Predominant Histologic Pattern Research Articles

Histopathologic Analysis of Chronic Cutaneous Graft-Versus-Host Disease.

Chronic graft-versus-host disease (cGVHD) is the leading cause of morbidity and nonrelapse mortality after allogeneic hematopoietic cell transplantation. Skin biopsy of cGVHD is recommended when clinical features are not diagnostic, yet the histopathologic features of skin cGVHD are not well described. The objective of this study is to describe the histopathologic features of skin cGVHD in epidermal, sclerotic, and combination cGVHD. Of 49 patients with skin cGVHD, 30 of 49 (61.2%) were male, and mean age was 55 years (SD 11.1). Clinically, 33 of 49 (67.3%) had epidermal cGVHD (E-cGVHD), 1 of 49 (2.1%) had sclerotic cGVHD (S-cGVHD), and 15 of 49 (30.6%) had combination disease. The 49 patients corresponded to 83 unique pathologic specimens with 67 of 83 (80.7%) taken from E-cGVHD, and 16 of 83 (19.3%) from S-cGVHD lesions. Nearly all biopsy specimens from E-cGVHD showed minimal features of active GVHD, including apoptosis in the epidermal basal layer (n = 63, 94.0%), vacuolar change (n = 62, 92.5%), and lymphocyte satellitosis (n = 57, 85.1%). The predominant histologic pattern of E-cGVHD was lichen planus/interface dermatitis (n = 31, 47.0%). S-cGVHD specimens also showed minimal features of active GVHD with apoptosis of the epidermal basal layer (n = 11, 68.8%) and vacuolar change (n = 8, 50.0%). In addition, S-cGVHD showed sclerosis of the papillary and reticular dermis and subcutaneous septae (n = 8, 50.0%; n = 11, 68.8%; n = 5, 31.2%, respectively). The predominant histologic pattern of S-cGVHD was lichen sclerosus/morphea-like pattern (n = 10, 62.5%). Although minimal pathologic features of active GVHD are common, the majority of cGVHD biopsies share features with the inflammatory skin diseases that they clinically resemble. Complete histologic reporting is recommended with implications for disease endotyping and personalized therapy.

Intratumoral heterogeneity of oncogenic drivers in mixed histology lung adenocarcinomas: How tissue selection impacts molecular testing?

Majority of the lung adenocarcinomas show a mixture of different histological patterns. The possibility of histologically heterogeneous areas of the adenocarcinoma showing genetic heterogeneity and harboring different driver mutations, with potentially significant clinical impact, has not been adequately addressed. Currently, there are no guidelines to suggest how to submit tumor tissue in adenocarcinomas with mixed histological features for molecular testing.The objective of this study is to assess intra-tumoral heterogeneity in prominent driver mutations among different morphological patterns of lung adenocarcinoma, its implications on the future of molecular testing as well as its potential impact on patient management.Twenty-three cases of mixed histology lung adenocarcinoma resected between 2018 and 2023 were retrieved from the archives. H&E slides were reviewed to identify the predominant and second most predominant histological patterns. The morphologically different tumor areas were manually macro-dissected for DNA extraction. Next-Generation Sequencing with Ion AmpliSeq™ Cancer Hotspot Panel v2 (Thermo Fisher Scientific, USA).Thirteen cases showed the same pathological variant in both histological components tested. Three cases (13 %) exhibited disparities in the variants detected across the different histological patterns tested (p=0.025). The discrepant findings had a direct therapeutic impact in 4.3 % cases. Seven cases showed no pathogenic variants detected on either of the histological components tested.This study elucidates the presence of infrequent yet significant intra-tumoral heterogeneity in the molecular profiles of mixed histology adenocarcinomas, highlighting the need for guidelines directing tissue selection for molecular testing to avoid missed therapeutic opportunities and mitigate disease relapse.

Integrating IASLC grading and radiomics for predicting postoperative outcomes in stage IA invasive lung adenocarcinoma.

The International Association for the Study of Lung Cancer (IASLC) Pathology Committee introduced a histologic grading system for invasive lung adenocarcinoma (LUAD) in 2020. The IASLC grading system, hinging on the evaluation of predominant and high-grade histologic patterns, has proven to be practical and prognostic for invasive LUAD. However, there are still limitations in evaluating the prognosis of stage IA LUAD. Radiomics may serve as a valuable complement. To establish a model that integrates IASLC grading and radiomics, aimed at predicting the prognosis of stage IA LUAD. We conducted a retrospective analysis of 628 patients diagnosed with stage IA LUAD who underwent surgical resection between January 2015 and December 2018 at our institution. The patients were randomly divided into the training set (n=439) and testing set (n=189) at a ratio of 7:3. Overall survival (OS) and disease-free survival (DFS) were taken as the end points. Radiomics features were obtained by PyRadiomics. Feature selection was performed using the least absolute shrinkage and selection operator (LASSO). The prediction models for OS and DFS were developed using multivariate Cox regression analysis, and the models were visualized through nomogram plots. The model's performance was evaluated using area under the curves (AUC), concordance index (C-index), calibration curves, and survival decision curve analysis (DCA). In total, nine radiomics features were selected for the OS prediction model, and 15 radiomics features were selected for the DFS prediction model. Patients with high radiomics scores were associated with a worse prognosis (p<0.001). We built separate prediction models using radiomics or IASLC alone, as well as a combined prediction model. In the prediction of OS, we observed that the combined model (C-index: 0.812±0.024, 3 years AUC: 0.692, 5 years AUC: 0.792) achieved superior predictive performance than the radiomics (C-index: 0.743±0.038, 3 years AUC: 0.633, 5 years AUC: 0.768) and IASLC grading (C-index: 0.765±0.042, 3 years AUC: 0.658, 5 years AUC: 0.743) models alone. Similar results were obtained in the models for DFS. The combination of radiomics and IASLC pathological grading proves to be an effective approach for predicting the prognosis of stage IA LUAD. This has substantial clinical relevance in guiding treatment decisions for early-stage LUAD.

The Grading System for Lung Adenocarcinoma: Brief Review of its Prognostic Performance and Future Directions.

Histologic grading of tumors is associated with prognosis in many organs. In the lung, the most recent grading system proposed by International association for the Study of Lung Cancer (IASLC) and adopted by the World Health Organization (WHO) incorporates the predominant histologic pattern, as well as the presence of high-grade architectural patterns (solid, micropapillary, and complex glandular pattern) in proportions >20% of the tumor surface. This system has shown improved prognostic ability when compared with the prior grading system based on the predominant pattern alone, across different patient populations. Interobserver agreement is moderate to excellent, depending on the study. IASLC/WHO grading system has been shown to correlate with molecular alterations and PD-L1 expression in tumor cells. Recent studies interrogating gene expression has shown correlation with tumor grade and molecular alterations in the tumor microenvironment that can further stratify risk of recurrence. The use of machine learning algorithms to grade nonmucinous adenocarcinoma under this system has shown accuracy comparable to that of expert pulmonary pathologists. Future directions include evaluation of tumor grade in the context of adjuvant and neoadjuvant therapies, as well as the development of better prognostic indicators for mucinous adenocarcinoma.

Histopathological spectrum of endometrial biopsies in abnormal uterine bleeding at tertiary care centre, Jodhpur

Introduction: Abnormal uterine bleeding (AUB) shows spectrum of patterns on histopathology and pathologist plays a vital role in reporting of endometrial biopsies and helps in differentiating nonneoplastic lesion from neoplastic lesions, early detection of the precursor lesions and exclusion of malignancy. Aim - The aim of this study is to study the spectrum of endometrial patterns in women with AUB and to correlate it with the different age groups. Materials and Methods: 200 samples of endometrial biopsies with AUB were received from the gynecology department, processed and stained with hematoxylin &amp; eosin and subjected to histopathological examination. Results: The peak incidence is observed in the age group of 41-50 years. The predominant histological pattern observed is secretory and proliferative pattern and disordered endometrium (68%) followed by endometrial hyperplasia (10%) and the least common pattern is atrophic endometrium (1%). 2% cases are of endometrial carcinoma found in our study. Conclusion: AUB significantly affects the quality life of women and leads to anemia. Hence histopathological examination should be considered which plays a critical role in early diagnosis of endometrial pathology and to provide appropriate gynecological management. Endometrial sampling is an effective diagnostic tool and it needs to be considered in all patients from peri- and post-menopausal age groups with AUB so to provide appropriate management.

Histopathologic Features of Unmasked Inflammatory Bowel Disease Following Immune Checkpoint Inhibitor Therapy in Colon Biopsies

Typical immune checkpoint inhibitor-induced colitis (T-ICI) has significant histomorphologic overlap with inflammatory bowel disease (IBD), a distinction further complicated in ICI-treated patients with pre-existing inflammatory bowel disease (P-IBD) and those with potentially "unmasked" inflammatory bowel disease (U-IBD) after ICI therapy. This study describes histopathologic findings seen in U-IBD colonic biopsies and assesses for distinguishing features from T-ICI and P-IBD biopsies. Initial colon biopsies after symptom onset from 34 patients on ICI therapy were reviewed, and histopathologic features were tabulated. U-IBD patients were identified clinically based on rapid toxicity development post-ICI treatment with multiple recurrences after immune suppression, frequently with regional colitis (versus pancolitis). The study cohort was classified into T-ICI (n= 20), P-IBD (n= 9), and U-IBD (n= 5) groups. The predominant histological patterns were diffuse active colitis (35%) in the T-ICI, and chronic active colitis in both the P-IBD (67%) and U-IBD (60%) groups (overall P= .003, P > .05 between the two IBD groups). None of the T-ICI biopsies demonstrated chronicity features (ie, architectural distortion score 2, basal lymphoplasmacytosis, or Paneth cell metaplasia). Only U-IBD biopsies demonstrated basal lymphoplasmacytosis (60% vs 0% in T-ICI/P-IBD, P= .002). Among available follow-up biopsies, chronicity features were present in all (4/4) U-IBD patients, including those without chronicity seen in the initial biopsy, but none (0/7) of T-ICI patients. These early results show that no definite features of chronicity were seen in colon biopsies from T-ICI patients, suggesting that the presence of those features may be a clue to U-IBD in patients without a known IBD diagnosis. Frequent basal lymphoplasmacytosis seen in U-IBD may support a recent onset of mucosal injury and early architectural remodeling.

Patterns of gastrointestinal injury in patients with chronic kidney disease: Comparison of cases with and without sevelamer crystals.

Sevelamer is a phosphate-binding resin implicated in gastrointestinal (GI) injury. This study aimed to investigate the role of sevelamer in GI injury among chronic kidney disease (CKD) patients. The study included 17 CKD patients (cases) with and 18 CKD patients (comparisons) without sevelamer crystals in specimens. All cases were on sevelamer. Six comparison patients were also taking sevelamer, but crystals were absent in tissue sections. The comparison group was thus subclassified into patients who were and were not taking sevelamer. The frequency of underlying disorders was similar between two groups, including hypertension (cases = 82%; comparisons = 78%) and diabetes mellitus (cases = 53%, comparisons = 50%). The most common presentation was GI bleeding (cases = 41%, comparisons = 33%). Predominant histological patterns were also similar, with ulcers (cases = 42%; comparisons = 39%) and acute ischaemia (cases = 35%; comparisons = 28%) being predominant in both cohorts. Of note, sevelamer was present with amyloidosis and cytomegalovirus in one study case each. Two study patients who continued sevelamer had follow-up biopsies; one showed persistent ulceration and the other appeared normal. Crystals were absent in both. GI injury in CKD patients in both groups had similar features regardless of presence of sevelamer, suggesting that it adheres to tissue rather than causes injury. The study highlights other histologically identifiable causes of intestinal injury, as well as injuries unassociated with sevelamer in patients undergoing therapy. Therefore, physicians should be cautious in attributing GI injuries to sevelamer to avoid overlooking other causes and unnecessary treatment discontinuation.

Ameloblastoma in Siriraj Hospital: A 14-Year Retrospective Analysis of Clinicopathological Characteristics Correlating to the WHO 2017 Classification

Background: Ameloblastoma is a benign, locally aggressive neoplasm eliciting frequent relapse and morbidity. Based on many updates, there is an introduction of the World Health Organization (WHO) 2017 Classification in which the terminology has been modified and re-categorized. Objective: To study natural courses, the clinicopathological characteristics, and rate of recurrence of ameloblastoma patients in Siriraj Hospital. Materials and Methods: The H&amp;E stained slides of 122 patients diagnosed with ameloblastoma between 2006 and 2019 at Siriraj Hospital were reviewed and re-classified according to the WHO 2017 Classification. The natural course of disease and the clinicopathological characteristics were analyzed. A descriptive statistical analysis was used to calculate the frequency and percentages of different variables. Results: There were 86.9% of the cases being conventional ameloblastomas, whilst the predominant histologic pattern being the follicular pattern. The treatment of choice is excision. Recurrence of ameloblastoma is thought to be the consequence of several risk factors, clinicoradiological characteristics of the tumor, anatomical locations, treatments of choice, tumoral behavior, and tumor subtypes in particular. Thirty cases presented with recurrence, of which 83.3% were conventional ameloblastomas. Most of the cases were treated with radical treatment and have free surgical resection margins. Conclusion: The clinicopathological characteristics and natural course of ameloblastoma patients in Siriraj Hospital corresponds to the WHO Classification. The present study demonstrated a high recurrence rate in patients treated with conservative surgery. Thus, the authors agree with the WHO 2017 Classification that radical surgery is recommended for patients with a history of recurrence and some specific subtypes of ameloblastomas. Keywords: Ameloblastoma; Mandible; Neoplasm; Odontogenic tumors; Oral pathology

A Pathology-based Case Series of Influenza- and COVID-19-associated Pulmonary Aspergillosis: The Proof Is in the Tissue.

Invasive pulmonary aspergillosis has emerged as a frequent coinfection in severe COVID-19, similarly to influenza; yet the clinical invasiveness is more debated. We investigated the invasive nature of pulmonary aspergillosis in histology specimens of influenza and COVID-19 intensive care unit (ICU) fatalities in a tertiary care center. In this monocentric, descriptive, retrospective case series we included adult ICU patients with PCR-proven influenza/COVID-19 respiratory failure that underwent postmortem examination and/or tracheobronchial biopsy during ICU admission from September 2009 until June 2021. Diagnosis of probable/proven viral-associated pulmonary aspergillosis (VAPA) was made based on the ICM-IAPA and ECMM/ISHAM-CAPA consensus criteria. All respiratory tissues were independently reviewed by two experienced pathologists. In the 44 patients of the autopsy-verified cohort, 6 proven influenza-associated and 6 proven COVID-19-associated pulmonary aspergillosis diagnoses were identified. Fungal disease was identified as missed-diagnosis upon autopsy in 8% of proven cases (n=1/12), yet most frequently found as confirmation of probable antemortem diagnosis (n=11/21, 52%) despite receiving antifungal treatment. Bronchoalveolar lavage galactomannan testing showed highest sensitivity for VAPA diagnosis. Among both viral entities, an impeded fungal growth was the predominant histologic pattern of pulmonary aspergillosis. Fungal tracheobronchitis was histologically indistinguishable in influenza (n=3) and COVID-19 (n=3) cases, yet macroscopically more extensive at bronchoscopy in influenza setting. Proven invasive pulmonary aspergillosis diagnosis was found regularly and with a similar histological pattern in influenza and in COVID-19 ICU case-fatalities. Our findings highlight an important need for VAPA awareness with an emphasis on mycological bronchoscopic work-up. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

Clinicopathological Features of Invasive Breast Cancer: A Five-Year Retrospective Study in Southern and South-Western Ethiopia.

Background: Breast cancer (BC) is the most common type of cancer in Ethiopia. The incidence of BC is also rising, but the exact figure is still poorly known. Therefore, this study was conducted to address the gap in epidemiological data on BC in southern and southwestern Ethiopia. Materials and Methods: This is a five-year (2015-2019) retrospective study. The demographic and clinicopathological data were collected from biopsy reports of different kinds of breast carcinomas in the pathology department of Jimma University Specialized Hospital and Hawassa University Specialized Referral Hospital. Histopathological grades and stages were conducted using Nottingham grading and TNM staging system, respectively. Collected data were entered and analyzed using SPSS Version-20 software. Results: The mean age of patients at diagnosis was 42.27 (SD = 13.57) years. The pathological stage of most BC patients was stage III, and most of them had tumor sizes greater than 5 cm. Most patients had moderately differentiated tumor grade, and mastectomy was the most common type of surgery at the time of diagnosis. Invasive ductal carcinoma was the most common histological type of BC, followed by invasive lobular carcinoma. Lymph node involvement was seen in 60.5% of cases. Lymph node involvement was associated with tumor size (χ2 = 8.55, p = 0.033) and type of surgery (χ2 = 39.69, p < 0.001). Conclusions: This study showed that BC patients in southern and southwestern Ethiopia displayed advanced pathological stages, relatively young age at diagnosis, and predominant invasive ductal carcinoma histological patterns.

A Simplified Version of the IASLC Grading System for Invasive Pulmonary Adenocarcinomas With Improved Prognosis Discrimination.

Tumor grading enables better management of patients and treatment options. The International Association for the Study of Lung Cancer (IASLC) Pathology Committee has recently released a 3-tier grading system for invasive pulmonary adenocarcinoma consisting of predominant histologic patterns plus a cutoff of 20% of high-grade components including solid, micropapillary, and complex glandular patterns. The goal of this study was to validate the prognostic value of the new IASLC grading system and to compare its discriminatory performance to the predominant pattern-based grading system and a simplified version of the IASLC grading system without complex glandular patterns. This was a single-site retrospective study based on a 20-year data collection of patients that underwent lung cancer surgery. All invasive pulmonary adenocarcinomas confirmed by the histologic review were evaluated in a discovery cohort (n=676) and a validation cohort (n=717). The median duration of follow-up in the combined dataset (n=1393) was 7.5 years. The primary outcome was overall survival after surgery. The 3 grading systems had strong and relatively similar predictive performance, but the best parsimonious model was the simplified IASLC grading system (log-rank P =1.39E-13). The latter was strongly associated with survival in the validation set ( P =1.1E-18) and the combined set ( P =5.01E-35). We observed a large proportion of patients upgraded to the poor prognosis group using the IASLC grading system, which was attenuated when using the simplified IASLC grading system. In conclusion, we identified a histologic simpler classification for invasive pulmonary adenocarcinomas that outperformed the recently proposed IASLC grading system. A simplified grading system is clinically convenient and will facilitate widespread implementation.

Frontal fibrosing alopecia, clinical and histopathological characteristics of mexican patients: an original research study and review of literature

Background: Frontal Fibrosing Alopecia (FFA) was described at twenty-century, and cases increased exponentially. FFA has a great impact on patient’s quality life. Objective: Thus, the aim of this work was report FFA cases attended during a fifteen-year period. Material and methods: A retrospective study was carried out, including patients with FFA diagnosis treated at Dermatology department. Data were obtained from the clinical files, and tissue slices were reviewed. Results: Thirty-seven patients FFA were identified. Ninety-seven percent (n= 36) were women, with an average age of 57.8 years (range between 35 to 86 years). Eighty-one percent presented with recession of implantation line as the main clinical manifestation; the predominant histological pattern was scarring alopecia, presented in 34 patients (91.8%). Discussion: Increased of the pathology was observed in the last five years, since 2017. FFA is a newly diagnosed disease with increased prevalence in Mexico, where it occurs predominantly in postmenopausal women. Conclusion: Mexican patients presented in late stages of the disease, with mean ages lower than other series, so in our country the challenge is to identify the FFA in early stage and prevent disease progression and the irreversible alopecia.

Clinicopathological Features and Status of Programmed Death Ligand-1 (PD-L1) Expression in Lung Cancer: A Single Centre Study From North India.

Introduction Programmed death ligand-1 (PD-L1) is an immunological checkpoint that supports the inhibition of the anti-tumor immune system. A higher level of PD-L1 expression was also discovered on the cell surfaces of several cancer cells, including non-small cell lung carcinoma (NSCLC). Identifying individuals who would benefit from PD-1/PD-L1 antibody immunotherapy is crucial in the era of precision medicine. The study's objective was to assess the distribution and degree of PD-L1 ligand expression in various forms of lung cancer and examine its link to clinicopathological variables. Methods This prospective, observational, cross-sectional study was done in a tertiary care hospital in North India over 2 years from 2019 to 2021. A total of 100 patients diagnosed with lung cancer through either endobronchial or image-guided biopsies were enrolled. The biopsy specimens of lung cancer patients have been subjected to immunohistochemistry (IHC) staining. PD-L1 expression was positive when at least 1% of tumor cells were stained. In our study, we used the rabbit monoclonal Anti-PD-L1 antibody (CAL10) (ab237726) (Abcam Plc, UK). Results Of the 100 patients, Squamous cell carcinoma (SQCC) was the predominant histological pattern. The mean age of the study group was 57.26 ± 10.53 years. High PDL-1 positivity (>50% ) is seen in a total of 10 patients, while low PD-L1 positivity (1-50%) is seen in 24 patients. Of all patients with high PD-L1 positivity (n=10), 80% had stage IV at the time of diagnosis. However, on similar lines, 71 % of patients with low PD-L1 positivity presented with stage IV at the time of diagnosis. (p value=0.09). Among 10 patients with epidermal growth factor receptor (EGFR) positive status, high PD-L1 positivity is seen in 20%. Among 3 patients with anaplastic lymphoma kinase (ALK) positive status, only one patient showed high PD-L1 positivity, whereas negative PDL-1 was seen in 2 patients, which was not statistically significant. Conclusion The management of lung cancer is driven by precision medicine, including PDL-1 expression, which correlates with immune checkpoint inhibitor response. In our cohort, PD-L1 expression appears to be mostly linked to the squamous cell subtype of lung cancer, with elevated tumor stage and mediastinal lymphadenopathy in Kashmiri people. Other oncogenic driver mutations are not connected to PD-L1 expression. The function of PD-L1 expression in lung tumors requires more study.

Invasive Micropapillary Urothelial Carcinoma: an Uncommon and Underreported Variant in Cystectomy Specimens.

Conventional urothelial carcinoma is the most common histological type of urinary bladder carcinoma. The latest edition of the WHO classification of tumours of the urothelial tract lays special emphasis on the ability of urothelial tumours to exhibit divergent differentiation with multiple histologic variants and a diverse genomic landscape. The presence of a micropapillary component (MPC) in urothelial carcinoma is associated with high-grade disease and poor response to intravesical chemotherapy. The present study aims to enumerate the clinicohistological features of urothelial carcinomas with micropapillary differentiation. Slides from 144 radical cystectomy specimens received over 6 years were reviewed independently by two pathologists. A predominant histological pattern along with co-existing pathology was noted. Of these, five cases were pure micropapillary carcinomas, four had conventional urothelial carcinoma with a MPC, one had a microscopic tumour at the mucosal surface, and two cases showed micropapillary histology in the lymph node metastasis, following transurethral resection of bladder tumour and Bacillus Calmette-Guerin therapy. The tumours with pure micropapillary carcinoma presented with a higher pathological stage and poor overall survival. Organ and lymph node metastasis was noted in five and eight cases, respectively, of which six showed a micropapillary pattern in the lymph nodes. Micropapillary urothelial carcinoma is a rare and aggressive variant of urothelial carcinoma with unique histologic features. This variant is often missed and underreported in biopsy and surgical resection specimens. Since the presence of MPC confers a poorer prognosis, the identification and reporting of this entity are important.

Combined analysis of gut microbiome and serum metabolomics reveals novel biomarkers in patients with early-stage non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the predominant form of lung cancer and is one of the most fatal cancers worldwide. Recently, the International Association for the Study of Lung Cancer (IASLC) proposed a novel grading system based on the predominant and high-grade histological patterns for invasive pulmonary adenocarcinoma (IPA). To improve outcomes for NSCLC patients, we combined serum metabolomics and fecal microbiology to screen biomarkers in patients with early-stage NSCLC and identified characteristic microbial profiles in patients with different grades of IPA. 26 genera and 123 metabolites were significantly altered in the early-stage NSCLC patients. Agathobacter, Blautia, Clostridium, and Muribaculacea were more abundant in the early-stage NSCLC patients compared with healthy controls. For the different grades of IPA, the characteristic microorganisms are as follows: Blautia and Marinobacter in IPA grade type 1; Dorea in IPA grade type 2; and Agathobacter in IPA grade type 3. In the metabolome results, the early-stage NSCLC group mainly included higher levels of sphingolipids (D-erythro-sphingosine 1-phosphate, palmitoyl sphingomyelin), fatty acyl (Avocadyne 1-acetate, 12(S)-HETE, 20-Carboxy-Leukotriene B4, Thromboxane B3, 6-Keto-prostaglandin f1alpha, Sebacic acid, Tetradecanedioic acid) and glycerophospholipids (LPC 20:2, LPC 18:0, LPC 18:4, LPE 20:2, LPC 20:1, LPC 16:1, LPC 20:0, LPA 18:2, LPC 17:1, LPC 17:2, LPC 19:0). Dysregulation of pathways, such as sphingolipid metabolism and sphingolipid signaling pathway may become an emerging therapeutic strategy for early-NSCLC. Correlation analysis showed that gut microbiota and serum metabolic profiles were closely related, while Muribaculacea and Clostridium were the core genera. These findings provide new biomarkers for the diagnosis of early-stage NSCLC and the precise grading assessment of prognostic-related IPAs, which are of clinical importance and warrant further investigation of the underlying molecular mechanisms.

Deep Domain Adversarial Learning for Species-Agnostic Classification of Histologic Subtypes of Osteosarcoma

Osteosarcomas (OSs) are aggressive bone tumors with many divergent histologic patterns. During pathology review, OSs are subtyped based on the predominant histologic pattern; however, tumors often demonstrate multiple patterns. This high tumor heterogeneity coupled with scarcity of samples compared with other tumor types render histology-based prognosis of OSs challenging. To combat lower case numbers in humans, dogs with spontaneous OSs have been suggested as a model species. Herein, we adversarially train a convolutional neural network to classify distinct histologic patterns of OS in humans using mostly canine OS data during training. We show that adversarial training improves domain adaption of a histologic subtype classifier from canines to humans, achieving an average multiclass F1 score of 0.77 (95% CI, 0.74-0.79) and 0.80 (95% CI, 0.78-0.81) when compared with the ground truth in canines and humans, respectively. Finally, we applied our trained model to characterize the histologic landscape of 306 canine OSs and uncovered distinct clusters with markedly different clinical responses to standard-of-care therapy.

Clinicopathological Characteristics of Advanced Epstein-Barr Virus-associated Gastric Cancer Highlighting Aberrant p53 Expression.

Epstein-Barr virus (EBV)-associated gastric cancer is a distinct subtype of stomach adenocarcinoma. Although previous studies have investigated its clinicopathological characteristics, there is a lack of research focusing on advanced EBV-associated gastric cancer. In this study, we performed a comprehensive review of advanced EBV-associated gastric cancer cases. We retrospectively collected 18 consecutive cases of surgically resected advanced EBV-associated gastric cancer. Clinicopathological parameters were investigated using histological review, immunohistochemistry, and a review of the electronic medical records of the hospital. The predominant histological pattern of advanced EBV-associated gastric cancer, according to the Laurén classification, was intestinal-type adenocarcinoma with varying degrees of differentiation. However, focal areas showing conventional gastric carcinoma with a lymphoid stromal pattern were found in all cases except one. In addition to the previously described histological patterns of EBV-associated gastric cancer, one case displayed chronic granulomatous inflammation-like histology with barely identifiable malignant epithelial cells. Another case had a pure signet-ring cell carcinoma component showing nuclear positivity for the EBV-encoded RNA in situ hybridization assay. Remarkably, five out of 18 cases (27.8%) showed aberrant p53 expression on immunostaining, which is known to occur rarely in EBV-associated gastric cancer. All cases with aberrant p53 expression had intestinal-type adenocarcinoma-like components. Advanced EBV-associated gastric cancer had distinct histology and a higher rate of aberrant p53 immunostaining pattern than conventional EBV-associated gastric cancer. Therefore, their biological behavior should be investigated separately.

Challenges Encountered and Pattern-Based Analysis of Bone Marrow Biopsy in Lymphomas: An Institutional Experience.

Objective The evaluation of bone marrow (BM) status is an integral part of the initial workup of patients diagnosed with lymphoma as it plays an important role in staging and predicting prognosis in these patients. This article determines the incidence and pattern of BM involvement in lymphoma cases and distinguishes benign from malignant lymphoid aggregates in BM biopsies. Materials and Methods The study group included 121 cases of Hodgkin and non-Hodgkin lymphomas for which BM biopsies were performed, fixed in acetic acid-zinc formalin solution, decalcified using 10% formic acid, and subjected to hematoxylin and eosin and immunohistochemistry. Results The overall incidence of BM biopsy involvement in our study was 31.4% (37/118), including 34.7% (35/101) in cases of B cell lymphomas, 25% (2/8) in cases of T cell lymphomas, and no involvement in Hodgkin lymphoma. The predominant histological pattern of BM involvement was diffused (14/37; 37.8%), followed by interstitial (10/37; 27.1%). Five cases revealed benign nonparatrabecular lymphoid aggregates which could be confused with lymphomatous involvement, especially in low grade lymphomas. Conclusion A careful examination of the BM biopsies along with clinical history, peripheral blood examination, flow cytometry, and immunohistochemistry will help in arriving at the correct diagnosis.

Validation Study of New IASLC Histology Grading System in Stage I Non-Mucinous Adenocarcinoma Comparing With Minimally Invasive Adenocarcinoma

BackgroundA new histologic grading system for pulmonary non-mucinous invasive adenocarcinoma was proposed by the International Association for the Study of Lung Cancer (IASLC). We evaluated its clinical impact on prognosis in stage I patients, including minimally invasive adenocarcinoma (MIA). Patients and Methods919 patients underwent surgery for lung adenocarcinoma between 2012 and 2019. Stage I patients (n = 500) were retrospectively reviewed. They were divided into 4 categories: MIA and 3 new IASLC grades (grades 1-3). Cox proportional hazards analysis was performed to identify risk factors associated with recurrence and mortality. Furthermore, we compared the predictability of the IASLC grading system with different models that are based on the clinicopathologic characteristics (baseline model), TNM staging, and predominant histologic pattern. The area under the receiver operating characteristic curve (AUC) was calculated for comparison. ResultsRecurrence-free survival (RFS) and overall survival (OS) were significantly stratified by the IASLC grading system in patients with stage I adenocarcinoma (P < .001 and P = .003, respectively). In multivariate analyses, IASLC grade 3 was a significant factor for RFS (hazard ratio [HR] 3.18, P < .001) and OS (HR 2.31, P = .013). The AUCs of the new IASLC model were 0.781 for recurrence and 0.770 for mortality, compared with those of the predominant pattern (0.769 for recurrence, 0.747 for death) and TNM staging (0.762 for recurrence, 0.747 for death). ConclusionThe IASLC grading system effectively predicted the prognosis of early-stage adenocarcinoma compared with previous models. The IASLC classification appears to improve the current system; therefore, precise pathologic examination for early-stage adenocarcinoma is warranted.

Glomerulonephritis with non-Randall-type, non-cryoglobulinaemic monoclonal immunoglobulin G deposits (PGNMID and ITG).

ABSTRACTBackgroundGlomerulonephritis (GN) with non-Randall-type, non-cryoglobulinaemic monoclonal immunoglobulin G deposits encompasses rare diseases [proliferative GN with non-organized deposits (PGNMID) and immunotactoid GN] that cannot be distinguished without ultrastructural analysis by electron microscopy (EM).MethodsHere, we report and analyse the prognosis of 41 EM-proven (PGNMID for 39/41) and 22 non-EM-proven/DNAJB9-negative cases, diagnosed between 2001 and 2019 in 12 French nephrology centres.ResultsMedian (interquartile range) serum creatinine (SCr) at presentation was 150 (92–256) µmol/L. The predominant histological pattern was membranoproliferative GN (79%), with IgG3 (74%) kappa (78%) deposits the most frequently observed. Disease presentation and patient management were similar between EM-proven and non-EM-proven cases. A serum monoclonal spike was detected for 21 patients and 10 had an underlying haematological malignancy. First-line therapy was mixed between clone-targeted therapy (n = 33), corticosteroids (n = 9) and RAAS inhibitors (n = 19). After 6 months, nine patients achieved complete and 23 partial renal recovery. In univariate analysis, renal recovery was associated with baseline SCr (odds ratio 0.70, P = 0.07). After a median follow-up of 52 (35–74) months, 38% of patients had progressed to end-stage kidney disease independently associated with baseline SCr [hazard ratio (HR) 1.41, P = 0.003] and glomerular crescentic proliferation (HR 4.38, P = 0.004).ConclusionsOur results confirm that non-cryoglobulinaemic and non-Randall GN with monoclonal IgG deposits are rarely associated with haematological malignancy. The prognosis is uncertain but may be improved by early introduction of a specific therapy.