced the changes of related pathologic diagnosis, in the WHO Classification of Thoracic Tumors (5(th) edition) and discussed its clinical significance.