Citations

E-cigarette or vaping-associated lung injury (EVALI) was initially recognized as a public health problem in 2019, but pathologic changes from vaping (if any) outside the context of EVALI remain unknown. We aimed to further characterize the pathology of EVALI and vaping-associated changes in otherwise healthy patients without EVALI, including those presenting with spontaneous pneumothorax. Archives were searched for lung specimens from these patient groups (2019 to 2025). Previously reported cases were excluded. Clinical history and pathology slides were reviewed. Sixty-three patients (43 men; mean age: 36.0±15.2 y) were enrolled, including 47 wedge resections, 15 transbronchial biopsies, and 1 core biopsy. All reported current or recent vaping, and 24 reported prior or concurrent cigarette smoking. Thirty-six met criteria for EVALI and showed characteristic histologic features; novel findings included 12 (35%) with coarse lipid vacuolization and 6 (18%) with grungy proteinosis-like deposits. Eleven patients with prior suspected EVALI had chronic respiratory symptoms with airway-centered macrophages and variable airway-centered fibrosis. The remaining 16 patients presented with spontaneous pneumothoraces without EVALI and had rare foamy or lightly pigmented macrophages in airspaces but no other abnormalities beyond secondary changes from the pneumothorax. To our knowledge, this is the largest pathologic study of EVALI and the first to review histologic findings in the lungs of otherwise healthy vapers. EVALI is less common than in 2019 but is still encountered. Outside the context of EVALI, patients who vape and develop spontaneous pneumothorax have minimal histologic changes. The role (if any) of vaping in the development of pneumothorax remains unknown.

IgA vasculitis (IgAV) and IgA nephropathy (IgAN) are closely related disorders that usually present in childhood. Pulmonary involvement is rare and histopathologic features thereof in adults are poorly understood. Institutional archives were searched for adults with IgAV or IgAN and diffuse parenchymal lung disease. Ten patients (6 men, median age 59 years) with lung tissue sampling were enrolled. Clinical history and pathology slides were reviewed. All patients were diagnosed with IgAV or IgAN before or concurrently with lung disease. Symptoms were nonspecific but hemoptysis was common. Radiologically, bilateral ground-glass opacities, consolidation, and reticulonodular densities were typical. Histologically, 6 cases (60%) featured acute or subacute diffuse alveolar hemorrhage (DAH) accompanied by definite (40%) or probable (20%) capillaritis. Two cases (20%) featured resolved DAH only, manifesting as alveolar hemosiderosis without other changes. And 2 cases featured organizing pneumonia without DAH. Five patients had a chronic interstitial pneumonia in the background, including 3 with nonspecific interstitial pneumonia (NSIP) and 2 with unclassifiable fibrosis. Findings were similar in IgAV versus IgAN. Of 4 patients with follow-up information, 2 died during hospitalization, one died 9 weeks later of secondary complications, and one was treated with rituximab and nintedanib and is alive 2 years later. To our knowledge, this is the largest series detailing pulmonary histopathologic findings in adults with IgAV or IgAN. Most cases show acute DAH with capillaritis; less commonly, old DAH, organizing pneumonia, NSIP, or unclassifiable fibrosis may be observed. Some patients do well with treatment but fatal cases also occur.

Context.— Distinguishing benign from malignant processes in small lung biopsy specimens is challenging, particularly in the presence of architectural distortion and crush artifacts. Mimics include reactive type II pneumocytes in peribronchiolar metaplasia or organizing pneumonia and benign mucinous elements, including goblet cells and submucosal glands, which can mimic adenocarcinoma with mucinous features. Objective.— To understand whether caudal-type homeobox 2 (CDX2) and cytokeratin 20 (CK20) immunoreactivity is specific to malignant epithelial processes and evaluate their expression in a range of benign, premalignant, and malignant pulmonary lesions. Design.— We assessed CDX2 and CK20 immunohistochemistry in 48 cases of interstitial lung disease with reactive type II pneumocytes, 13 foci of atypical adenomatous hyperplasia, 11 bronchiolar adenomas, 4 adenocarcinomas in situ, 25 minimally invasive adenocarcinomas, 39 pulmonary adenocarcinomas with mucinous features, 6 mucoepidermoid carcinomas, and 1 squamous papilloma with goblet cell hyperplasia. Results.— No expression of CDX2 or CK20 was observed in reactive processes, goblet cells, bronchial glands, atypical adenomatous hyperplasia, or bronchiolar adenomas. In adenocarcinomas with mucinous features (n = 39), 9 (23%) were CK20-reactive and 8 (20%) were CDX2-reactive. A minority of nonmucinous and mucinous minimally invasive adenocarcinomas (n = 25) showed immunoreactivity (3 [12%] for each marker), while all in situ adenocarcinomas were negative. Conclusions.— Our findings demonstrate that CDX2 and CK20 are not expressed in benign or reactive type II pneumocytes and are specific for malignancy, particularly adenocarcinomas with mucinous features. Immunoreactivity with either marker in small biopsy specimens can support a diagnosis of malignancy, especially in morphologically equivocal or limited samples. Absence of staining does not exclude malignancy, but immunoreactivity with CDX2 and/or CK20 provides strong supportive evidence for a malignant process.

ABSTRACT We report the first known use of a trans-sigmoidal endoscopic ultrasound-guided biopsy in a patient with a simultaneous pancreas-kidney transplant, following failed conventional percutaneous biopsy methods. A 50-year-old man with a simultaneous pancreas-kidney transplant was suspected of graft dysfunction. Multiple percutaneous biopsies were unsuccessful due to anatomical barriers. After a multidisciplinary review, a trans-sigmoidal endoscopic ultrasound approach was attempted, yielding sufficient tissue for histopathology without complications. Histology revealed no evidence of acute rejection. This novel technique expands the potential for biopsy in complex transplant anatomies and should be considered in highly selected cases within specialized centers.

AimsPolymyalgia rheumatica (PMR) is a chronic autoimmune disorder that mainly affects older adults. Pulmonary disease in PMR is rare but may be under‐recognized and pathological descriptions thereof are few. We aimed to characterize diffuse parenchymal lung disease (DPLD) in PMR.Methods and resultsInstitutional archives were searched for patients having PMR and DPLD with lung tissue sampling. After excluding cases with infection, concomitant rheumatoid arthritis, or smoking‐related DPLD only, 11 patients (9 women, median age 75 years) were enrolled. Clinical history and pathology slides were reviewed. One of the 11 patients (9%) had concomitant giant cell arteritis; the remaining patients had no other rheumatological diseases. All had been treated for PMR with immunosuppression, and most presented years later (median 6 years) with non‐specific respiratory symptoms. Radiographically, bilateral ground‐glass opacities and reticulation were typical and were usually lower lobe predominant. Histologically, fibrosis was seen in 8 of 11 (73%) patients and was unclassifiable in four; non‐specific interstitial pneumonia was encountered in three patients, and usual interstitial pneumonia was seen in only one case. Evidence of acute lung injury occurred in 9 (82%) patients, including three with acute lung injury only, usually manifesting as organizing pneumonia. Diffuse alveolar haemorrhage was seen in four cases (29%), including two patients with haemoptysis and capillaritis.ConclusionsOur data corroborate prior reports of clinically significant DPLD in some patients with PMR. Histopathological findings mirror other rheumatological disorders and include diffuse alveolar haemorrhage with capillaritis. Additional studies are warranted to clarify the association between PMR and DPLD.

Introduction. Increased steatosis on preimplant liver frozen section is associated with delayed graft function and primary nonfunction. Efforts to standardize histologic assessment have proven difficult. Frozen section artifact and lipopeliosis complicate the detection of steatosis. We aimed to develop and validate an AI model to recognize large droplet fat and fat induced artifact (FIA)/lipopeliosis on preimplantation frozen section and to correlate the AI results with post-transplant clinical parameters. Methods. The model was applied to 161 consecutive liver transplant specimens with preimplant slides. Results were correlated with traditional and Banff histologic assessment and clinical parameters. Results. By traditional assessment, steatosis ranged from 0%–40%. The AI model identified a range of 0 to 15.9% steatosis. There was no difference in patient survival by any measures of steatosis. AI steatosis correlated with increased risk of early allograft dysfunction (OR = 1.63, P < .001), respiratory failure (OR = 1.21, P = .003), and more advanced fibrosis (OR = 1.18, P = .030), but was not correlated with graft or patient survival. FIA/lipopeliosis were identified in a range of 0 to 6.42%. In univariate analysis the percentage of FIA/lipopeliosis correlated with both graft and patient survival ( P = .044 and P = .009, respectively), but was not associated with increased risk of early allograft dysfunction, respiratory failure, or advanced fibrosis. Conclusions. We developed an AI model that quantitates large droplet fat and FIA/lipopeliosis on frozen section slides and found a correlation with post-transplant outcomes. Further studies on larger, multi-institutional cohorts with higher fat containing donors are necessary to determine the role this model may have in organ acceptance decisions.

ABSTRACT Capillary malformation-arteriovenous type 2 syndrome (CM-AVM2) is a rare, genetic vascular disorder associated with abnormal capillary malformations and arteriovenous malformations. We present a case of CM-AVM2 with refractory diarrhea and failure to thrive due to aberrant, telangiectatic capillaries, and subepithelial collagen deposition found throughout the GI tract on bidirectional endoscopy. The patient was recalcitrant to standard therapies, so bevacizumab was trialed, but the patient expired. This is the first case of CM-AVM2 with diffuse GI mucosal involvement resulting in malabsorption. There is no treatment for this pathology, but treatment with bevacizumab or a mammalian target of rapamycin inhibitor may be efficacious.

Transbronchial cryobiopsies (CB) are increasingly replacing surgical biopsies (video-assisted thoracoscopic/VATS biopsies) for diagnosing diffuse parenchymal lung disease (interstitial lung disease, ILD), but there is very little guidance for pathologists on CB interpretation. Here we propose a fairly simple approach. First, if the diagnosis can be made on a traditional forceps biopsy, it can be made on a cryobiopsy. Many diseases with specific features will fall into this category (eg, sarcoidosis or Langerhans cell histiocytosis). More problematic are patterns such as usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia (NSIP), in which low-power architecture is the key to diagnosis. In this circumstance, an adequate sample is crucial to look for features such as fibroblast foci, because a combination of fibroblast foci plus any patchy old fibrosis, fibrotic architectural remodeling, or honeycombing, allows a diagnosis of a UIP pattern. However, in most instances, CB will not separate the UIP patterns seen in idiopathic pulmonary fibrosis, fibrotic hypersensitivity pneumonitis, or connective tissue disease-interstitial lung disease (CTD-ILD), although giant cells/granulomas (uncommon findings) in this setting favor fibrotic hypersensitivity pneumonitis. Fibroblast foci can be difficult to differentiate from organizing pneumonia (OP), but granulation tissue plugs clearly in airspaces favor OP. Absent fibroblast foci, patchy old fibrosis, architectural distortion, and honeycombing by themselves do not allow a specific diagnosis. NSIP in CB microscopically looks like NSIP in VATS biopsies, and the presence of an NSIP or an NSIP+OP pattern is typical of CTD-ILD. All the above diagnoses require correlation with clinical and radiologic findings.

Abstract Introduction: Endobronchial optical coherence tomography (EB-OCT) imaging has unique potential to diagnose and quantify early, microscopic disease changes and assess therapeutic responsivity in interstitial lung disease (ILD). However, training and time requirements for interpretation and quantitative evaluation of large volumetric EB-OCT datasets need to be optimized to facilitate clinical adoption. We develop and validate a computationally-efficient, rapid EB-OCT quantitative image analysis framework using artificial intelligence (AI) with deep learning architecture for 2D feature segmentation, 3D feature burden and spatial distribution mapping, and computer-aided diagnosis in early ILD subjects. Methods: Volumetric EB-OCT datasets, consisting of 2D cross-sectional images, were acquired from multiple locations in the bilateral lungs of ILD and healthy control subjects. EB-OCT features were manually segmented from cross-sectional images by an expert EB-OCT reader, including fibrosis, microscopic honeycombing, traction bronchiolectasis, normal parenchyma, and emphysema. EB-OCT images with corresponding feature segmentations were used to train and validate a multiclass convolutional neural network. The 2D AI-based segmentation model was subsequently evaluated against manual ‘ground truth’ segmentations for each feature in a de novo ‘test’ dataset of independent subjects using dice similarity score, precision, recall/sensitivity, specificity, and balanced accuracy. To generate 3D AI-based quantitative feature burden and spatial distribution maps, AI-based feature segmentation was performed on each EB-OCT 2D cross-sectional image within a volumetric imaging site. Three external pathologist readers independently interpreted 3D AI-based features maps for each EB-OCT imaging site acquired for a subject (without access to EB-OCT images) and provided a single diagnosis of usual interstitial pneumonia (UIP) or non-UIP ILD. Performance of computer-aided ILD diagnosis was compared against independently evaluated histopathology, clinical diagnosis, and prior EB-OCT image interpretation. Results: EB-OCT was acquired in 51 subjects: 30 in vivo early ILD, 5 in vivo non-ILD controls, and 16 ex vivo end-stage ILD. Overall pixel similarity between 2D manual and AI-based segmentation demonstrated high accuracy for each ILD feature (mean balanced accuracy 0.9). 3D quantitative AI-based feature maps demonstrated strong agreement (Spearman ρ0.87, p&lt;0.001) between manual and AI-based segmentation. AI-based computer-aided diagnosis demonstrated 100% sensitivity/specificity for histologic UIP and clinical IPF for all pathologist readers, with improved diagnostic accuracy and significantly reduced training (45-minute training, 75% reduction) and interpretation time (&lt;1 minute per subject for computer-aided diagnosis, 88% reduction) compared to EB-OCT image interpretation. Conclusion: The AI-based EB-OCT image analysis framework could expedite computer-aided diagnosis of early ILD and robust, quantitative assessment of microscopic disease burden, progression, and therapeutic responsivity.