Histopathology and its clinical correlation of liver biopsy in patients with treated autoimmune hepatitis.

The diagnosis of autoimmune hepatitis (AIH) relies on well-established criteria encompassing histological, serological, and clinical features. Diagnosing AIH may become challenging when encountering patients who have undergone steroid therapy for other co-existing diseases. Thirty-nine liver biopsies from 25 patients with treated and untreated AIH were classified into three groups: 1) Newly diagnosed untreated biopsies (n = 16); 2) Newly diagnosed partially treated biopsies from patients already on steroid treatment for other co-existing diseases (n = 9); 3) Previously diagnosed biopsies from patients who had undergone complete treatment (n = 14). In the untreated AIH group, at least 50 % of the cases exhibited the following features: at least moderate portal inflammation (81 %), at least moderate lobular inflammation (56 %), ductular reaction (94 %), inflammation gradient from bile duct to interface (88 %), unequivocal interface hepatitis (100 %), emperipolesis (56 %), plasma cell cluster (88 %), apoptosis or necrosis (63 %), pericentral inflammation (63 %), and periportal fibrosis (88 %). Although all these diagnostically sensitive histologic features were present in significantly fewer cases after treatment (p < 0.05), the features of ductular reaction, inflammation gradient from bile duct to interface, pericentral inflammation, and periportal fibrosis were likely to persist after treatment, especially in partially treated cases; these features did not show a significant association with higher transaminase levels (P > 0.05) and were considered as indirect features of hepatocytic injury. Our data suggest categorizing AIH histological features into direct and indirect hepatocytic injuries. Direct hepatocytic injury features significantly correlate with transaminase levels and respond well to treatment, while indirect ones show weaker transaminase correlation and relative treatment resistance.

Histology and clinical correlations in autoimmune hepatitis, primary biliary cholangitis, and autoimmune hepatitis-primary biliary cholangitis overlap syndrome.

OBJECTIVES: The diagnosis of autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and AIH-PBC overlap syndrome (OS) relies on their histologic features and clinical findings. In this study, we aimed to identify specific morphologic features of these diseases and evaluate their clinical correlation. METHODS: We included initial biopsies from untreated patients with AIH (n = 14), PBC (n = 10), and OS (n = 7). Histologic features of the portal tract, portal-lobular interface, and hepatic lobule, fibrosis, as well as clinical data including serology, autoantibodies, treatment, and prognosis were reviewed and analyzed. RESULTS: Our results showed that several histologic features differed significantly between AIH and PBC (p < 0.05). Among these features, OS cases were more likely to present with bile duct-centered processes (presence of bile duct damage while absence of inflammation gradient from bile duct to interface, plasma cell cluster and pericentral inflammation) unlike those seen in AIH (p < 0.05), and interface-centered processes (unequivocal interface hepatitis, ductular reaction, and periportal fibrosis) which were not seen in PBC (p < 0.05). We observed a significant correlation between transaminase levels and lobular inflammation, including numbers of lymphocyte, plasma cell and eosinophil. Our study also found that anti-smooth muscle antibody positivity was associated with interface hepatitis (p < 0.01), while antimitochondrial antibody positivity was associated with duct damage (including ductopenia) and granulomas (p < 0.05). CONCLUSION: Our results highlight distinctive morphological features between AIH and PBC. The possibility of overlap syndrome should be considered when encountering AIH with bile duct-centered processes or PBC with interface-centered processes in morphology and correlation with autoantibodies.

Highly-Active Chiral Organic Photovoltaic Catalysts with Suppressed Charge Recombination.

Recombination of free charges in organic semiconductors reduces the available photo-induced charge-carriers and restricts photovoltaic efficiency. In this work, the chiral organic semiconductors (Y6-R and Y6-S with enantiopure R- and S- chiral alkyl sidechains) are designed and synthesized, which show effective aggregation-induced chirality through mainchain packing with chiral conformations in non-centrosymmetric space groups with tilt chirality. Based on the analysis of spin-injection, magnetic-hysteresis loop, and thermodynamics and dynamics of the excited state, we suggest that the aggregation-induced chirality can generate spin-polarization, which suppresses charge recombination and offers more available charge-carriers within Y6-R and Y6-S relative to the achiral counterpart (Y6). Then the chiral Y6-R and Y6-S show enhanced catalytic activity with optimal average hydrogen evolution rates of 205 and 217 mmol h-1 g-1 , respectively, 60-70 % higher than Y6, when they are employed as nanoparticle photocatalysts in photocatalytic hydrogen evolution under simulated solar light, AM1.5G, 100 mW cm-2 .

Organic Photovoltaic Catalyst with σ-π Anchor for High-Performance Solar Hydrogen Evolution.

Efficient in situ deposition of metallic cocatalyst, like zero-valent platinum (Pt), on organic photovoltaic catalysts (OPCs) is the prerequisite for their high catalytic activities. Here we develop the OPC (Y6CO), by introducing carbonyl in the core, which is available to σ-π coordinate with transition metals, due to the high-energy empty π* orbital of carbonyl. Y6CO exhibits a stronger capability to anchor Pt species and reduce them to metallic state, resulting in more Pt0 deposition, relative to the control OPC without the central σ-π anchor. Single-component and heterojunction nanoparticles (NPs) employing Y6CO show enhanced average hydrogen evolution rates of 230.98 and 323.22 mmol h-1 g[OPC] -1 , respectively, under AM 1.5G, 100 mW cm-2 for 10 h, and heterojunction NPs yield the external quantum efficiencies of ca. 10 % in 500-800 nm. This work demonstrates that σ-π anchoring is one efficient strategy for integrating metallic cocatalyst and OPC for high-performance photocatalysis.

Constrictive and Hypertrophic Strictures in Ileal Crohn's Disease.

BACKGROUND & AIMS: Strictures in Crohn's disease (CD) are classically attributed to fibromuscular hypertrophy of the intestinal wall. We have identified and characterized CD-related ileal strictures that result instead from mural constriction (ie, reduced external circumference). METHODS: Twenty-four strictures and internal controls from 17 adults with obstructive CD were analyzed by cross-sectional morphometry. RESULTS: The stricture-to-control circumference ratios (CRs) ranged from 0.53 to 1.7. Six strictures with CR ≥1.0, designated hypertrophic, had concentrically thickened walls, mean 3-fold increases in cross-sectional area and stainable fibromucular tissue, and high transmural inflammation scores. In contrast, 18 strictures with CR <1.0, designated constrictive, had thin, pliant walls, cross-sectional areas and stainable fibromuscular tissue comparable with control values, and low transmural inflammation scores. Eight mildly constrictive strictures also showed mild fibromuscular mural expansion that fell short of statistical significance. Twelve of 18 constrictive strictures (67%) occurred multiply (2-4 strictures per specimen) in contrast with hypertrophic strictures, all of which occurred singly (P = .01). Constriction correlated quantitatively with circumferential serosal fat wrapping (P = .003) and was associated with myenteric lymphocytic plexitis (P = .02). Disease duration was shortest among subjects with constrictive strictures and correlated with increasing circumference (CR ≤0.8, 6.3 ± 6.2 years; CR >0.8, 8.7 ± 6.4 years; and CR ≥1.00, 13.7 ± 5.0 years, respectively; P = .03). CONCLUSIONS: Constrictive ileal strictures in CD differ pathologically and clinically from hypertrophic strictures, featuring little or no fibromuscular mural expansion, frequent multiplicity, and earlier onset. Mesenteric fat wrapping and myenteric plexitis may contribute to their pathogenesis. Pathologic manifestations of constriction and hypertrophy can coexist, suggesting that stricture heterogeneity may be shaped in part by the dynamics of constrictive and hypertrophic processes.

Clinicopathological characteristics and aetiological factors of granulomatous gastritis.

AIMS: To examine the clinicopathological characteristics of granulomatous gastritis (GG) among different aetiologies, particularly Crohn disease (CD), and determine the contribution of Helicobacter pylori and the clinical significance of isolated GG. METHODS AND RESULTS: We identified 269 GG cases overall (0.19% prevalence): 220 had an underlying granulomatous disease (CD, sarcoidosis, tuberculosis) and only eight of these (3.6%) had H. pylori, fewer than the 10.3% rate among non-GG biopsies (P < 0.001). Conversely, among 49 GG cases without known cause (foreign body, undetermined, idiopathic), 13 (26.5%) had H. pylori more than background (P = 0.001). Most patients (n = 185/68.8%) had CD and these were more probably male (P < 0.001), younger (P < 0.001), white (P < 0.001) and had single (P = 0.010), smaller (P = 0.005) and antral (P = 0.027) granulomas amid inflammation (P = 0.005) compared to non-CD GG cases; younger age was independently associated with CD [P = 0.003; odds ratio (OR) = 1.13, 95% confidence interval (CI) = 1.04-1.22]. Among CD patients, younger age (P = 0.003; OR = 1.04, 95% CI = 1.01-1.07) and upper gastrointestinal (GI) symptoms (P = 0.017; OR = 2.53, 95% CI = 1.18-5.43) were associated with new (versus established) diagnosis, whereas multiple gastric granulomas (P = 0.003; OR = 4.67, 95% CI = 1.67-13.04) and lack of upper GI symptoms (P < 0.001; OR = 6.75, 95% CI = 2.94-15.49) were associated with lower GI granulomas. Of 86 isolated GG cases (i.e. no prior diagnosis or lower GI granulomas), 51 (59.3%) were eventually diagnosed with CD, and this was independently associated with younger age (P = 0.014; OR = 1.11, 95% CI = 1.02-1.21) and upper GI symptoms (P = 0.033; OR = 19.27, 95% CI = 1.27-293.31). The positive predictive value of finding isolated GG towards a CD diagnosis in patients aged <30 years was 91%, increasing in males (93%), with single (94%), antral (97%) granulomas or upper GI symptoms (94%). CONCLUSIONS: GG does not correlate with H. pylori in patients with granulomatous disease, but may be associated with the organism when such diagnosis is lacking. In CD patients with GG, younger age and upper GI symptoms are associated with a new CD diagnosis, whereas multiple gastric granulomas and lack of upper GI symptoms correlate with lower GI granulomas. GG, including in isolated cases with no prior clinical history or granuloma, probably signifies CD, particularly in younger, male patients or those with single, antral granulomas or upper GI symptoms.

Malignant and High-Risk Lesions in the Contralateral Breast Symmetry Mastopexy and Reduction Specimens When Performing Large-Volume Displacement Oncoplastic Surgery.

BACKGROUND: Large-volume displacement oncoplastic surgery using mastopexy/reduction mammaplasty designs is becoming increasingly popular in breast cancer surgery. A contralateral symmetry operation using similar mastopexy or breast reduction designs is also commonly performed by the plastic surgeon. Our goal was to analyze contralateral symmetry specimens to review the prevalence of high-risk or malignant lesions. METHODS: We conducted a retrospective study of the first consecutive 100 large-volume displacement oncoplastic surgeries at our institution between August 2015 and June 2018. Eighty-five patients had an immediate symmetry operation performed on the contralateral breast. Information on malignant lesions and high-risk lesions was obtained from the patient's pathology report. RESULTS: Seven different surgical techniques were used for both the cancerous and contralateral breasts. The WISE pattern skin incision pattern was most frequently used, along with the superomedial pedicle design. Fourteen cases (16.5%) had malignant and/or high-risk lesions incidentally detected. Specifically, there was a breast cancer prevalence of 4.8% in the contralateral symmetry breast specimen. CONCLUSION: Plastic surgeons should be aware that there is a substantial minority of contralateral specimens that have high-risk or malignant lesions, which underscores the importance of specimen orientation and communication with the associated pathologist.

Anatomic and terminological description and processing of breast pathologic specimens from oncoplastic large volume displacement surgeries.

Oncoplastic surgery provides breast cancer patients with greater aesthetic satisfaction without compromising disease-free survival or overall survival rate. Large volume displacement oncoplastic surgical techniques have become increasingly popular as a strategy for improving aesthetic outcomes and extending the option of breast conservation therapy. They often involve breast reduction or mastopexy reconstructive techniques to facilitate resection of large breast volumes on the side of the breast cancer and accompanied with symmetry contralateral breast reductions or mastopexies. However, dissection of large volume displacement oncoplastic surgical specimens presents unique challenges. Compared with traditional mastectomy specimens, they are relatively complicated, which requires the pathologist to understand the surgical procedure and the anatomy of the specimens. Given this, we introduce the standard anatomical and terminological description for the breast pathologic specimens of five large volume displacement oncoplastic surgical techniques commonly performed in our institution for breast cancer management. The individual surgical specimen is composed of one or several components, which include lateral wall, superior keyhole, medial wall, lateral wing, inferior pole, and medial wing. We also present specimen documentation and sectioning procedures used in our institution. The advantages for the patient provided by large volume reduction oncoplastic surgery must be supported by proper evaluation of the surgical pathology specimen. Therefore, we recommend that each section taken from the oncoplastic specimen be labeled as to its specific location in the specimen components. Standardized nomenclature and technique will assist pathologists in accurately evaluating the surgical margins.

Emerging drugs for squamous cell lung cancer.

INTRODUCTION: The management of advanced NSCLC has been shifted by histology-driven treatment and molecularly targeted therapy, especially in lung adenocarcinoma. However, as the second most common histology in NSCLC, the treatment options for squamous cell lung cancer (SQCLC) remain very limited. AREAS COVERED: The review first discusses the role of histology in management of NSCLC and new cytotoxic agents in SQCLC, and then addresses genomic characterization and potential molecular targets in SQCLC. The article then provides an overview for several major categories of novel molecularly targeted therapies and immune-based strategies with particular attention to ongoing SQCLC trials. EXPERT OPINION: The key challenges in drug development are to uncover novel actionable targets and to identify predictive biomarkers. Progress in genomic analysis has identified some promising targetable genes and oncogenic pathways in SQCLC with a wave of targeted agents being tested in clinical trials. Immunotherapy has also raised great interest in management of SQCLC, especially agents targeting immune check points, cytotoxic T-lymphocyte antigen-4, programmed death-1 receptor and its ligands. Better understanding of tumor biology and development of novel targeted therapies will help to facilitate more effective personalized therapy for patients with this devastating illness.

Confined Low Grade Appendiceal Mucinous Neoplasm With Coexisting Distant Metastasis.

BACKGROUND/AIM: Appendiceal mucinous neoplasms (AMNs) are tumors with dysplastic mucinous epithelium, a pushing growth pattern but no infiltrative invasion to the appendiceal wall. Some AMNs are associated with pseudomyxoma peritonei, characterized by intraperitoneal mucinous involvement. Recent studies have demonstrated that LAMNs confined to the appendix have low or no risk for disease recurrence, progression, and peritoneal involvement during follow up. CASE REPORT: Here, we present two extremely rare cases with confined low grade appendiceal mucinous neoplasm (pTis and pT3) and simultaneous extraperitoneal subcutaneous or ovary involvement at the time of diagnosis. CONCLUSION: Our cases demonstrate that although the primary tumor is limited to the appendix, coexisting distant metastasis may occur on very rare occasions.

Clinicopathologic Characteristics of MYC Copy Number Amplification in Breast Cancer.

Introduction. MYC overexpression is a known phenomenon in breast cancer. This study investigates the correlation of MYC gene copy number amplification and MYC protein overexpression with coexisting genetic abnormalities and associated clinicopathologic features in breast cancer patients. Methods. The study analyzed data from 81 patients with localized or metastatic breast cancers using targeted next-generation sequencing and MYC immunohistochemical studies, along with pathological and clinical data. Results. Applying the criteria of MYC/chromosome 8 ratio ≥5, MYC copy number amplified tumors (n = 11, 14%) were associated with invasive ductal carcinoma (91% vs 68%, P = .048), poorly differentiated (grade 3, 64% vs 30%, P = .032), mitotically active (Nottingham mitotic score 3, 71% vs 20%, P = .004), estrogen receptor (ER)-negative (45% vs 12%, P = .008), and triple-negative (56% vs 12%, P = .013) compared to MYC non-amplified tumors. Among MYC-amplified breast cancer patients, those with triple-negative status showed significantly shorter disease-free survival time than non-triple negative MYC-amplified patients (median survival month: 25.5 vs 127.6, P = .049). MYC amplification is significantly associated with TP53 mutation (P = .007). The majority (10 of 11; 91%) of MYC-amplified tumors showed positive c-MYC immunostaining. Conclusion. Breast cancers with MYC copy number amplication display distinct clinicopathologic characteristics indicative of more aggressive behavior.

Columnar optical-radiative properties and components of aerosols in the Arctic summer from long-term AERONET measurements.

Aerosols as an external factor have an important role in the amplification of Arctic warming, yet the geography of this harsh region has led to a paucity of observations, which has limited our understanding of the Arctic climate. We synthesized the latest decade (2010-2021) of data on the microphysical-optical-radiative properties of aerosols and their multi-component evolution during the Arctic summer, taking into consideration the important role of wildfire burning. Our results are based on continuous observations from eight AERONET sites across the Arctic region, together with a meteorological reanalysis dataset and satellite observations of fires, and utilize a back-trajectory model to track the source of the aerosols. The summer climatological characteristics within the Arctic Circle showed that the aerosols are mainly fine-mode aerosols (fraction >0.95) with a radius of 0.15-0.20 µm, a slight extinction ability (aerosol optical depth âˆ¼ 0.11) with strong scattering (single scattering albedo ∼0.95) and dominant forward scattering (asymmetry factor âˆ¼ 0.68). These optical properties result in significant cooling at the Earth's surface (∼-13 W m-2) and a weak cooling effect at the top of the atmosphere (∼-5 W m-2). Further, we found that Arctic region is severely impacted by wildfire burning events in July and August, which primarily occur in central and eastern Siberia and followed in subpolar North America. The plumes from wildfire transport aerosols to the Arctic atmosphere with the westerly circulation, leading to an increase in fine-mode aerosols containing large amounts of organic carbon, with fraction as high as 97-98 %. Absorptive carbonaceous aerosols also increase synergistically, which could convert the instantaneous direct aerosol radiative effect into a heating effect on the Earth-atmosphere system. This study provides insights into the complex sources of aerosol loading in the Arctic atmosphere in summer and emphasizes the important impacts of the increasingly frequent occurrence of wildfire burning events in recent years.

Digital Pathology in the Detection of Infectious Microorganisms: An Evaluation of Its Strengths and Weaknesses Across a Panel of Immunohistochemical and Histochemical Stains Routinely Used in Diagnostic Surgical Pathology.

CONTEXT.­: The diagnosis of some infectious diseases requires their identification in tissue specimens. As institutions adopt digital pathology for primary diagnosis, the limits of microorganism detection from digital images must be delineated. OBJECTIVE.­: To assess the reliability of microorganism detection from digitized images of histochemical and immunohistochemical stains commonly used in pathology. DESIGN.­: Original glass slides from 620 surgical pathology cases evaluated for the presence of infectious microorganisms were digitized. Immunohistochemical stains included those for herpes simplex virus (n = 100), cytomegalovirus (n = 100), Helicobacter pylori (n = 100), and spirochetes (n = 80). Histochemical stains included mucicarmine for Cryptococcus spp (n = 20), Grocott methenamine silver for fungi (n = 100), Giemsa for H pylori (n = 100), and Ziehl-Neelsen for acid-fast bacilli (n = 20). The original diagnosis based on the glass slides was regarded as the reference standard. Six pathologists reviewed the digital images. RESULTS.­: Digital review was generally associated with high (ie, ≥90%) specificity and positive predictive value owing to a low percentage of false positive reads, whereas a high percentage of false negatives contributed to low sensitivity and negative predictive value for many stains. Fleiss κ showed substantial interobserver agreement in the interpretation of Grocott methenamine silver and immunostains for herpes simplex virus, H pylori, and cytomegalovirus; moderate agreement for spirochete, Ziehl-Neelsen, and mucicarmine; and poor agreement for Giemsa. CONCLUSIONS.­: Digital immunohistochemistry generally outperforms histochemical stains for microorganism detection. Digital interpretation of Ziehl-Neelsen and mucicarmine stains is associated with low scores for interrater reliability, accuracy, sensitivity, and negative predictive value such that it should not substitute for conventional review of glass slides.

MYC overexpression in inflammatory bowel disease-associated conventional dysplasia and association of subsequent low-grade dysplasia in follow-up biopsies.

OBJECTIVE: Diagnosis of inflammatory bowel disease (IBD)-associated dysplastic lesions can be challenging. This study aims to evaluate MYC immunohistochemistry (IHC) as a potential biomarker for IBD-associated dysplasia and compare its effectiveness with p53 IHC. METHODS: The study cohort included resections from 12 IBD patients with carcinoma and concurrent conventional low-grade dysplasia (LGD), as well as biopsies from 21 patients with visible conventional LGD, which were followed up for 2 years with subsequent endoscopic examination. MYC and p53 IHC and MYC-FISH analysis were performed. RESULTS: Sensitivity for LGD detection was 67% (8/12) and 50% (6/12) for MYC and p53, respectively, but the difference was not statistically significant (p = 0.2207). MYC and p53 overexpression were not always mutually exclusive, nor were they always present simultaneously. Patients who presented dysplasia in subsequent biopsies (7/21) were found to be more likely present with multiple LGD polyps and MYC-overexpressed LGD in the initial biopsies, compared to those without subsequent dysplasia (p < 0.05). These dysplastic lesions were commonly associated with chronic colitis (p = 0.0614). The distribution of LGD sites did not show a significant difference between patients with and without subsequent LGD. In MYC overexpressed cases, homogeneously strong nuclear expression was not identified in all dysplastic epithelial cells, and no MYC amplification was found in these cases by FISH. CONCLUSION: MYC IHC can complement p53 IHC as an adjunct biomarker for diagnosing IBD-associated conventional LGD and can be used for the prediction of subsequent LGD in the follow-up biopsies combined with endoscopic features.

Further prognostic stratification of intestinal type of gastric adenocarcinoma by CDX2 expression pattern.

Gastric cancer is one of the most deadly malignancies worldwide. It is routinely divided into 2 common histologic subtypes by the Lauren classification, intestinal type and diffuse type. In recent years, the intestinal type of gastric cancer has been found to represent a heterogeneous disease with divergent prognosis. Our objective was to investigate the CDX2/CK7 immunohistochemical pattern and its role in further stratifying this type of gastric cancer. Gastrectomy cases with a diagnosis of the intestinal type of gastric adenocarcinoma from a single large institution between 2008 and 2022 were collected. Forty-four cases with available blocks and enough tumor tissue were included in this study. Four different immunohistochemical patterns were identified: CDX2+/CK7+ (40.9%), CDX2-/CK7+ (34.1%), CDX2+/CK7- (18.2%), and CDX2-/CK7- (6.8%). Compared to CDX2-negative cases, CDX2-positive ones are more likely to present better prognostic histopathological features including early stage, less perineural and lymphovascular invasion, and lower nodal metastasis. In addition, CDX2 expression was associated with specific molecular features like HER2 overexpression and genetic alterations of receptor tyrosine kinase (TRK) genes including EGFR, ERBB2, ERBB3, DDR2, and MET. In conclusion, according to the CDX2 expression pattern, the intestinal type of gastric cancer could be further divided into 2 subgroups, which have different histopathological and molecular features and different prognosis.

The correlation of ESR1 genetic aberrations with estrogen receptor and progesterone receptor status in metastatic and primary estrogen receptor-positive breast carcinomas.

Genetic aberrations in the Estrogen Receptor 1 (ESR1) gene have been identified as an important mechanism of resistance to endocrine therapy in metastatic breast carcinoma. In this study, we aimed to correlate ESR1 genetic aberrations with the ER and PR status in paired metastatic and primary breast carcinomas. Patients with ER-positive breast cancer were divided into two groups: ESR1 genetic aberration (n = 26) and wild-type control (n = 29) based on genetic profiling of their metastatic tumors. Clinicopathological features and ER/PR status were analyzed in paired primary and metastatic tumors. Although there was no significant difference in ER expression between the ESR1 aberration and control groups in primary tumors, ER positivity rate in metastatic tumors was significantly higher in the ESR1 aberration group than in the control group (100% vs. 86%, P < .05). ESR1 aberrated cases were associated with more liver metastases than control tumors (46% vs. 10%, P < .01). The ER percentage and intensity slightly increased from primary to metastatic tumors in the ESR1 aberration group compared to a decrease in both in the wild-type group (percentage increase 2% vs. decrease 19%, P = .0594; intensity increase 0.04 vs. decrease 0.8, p < .05). Patients with ESR1 aberrated metastases were more likely than those with wild-type ESR1 metastases to have the following characteristics: 1) ER percentage ≥90% and intensity >2, as well as PR percentage ≥30% and intensity >1 in metastatic tumors; 2) ER percentage ≥90% and PR percentage ≥70% in primary tumors; and 3) slightly increase in ER percentage and intensity from primary to metastatic tumors. Based on the ER/PR parameters of paired primary and metastatic breast cancer, ESR1 aberration in metastasis may be predicted.

Prognostic impact of reduced HER2 protein expression in post-neoadjuvant therapy resection specimens: A single institution experience and review of the literature.

BACKGROUND: Retesting for Human epidermal growth factor receptor-2 (HER2) in post-neoadjuvant therapy resection is variable, and data is conflicting regarding the prognostic significance of changes in HER2 expression pre and post therapy. METHODS: We identified 104 patients with localized HER2 IHC 3+ breast cancer who received neoadjuvant trastuzumab(T)/pertuzumab(P) containing chemotherapy at Yale Cancer Center between 2012 and 2022. Patients were divided into 3 cohorts by response and HER2 IHC in the residual disease: Cohort 1 pathologic complete response (pCR), Cohort 2 pre-treatment IHC 3+/post treatment IHC 1+/2+, and Cohort 3 pre-treatment IHC 3+/post-treatment IHC 3+. Kaplan-Meier survival analysis was performed to assess recurrence free survival at 36 months. RESULTS: The overall pCR rate was 62.5% (65/104), while 37.5% (39/104) of patients had residual disease (RD). Among patients with RD, 58.9% (23/39) remained IHC 3+ and 41.1% (16/39) had reduced HER2 expression IHC1+ or 2+. In patients with HER2 IHC 3+ RD, 26% (6/23) developed local recurrence or distant metastasis while none of patients with post NAT HER2 IHC 1+ or 2+ RD had relapse (p = 0.0309). In patients with pCR, 6.15% (4/65) had recurrence. Kaplan-Meier survival analysis revealed superior disease-free survival in patients with reduced HER2 IHC expression compared to those with remained IHC 3+ (log rank p = 0.004). CONCLUSION: We conclude that reduced HER2 expression by IHC following neoadjuvant treatment was associated with lower recurrence rates in HER2 IHC 3+ breast cancer. If confirmed, RD HER2 IHC expression could be used as a prognostic biomarker to stratify patients in adjuvant trials and identify patients who may benefit from more intensive adjuvant therapy and post therapy surveillance.

Changes in aerosol loading before, during and after the COVID-19 pandemic outbreak in China: Effects of anthropogenic and natural aerosol.

Anthropogenic emissions reduced sharply in the short-term during the coronavirus disease pandemic (COVID-19). As COVID-19 is still ongoing, changes in atmospheric aerosol loading over China and the factors of their variations remain unclear. In this study, we used multi-source satellite observations and reanalysis datasets to synergistically analyze the spring (February-May) evolution of aerosol optical depth (AOD) for multiple aerosol types over Eastern China (EC) before, during and after the COVID-19 lockdown period. Regional meteorological effects and the radiative response were also quantitatively assessed. Compared to the same period before COVID-19 (i.e., in 2019), a total decrease of -14.6 % in tropospheric TROPOMI nitrogen dioxide (NO2) and a decrease of -6.8 % in MODIS AOD were observed over EC during the lockdown period (i.e., in 2020). After the lockdown period (i.e., in 2021), anthropogenic emissions returned to previous levels and there was a slight increase (+2.3 %) in AOD over EC. Moreover, changes in aerosol loading have spatial differences. AOD decreased significantly in the North China Plain (-14.0 %, NCP) and Yangtze River Delta (-9.4 %) regions, where anthropogenic aerosol dominated the aerosol loading. Impacted by strong wildfires in Southeast Asia during the lockdown period, carbonaceous AOD increased by +9.1 % in South China, which partially offset the emission reductions. Extreme dust storms swept through the northern region in the period after COVID-19, with an increase of +23.5 % in NCP and + 42.9 % in Northeast China (NEC) for dust AOD. However, unfavorable meteorological conditions overwhelmed the benefits of emission reductions, resulting in a +20.1 % increase in AOD in NEC during the lockdown period. Furthermore, the downward shortwave radiative flux showed a positive anomaly due to the reduced aerosol loading in the atmosphere during the lockdown period. This study highlights that we can benefit from short-term controls for the improvement of air pollution, but we also need to seriously considered the cross-regional transport of natural aerosol and meteorological drivers.

Breast Carcinoma With Tubulopapillary Features Has a Distinct Immunophenotypic and Molecular Signature: A Report of Two Tumors and Literature Review.

Breast carcinoma with tubulopapillary features is a newly described entity associated with poor prognosis with only 14 tumors reported in the literature. We report 2 additional tumors and identify novel immunohistochemical and molecular features of the tumor. The first tumor was from a 72-year-old woman with nonmetastatic breast carcinoma and the second was from a 32-year-old woman with metastatic breast carcinoma who received neoadjuvant therapy. Both tumors had high-grade nuclear features with a distinctive morphology characterized by infiltrating open glands with intratubular papillary and micropapillary projections in >90% of the invasive carcinoma. In addition to the usual predictors of aggressive behavior, both tumors showed a high expression of p16 and SOX10, which has not been previously described. Targeted tumor sequencing revealed pathogenic variants of TP53 in both tumors, in agreement with previous reports. Prior studies have shown a correlation between p16 and SOX10 expression with high-grade features and worse prognosis; typically seen in triple-negative carcinomas as demonstrated in both of our tumors. However, not all reported tumors of breast carcinoma with tubulopapillary features have demonstrated a triple-negative profile as there are a few reports of tumors with estrogen receptor and/or human epidermal growth factor 2 expression. Due to their distinct morphologic and molecular characteristics, breast carcinoma with tubulopapillary features may represent a new breast cancer histologic subtype.

Current and Emerging Molecular Markers of Liver Diseases: A Pathogenic Perspective.

In the past decade, with the rapid development of molecular medicine and the application of more sophisticated methods for disease diagnosis and treatment, a number of molecular markers have become available for liver diseases. Pathogenesis-related markers are likely to be effectively discovered and rigorously validated, due to the unique biological links to diseases. The present study reviews the predominant clinical and research articles in the previous decade to provide a pathogenic perspective of current and emerging biomarkers for liver diseases, including hepatocellular neoplasms (e.g. hepatocellular carcinoma), non-neoplastic hepatocellular diseases, intrahepatic biliary diseases, and other liver diseases. Although it remains challenging to cover all markers for the diagnosis and prognosis of liver diseases, current and emerging molecular markers in clinical practice and under investigation are reviewed in a wide spectrum of liver diseases, in order to help clinicians and researchers identify liver disease markers for reference.