Continuity of interstitial spaces within and outside the human lung.

There is a body-wide network of interstitial spaces that includes three components: a large-scale fascial network made up of fluid-filled spaces containing collagens and other extracellular matrix components like hyaluronic acid (HA), the peri-vascular/capillary interstitium, and intercellular interstitial spaces. Staining for HA within the colon, skin, and liver has demonstrated spatial continuity of the fascial interstitium across tissue layers and between organs, while continuity of HA staining between perineurial and adventitial sheathes beyond organ boundaries confirmed that they also participate in this body-wide network. We asked whether the pulmonary interstitium comprises a continuous organ-wide network that also connects to the body-wide interstitium via routes along nerves and the vasculature.

Whipple Disease Initial Presentation as Supraclavicular Lymphadenopathy in a Patient With Rheumatoid Arthritis: A Diagnostic Challenge.

Whipple disease is a rare systemic disease caused by It can present with a wide range of nonspecific symptoms that might overlap with underlying medical conditions, posing a diagnostic challenge. We present a 61-year-old man with a past medical history of rheumatoid arthritis and chronic inflammatory demyelinating polyneuropathy, who presented with persistent leukocytosis and supraclavicular lymphadenopathy. A positron emission tomography scan revealed hypermetabolic activity in the supraclavicular, abdominal, and pelvic lymph nodes along with a myocardial hypermetabolic lesion, concerning a lymphoproliferative disorder versus sarcoidosis.

Pathobiology of Aortic Aneurysms and Dissections: Synthesis of Recent Investigations and Evolving Insights.

The pathobiology of aortic disease is linked to aortic region: atherosclerosis for abdominal aorta, primary medial degeneration or aortitis for ascending thoracic aorta, and all causes for descending thoracic aorta and thoracoabdominal lesions. The pathogenesis of aortic dissection involves damage of the outer media from impaired perfusion from dysfunctional vasa vasorum, formation of discrete foci of disrupted vascular smooth muscle cell-elastic fiber extension-contractile units, and imbalance of radial sheer stress across the aortic wall, thereby creating an intimal tear and linear dissection. Thoracic aortic aneurysms develop from the chronic progression of medial degeneration coupled with the weakening of the remodeled adventitia, allowing for aortic dilatation.

Co-occurrence of thymoma and acute T-lymphoblastic leukemia/lymphoma: a case report and literature review.

Background: A thymoma is a tumor originating from thymic epithelial cells variably associated with non-neoplastic lymphocytes. T-lymphoblastic leukemia/lymphoma (T-LBL) is thought to arise from precursor T-cells from bone marrow-derived hematopoietic stem cells that migrate to the thymus. While the association of secondary hematopoietic malignancies in thymoma is well established, only rarely in the literature have T-LBL and thymoma been seen in association and the relationship is poorly understood.

Insights from autopsy-initiated pathological studies of the pathogenesis and clinical manifestations of atherosclerosis and ischemic heart disease: Part I. Atherosclerosis.

Context: Ischemic heart disease (IHD) due to coronary atherosclerosis constitutes the leading cause of morbidity and mortality worldwide. This review was undertaken to document the historical basis for our contemporary understanding of atherosclerosis-based disease and to provide a rationale for continued support for autopsy-based research to make further progress in reducing the morbidity and mortality from atherosclerosis-related disease.

Objectives: To analyze the contributions of the autopsy-initiated pathological studies to complement and validate other lines of investigation in determining the pathology and pathogenesis of the leading worldwide cause of morbidity and mortality, namely, atherosclerosis and its major complications of coronary atherosclerosis, ischemic heart disease, coronary thrombosis, acute myocardial infarction, and sudden cardiac death.

Insights from autopsy-initiated pathological studies of the pathogenesis and clinical manifestations of atherosclerosis and ischemic heart disease: Part II. Ischemic heart disease.

Context: Ischemic heart disease (IHD) due to coronary atherosclerosis constitutes the leading cause of morbidity and mortality worldwide. This review was undertaken to retrospectively analyze the lines of research that generated the evidence for our contemporary understanding of atherosclerosis-based coronary artery disease and to provide a rationale for continued support for autopsy-based research in order to make further progress in reduction of the morbidity and mortaility from IHD.

Objectives: To analyze the contributions of the autopsy to complement and validate other lines of investigation in determining the complex interactions between coronary artery alterations linked to the major manifestations of coronary atherosclerosis, namely, coronary thrombosis, acute myocardial infarction, and sudden cardiac death.

Diseases Involving the Lung Peribronchovascular Region: A CT Imaging Pathologic Classification.

Topic Importance: Chest CT imaging holds a major role in the diagnosis of lung diseases, many of which affect the peribronchovascular region. Identification and categorization of peribronchovascular abnormalities on CT imaging can assist in formulating a differential diagnosis and directing further diagnostic evaluation.

Review Findings: The peribronchovascular region of the lung encompasses the pulmonary arteries, airways, and lung interstitium.

Mapping the landscape of histomorphological cancer phenotypes using self-supervised learning on unannotated pathology slides.

Cancer diagnosis and management depend upon the extraction of complex information from microscopy images by pathologists, which requires time-consuming expert interpretation prone to human bias. Supervised deep learning approaches have proven powerful, but are inherently limited by the cost and quality of annotations used for training. Therefore, we present Histomorphological Phenotype Learning, a self-supervised methodology requiring no labels and operating via the automatic discovery of discriminatory features in image tiles.

Amyloid and collagen templates in aortic valve calcification.

Calcific aortic valve disease (CAVD) is a widely prevalent heart disorder in need of pharmacological interventions. Calcified areas in aortic valves often contain amyloid fibrils that promote calcification in vitro. This opinion paper suggests that amyloid contributes to CAVD development; amyloid-assisted nucleation can accelerate hydroxyapatite deposition onto collagen matrix.

Integrative multi-omics profiling in human decedents receiving pig heart xenografts.

In a previous study, heart xenografts from 10-gene-edited pigs transplanted into two human decedents did not show evidence of acute-onset cellular- or antibody-mediated rejection. Here, to better understand the detailed molecular landscape following xenotransplantation, we carried out bulk and single-cell transcriptomics, lipidomics, proteomics and metabolomics on blood samples obtained from the transplanted decedents every 6 h, as well as histological and transcriptomic tissue profiling. We observed substantial early immune responses in peripheral blood mononuclear cells and xenograft tissue obtained from decedent 1 (male), associated with downstream T cell and natural killer cell activity.

Inflammation in the tumor-adjacent lung as a predictor of clinical outcome in lung adenocarcinoma.

Approximately 30% of early-stage lung adenocarcinoma patients present with disease progression after successful surgical resection. Despite efforts of mapping the genetic landscape, there has been limited success in discovering predictive biomarkers of disease outcomes. Here we performed a systematic multi-omic assessment of 143 tumors and matched tumor-adjacent, histologically-normal lung tissue with long-term patient follow-up.

DIAPH1-MFN2 interaction regulates mitochondria-SR/ER contact and modulates ischemic/hypoxic stress.

Inter-organelle contact and communication between mitochondria and sarco/endoplasmic reticulum (SR/ER) maintain cellular homeostasis and are profoundly disturbed during tissue ischemia. We tested the hypothesis that the formin Diaphanous-1 (DIAPH1), which regulates actin dynamics, signal transduction and metabolic functions, contributes to these processes. We demonstrate that DIAPH1 interacts directly with Mitofusin-2 (MFN2) to shorten mitochondria-SR/ER distance, thereby enhancing mitochondria-ER contact in cells including cardiomyocytes, endothelial cells and macrophages.

Updates on lung adenocarcinoma: invasive size, grading and STAS.

Advancements in the classification of lung adenocarcinoma have resulted in significant changes in pathological reporting. The eighth edition of the tumour-node-metastasis (TNM) staging guidelines calls for the use of invasive size in staging in place of total tumour size. This shift improves prognostic stratification and requires a more nuanced approach to tumour measurements in challenging situations.

Immune response after pig-to-human kidney xenotransplantation: a multimodal phenotyping study.

Background: Cross-species immunological incompatibilities have hampered pig-to-human xenotransplantation, but porcine genome engineering recently enabled the first successful experiments. However, little is known about the immune response after the transplantation of pig kidneys to human recipients. We aimed to precisely characterise the early immune responses to the xenotransplantation using a multimodal deep phenotyping approach.

HHV-6 Myocarditis Progressing to Ventricular Standstill Requiring Cardiac Transplant.

Human herpesvirus-6 (HHV-6) is an increasingly recognized cause of myocarditis. We present the case of a 46-year-old woman who presented with fulminant HHV-6 myocarditis requiring heart transplantation. ().

Correlation of Programmed Death-Ligand 1 Expression With Lung Adenocarcinoma Histologic and Molecular Subgroups in Primary and Metastatic Sites.

Programmed death-ligand 1 (PD-L1) expression in terms of the tumor proportion score (TPS) is the main predictive biomarker approved for immunotherapy against lung nonsmall cell carcinoma. Although some studies have explored the associations between histology and PD-L1 expression in pulmonary adenocarcinoma, they have been limited in sample size and/or extent of examined histologic variables, which may have resulted in conflicting information. In this observational retrospective study, we identified primary and metastatic lung adenocarcinoma cases in the span of 5 years and tabulated the detailed histopathologic features, including pathological stage, tumor growth pattern, tumor grade, lymphovascular and pleural invasion, molecular alterations, and the associated PD-L1 expression for each case.

Extensive fibrosis in mediastinal seminoma is a diagnostic pitfall in small biopsies: two case reports.

Background: In mediastinal biopsies that show fibrosis, the differential diagnosis includes fibrosing mediastinitis, immunoglobulin G subclass 4-related disease, Hodgkin lymphoma, as well as reactive fibrotic and inflammatory changes adjacent to other processes including neoplasms.

Cases Description: We report two cases of incidentally detected mediastinal seminoma that contained extensive areas of paucicellular fibrosis, which precluded accurate preoperative biopsy diagnosis. The fibrosis consisted of mildly inflamed, densely scarred tissue with thin dilated vessels, and was present to a significant extent that is suggestive of spontaneous regression.