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* Context.--The pathologic diagnosis of usual interstitial pneumonia (UIP) remains a challenging area, and application of histologic UIP guidelines has proved difficult. Objective.--To understand current practice approaches by pulmonary pathologists for the histologic diagnosis of UIP and other fibrotic interstitial lung diseases (ILDs). Design.--The Pulmonary Pathology Society (PPS) ILD Working Group developed and sent a 5-part survey on fibrotic ILD electronically to the PPS membership. Results.--One hundred sixty-one completed surveys were analyzed. Of the respondents, 89% reported using published histologic features in clinical guidelines for idiopathic pulmonary fibrosis (IPF) in their pathologic diagnosis; however, there was variability in reporting terminology, quantity and quality of histologic features, and the use of guideline categorization. Respondents were very likely to have access to pulmonary pathology colleagues (79%), pulmonologists (98%), and radiologists (94%) to discuss cases. Half of respondents reported they may alter their pathologic diagnosis based on additional clinical and radiologic history if it is pertinent. Airway-centered fibrosis, granulomas, and types of inflammatory infiltrates were considered important, but there was poor agreement on how these features are defined. Conclusions.--There is significant consensus among the PPS membership on the importance of histologic guidelines/features of UIP. There are unmet needs for (1) consensus and standardization of diagnostic terminology and incorporation of recommended histopathologic categories from the clinical IPF guidelines into pathology reports, (2) agreement on how to incorporate into the report relevant clinical and radiographic information, and (3) defining the quantity and quality of features needed to suggest alternative diagnoses. (Arch Pathol Lab Med. 2024;148:168-177; doi: 10.5858/arpa.2022-0530-OA), The histologic features of usual interstitial pneumonia (UIP), the fibrotic interstitial lung disease (ILD) pattern seen in, but not limited to, clinical idiopathic pulmonary fibrosis (IPF), was first described by [...]

* Context.--Transbronchial cryobiopsy is an emerging procedure to obtain lung tissue for diagnosis of interstitial lung disease and has gained popularity because it is less invasive and has a lower rate of complications compared with nonselective surgical lung biopsy. Objective.--To provide an overview of the status of the medical literature regarding transbronchial cryobiopsy. Data Sources.--A literature search was performed using PubMed search engine. The terms 'cryobiopsy' or 'cryo-probe' and 'interstitial lung disease' or 'diffuse parenchymal lung disease' or 'pulmonary fibrosis' were used, with the search concluding at the end of November 2019. Conclusions.--While the diagnostic yield of transbronchial cryobiopsy is slightly lower than surgical lung biopsy, a growing amount of literature suggests that with a multidisciplinary approach cryobiopsy provides diagnostic and prognostic information approaching that of surgical lung biopsy with lower morbidity and mortality. doi: 10.5858/arpa.2020-0007-RA, Diffuse interstitial lung diseases (ILD) are a heterogeneous group that differ widely in their pathogenesis, clinicopathologic features, therapeutic options, and prognosis. In approximately 30% of ILD patients, the specific diagnosis [...]

* Context.--Accurate diagnosis of idiopathic pulmonary fibrosis (IPF) requires multidisciplinary diagnosis that includes clinical, radiologic, and often pathologic assessment. In 2018, the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and the Latin American Thoracic Society (ATS/ERS/JRS/ALAT) and the Fleischner Society each published guidelines for the diagnosis of IPF, which include criteria for 4 categories of confidence of a histologic usual interstitial pneumonia (UIP) pattern. Objective.--To (1) identify the role of the guidelines in pathologic assessment of UIP; (2) analyze the 4 guideline categories, including potential areas of difficulty; and (3) determine steps the Pulmonary Pathology Society and the greater pulmonary pathology community can take to improve current guideline criteria and histopathologic diagnosis of interstitial lung disease. Data Sources.--Data were derived from the guidelines, published literature, and clinical experience. Conclusions.--Both guidelines provide pathologists with a tool to relay to the clinician the likelihood that a biopsy represents UIP, and serve as an adjunct, not a replacement, for traditional histologic diagnosis. There are multiple challenges with implementing the guidelines, including (1) lack of clarity on the quantity and quality of histologic findings required, (2) lack of recognition that histologic features cannot be assessed independently, and (3) lack of guidance on how pathologists should incorporate clinical and radiographic information. Current criteria for 'probable UIP' and 'indeterminate for UIP' hinder accurate reflection of the likelihood of IPF. These challenges highlight the need for further morphologic-based investigations in the field of pulmonary pathology. doi: 10.5858/arpa.2020-0052-RA, Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrosing interstitial lung disease (ILD) associated with a histologic and/or radiographic pattern of usual interstitial pneumonia (UIP) and a prognosis similar to [...]

BackgroundThe National Heart, Lung, and Blood Institute-sponsored IPF Clinical Research Network (IPFnet) studies enrolled subjects with idiopathic pulmonary fibrosis (IPF) to evaluate drug therapies in treatment trials. An adjudication committee (AC) provided a structured review of cases in which there was uncertainty or disagreement regarding diagnosis or clinical event classification. This article describes the diagnosis and adjudication processes.MethodsThe diagnostic process was based on review of clinical data and high-resolution CT scans with central review of lung biopsies when available. The AC worked closely with the data coordinating center to obtain clinical, radiologic, and histologic data and to communicate with the clinical centers. The AC used a multidisciplinary discussion model with four clinicians, one radiologist, and one pathologist to adjudicate diagnosis and outcome measures.ResultsThe IPFnet trials screened 1,015 subjects; of these, 23 cases required review by the AC to establish eligibility. The most common diagnosis for exclusion was suspected chronic hypersensitivity pneumonitis. The AC reviewed 88 suspected acute exacerbations (AExs), 93 nonelective hospitalizations, and 16 cases of bleeding. Determination of AEx presented practical challenges to adjudicators, as necessary clinical data were often not collected, particularly when subjects were evaluated outside of the primary study site.ConclusionsThe IPFnet diagnostic process was generally efficient, but a multidisciplinary adjudication committee was critical to assure correct phenotype for study enrollment. The AC was key in adjudicating all adverse outcomes in two IPFnet studies terminated early because of safety issues. Future clinical trials in IPF should consider logistical and cost issues as they incorporate AExs and hospitalizations as outcome measures.Trial registryClinicalTrials.gov; No.: NCT00517933, NCT00650091, NCT00957242; URL: www.clinicaltrials.gov.

Cigarette smoking is a key factor in the development of numerous pulmonary diseases. An international group of clinicians, radiologists and pathologists evaluated patients with previously identified idiopathic interstitial pneumonia (IIP) to determine unique features of cigarette smoking. Phase 1 (derivation group) identified smoking-related features in patients with a history of smoking (n=41). Phase 2 (validation group) determined if these features correctly predicted the smoking status of IIP patients (n=100) to participants blinded to smoking history. Finally, the investigators sought to determine if a new smoking-related interstitial lung disease phenotype could be defined. Phase 1 suggested that preserved forced vital capacity with disproportionately reduced diffusing capacity of the lung for carbon monoxide, and various radiographic and histopathological findings were smoking-related features. In phase 2, the kappa coefficient among clinicians was 0.16 (95% CI 0.11-0.21), among the pathologists 0.36 (95% CI 0.32-0.40) and among the radiologists 0.43 (95% CI 0.35-0.52) for smoking-related features. Eight of the 100 cases were felt to represent a potential smoking-related interstitial lung disease. Smoking-related features of interstitial lung disease were identified in a minority of smokers and were not specific for smoking. This study is limited by its retrospective design, the potential for recall bias in smoking history and lack of information on second-hand smoke exposure. Further research is needed to understand the relationship between smoking and interstitial lung disease.

PURPOSE: To determine the accuracy of computed tomography (CT) in identifying the histopathologic usual interstitial pneumonia (UIP) pattern in rheumatoid arthritis-associated interstitial lung disease (RA-ILD). MATERIALS AND METHODS: All patients were enrolled into institutional review board-approved longitudinal cohorts at their respective institution, and informed consent was obtained at the time of enrollment. Images of patients with surgical lung biopsy-proved RA-ILD (n = 69) were collected from three tertiary care centers. Two experienced thoracic radiologists independently reviewed the CT scans. The CT pattern was categorized as definite UIP, possible UIP, or inconsistent with UIP in accordance with published criteria. Findings of biopsies were reviewed by an experienced lung pathologist. The sensitivity and specificity of definite CT UIP pattern to histopathologic UIP pattern were determined. The agreement between radiologists was assessed by calculating a κ score. RESULTS: The histopathologic UIP pattern was present in 42 of 69 (61%) patients. Men were more likely than women to have a histopathologic UIP pattern (P = .02). Twenty patients (29%, 20 of 69) had a definite UIP pattern on CT scans. The specificity of CT UIP pattern was 96% (26 of 27; 95% confidence interval [CI]: 81%, 100%), with a negative predictive value of 53% (26 of 49). The sensitivity of CT UIP pattern was 45% (19 of 42; 95% CI: 30%, 61%), with a positive predictive value of 95% (19 of 20). The agreement between radiologists for definite UIP pattern versus not was 87% (κ = 0.67, P < .0001). CONCLUSION: Definite UIP pattern on a CT scan in RA-ILD is highly specific and moderately sensitive for histopathologic UIP pattern. CT can therefore help accurately identify the UIP pattern in RA-ILD.

BackgroundIn 2002 the American Thoracic Society/European Respiratory Society (ATS/ERS) classification of idiopathic interstitial pneumonias (IIPs) defined seven specific entities, and provided standardized terminology and diagnostic criteria. In addition, the historical "gold standard" of histologic diagnosis was replaced by a multidisciplinary approach. Since 2002 many publications have provided new information about IIPs.PurposeThe objective of this statement is to update the 2002 ATS/ERS classification of IIPs.MethodsAn international multidisciplinary panel was formed and developed key questions that were addressed through a review of the literature published between 2000 and 2011.ResultsSubstantial progress has been made in IIPs since the previous classification. Nonspecific interstitial pneumonia is now better defined. Respiratory bronchiolitis-interstitial lung disease is now commonly diagnosed without surgical biopsy. The clinical course of idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia is recognized to be heterogeneous. Acute exacerbation of IIPs is now well defined. A substantial percentage of patients with IIP are difficult to classify, often due to mixed patterns of lung injury. A classification based on observed disease behavior is proposed for patients who are difficult to classify or for entities with heterogeneity in clinical course. A group of rare entities, including pleuroparenchymal fibroelastosis and rare histologic patterns, is introduced. The rapidly evolving field of molecular markers is reviewed with the intent of promoting additional investigations that may help in determining diagnosis, and potentially prognosis and treatment.ConclusionsThis update is a supplement to the previous 2002 IIP classification document. It outlines advances in the past decade and potential areas for future investigation.

Context.--Malignant mesothelioma (MM) is an uncommon tumor that can be difficult to diagnose.Objective.--To provide updated, practical guidelines for the pathologic diagnosis of MM.Data Sources.--Pathologists involved in the International Mesothelioma Interest Group and others with an interest and expertise in the field contributed to this update. Reference material included up-to-date, peer-reviewed publications and textbooks.Conclusions.--There was discussion and consensus opinion regarding guidelines for (1) distinguishing benign from malignant mesothelial proliferations (both epithelioid and spindle cell lesions), (2) cytologic diagnosis of MM, (3) recognition of the key histologic features of pleural and peritoneal MM, (4) use of histochemical and immunohistochemical stains in the diagnosis and differential diagnosis of MM, (5) differentiating epithelioid MM from various carcinomas (lung, breast, ovarian, and colonic adenocarcinomas, and squamous cell and renal cell carcinomas), (6) diagnosis of sarcomatoid MM, (7) use of molecular markers in the diagnosis of MM, (8) electron microscopy in the diagnosis of mM, and (9) some caveats and pitfalls in the diagnosis of MM. Immunohistochemical panels are integral to the diagnosis of MM, but the exact makeup of panels employed is dependent on the differential diagnosis and on the antibodies available in a given laboratory. Depending on the morphology, immunohistochemical panels should contain both positive and negative markers for mesothelial differentiation and for lesions considered in the differential diagnosis. Immunohistochemical markers should have either sensitivity or specificity greater than 80% for the lesions in question. Interpretation of positivity generally should take into account the localization of the stain (eg, nuclear versus cytoplasmic) and the percentage of cells staining (>10% is suggested for cytoplasmic and membranous markers). Selected molecular markers are now being used to distinguish benign from malignant mesothelial proliferations. These guidelines are meant to be a practical diagnostic reference for the pathologist; however, some new pathologic predictors of prognosis and response to therapy are also included.(Arch Pathol Lab Med. 2018;142:89-108; doi: 10.5858/arpa.2017-0124-RA), The pathologic diagnosis of malignant mesothelioma (MM) continues to evolve and be refined as more antibodies and molecular tests become available for general use. This is especially applicable to distinguishing [...]