Diagnostic Lung Biopsy Research Articles

A fibroblast-dependent TGF-β1/sFRP2 noncanonical Wnt signaling axis promotes epithelial metaplasia in idiopathic pulmonary fibrosis.

Reciprocal interactions between alveolar fibroblasts and epithelial cells are crucial for lung homeostasis, injury repair, and fibrogenesis, but underlying mechanisms remain unclear. To investigate, we administered the fibroblast-selective TGF-β1 signaling inhibitor epigallocatechin gallate (EGCG) to interstitial lung disease (ILD) patients undergoing diagnostic lung biopsy and conducted single-cell RNA-Seq on spare tissue. Biopsies from untreated patients showed higher fibroblast TGF-β1 signaling compared with nondisease donor or end-stage ILD tissues. In vivo, EGCG downregulated TGF-β1 signaling and several proinflammatory and stress pathways in biopsy samples. Notably, EGCG reduced fibroblast secreted frizzled-related protein 2 (sFRP2), an unrecognized TGF-β1 fibroblast target gene induced near type II alveolar epithelial cells (AEC2s) in situ. Using AEC2-fibroblast coculture organoids and precision-cut lung slices (PCLSs) from nondiseased donors, we found TGF-β1 signaling promotes a spread AEC2 KRT17+ basaloid state, whereupon sFRP2 then activates a mature cytokeratin 5+ (Krt5+) basal cell program. Wnt-receptor Frizzled 5 (Fzd5) expression and downstream calcineurin signaling were required for sFRP2-induced nuclear NFATc3 accumulation and KRT5 expression. These findings highlight stage-specific TGF-β1 signaling in ILD and the therapeutic potential of EGCG in reducing idiopathic pulmonary fibrosis-related (IPF-related) transcriptional changes and identify TGF-β1/noncanonical Wnt pathway crosstalk via sFRP2 as a mechanism for dysfunctional epithelial signaling in IPF/ILD.

The association between patient preoperative disposition and outcomes after diagnostic lung biopsy.

Surgical diagnostic lung biopsy (DLB) is performed to guide the management of pulmonary disease with unclear etiology. However, the utilization of surgical DLB in critically ill patients remains unclear. The purpose of this study was to determine if patient preoperative disposition impacts complication rates after DLB. This was retrospective cohort study using electronic health record (EHR) data at one academic institution [2013-2021]. Patients who underwent DLB were identified using current procedural terminology (CPT) codes and cohorted based on preoperative disposition. The primary outcome was 30-day mortality; secondary outcomes were overall morbidity, individual complications, and changes to medical therapy. Complication rates were compared using chi-squared tests, Fisher's exact tests, or analysis of variance (ANOVA). Multivariable logistic regression was performed to generate risk-adjusted odds ratios (ORs) for each complication. Of 285 patients, 238 (83.5%) presented from home, 26 (9.1%) from inpatient floor units, and 21 (7.4%) from intensive care units (ICUs). Patients requiring ICU had the highest 30-day rates of mortality, overall morbidity, and all individual complications (all P<0.05). After risk adjustment, non-ICU inpatients had higher odds of postoperative ventilator use, prolonged ventilation, and ICU need than outpatients (all P<0.05). Preoperative ICU disposition was associated with increased OR of 30-day mortality [OR, 70.92; 95% confidence interval (CI): 5.55-906.32] and overall morbidity (OR, 7.27; 95% CI: 1.93-27.42) compared to patients with other preoperative dispositions. There were no differences in changes to medical therapy between the cohorts. Patients requiring ICU before DLB had significantly higher risk-adjusted rates of mortality and postoperative complications than outpatients and other inpatients. A clear benefit from tissue diagnosis should be defined prior to performing DLB on critically ill patients.

Lung biopsy in the diagnosis and management of chILD.

Children's interstitial and diffuse lung disease (chILD) comprises a large number of diverse entities ranging from disorders of lung development, maturation and function unique in infancy to immune-mediated, environmental, vascular and other conditions overlapping with adult disease. Pathologic evaluation of the lung has played a central role in characterizing many of these disorders, resulting in revised nomenclature and classifications to help guide clinical management(1-4). Technological advancements are rapidly uncovering genetic and molecular underpinnings of these conditions, as well as widening the phenotypes which bridge adult disease, often reducing the perceived need for diagnostic lung biopsy. As such the decision to get a lung biopsy in chILD is frequently for rapid ascertainment of disease in a critically ill child or when clinical presentation, imaging and laboratory studies fail to provide a cohesive diagnosis needed for treatment. While there have been modifications in surgical procedures for lung biopsy that minimize postoperative morbidity, it remains a high-risk invasive procedure, especially in a medically complex patient(5). Thus, it is essential that the lung biopsy be handled properly to maximize diagnostic yield, including close communication between the clinician, radiologist, surgeon, and pathologist before biopsy to determine best sampling site(s) and prioritization of tissue utilization. This review provides an overview of optimal handling and evaluation of a surgical lung biopsy for suspected chILD, with emphasis on specific conditions in which pathologic features play a critical role in providing an integrated diagnosis and guiding management.

Pilot study of archimedes virtual bronchoscopic navigation system-guided biopsy to diagnose lung nodules in children.

Peripheral pulmonary lesions are uncommon in children. Bronchoscopy is a minimal invasive method to obtain a diagnostic lung biopsy. However, due to the lack of effective guidance methods, the diagnostic efficacy of transbronchial lung biopsy for peripheral solitary pulmonary diseases is still limited. Is the Archimedes virtual bronchoscopic navigation system safe and effective for the diagnosis of peripheral pulmonary lesions in children? This pilot study retrospectively analyzed the clinical features, radiological characteristics, operation processes, intra-and postoperative complications, and pathological results of five children who underwent Archimedes-guided biopsy of peripheral pulmonary lesions in Beijing Children's Hospital from May 2021 to May 2022. The cohort comprised five children (all males) with age of 7.1-15.8 years. A guide sheath was inserted through the bronchoscope under the guidance of Archimedes combined with radial endobronchial ultrasound to complete the biopsy under general anesthesia. The fused fluoroscopy technique was used to reconfirm the location of the forceps prior to biopsy in all children. The forceps reached the lesion under the guidance of the navigation and the samples were collected successfully in all children. Pathological examination of the biopsy specimens showed Epstein-Barr virus infection-related lymphoproliferative disease in one child, pulmonary metastasis of rhabdomyosarcoma in one child, and pulmonary vasculitis in one child; high-throughput sequencing of the biopsy tissue sample identified Mycobacterium tuberculosis (sequence no. 80) in one child and Aspergillus (sequence no. 40) in another child. All five children tolerated the biopsy procedure without developing postoperative complications, such as pneumothorax and hemoptysis. Archimedes-guided bronchoscopic lung biopsy is a feasible and efficient way to diagnose peripheral pulmonary lesions in children with manageable complications.

Surgical lung biopsy for interstitial lung diseases-a single center study of 129 patients.

BackgroundAccording to guidelines for the diagnosis and treatment of interstitial lung diseases (ILDs), a diagnostic surgical lung biopsy should be used to obtain the differential diagnosis of an ILD in patients with ILDs, which are difficult to distinguish clinically. However, the risk of developing postoperative complications such as postoperative pulmonary fistula or acute exacerbation is a concern. The purpose of this study was to evaluate the safety of surgical lung biopsy for the differential diagnosis of ILDs.MethodsFrom October 2007 to July 2019, 129 patients thought to have ILD underwent a surgical lung biopsy at Toho University Omori Medical Center. We conducted a retrospective study on the diagnosis and safety of surgical lung biopsy for patients with ILD.ResultsThe 30- and 60-day mortality was 0%. Postoperative complications occurred in 13 of 129 (10.1%) patients. The complications included pneumothorax in 8 (6.2%) patients after removal of the chest tube, postoperative pneumonia in 2 (1.0%), and acute exacerbation in 1 (0.8%). Postoperative pneumothorax was observed in 4 of 13 patients (30.7%) who underwent a biopsy of the apex of the lung (right S1, left S1+2), which was a significantly higher rate of postoperative pneumothorax than seen for patients undergoing biopsy at other sites (P=0.0086).ConclusionsSurgical lung biopsy for the differential diagnosis of an ILD was performed safely. However, biopsy sites for ILDs need to be carefully selected to avoid postoperative complications.

Is the combination of bilateral pulmonary nodules and mosaic attenuation on chest CT specific for DIPNECH?

BackgroundDiffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is characterized by multifocal proliferation of pulmonary neuroendocrine cells. On chest CT, DIPNECH exhibits bilateral pulmonary nodules and mosaic attenuation in most patients. We sought to: (1) assess the specificity of this pattern (i.e., bilateral pulmonary nodules together with mosaic attenuation) for DIPNECH; (2) describe its differential diagnosis; and (3) identify the clinico-radiologic features that may help prioritize DIPNECH over other diagnostic considerations.MethodsWe searched the Mayo Clinic records from 2015 to 2019 for patients with bilateral pulmonary nodules and mosaic attenuation on CT who had a diagnostic lung biopsy. A thoracic radiologist reviewed all CT scans. Chi-square test was used for categorical variables, and odds ratios were utilized to measure the association between certain variables and DIPNECH.ResultsFifty-one patients met our inclusion criteria; 40 (78%) were females and 34 (67%) were never-smokers. Median age was 65 (interquartile range 55–73) years. Lung biopsy was surgical in 21 patients (41%), transbronchial in 17 (33%), and transthoracic in 12 (24%); explanted lungs were examined in 1 (2%). Metastatic/multifocal cancer was the most common diagnosis, and was found in 17 (33%) cases. Bronchiolitis was diagnosed in 12 patients (24%), interstitial lung disease in 10 (20%), and DIPNECH in 5 (10%). Previous diagnosis of an obstructive lung disease (odds ratio 15.8; P = 0.002), and peribronchial nodular distribution on CT (odds ratio 14.4; P = 0.006) were significantly correlated with DIPNECH. Although statistical significance was not reached, DIPNECH nodules were more likely to display solid attenuations (80% vs. 67%, P = 0.45), and were more numerous; > 10 nodules were seen in 80% of DIPNECH cases vs. 52% in others (P = 0.23). Because DIPNECH primarily affects women, we analyzed the women-only cohort and found similar results.ConclusionsVarious disorders can manifest the CT pattern of bilateral pulmonary nodules together with mosaic attenuation, and this combination is nonspecific for DIPNECH, which was found in only 10% of our cohort. Previous diagnosis of an obstructive lung disease, and peribronchial distribution of the nodules on CT increased the likelihood of DIPNECH vs. other diagnoses.

The Extent of Inflammatory Cell Infiltrate and Fibrosis in Lungs of Telomere- and Surfactant-Related Familial Pulmonary Fibrosis.

Familial pulmonary fibrosis (FPF) is a monogenic disease most commonly involving telomere- (TERT) or surfactant- (SFTP) related mutations. These mutations have been shown to alter lymphocytic inflammatory responses, and FPF biopsies with histological lymphocytic infiltrates have been reported. Recently, a model of a surfactant mutation in mice showed that the disease initially started with an inflammatory response followed by fibrogenesis. Since inflammation and fibrogenesis are targeted by different drugs, we investigated whether the degree of these two features co-localize or occur independently in different entities of FPF, and whether they influence survival. We quantified the number of lymphocyte aggregates per surface area, the extent of diffuse lymphocyte cell infiltrate, the number of fibroblast foci per surface area, and the percentage of fibrotic lung surface area in digitally scanned hematoxylin and eosin (H&E) sections of diagnostic surgical biopsies of patients with TERT-related FPF (TERT-PF; n = 17), SFTP-related FPF (SFTP-PF; n = 7), and sporadic idiopathic pulmonary fibrosis (sIPF; n = 10). For comparison, we included biopsies of patients with cellular non-specific interstitial pneumonia (cNSIP; n = 10), an inflammatory interstitial lung disease with high lymphocyte influx and usually responsive to immunosuppressive therapy. The degree of inflammatory cell infiltrate and fibrosis in TERT-PF and SFTP-PF was not significantly different from that in sIPF. In comparison with cNSIP, the extent of lymphocyte infiltrates was significantly lower in sIPF and TERT-PF, but not in SFTP-PF. However, in contrast with cNSIP, in sIPF, TERT-PF, and SFTP-PF, diffuse lymphocyte cell infiltrates were predominantly present and lymphocyte aggregates were only present in fibrotic areas (p < 0.0001). Furthermore, fibroblast foci and percentage of fibrotic lung surface were associated with survival (p = 0.022 and p = 0.018, respectively), while this association was not observed for lymphocyte aggregates or diffuse lymphocytic infiltration. Inflammatory cells in diagnostic lung biopsies of TERT-PF, SFTP-PF, and sIPF were largely confined to fibrotic areas. However, based on inflammation and fibrosis, no differences were found between FPF and sIPF, substantiating the histological similarities between monogenic familial and sporadic disease. Furthermore, the degree of fibrosis, rather than inflammation, correlates with survival, supporting that fibrogenesis is the key feature for therapeutic targeting of FPF.

Pulmonary fibrosis in dyskeratosis congenita: a case report with a PRISMA-compliant systematic review

BackgroundDyskeratosis congenita (DC) is a rare genetic disorder of poor telomere maintenance. Pulmonary fibrosis (PF) related to DC is rarely reported.Case presentationA 23-year-old student presented with a four-year history of progressive cough and exertional dyspnea. Physical examination was remarkable for typical mucocutaneous abnormalities. Chest computerized tomography scan revealed interstitial fibrosis. Testing of peripheral blood leukocytes confirmed that his telomeres were 30th percentile of age-matched controls. A heterozygous missense mutation located in exon 22 of PARN gene was identified in the patient by whole exome sequencing. The patient refused danazol therapy and lung transplantation, and died of respiratory failure 2 years later. In addition, this case and 26 reported cases of DC-related PF identified through the comprehensive search of PubMed, Web of Science, WANFANG and CNKI were reviewed. Later-onset PF was observed in 11 patients (40.7%). Radiological usual interstitial pneumonia (UIP) pattern or possible UIP pattern was noted only in half of patients. However, histopathological UIP or probable UIP patterns were found in 63.6% of patients. Age at bone marrow failure (BMF) and the frequency of normal to mild thrombocytopenia in later-onset patients was significantly higher than in early-onset patients (p = 0.017 and p = 0.021, respectively). Age at PF and age at BMF in DC patients with TERC/TERT variants was significantly higher than in those with TINF2 variants or DKC1/NHP2 variants (p = 0.004 and p = 0.003, respectively). The patients with TERT/TERC/RTEL1/PARN variants had a significantly better transplant-free survival than those with TINF2 variants or DKC1/NHP2 variants (p < 0.05). Patients who underwent surgical lung biopsy had significantly worse transplant-free survival than those without lung biopsy (p = 0.042). Worse survival was found in patients with immunosuppression therapy than in those without (p = 0.012).ConclusionsIt is common for DC-associated PF to occur later in life without significant hematological manifestations. Mutations in the genes encoding different components of the telomere maintenance pathway were associated with clinical phenotypes and prognosis. PF caused by DC should be kept in mind by clinicians in the differential diagnosis of patients with unexplained PF and should be excluded before diagnostic surgical lung biopsy is undertaken or empirical immunosuppression therapy is prescribed.

Pneumothorax after percutaneous transthoracic lung biopsy. Non-invasive management in order to avoid unnecessary hospitalizations

Image-guided percutaneous transthoracic lung biopsy has become a widely used and less invasive diagnostic method. Pneumothorax is the most frequent complication after lung biopsy. The aim of the present study is to describe the experience with expectant management of asymptomatic small post-biopsy pneumothorax in order to reduce unnecessary hospital admissions. A retrospective review was performed analyzing the results of subjects who underwent expectant and conservative treatment after presenting pneumothorax following percutaneous lung biopsy, in a period of 6 years (January 2013 - December 2019) 160 subjects who underwent diagnostic percutaneous lung biopsy of lung nodules were evaluated. Of these, 46 subjects (29%) presented pneumothorax, of which 36 were small. This group of subjects was managed expectantly, with a therapeutic success of 81% (7 subjects had to undergo percutaneous pleural drainage). Expectant management in subjects with pneumothorax following percutaneous lung biopsy is a useful tool and should be applied by surgeons in order to avoid hospitalizations and / or unnecessary and expensive procedures.

Patient out-of-pocket costs for suspicious pulmonary nodule biopsy in lung cancer patients

Aims Dynamic changes in the payer landscape have resulted in increasing out-of-pocket costs (OOPC). Little is known about OOPC for patients undergoing biopsy for suspicious pulmonary nodules in the U.S. This study seeks to describe the spectrum of OOPC for diagnostic tissue sampling for suspicious pulmonary nodule with an ultimate diagnosis of lung cancer. Methods Retrospective cohort study of adult patients with a primary lung cancer diagnosis and treatment who underwent diagnostic biopsy for suspicious pulmonary nodule utilizing IBM Marketscan® Databases (2013 to 2017). Claims data included both total hospital and physician billed costs, insurer reimbursement and OOPC. Out-of-pocket costs were further stratified by type of biopsy, whether the patient underwent a single or multiple biopsies, and year of biopsy. Results A total of 22,870 patients age 18-95 who underwent diagnostic lung biopsy were identified. The gender ratio was 49 to 51 for female;male, and 50% of patients were aged 65 or above. 78% of patients had a co-morbidity. The median OOPC for a patient receiving a single biopsy (any type) was $600, two biopsies: $706, three biopsies: $811, four biopsies: $1177. By biopsy type, the median OOPC for a patient requiring a single biopsy was $604 for percutaneous biopsy, $316 for surgical biopsy, $674 for bronchoscopic biopsy, and $545 for mediastinoscopic biopsy. Limitations Under-estimation of OOP expenses from costs of transportation, job loss, and loss of productivity. Over-estimation of OOPC from lack of individual claim adjudication. Conclusion The median OOPC for lung cancer patient requiring a single diagnostic lung biopsy is $600. Prior research indicates that almost 50% of the lung cancer patient population undergoes multiple biopsies increasing costs anywhere between 20-100% resulting in further patient financial burden for each episodic biopsy attempt. Further cost effectiveness research is needed to differentiate various diagnostic technologies for lung biopsy.

Novel Risk Factors of Pulmonary Hemorrhage Complicating CT-Guided Lung Biopsy in Coaxial Technique

Diagnostic lung biopsies using coaxial biopsy systems have become a standard procedure in most interventional radiology departments and are associated with comparable diagnostic accuracy to other biopsy systems.

The Role of Primary Tumor Resection in Patients with Pleural Metastasis Encountered at the Time of Surgery.

BackgroundEvidence is lacking on whether the resection of lung parenchymal cancer improves the survival of patients with unexpected pleural metastasis encountered during surgery. We conducted a single-center retrospective study to determine the role of lung resection in the long-term survival of these patients.MethodsAmong 4683 patients who underwent lung surgery between 1995 and 2014, 132 (2.8%) had pleural metastasis. After excluding 2 patients who had incomplete medical records, 130 patients’ data were collected. Only a diagnostic pleural and/or lung biopsy was performed in 90 patients, while the lung parenchymal mass was resected in 40 patients.ResultsThe mean follow-up duration was 29.8 months. The 5-year survival rate of the resection group (34.7%±9.4%) was superior to that of the biopsy group (15.9%±4.3%, p=0.016). Multivariate Cox regression analysis demonstrated that primary tumor resection (p=0.041), systemic treatment (p<0.001), lower clinical N stage (p=0.018), and adenocarcinoma histology (p=0.009) were significant predictors of a favorable outcome. Interestingly, primary tumor resection only played a significant prognostic role in patients who received systemic treatment.ConclusionWhen pleural metastasis is unexpectedly encountered during surgical exploration, resection in conjunction with systemic treatment may improve long-term survival, especially in adenocarcinoma patients without lymph node metastasis.

A Case of Unresectable Papillary Thyroid Carcinoma Treated with Lenvatinib as Neoadjuvant Chemotherapy

A 75-year-old woman visited a nearby clinic with complaints of right clavicle discomfort, and she underwent diagnostic thoracoscopic lung biopsy, being diagnosed with lung metastasis and a right-upper mediastinal mass. The superior mediastinum mass was extrapulmonary and covered by the pleura, and it was not biopsied. Papillary thyroid carcinoma was diagnosed following biopsy of the lung metastasis. Only a small tumor, with a maximum diameter of 70 mm from the right neck to the superior mediastinum, in the thyroid gland invades the internal jugular vein and subclavian vein, forming a tumor embolus in the right brachiocephalic vein and reaching the vicinity of the superior vena cava. For life-saving purposes, we obtained approval from the Cancer Board of Kanagawa Cancer Center and used lenvatinib according to unresectable undifferentiated cancer IRB approval number 28–41. The tumor had shrunk after 4 months, and surgery was performed. The postoperative course has been good, and the patient is being followed up. The patient is alive three months after surgery, and lung metastases have disappeared on CT images. This case is reported as a successful case of neoadjuvant chemotherapy and interval debulking surgery.

From organ to cell: Multi-level telomere length assessment in patients with idiopathic pulmonary fibrosis.

RationaleA subset of patients with idiopathic pulmonary fibrosis (IPF) contains short leukocyte telomeres or telomere related mutations. We previously showed that alveolar type 2 cells have short telomeres in fibrotic lesions. Our objectives were to better understand how telomere shortening associates with fibrosis in IPF lung and identify a subset of patients with telomere-related disease.MethodsAverage telomere length was determined in multiple organs, basal and apical lung, and diagnostic and end-stage fibrotic lung biopsies. Alveolar type 2 cells telomere length was determined in different areas of IPF lungs.ResultsIn IPF but not in controls, telomere length in lung was shorter than in other organs, providing rationale to focus on telomere length in lung. Telomere length did not correlate with age and no difference in telomere length was found between diagnostic and explant lung or between basal and apical lung, irrespective of the presence of a radiological apicobasal gradient or fibrosis. Fifteen out of 28 IPF patients had average lung telomere length in the range of patients with a telomerase (TERT) mutation, and formed the IPFshort group. Only in this IPFshort and TERT group telomeres of alveolar type 2 cells were extremely short in fibrotic areas. Additionally, whole exome sequencing of IPF patients revealed two genetic variations in RTEL1 and one in PARN in the IPFshort group.ConclusionsAverage lung tissue telomere shortening does not associated with fibrotic patterns in IPF, however, approximately half of IPF patients show excessive lung telomere shortening that is associated with pulmonary fibrosis driven by telomere attrition.

EP1.05-08 Obtaining Diagnostic Lung Biopsies in Suspected Lung Cancer Patients

EP1.05-08 Obtaining Diagnostic Lung Biopsies in Suspected Lung Cancer Patients

High Diagnostic Accuracy of Transbronchial Cryobiopsy in Fibrotic Interstitial Lung Diseases Compared to Final Explant Diagnosis

Background: A diagnostic lung biopsy may be required in some cases of fibrotic interstitial lung diseases (ILD). Transbronchial cryobiopsy has been suggested as a possible alternative to surgical lung biopsy. However, previous estimates of its diagnostic yield were not validated compared to the definitive diagnosis in explanted lungs. Objectives: We aimed to assess the diagnostic accuracy of cryobiopsy in fibrotic ILD patients who subsequently had lung transplantation. Methods: All 197 patients who underwent lung transplantation at our Center due to fibrotic ILD from January 2010 to May 2018, were screened for the presence of a pre-transplant cryobiopsy. Fourteen patients who underwent cryobiopsy before transplantation were identified. Two expert lung pathologists blindedto the explant diagnoses, independently examined these cryobiopsy specimens to decide if they match guideline criteria for usual interstitial pneumonia (UIP) pattern or an alternative diagnosis. The primary measure was the diagnostic accuracy of cryobiopsy to detect or refute a UIP pattern, as compared to the final explant diagnosis. Results: Median time between cryobiopsy and transplantation was 1.4 years. All 14 cryobiopsy samples contained adequate alveolar tissue. The explant diagnosis of 13/14 patients was UIP. The two pathologists correctly diagnosed or refuted UIP in the cryobiopsy specimen in 12/14 cases (85.7%) and 11/14 cases (78.6%), respectively. The level of diagnostic agreement between pathologists was good (kappa 0.59, p = 0.016). Conclusions: Compared to the final explant diagnosis, transbronchial cryobiopsy had high diagnostic accuracy and good inter-observer agreement for UIP pattern. These findings support a potential diagnostic role for cryobiopsy in experienced centers.

Prevention of PNX and Haemorrhagic Complications in Diagnostic Percutaneous Lung Biopsy Using the MIPP-Kit Device

Prevention of PNX and Haemorrhagic Complications in Diagnostic Percutaneous Lung Biopsy Using the MIPP-Kit Device

AML Subtype M5 Linked to Pulmonary Leukemic Infiltrates and Respiratory Failure and the Importance of Early Induction Chemotherapy

Currently there are no practice guidelines for evaluating lung infiltrates in patients with newly diagnosed acute myeloid leukemia (AML). More specifically, it remains unclear if there is a need to obtain a lung tissue biopsy prior to the initiation of induction chemotherapy. This clinical question is particularly important in instances in which obtaining a lung tissue diagnosis can potentially delay anti-leukemic treatment. Here we describe a case of such lung infiltrates in which a newly diagnosed AML patient underwent a diagnostic lung biopsy before receiving chemotherapy, was shown to have leukemic infiltration of lung tissue, and subsequently had complete resolution of lung infiltrates following initiation of chemotherapy.

Targeted Next-Generation Sequencing of Plasma DNA from Cancer Patients: Factors Influencing Consistency with Tumour DNA and Prospective Investigation of Its Utility for Diagnosis.

Use of circulating tumour DNA (ctDNA) as a liquid biopsy has been proposed for potential identification and monitoring of solid tumours. We investigate a next-generation sequencing approach for mutation detection in ctDNA in two related studies using a targeted panel. The first study was retrospective, using blood samples taken from melanoma patients at diverse timepoints before or after treatment, aiming to evaluate correlation between mutations identified in biopsy and ctDNA, and to acquire a first impression of influencing factors. We found good concordance between ctDNA and tumour mutations of melanoma patients when blood samples were collected within one year of biopsy or before treatment. In contrast, when ctDNA was sequenced after targeted treatment in melanoma, mutations were no longer found in 9 out of 10 patients, suggesting the method might be useful for detecting treatment response. Building on these findings, we focused the second study on ctDNA obtained before biopsy in lung patients, i.e. when a tentative diagnosis of lung cancer had been made, but no treatment had started. The main objective of this prospective study was to evaluate use of ctDNA in diagnosis, investigating the concordance of biopsy and ctDNA-derived mutation detection. Here we also found positive correlation between diagnostic lung biopsy results and pre-biopsy ctDNA sequencing, providing support for using ctDNA as a cost-effective, non-invasive solution when the tumour is inaccessible or when biopsy poses significant risk to the patient.

Predictors of idiopathic pulmonary fibrosis in absence of radiologic honeycombing: A cross sectional analysis in ILD patients undergoing lung tissue sampling

BackgroundIdiopathic pulmonary fibrosis (IPF) can be diagnosed confidently and non-invasively when clinical and computed tomography (CT) criteria are met. Many do not meet these criteria due to absence of CT honeycombing. We investigated predictors of IPF and combinations allowing accurate diagnosis in individuals without honeycombing. MethodsWe utilized prospectively collected clinical and CT data from patients enrolled in the Lung Tissue Research Consortium. Included patients had no honeycombing, no connective tissue disease, underwent diagnostic lung biopsy, and had CT pattern consistent with fibrosing ILD (n = 200). Logistic regression identified clinical and CT variables predictive of IPF. The probability of IPF was assessed at various cut-points of important clinical and CT variables. ResultsA multivariable model adjusted for age and gender found increasingly extensive reticular densities (OR 2.93, CI 95% 1.55–5.56, p = 0.001) predicted IPF, while increasing ground glass densities predicted a diagnosis other than IPF (OR 0.55, CI 95% 0.34–0.89, p = 0.02). The model-based probability of IPF was 80% or greater in patients with age at least 60 years and extent of reticular density one-third or more of total lung volume; for patients meeting or exceeding these clinical thresholds the specificity for IPF is 96% (CI 95% 91–100%) with 21 of 134 (16%) biopsies avoided. ConclusionsIn patients with suspected fibrotic ILD and absence of CT honeycombing, extent of reticular and ground glass densities predict a diagnosis of IPF. The probability of IPF exceeds 80% in subjects over age 60 years with one-third of total lung having reticular densities.