Findings Of Surgical Lung Biopsy Research Articles

Impact of radiographic honeycombing on transplant free survival and efficacy of immunosuppression in fibrotic hypersensitivity pneumonitis

BackgroundThe distinction between hypersensitivity pneumonitis (HP) and idiopathic pulmonary fibrosis (IPF) was thought to be important due to the difference in mortality between the conditions as well as the response to treatment. However, recent work suggests that the clinical diagnosis may matter less than certain radiographic features, namely usual interstitial pneumonia (UIP) pattern. The purpose of this study is to evaluate whether radiographic honeycombing is more predictive of transplant-free survival (TFS) than other clinical, radiographic, or histologic findings that distinguish HP from IPF in the current guidelines and to evaluate the impact of radiographic honeycombing on the efficacy of immunosuppression in fibrotic HP.MethodsWe retrospectively identified IPF and fibrotic HP patients evaluated between 2003 and 2019. Univariable and multivariable logistic regression was performed for patients with fibrotic HP and IPF to evaluate TFS. To assess the impact of treatment with immunosuppression on TFS in fibrotic HP, a cox proportional hazard model adjusted for known predictors of survival in HP including age, gender, and baseline pulmonary function testing results was constructed, and p-interaction for the presence of honeycombing on high resolution computed tomography and use of immunosuppression was calculated.ResultsOur cohort included 178 with IPF and 198 with fibrotic HP. In a multivariable analysis, the presence of honeycombing had a greater impact on the TFS than the diagnosis of HP vs. IPF. Among the criteria used in the HP diagnostic guidelines, only typical HP scan impacted survival in a multivariable model, while identification of antigen and surgical lung biopsy findings had no impact on survival. We identified a trend toward worse survival on immunosuppression in those with HP with radiographic honeycombing.ConclusionOur data suggests that honeycombing and baseline pulmonary function testing have a greater impact on TFS than the clinical diagnosis of IPF vs. fibrotic HP and that radiographic honeycombing is a predictor of poor TFS in fibrotic HP. We suggest that invasive diagnostic testing including surgical lung biopsy may not be useful in predicting mortality in HP patients with honeycombing and may potentially increase risk of immunosuppression.

Small airways and airspace inflammation and injury distinguish lung histopathology in deployed military personnel from healthy and diseased lungs

The link between military deployment to Southwest Asia and Afghanistan, and the risk for lung disease, including bronchiolitis, is increasingly well-recognized. However, histopathologic features that distinguish deployment-related lung diseases from other diseases affecting the small airways and airspaces are uncertain. A computer-based scoring system was developed to characterize surgical lung biopsy findings in 65 soldiers with persistent respiratory symptoms following military deployment ("deployers"). Deployer lung biopsies were compared to those from 8 patients with chronic hypersensitivity pneumonitis (cHP), 10 with smoking-related respiratory bronchiolitis, 11 with autoimmune or post-transplant obliterative bronchiolitis, and 10 normal donor lungs. Upper, middle, and lower lobe-specific findings in deployer samples were analyzed to inform optimum biopsy location choice for future patients. Surgical lung biopsies from symptomatic deployed military service members were distinguished by a combination of small airways abnormalities including smooth muscle hypertrophy (SMH), peribronchiolar metaplasia (PBM), and lymphocytic inflammation, often with constrictive/obliterative (C/O) and/or respiratory bronchiolitis (43.1%), granulomatous inflammation (38.5%), and moderate/severe emphysema (46.2%, mainly in nonsmokers). Lymphocytic pleural inflammation was common (89.2%), and vascular abnormalities occurred in nearly one-third. Histopathologic features in deployers were most strongly overlapping with cases of cHP, both showing granulomatous inflammation, PBM, and emphysema. SMH along with C/O and respiratory bronchiolitis were common in deployers but not in cHP cases. In deployers, there were significantly higher odds of small airways injury in the lower lobe compared with upper lobe samples.

Rare Surgical Lung Biopsy Findings of Metastatic Pulmonary Calcification Associated with Chronic Renal Failure

Abstract Introduction/Objective Metastatic pulmonary calcification is a metabolic lung disease characterized by depositions of calcium in lung parenchyma. Depositions of calcium salts are usually caused by hypercalcemia and are associated with end-stage renal disease, primary and secondary hyperparathyroidism, and hemodialysis. It is mostly asymptomatic and clinically silent but can lead to life-threatening respiratory failure. Methods We present a case of a 53-year-old woman, with a failed renal transplant and on hemodialysis, admitted with cough and shortness of breath. Computed tomography showed extensive diffuse bilateral groundglass and nodular opacities. Bronchoscopy was unremarkable. BAL results were negative for infection. The initial differential diagnosis included pneumonitis, interstitial lung disease, and chronic obstructive pulmonary disease. VATS lung wedge resection was performed. Results Microscopically there were numerous interstitial, peribronchial and perivascular calcifications highlighted by Van Kossa stain. Calcifications were associated with a marked interstitial fibrosis confirmed by trichrome stain. There was no evidence of significant acute and chronic inflammation, granulomas, fibroblastic foci and vasculitis. Conclusion Metastatic pulmonary calcification is found in 60–80% of autopsies of patients undergoing dialysis treatment. It is rarely diagnosed during their lifetime, because patients are usually asymptomatic, or the imaging findings are negative. The diagnosis of metastatic pulmonary calcification in our patient prompt further evaluation for repeat kidney transplant and the patient is being considered for parathyroidectomy for her tertiary hyperparathyroidism.

Transbronchial cryobiopsy increases diagnostic confidence in interstitial lung disease: a prospective multicentre trial.

The accurate diagnosis of individual interstitial lung diseases (ILD) is often challenging, but is a critical determinant of appropriate management. If a diagnosis cannot be made after multidisciplinary team discussion (MDTD), surgical lung biopsy is the current recommended tissue sampling technique according to the most recent guidelines. Transbronchial lung cryobiopsy (TBLC) has been proposed as an alternative to surgical lung biopsy. This prospective, multicentre, international study analysed the impact of TBLC on the diagnostic assessment of 128 patients with suspected idiopathic interstitial pneumonia by a central MDTD board (two clinicians, two radiologists, two pathologists). The level of confidence for the first-choice diagnoses were evaluated in four steps, as follows: 1) clinicoradiological data alone; 2) addition of bronchoalveolar lavage (BAL) findings; 3) addition of TBLC interpretation; and 4) surgical lung biopsy findings (if available). We evaluated the contribution of TBLC to the formulation of a confident first-choice MDTD diagnosis. TBLC led to a significant increase in the percentage of cases with confident diagnoses or provisional diagnoses with high confidence (likelihood ≥70%) from 60.2% to 81.2%. In 32 out of 52 patients nondiagnostic after BAL, TBLC provided a diagnosis with a likelihood ≥70%. The percentage of confident diagnoses (likelihood ≥90%) increased from 22.7% after BAL to 53.9% after TBLC. Pneumothoraces occurred in 16.4% of patients, and moderate or severe bleeding in 15.7% of patients. No deaths were observed within 30 days. TBLC increases diagnostic confidence in the majority of ILD patients with an uncertain noninvasive diagnosis, with manageable side-effects. These data support the integration of TBLC into the diagnostic algorithm for ILD.

SEVERE PANCOLITIS: A RARE ADVERSE EFFECT OF NINTEDANIB

SESSION TITLE: Diffuse Lung Disease SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/09/2018 01:15 pm - 02:15 pm INTRODUCTION: Nintedanib is a tyrosine kinase receptor blocker that inhibits multiple fibrogenic growth factors. It is one of the only two currently available drugs that have been shown to slow the decline in lung function in patients with idiopathic pulmonary fibrosis (IPF). While some gastrointestinal adverse effects are common in patients taking nintedanib, severe pancolitis has only been reported once before [1]. CASE PRESENTATION: Our patient is a 61-year-old Caucasian gentleman who was diagnosed with IPF based clinico-radiologic and surgical lung biopsy findings. He was started on nintedanib and tolerated 150 mg twice a day dose well. While on therapy his pulmonary function tests remained fairly stable. 1.5 years after having been on nintedanib he developed severe diarrhea. Nintedanib was discontinued however his diarrhea did not improve. He underwent colonoscopy that revealed pancolitis. Colonic biopsies showed severe active inflammation with frequent crypt abscess formation. Dense basal lymphoplasmocytic infiltrates were not seen, therefore, making ulcerative colitis less likely. Rather, drug induced colitis caused by nintedanib was considered. Patient was treated with prednisone with rapid resolution of symptoms. At this point, patient was rechallenged with nintedanib. He tolerated low dose therapy, but as soon as the dose was increased back to 150 mg twice a day, the symptoms recurred. This further confirmed his colitis as being drug induced. Nintedanib has since been discontinued and the patient has been switched to pirfenidone, which he has been tolerating well. DISCUSSION: In nintedanib’s clinical trials up to 62% of the patients experienced diarrhea. However, it was mostly mild to moderate in intensity. Diarrhea led to discontinuation of therapy in less than 5% of the cases. Our case is unique for two reasons. Firstly, our patient had severe pancolitis seen on colonoscopy and further confirmed by histopathology. Inflammatory bowel disease (IBD) and infections were adequately excluded. There has been only one prior published report of nintedanib induced severe pancolitis that was confirmed histopathologically. Secondly, our patient tolerated nintedanib well for 1.5 years before the onset of symptoms. Most of the times diarrhea is seen with in the first few weeks of initiation of therapy. Nintedanib slows down pulmonary fibrosis by inhibiting fibroblast growth factor, vascular endothelial growth factor and platelet derives growth factor. Unfortunately, these mediators are also involved in angiogenesis and repair of gastrointestinal tract. Therefore, their inhibition by nintedanib predisposes patients to adverse effects like colitis. CONCLUSIONS: Nintedanib can rarely cause severe pancolitis, even several months after initiation of therapy. After excluding alterative etiologies, nintedanib induced pancolitis can be treated with drug discontinuation and steroids. Reference #1: Oda K, Matsunaga T, Sennari K, Yatera K. Colitis Associated with Nintedanib Therapy for Idiopathic Pulmonary Fibrosis (IPF). Intern Med 2017;56(10):1267–1268. DISCLOSURES: No relevant relationships by Muhammad Ali, source=Web Response No relevant relationships by Mark Barash, source=Web Response No relevant relationships by Aasim Mohammed, source=Web Response Speaker/Speaker's Bureau relationship with Boehringer-Ingelheim pharmaceuticals Please note: $5001 - $20000 Added 03/03/2018 by Vijay Ramalingam, source=Web Response, value=HonorariaRemoved 03/03/2018 by Vijay Ramalingam, source=Web Response Speaker/Speaker's Bureau relationship with Boehringer-Ingelheim pharmaceuticals Please note: $1001 - $5000 Added 03/03/2018 by Vijay Ramalingam, source=Web Response, value=Honoraria

Histological variability and consequences in chronic bird-related hypersensitivity pneumonitis.

Lobar and temporal histological variability in chronic bird-related hypersensitivity pneumonitis (BRHP) has not been clearly elucidated. This study was designed to evaluate the spatio-temporal histopathological variability in chronic BRHP. Fifty-two patients with chronic BRHP who underwent a surgical lung biopsy (SLB) between 1992 and 2008 were evaluated. The histopathological characteristics of the lung biopsy specimens were classified by the 2002 American Thoracic Society/European Respiratory Society (ATS/ERS) consensus classification of idiopathic interstitial pneumonias (IIPs). Autopsy specimens from seven patients were also evaluated to examine the serial changes from SLB to autopsy. In a study of lobar histological variability based on the findings of SLB, 7 patients were diagnosed with cellular nonspecific interstitial pneumonia (NSIP) pattern, 16 with fibrotic NSIP pattern, 20 with fibrotic NSIP pattern and usual interstitial pneumonia (UIP) (discordant UIP) pattern and 9 with UIP (concordant UIP) pattern. In a study of sequential changes, specimens of SLBs with fibrotic NSIP pattern changed to a bronchiolocentric interstitial pneumonia (BIP) pattern or UIP pattern. Interlobar and intralobar histological variability is present in chronic BRHP. In several patients with chronic BRHP, a fibrotic NSIP pattern may be an early lesion that progresses to a UIP pattern.

The current position of surgical lung biopsy in the diagnosis of idiopathic pulmonary fibrosis

A new international statement defines usual interstitial pneumonia (UIP) which is a histological and radiological form of idiopathic pulmonary fibrosis (IPF) more precisely than previously. In the diagnosis of IPF, either in high resolution computed tomography (HRCT) a UIP pattern must be present or alternatively specific combinations of HRCT and surgical lung biopsy findings can be accepted. In about two third of the cases IPF can be diagnosed by clinical and radiological criteria. Thus surgical lung biopsy is needed in about one third of cases to achieve the ultimate diagnosis, which requires multidisciplinary cooperation. In large clinical trials conducted during the last decade, lung biopsy was performed in about 30–60% of the cases. The most serious complication of lung biopsy is mortality within 30 days after the procedure, with a frequency of about 3–4% reported in most studies. Because of the histological variability, surgical lung biopsy should be taken from a minimum of two lobes. The number of fibroblast foci in surgical lung biopsy has been shown to correlate with survival in several studies.

Pathological and High Resolution CT Findings in Churg-Strauss Syndrome

To investigate the Churg-Strauss syndrome (CSS) associated lung involvement, concentrating on clinical characteristics, pathological findings of lung involvements, response to treatment, and prognosis. We retrospectively analyzed the characters of the clinical manifestations, thin-section CT and pathological findings of CSS. The study involved 16 patients. Clinical data were obtained by chart review. All patients underwent transbronchial lung biopsy (TBLB). Six of them underwent surgical lung biopsy as well. The patients included 7 men and 9 women, aged from 14 to 61 years (median, 47.5 years). Extrathoracic organs involved included nervous system (7/16) and skin (5/16). Respiratory symptoms included cough (12/16), exertional dyspnea (11/16), hemoptysis (4/16), and chest pain (3/16). CT findings included bilateral ground-glass opacities (12/16), bilateral patchy opacities (12/16), and centrilobular nodules (6/16). The pathological findings of TBLB demonstrated increased eosinophils (3/16), vasculitis (3/16), and interstitial pneumonia (16/16). The pathological findings of surgical lung biopsy of 6 cases showed necrotizing vasculitis in 4 cases, capillaries in 5, eosinophilic pneumonia in 3, granulomas in 2, and airway abnormalities in 3. All patients improved in symptoms after therapy during the study period (range, 3 to 51 months; median, 15 months). Asthma may be present in CSS patient when there is bronchial involvement. Ground-glass opacities and consolidation seen on high-resolution CT reflect the presence of eosinophilic pneumonia, vasculitis, and pulmonary alveolar hemorrhage. TBLB has significant limitations for the diagnosis of CSS. Early diagnosis and therapy can result in satisfactory prognosis.

A case of non‐specific interstitial pneumonia effectively treated with a combination of prednisolone and colchicine, in which granulation tissue was extensive

A 56-year-old woman was admitted for interstitial pneumonia, and subsequently diagnosed with idiopathic non-specific interstitial pneumonia with a bronchiolitis obliterans organizing pneumonia pattern, on the basis of clinical and surgical lung biopsy findings. Histological findings revealed diffuse thickness of alveolar walls accompanied by lymphocyte infiltration and fibrosis in the lobules. In addition to those findings, granulation tissue was extensive. Although initial symptom and CT improvement occurred following high-dose prednisolone therapy, the CT did not show further improvement and her serum KL-6 level began increasing again as prednisolone was reduced. With the addition of colchicine therapy, clinical and CT findings improved remarkably and a further reduction of the prednisolone dose was achieved. This case suggests that the combination of colchicine and corticosteroids may be an effective therapy for non-specific interstitial pneumonia.

Usual Interstitial Pneumonia Complicating Dyskeratosis Congenita

Usual Interstitial Pneumonia Complicating Dyskeratosis Congenita

The Findings of Surgical Lung Biopsy in HIV Patients in the Era of Highly Active Antiretroviral Therapy

Surgical lung biopsy (SLB) is rarely necessary in the evaluation of pulmonary infiltrates in patients with human immunodeficiency virus (HIV). The aim of this study is to describe the findings of SLB in a recent cohort of HIV-infected patients with unexplained pulmonary infiltrates, and determine the impact of this procedure on management and outcome of these patients. We used a retrospective review of medical records for this study. Twenty-six patients who underwent SLB where evaluated. The procedure was performed either by video-assisted thoracoscopy, in 42% of the cases, or by thoracotomy in 58%. Eleven patients (42%) had focal infiltrates, and 15 (58%) had diffuse infiltrates. There were 31 diagnoses in the 26 patients; 26 (84%) were specific and 5(16%) were nonspecific. The most common specific diagnoses were infection (58%), malignancy (16%), and inflammatory conditions (10%). Pneumocystis carinii, alone or in combination with other conditions, was the most common diagnosis of all biopsies (34%). Surgical lung biopsy led to a change in management in 17 patients (65%), and was associated with complications in 4 patients (15%). The in-hospital mortality rate was 27%. Surgical lung biopsy is a relatively safe procedure, and provides a specific diagnosis in the majority of patients with HIV infection and unexplained pulmonary infiltrates. Pneumocystis carinii alone or in combination with other conditions is the most common finding.

Surgical lung biopsy in patients with hematological malignancy or hematopoietic stem cell transplantation and unexplained pulmonary infiltrates: Improved Outcome with specific diagnosis

Using a retrospective review of medical records, we sought the findings of surgical lung biopsy (SLB) in patients with hematological malignancy or hematopoietic stem cell transplantation (HSCT) and unexplained pulmonary infiltrates and to determine the impact of this procedure on management and outcome of these patients. Sixty-two patients who underwent SLB were evaluated; 31 patients had underlying hematological malignancy and 31 patients were HSCT recipients; 58% of whom underwent allogeneic HSCT. Thirty-three patients (53%) had focal infiltrates on chest CT scan while 29 (47%) had diffuse infiltrates. Thirteen patients were mechanically ventilated prior to SLB, and 27 (43%) were neutropenic. There were 66 diagnoses in the 62 patients, 44 (67%) were specific and 22 (33%) were nonspecific. The most common specific diagnoses were infection (29%), malignancy (27%), and inflammatory conditions (11%). Aspergillosis was the most common diagnosis of all biopsies (21%). SLB led to a change in therapy in 40% of patients and was associated with complications in 7 patients (11%). Specific diagnosis was more likely to lead to a change in therapy (48% vs. 27%, P = 0.06) and was associated with a lower mortality when compared to a nonspecific finding (30% vs. 59%, P = 0.02). Nonspecific diagnosis, on the other hand, was seen more in patients on mechanical ventilation prior to SLB compared to those off mechanical ventilation (69% vs. 27%, P = 0.02). SLB provides a specific diagnosis in the majority of patients with hematologic malignancy or HSCT recipients and unexplained pulmonary infiltrates. Specific diagnosis is more likely to lead to a change in therapy and is associated with a better outcome.

Idiopathic Pleuroparenchymal Fibroelastosis: Description of a Novel Clinicopathologic Entity

Between 1996 and 2001, we identified five cases of a unique idiopathic pleuroparenchymal lung disease characterized by a clinical presentation suggestive of a chronic idiopathic interstitial pneumonia, marked pleural and parenchymal radiographic involvement with an upper lobe predominance, and surgical lung biopsy findings that did not fit with any of the currently defined interstitial pneumonias. The pathologic findings included the following: (1) intense fibrosis of the visceral pleura; (2) prominent, homogenous, subpleural fibroelastosis; (3) sparing of the parenchyma distant from the pleura; (4) mild, patchy lymphoplasmacytic infiltrates; and (5) small numbers of fibroblastic foci present at the leading edge of the fibrosis. In this report, we characterize the clinical, radiographic, physiologic, and pathologic findings of this entity, which we term idiopathic pleuroparenchymal fibroelastosis.

Histopathologic variability in usual and nonspecific interstitial pneumonias.

Findings of surgical lung biopsy (SLB) are important in categorizing patients with idiopathic interstitial pneumonia (IIP). We investigated whether histologic variability would be evident in SLB specimens from multiple lobes in patients with IIP. SLBs from 168 patients, 109 of whom had multiple lobes biopsied, were reviewed by three pathologists. A diagnosis was assigned to each lobe. A different diagnosis was found between lobes in 26% of the patients. Patients with usual interstitial pneumonia (UIP) in all lobes were categorized as concordant for UIP (n = 51) and those with UIP in at least one lobe were categorized as discordant for UIP (n = 28). Patients with nonspecific interstitial pneumonia (NSIP) in all lobes were categorized as having fibrotic (n = 25) or cellular NSIP (n = 5). No consistent distribution of lobar histology was noted. Patients concordant for UIP were older (63 +/- 9 [mean +/- SD] yr; p < 0.05 as compared with all other groups) than those discordant for UIP (57 +/- 12 yr) or with fibrotic NSIP (56 +/- 11 yr) or cellular NSIP (50 +/- 9 yr). Semiquantitative high-resolution computed tomography demonstrated a varied profusion of fibrosis (p < 0.05 for all group comparisons), with more fibrosis in concordant UIP (2.13 +/- 0.62) than in discordant UIP (1.42 +/- 0.73), fibrotic NSIP (0.83 +/- 0.58), or cellular NSIP (0.44 +/- 0.42). Survival was better for patients with NSIP than for those in both UIP groups (p < 0.001), although survival in the two UIP groups was comparable (p = 0.16). Lobar histologic variability is frequent in patients with IIP, patients with a histologic pattern of UIP in any lobe should be classified as having UIP.