Imaging features of perinephric myxoid pseudotumors of fat.

OBJECTIVE: Retrospectively evaluate multimodality imaging features of perinephric myxoid pseudotumor of fat (PMPTF). METHODS: Institutional cases of PMPTF with CT, MRI and/or ultrasound evaluation from 1/1/2020 to 9/1/2023 were retrospectively reviewed. Patient demographics and clinical history were reviewed, and imaging features recorded. RESULTS: 14 patients with pathologically-proven PMPTF were identified (11 M, 3 F; mean age 66.7 ± 17.0 years; range 40-87 years). Three patients (18%) had bilateral lesions; a total of 17 PMPTFs were reviewed. 15/17 (88%) were biopsy-proven; two cases were diagnosed by imaging only in patients with a contralateral biopsy-proven PMPTF. All evaluable specimens were negative for MDM2 amplification. 11/17 (65%) occurred in patients with renal disease, including 4/17 (24%) in patients with renal transplant. 100% (17/17) had CT, 11/17 (65%) MRI, and 6/17 (35%) ultrasound. The mean largest lesion dimension was 10.9 ± 4.6 cm (range 4.3-17.0 cm). Of cases involving native kidneys, 7/13 (54%) presented as multifocal perinephric masses and 5/13 (38%) as a solitary perinephric mass. All four transplant cases presented as infiltrative-appearing masses involving the renal sinus with lesser perinephric involvement. 14/17 (82%) lesions contained macroscopic fat on CT and MRI and 3/17 (18%) showed no macroscopic fat, all involving renal transplants. All cases with MRI demonstrated T2 hyperintensity with signal dropout on opposed-phase imaging. 11/13 (85%) PMPTF showed no or equivocal CT enhancement. Enhancement was better seen on MRI in all cases evaluated by both CT and MRI. Of the six PMPTFs imaged by ultrasound, four (67%) were heterogeneously hypoechoic and two (33%) had mixed regions of hypo-, iso- and hyperechogenicity relative to adjacent renal parenchyma. CONCLUSIONS: PMPTF is a rare, benign, and underrecognized lesion that may mimic malignancy, particularly retroperitoneal well-differentiated liposarcoma. The imaging features of this unusual pseudosarcoma differ in native and transplanted kidneys. Improved awareness of this entity will facilitate appropriate patient management and avoid unnecessary intervention.

Primary Pulmonary Myxoid Sarcoma and Thoracic Angiomatoid Fibrous Histiocytoma: Two Sides of the Same Coin?

Primary pulmonary myxoid sarcoma (PPMS) and thoracic angiomatoid fibrous histiocytoma (AFH) are rare neoplasms with EWSR1 fusions and overlapping morphology. Both tumor types often show epithelial membrane antigen expression, but AFH characteristically co-expresses desmin. We encountered a case of PPMS with the unexpected finding of patchy, strong anaplastic lymphoma kinase (ALK) (previously reported in AFH) and synaptophysin expression. We evaluated a cohort of PPMS and thoracic AFH with systematic morphologic comparison and surveyed for aberrant expression of ALK and synaptophysin. Medical records and slides were reviewed for 16 molecularly confirmed cases of PPMS (n=5) and thoracic AFH (n=11). Each case was scored for morphologic characteristics typical of PPMS and/or AFH. ALK, synaptophysin, chromogranin, desmin, and epithelial membrane antigen immunostains were performed on cases with available tissue. AFH and PPMS cases showed similar age at presentation and long-term tumor behavior. Almost all cases of PPMS and AFH had a fibrous pseudocapsule and lymphoid rim. All PPMS had myxoid stroma and reticular growth pattern, but these features were also present in a subset of AFH. Synaptophysin expression was present in 6 of 11 AFH and 1 of 5 PPMS; all tested cases were negative for chromogranin (n=15). One case of AFH and 1 case of PPMS showed focally strong coexpression of synaptophysin and ALK. AFH and PPMS show considerable clinicopathologic overlap. When supportive, the immunohistochemical findings described may aid in diagnosis before molecular confirmation. PPMS and AFH may be morphologic variants of the same clinicopathologic entity, which can show more immunophenotypic variability than previously reported.

Usefulness and Limitations of Current Diagnostic Strategies for Pulmonary Mucosa-Associated Lymphoid Tissue Lymphoma: Lessons Learned From a Large Cohort.

CONTEXT.­: The pathologic diagnosis of pulmonary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) is challenging. OBJECTIVE.­: To evaluate the diagnostic usefulness and limitations of current diagnostic strategies for pulmonary MALT lymphoma. DESIGN.­: A retrospective review of 120 cases of pulmonary MALT lymphoma from 2014 through 2021 was performed. RESULTS.­: Clinicoradiologic presentations overlapped with previous observations in patients with MALT lymphoma, such as a wide age range, female predominance, frequent association with autoimmune disease or immunodeficiency, and broad imaging findings. The histopathologic diagnosis was based on a combination of morphology, immunohistochemistry, and demonstration of B-cell lineage clonality. Two-thirds (76 of 113) of MALT lymphomas had lymphoplasmacytoid cytomorphology. Occasionally, MALT lymphomas were associated with granulomas/giant cells (29%, 35 of 120) or immunoglobulin deposition disease (21%, 25 of 120), including light chain/heavy chain deposition disease, amyloidosis, and/or crystal storing histiocytosis. While CD5, CD10, Bcl-2, and Bcl-6 rarely revealed aberrancies, aberrant CD43 expression either on B-cells or on plasma cells was detected in 42% (27 of 64) of cases, including cases for which proof of clonality could not be obtained. κ/λ in situ hybridization was particularly useful for tumors with lymphoplasmacytoid morphology but performed poorly in lymphomas having no plasmacytic differentiation. κ/λ immunohistochemistry showed no additional usefulness when applied together with κ/λ in situ hybridization. Immunoglobulin gene rearrangement studies by polymerase chain reaction achieved high detection rates of clonality in all cytomorphologic subgroups. CONCLUSIONS.­: Our study offers a practical evaluation of common diagnostic tests in pulmonary MALT lymphoma. We offer recommendations for a diagnostic workup that takes into consideration the usefulness and the specific limitations of the various diagnostic strategies.

Two tumors with combined features of bronchiolar adenoma/ciliated muconodular papillary tumor and sclerosing pneumocytoma.

OBJECTIVES: Bronchiolar adenoma/ciliated muconodular papillary tumor (BA/CMPT) and sclerosing pneumocytoma (SP) are both rare and morphologically unique peripheral lung tumors with indolent behavior. These tumors have not been previously described as showing overlapping morphologic features and are generally genetically distinct. METHODS: Two cases were recently encountered that show hybrid morphologic features between BA/CMPT and SP, and the morphology and immunophenotype are described in detail. RESULTS: Both cases showed interstitial round cells typical of SP (TTF1+, EMA+), as well as areas more typical of BA/CMPT. One case showed BRAFV600E expression in the BA/CMPT areas but not in the SP-like cells. CONCLUSIONS: Although it is possible that these cases represent collision tumors or are examples of unusual metaplastic epithelial changes in SP, they also raise the possibility that these 2 entities could occasionally coexist in true hybrid tumors.

Standardized Classification of Lung Adenocarcinoma Subtypes and Improvement of Grading Assessment Through Deep Learning.

The histopathologic distinction of lung adenocarcinoma (LADC) subtypes is subject to high interobserver variability, which can compromise the optimal assessment of patient prognosis. Therefore, this study developed convolutional neural networks capable of distinguishing LADC subtypes and predicting disease-specific survival, according to the recently established LADC tumor grades. Consensus LADC histopathologic images were obtained from 17 expert pulmonary pathologists and one pathologist in training. Two deep learning models (AI-1 and AI-2) were trained to predict eight different LADC classes. Furthermore, the trained models were tested on an independent cohort of 133 patients. The models achieved high precision, recall, and F1 scores exceeding 0.90 for most of the LADC classes. Clear stratification of the three LADC grades was reached in predicting the disease-specific survival by the two models, with both Kaplan-Meier curves showing significance (P = 0.0017 and 0.0003). Moreover, both trained models showed high stability in the segmentation of each pair of predicted grades with low variation in the hazard ratio across 200 bootstrapped samples. These findings indicate that the trained convolutional neural networks improve the diagnostic accuracy of the pathologist and refine LADC grade assessment. Thus, the trained models are promising tools that may assist in the routine evaluation of LADC subtypes and grades in clinical practice.

Lymphoid Interstitial Pneumonia (LIP) Revisited: A Critical Reappraisal of the Histologic Spectrum of "Radiologic" and "Pathologic" LIP in the Context of Diffuse Benign Lymphoid Proliferations of the Lung.

The use of lymphoid interstitial pneumonia (LIP) as a diagnostic term has changed considerably since its introduction. Utilizing a multi-institutional collection of 201 cases from the last 20 years that demonstrate features associated with the LIP rubric, we compared cases meeting strict histologic criteria of LIP per American Thoracic Society (ATS)/European Respiratory Society (ERS) consensus ("pathologic LIP"; n=62) with cystic cases fulfilling radiologic ATS/ERS criteria ("radiologic LIP"; n=33) and with other diffuse benign lymphoid proliferations. "Pathologic LIP" was associated with immune dysregulation including autoimmune disorders and immune deficiency, whereas "radiologic LIP" was only seen with autoimmune disorders. No case of idiopathic LIP was found. On histology, "pathologic LIP" represented a subgroup of 70% (62/88) of cases with the distinctive pattern of diffuse expansile lymphoid infiltrates. In contrast, "radiologic LIP" demonstrated a broad spectrum of inflammatory patterns, airway-centered inflammation being most common (52%; 17/33). Only 5 cases with radiologic cysts also met consensus ATS/ERS criteria for "pathologic LIP." Overall, broad overlap was observed with the remaining study cases that failed to meet consensus criteria for "radiologic LIP" and/or "pathologic LIP." These data raise concerns about the practical use of the term LIP as currently defined. What radiologists and pathologist encounter as LIP differs remarkably, but neither "radiologic LIP" nor "pathologic LIP" present with sufficiently distinct findings to delineate such cases from other patterns of diffuse benign lymphoid proliferations. As a result of this study, we believe LIP should be abandoned as a pathologic and radiologic diagnosis.

Primary Pulmonary Hyalinizing Clear Cell Carcinoma: Case Series With Review of Literature.

Background: Hyalinizing clear cell carcinomas of tracheobronchial origin are very rare salivary gland type tumors accounting for less than 1% of lung tumors with only 13 cases reported to date. Their radiological features, morphological spectrum, and molecular features are not well described. Aim: To perform a clinicopathological analysis of primary pulmonary hyalinizing clear cell carcinomas. Method: A retrospective search of primary pulmonary hyalinizing clear cell carcinomas was conducted from authors' institutions and the clinicopathological features including details of molecular testing were analyzed. Results: Five primary pulmonary hyalinizing clear cell carcinomas were identified. The mean patient age at diagnosis was 48.2 years (range: 33-64 years). Three patients were women. All patients were nonsmokers and 3 were symptomatic; 2 were detected incidentally during health screening. The tumors were located in the main lobar bronchi ranging from 1.3 to 4.9 cm in maximum dimension. Microscopy showed cords and nests of at least, focally clear tumor cells. Mucin cysts lacking goblet cells were seen. All tumors were uniformly positive for p40, p63, AE1/AE3, keratin 7, and epithelial membrane antigen but negative for TTF1, KIT, neuroendocrine markers, and other myoepithelial markers. All cases showed Ewing sarcoma breakpoint region 1 (EWSR1) gene rearrangement. Perineural invasion and lymph node metastases were detected in patient 5. Two patients with available follow-up data were recurrence-free until 4 years (patient 1) and 9 months (patient 5) after resection. Conclusion: The present series adds to the scant available literature on primary pulmonary hyalinizing clear cell carcinomas highlighting the characteristic histomorphology, immunoprofiles, and benign outcomes of these rare tumors.

Diagnosing myocarditis in endomyocardial biopsies: survey of current practice.

BACKGROUND: Dallas criteria (DC) and European Society of Cardiology criteria (ESCC) have provided valuable frameworks for the histologic diagnosis and classification of myocarditis in endomyocardial biopsy (EMB) specimens. However, the adaptation and the usage of these criteria are variable and depend on local practice settings and regions/countries. Moreover, several ancillary tests that are not included in the current criteria, such as immunohistochemistry (IHC) or viral polymerase chain reaction (PCR), have proven useful for the diagnosis of myocarditis. METHOD: As a joint effort from the Association for European Cardiovascular Pathology (AECVP) and the Society for Cardiovascular Pathology (SCVP), we conducted an online survey to understand the current practice of diagnosing myocarditis. RESULT: A total of 100 pathologists from 23 countries responded to the survey with the majority practicing in North America (45%) and Europe (45%). Most of the pathologists reported to examine less than 200 native heart biopsies per year (85%), and to routinely receive 3-5 fragments of tissue per case (90%). The number of hematoxylin-eosin-stained levels for each case varies from 1 to more than 9 levels, with 20% of pathologists routinely asking for more than 9 levels per case. Among the 100 pathologists, 52 reported to use the DC alone, 12 the ESCC alone, 28 both DC and ESCC and 8 reported to use neither the DC nor the ESCC. Overall, 80 pathologists reported to use the DC and 40 the ESCC. Use of DC alone is more common among North American pathologists compared to European ones (80% vs 32.6%) while use of ESCC alone is more common in Europe (20.9% vs 2.5%). IHC is utilized in either every case or selected cases by 79% of participants, and viral PCR is performed by 35% of participants. Variable terminologies are used in reporting, including both histological and clinical terms. The diagnosis of myocarditis is rendered even in the absence of myocyte injury (e.g., in cases of borderline or inactive/chronic myocarditis) by 46% respondents. The majority of the participants think it is time to update the current criteria (83%). CONCLUSIONS: The survey data demonstrated that pathologists who render a myocarditis diagnosis practice with variable tissue preparation methods, use of ancillary studies, guideline usage, and reporting. This result highlights the clinically unmet need to update and standardize the current diagnostic criteria for myocarditis on EMB. Additional studies are warranted to establish standard of practice.

The E-cigarette or Vaping Product Use-Associated Lung Injury Epidemic: Pathogenesis, Management, and Future Directions: An Official American Thoracic Society Workshop Report.

E-cigarette or vaping product use-associated lung injury (EVALI) is a severe pulmonary illness associated with the use of e-cigarettes or vaping products that was officially identified and named in 2019. This American Thoracic Society workshop was convened in 2021 to identify and prioritize research and regulatory needs to adequately respond to the EVALI outbreak and to prevent similar instances of disease associated with e-cigarette or vaping product use. An interdisciplinary group of 26 experts in adult and pediatric clinical care, public health, regulatory oversight, and toxicology were convened for the workshop. Four major topics were examined: 1) the public health and regulatory response to EVALI; 2) EVALI clinical care; 3) mechanisms contributing to EVALI; and 4) needed actions to address the health effects of EVALI. Oral presentations and group discussion were the primary modes used to identify top priorities for addressing EVALI. Initiatives including a national EVALI case registry and biorepository, integrated electronic medical record coding system, U.S. Food and Drug Administration regulation and enforcement of nicotine e-cigarette standards, regulatory authority over nontobacco-derived e-cigarettes, training in evaluating exogenous exposures, prospective clinical studies, standardized clinical follow-up assessments, ability to more readily study effects of cannabinoid e-cigarettes, and research to identify biomarkers of exposure and disease were identified as critical needs. These initiatives will require substantial federal investment as well as changes to regulatory policy. Overall, the workshop identified the need to address the root causes of EVALI to prevent future outbreaks. An integrated approach from multiple perspectives is required, including public health; clinical, basic, and translational research; regulators; and users of e-cigarettes. Improving the public health response to reduce the risk of another substantial disease-inducing event depends on coordinated actions to better understand the inhalational toxicity of these products, informing the public of the risks, and developing and enforcing regulatory standards for all e-cigarettes.

Periosteal chondrosarcoma: an unusual juxtacortical sarcoma.

Periosteal chondrosarcoma is a rare tumor. It can be difficult to diagnose radiographically and pathologically and can be confused with periosteal osteosarcoma; however, the treatment of these two lesions is quite different. Increased awareness of imaging features of this lesion, particularly those that can help differentiate it from other surface-based tumors, can help one recognize this entity. We report the case of a periosteal chondrosarcoma in a young woman, highlighting the diagnostic imaging features of this disease, and her treatment with a joint-sparing geometric resection of the distal femur, using patient-specific 3D-printed cutting guides and matched allograft reconstruction.

Overcoming the Interobserver Variability in Lung Adenocarcinoma Subtyping: A Clustering Approach to Establish a Ground Truth for Downstream Applications.

CONTEXT.­: The accurate identification of different lung adenocarcinoma histologic subtypes is important for determining prognosis but can be challenging because of overlaps in the diagnostic features, leading to considerable interobserver variability. OBJECTIVE.­: To provide an overview of the diagnostic agreement for lung adenocarcinoma subtypes among pathologists and to create a ground truth using the clustering approach for downstream computational applications. DESIGN.­: Three sets of lung adenocarcinoma histologic images with different evaluation levels (small patches, areas with relatively uniform histology, and whole slide images) were reviewed by 17 international expert lung pathologists and 1 pathologist in training. Each image was classified into one or several lung adenocarcinoma subtypes. RESULTS.­: Among the 4702 patches of the first set, 1742 (37%) had an overall consensus among all pathologists. The overall Fleiss κ score for the agreement of all subtypes was 0.58. Using cluster analysis, pathologists were hierarchically grouped into 2 clusters, with κ scores of 0.588 and 0.563 in clusters 1 and 2, respectively. Similar results were obtained for the second and third sets, with fair-to-moderate agreements. Patches from the first 2 sets that obtained the consensus of the 18 pathologists were retrieved to form consensus patches and were regarded as the ground truth of lung adenocarcinoma subtypes. CONCLUSIONS.­: Our observations highlight discrepancies among experts when assessing lung adenocarcinoma subtypes. However, a subsequent number of consensus patches could be retrieved from each cluster, which can be used as ground truth for the downstream computational pathology applications, with minimal influence from interobserver variability.

Percutaneous biopsy of musculoskeletal tumors and the potential for needle tract seeding: technical considerations, current controversies, and outcomes.

Multidisciplinary communication and planning between the musculoskeletal radiologist and orthopedic oncologist are essential for proper biopsy planning when a primary musculoskeletal malignancy is suspected. Image-guided percutaneous biopsy allows for real-time visualization of the biopsy needle and surrounding structures, combining high diagnostic accuracy with safety and cost-effectiveness. However, determining a surgically optimal biopsy trajectory for a mass can be technically challenging due to critical surrounding anatomy or challenging needle approach angles. Inappropriately placed biopsies can have serious repercussions on patient function and oncological survival. The potential for needle tract seeding and local recurrence after biopsy of sarcoma has been central to the debate regarding the need for excision of the biopsy tract. This multidisciplinary review highlights current controversies in the field, including the issue of core needle biopsy tracts and their excision, technical considerations and advances in image-guidance in the setting of challenging biopsies, advances in histopathological diagnostics with implications for targeted therapy in sarcoma, as well as surgical and oncological outcomes after needle tract biopsy.

Angiolipoma: a review of 778 lesions in 344 patients.

BACKGROUND: Angiolipomas are benign subcutaneous nodules that are commonly multifocal and easily overlooked by those not familiar with their appearance. The objective of this study was to identify the spectrum of the clinical and imaging features of this lesion, to include MR, CT, and US features. METHODS: A retrospective review of our institutional pathology database for biopsy-proven cases of angiolipoma between January 1, 2019, through December 31, 2021, was done. We identified 334 patients who underwent surgical resection of 788 individual lesions. MR imaging studies were available in 43 cases, CT in 39 cases, and ultrasound imaging in 72 cases. Clinical features (patient age, gender, surgical indication, number of lesions) were reviewed. Imaging feature analysis included the anatomic location, content of fat, vascularity, and modality-specific imaging features. RESULTS: All 778 angiolipomas were located in the subcutaneous tissues (median size, 2.4 cm, range 0.4-7.7 cm), with over 51% located in the upper extremity. The most common presentation was a symptomatic mass or slowly growing symptomatic mass. Imaging showed a subcutaneous lesion with a lobulated bean shape, which typically abutted the skin. Intralesional fat was identified in 85% of lesions on CT and MRI. Vessels were commonly seen on CT and MR, with enhancement best seen on MR. On US, lesions were heterogeneous and mildly hyperechoic, most often with no identifiable vascularity. CONCLUSION: Angiolipomas typically have characteristic imaging features. Awareness of this diagnosis and the spectrum of its imaging features is important and can facilitate a definitive diagnosis.

Autologous Umbilical Cord Blood-Derived Mononuclear Cell Therapy Promotes Cardiac Proliferation and Adaptation in a Porcine Model of Right Ventricle Pressure Overload.

Congenital heart diseases, including single ventricle circulations, are clinically challenging due to chronic pressure overload and the inability of the myocardium to compensate for lifelong physiological demands. To determine the clinical relevance of autologous umbilical cord blood-derived mononuclear cells (UCB-MNCs) as a therapy to augment cardiac adaptation following surgical management of congenital heart disease, a validated model system of right ventricular pressure overload due to pulmonary artery banding (PAB) in juvenile pigs has been employed. PAB in a juvenile porcine model and intramyocardial delivery of UCB-MNCs was evaluated in three distinct 12-week studies utilizing serial cardiac imaging and end-of-study pathology evaluations. PAB reproducibly induced pressure overload leading to chronic right ventricular remodeling including significant myocardial fibrosis and elevation of heart failure biomarkers. High-dose UCB-MNCs (3 million/kg) delivered into the right ventricular myocardium did not cause any detectable safety issues in the context of arrhythmias or abnormal cardiac physiology. In addition, this high-dose treatment compared with placebo controls demonstrated that UCB-MNCs promoted a significant increase in Ki-67-positive cardiomyocytes coupled with an increase in the number of CD31+ endothelium. Furthermore, the incorporation of BrdU-labeled cells within the myocardium confirmed the biological potency of the high-dose UCB-MNC treatment. Finally, the cell-based treatment augmented the physiological adaptation compared with controls with a trend toward increased right ventricular mass within the 12 weeks of the follow-up period. Despite these adaptations, functional changes as measured by echocardiography and magnetic resonance imaging did not demonstrate differences between cohorts in this surgical model system. Therefore, this randomized, double-blinded, placebo-controlled pre-clinical trial establishes the safety of UCB-MNCs delivered via intramyocardial injections in a dysfunctional right ventricle and validates the induction of cardiac proliferation and angiogenesis as transient paracrine mechanisms that may be important to optimize long-term outcomes for surgically repaired congenital heart diseases.

Surgical Pathology of Diffuse Parenchymal Lung Disease in Patients With Psoriasis or Psoriatic Arthritis.

CONTEXT.­: Diffuse parenchymal lung disease (DPLD) is a well-recognized complication of systemic connective tissue disease (CTD) but rarely arises in patients with psoriasis or psoriatic arthritis, a poorly understood phenomenon. OBJECTIVE.­: To characterize DPLD associated with psoriasis or psoriatic arthritis, with or without prior immunomodulation. DESIGN.­: Pathology consultation files were searched for patients having psoriasis or psoriatic arthritis and DPLD. After excluding cases with active infection or smoking-related DPLD only, 44 patients (22 women; median age, 60 years; range, 23-81 years) were enrolled. Clinical history and pathology slides were reviewed. RESULTS.­: Twenty-seven of 44 patients (61%) had psoriatic arthritis; the remainder had psoriasis alone. Most presented many years later with nonspecific respiratory symptoms. Nearly one-third had no prior immunosuppression, and most had no concomitant CTD. Radiographically, ground-glass opacities, consolidation, and/or reticulation were typical. Histologically, nonspecific interstitial pneumonia and unclassifiable fibrosis were seen in 24 patients (55%) and 8 patients (18%), respectively; usual interstitial pneumonia and airway-centered fibrosis were rare. Superimposed acute lung injury was common, usually manifesting as organizing pneumonia. Lymphoplasmacytic infiltrates, lymphoid aggregates, and chronic pleuritis were frequent. Interstitial granulomas were seen in 17 patients (39%) but were usually rare, poorly formed, and nonnecrotizing. No histologic differences were apparent among patients with or without concomitant CTDs or prior therapy. CONCLUSIONS.­: Some patients with psoriasis or psoriatic arthritis develop clinically significant DPLD, even without prior therapy. Histopathologic findings mirror changes seen with other CTDs. Additional studies are warranted to clarify the association between psoriasis or psoriatic arthritis and DPLD.

Late Complications of COVID-19.

CONTEXT.­: Studies of lungs in patients with COVID-19 have focused on early findings. OBJECTIVE.­: To systematically study histopathologic and imaging features and presence of SARS-CoV-2 RNA in lung tissue from patients in later stages of COVID-19. DESIGN.­: Autopsies, explants, surgical lung biopsies, transbronchial biopsies, cryobiopsies, and needle biopsies from patients with COVID-19 whose onset of symptoms/confirmed diagnosis was more than 28 days before the procedure were studied. Available images were reviewed. Reverse transcription droplet digital polymerase chain reaction for SARS-CoV-2 RNA was performed on lung tissue. RESULTS.­: Of 44 specimens (43 patients; median age, 59.3 years; 26 [60.5%] male) features of acute lung injury (ALI) were seen in 39 (88.6%), predominantly organizing pneumonia and diffuse alveolar damage, up to 298 days after onset of COVID-19. Fibrotic changes were found in 33 specimens (75%), most commonly fibrotic diffuse alveolar damage (n = 22) and cicatricial organizing pneumonia (n = 12). Time between acquiring COVID-19 and specimen was shorter in patients with diffuse ALI (median, 61.5 days) compared with patients with focal (140 days) or no ALI (130 days) (P = .009). Sixteen (of 20; 80%) SARS-CoV-2 reverse transcription droplet digital polymerase chain reaction tests were positive, up to 174 days after COVID-19 onset. Time between COVID-19 onset and most recent computed tomography in patients with consolidation on imaging was shorter (median, 43.0 days) versus in patients without consolidation (87.5 days; P = .02). Reticulations were associated with longer time to computed tomography after COVID-19 onset (median, 82 versus 23.5 days; P = .006). CONCLUSIONS.­: ALI and SARS-CoV-2 RNA can be detected in patients with COVID-19 for many months. ALI may evolve into fibrotic interstitial lung disease.

Usual interstitial pneumonia: a clinically significant pattern, but not the final word.

Usual interstitial pneumonia (UIP) is a concept that is deeply entrenched in clinical practice and the prognostic significance of UIP is well established, but the field continues to suffer from the lack of a true gold standard for diagnosing fibrotic interstitial lung disease (ILD). The meaning and usage of UIP have shifted over time and this term is prone to misinterpretation and poor diagnostic agreement. For pathologists, it is worth reflecting on the limitations of UIP and our true role in the care of patients with ILD, a controversial topic explored in two point-counterpoint editorials published simultaneously in this journal. Current diagnostic guidelines are ambiguous and difficult to apply in clinical practice. Further complicating matters for the pathologist is the paradigm shift that occurred with the advent of anti-fibrotic agents, necessitating increased focus on the most likely etiology of fibrosis rather than simply the pattern of fibrosis when pulmonologists select appropriate therapy. Despite the wealth of information locked in tissue samples that could provide novel insights into fibrotic ILDs, pulmonologists increasingly shy away from obtaining biopsies, likely because pathologists no longer provide sufficient value to offset the risks of a biopsy procedure, and pathologic assessment is insufficiently reliable to meaningfully inform therapeutic decisionmaking. To increase the value of biopsies, pathologists must first recognize the problems with UIP as a diagnostic term. Second, pathologists must realize that the primary goal of a biopsy is to determine the most likely etiology to target with therapy, requiring a shift in diagnostic focus. Third, pathologists must devise and validate new classifications and criteria that are evidence-based, biologically relevant, easy to use, and predictive of outcome and treatment response. Only after the limitations of UIP are understood will pathologists provide maximum diagnostic value from biopsies to clinicians today and advance the field forward.