C. Gurioli

G. Casoni

V. Poletti

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Monaldi Arch Chest Dis2011; 75: 1, 39-41 BRONCHOSCOPYTransbronchial Pulmonary BiopsiesG. Casoni, C. Gurioli, V. PolettiThe ability to obtain the pulmonary tissuewithout the need for the patient to undergo a surgi-cal pulmonary biopsy is an important step forwardin the diagnosis of the lung diseases.The bronchoscopic pulmonary biopsy, definedalso as transbronchial lung biopsy (TBLB), is aprocedure with low morbidity and mortality. Infact the main indications for performing TBLB arethe evaluation of peripheral nodular lung lesions ordiagnosis of diffuse parenchymal lung disease.The first description of TBLB is attributed toAndersen et al. [1], as a result of their observationthat the specimens of bronchial biopsies of thesmall airways collected during a rigid bron-choscopy often contained pulmonary parenchyma.The forceps for TBLB collect the pulmonary tissuethrough the bronchi and enable specimens from thecentrolobular regions to be obtained [2]. The disor-ders that are centred around the terminal and respi-ratory bronchioles (respiratory bronchiolitis, tuber-culosis, lobular infectious pneumonia, cellularbronchiolitis) or significantly involve these struc-tures (organising pneumonia) or those that are dis-tributed along the lymphatic routes (sarcoidosis,carcinomatous lymphangitis) may be easily sam-pled by forceps. Multiple biopsy samples are re-quired for a good diagnostic yield [3]. Most studies[3-7] have shown that there is a direct correlationbetween the number of samples obtained per TBLBand the overall diagnostic yield (i.e 38% with oneto three tissue fragments vs. 69% with six to ten,p<0.01). Therefore if the procedure proceeds nor-mally, it is reasonable to perform 7-8 biopsies(fragments of valid tissue!) for examination. Agreater number of biopsies may be necessary if apart of tissue is likely to be sent away for specialstains or studies. Large forceps produce biggerspecimens. Loube et al. [6] prospectively com-pared the diagnostic yield of transbronchial biop-sies using large and small forceps (cup sizes, 3 x 2x 0.9 vs. 2 x 1.5 x 0.6 mm respectively). Large for-ceps obtained significantly more tissue than thesmall forceps [16 of 22 patients (73%) vs. 6 of 22patients (27%), p<0.05, with no alveolar tissue ob-tained in 5 patients]. Further, if larger forceps arenot withdrawn through the operative channel, crashartefacts may also be avoid [8] improving diagnos-tic yield. The main complication of TBLB is bleed-ing; less frequent complications are pneumothorax,hypoxemia, or cardiac arrhythmias during the pro-cedure. Bleeding occurs to some degree in virtual-ly all TBLB procedures and in some cases can besubstantial. The risk of bleeding is the main limit-ing factor in obtaining more or larger biopsy sam-ples. The suction channel of the typical fiber-bron-choscope is only 2 mm in diameter, and the volumeof blood that can be suctioned through the channelis hence limited. Therefore, a bronchoscopistshould be also trained in the use of a rigid bron-choscope to control any bleeding post TBLB.The effective execution of the TBLB beginswith an adapted selection and preparation of thepatient which includes the aims and risks of theprocedure. The bronchoscopy and the TBLBshould be performed in an appropriate and wellequipped room for the effective monitoring of thearterial pressure and oxygen saturation. Moreoverthe equipment for the additional oxygen therapy,the cardiopulmonary resuscitation must be avail-able. The use of radioscopy during the TBLB isdebated; however the TBLB is still usually per-formed with fluoroscopic guidance as the rate ofpneumothorax is reduced when fluoroscopy isused [9]. The bronchoscopist should be trained inthe employment of radioscopic equipment or havea staff trained during the procedure. The TBLBcan be performed both by fiber-bronchoscope orrigid bronchoscope in general anesthesia.IndicationsThe main indications for performing TBLB arethe evaluation of peripheral nodular lung lesions andthe diagnosis of diffuse parenchymal lung disease.Peripheral localised lesions of the lungPeripheral nodular pulmonary lesions can bediagnosed by TBLB. It has been demonstrated thatthe dimension of the pulmonary nodule (in particu-lar if this is < to 2 cm) represents the limiting fac-tor of the diagnostic yield of TBLB [10]. Howeverit has been shown an improvement of diagnosticyield of the TBLB in diagnosis of a peripheral pul-Monaldi Arch Chest Dis 2011; 75: 1, 39-41.Keywords: Transbronchial lung biopsy, Diffuse parenchimal lung disease, High definition computerised tomography,Peripheral nodular lung lesion, Endoscopic ultrasound.Dipartimento di Malattie del Torace, Ospedale Morgagni-Pierantoni, Forlì, Italy.Correspondence: Dr. Gian Luca Casoni, Dipartimento di Malattie del Torace, Ospedale Morgagni-Pierantoni, Via Forlanini 34,47100 Forlì, Italy; e-mail: casonig1970@libero.it40G. CASONI ET AL.monary nodule with diameter <3 cm using Endo-bronchial Ultrasound-Driven Biopsy (EBUS) [11].In particular, EBUS-guided TBLB is a safe andvery effective method for solitary pulmonary nod-ules that cannot be visualized by fluoroscopy. Theprocedure may increase the yield of endoscopicbiopsy in patients with these nodules and avert theneed for surgical procedures [12]. Then, thebronchus sign at a fourth-order bronchus is valu-able in predicting the success of transbronchialbiopsy. The presence of the sign on CT may be use-ful in determining if the work-up should includetransbronchial biopsy or transthoracic needle aspi-ration in patients with peripheral lung lesions [13].Diffuse parenchymal lung diseaseTBLB may be considered as the first choice fordiagnosis of diffuse parenchymal lung disease. His-tological examinations should be performed rou-tinely. The decision as to the type, size, and site ofthe biopsy sample is determined by the level of di-agnostic certainty before performing lung biopsy,the suspected nature, distribution and extent of thedisease, and the patient’s performance status. Theintroduction of the high definition computerised to-mography (HRCT) has enormously improved theresolution of pulmonary spaces and it has allowedthe lesions to be better defined the lesions throughthe interpretation of morphologic characteristicsand anatomical distribution (analysis for patterns)particularly in the context of diffuse parenchymallung disease [14]. HRCT is very useful in predictingthe yield of TBLB based on the anatomic distribu-tion and appearance of any abnormalities in partic-ular with the presence of some HRCT patterns suchas nodular, alveolar consolidations, ground glass,tree in bud and thickening of the interlobular septa(peri-lymphatic pattern) in which the diagnosticyield of the TBLB is better than others patterns (i.e.reticular pattern) [15]. The first step in the diagnosisof diffuse parenchymal lung disease is to divide anddifferentiate between immuno-compromised andimmuno-competent patients [16, 17].Immunocompromised patients who developdiffuse lung disease are usually acutely ill withfever, cough, shortness of breath, and often withprogressive hypoxemia [16, 17]. A prompt diag-nosis seems, therefore, to be crucial for a bettersurvival. In cases in which a TBLB is deemednecessary and is feasible (absence of significantcoagulation disorder, platelet >50,000/microliter)Bronchoscopic procedures should be performedunder general anaesthesia through a rigid bron-choscope or an orotracheal or ‘nasotracheal’ tubein order to better control the ventilation and bleed-ing [8]. Combined BAL and TBLB may also beperformed safely in mechanically ventilated pa-tients [22]. Non-specific pathological changes arecommon in TBLB specimens in these patients butif they are interpreted in the context of a specificclinical setting and of HRCT scan patterns theymay contribute to the definition of a specific diag-nosis (in particular drug-related lung toxicity,alveolar haemorrhage and vasculitis, alveolar pro-teinosis) [18, 19]. Also infections may have non-specific changes as the sole morphological fea-tures. Special stains are, therefore, mandatorywhen TBLB specimens are evaluated in immuno-compromised patients. Special stains are also use-ful for the classification of epithelial tumours andnecessary to better identify lymphoid infiltrates.Remarkable interest must be placed on the impactof invasive diagnostic techniques (TBLB) on thesurvival in the immunocompromised patients[20]. A reduction of mortality in those patientsthat were diagnosed at an earlier stage has beendemonstrated [21]. On other hand a delay of >5days in establishing a specific diagnosis, was di-rectly correlated with an increased mortality.In the immunocompetent patients TBLB may beconsidered as the first choice. Monomorphous histo-logical patterns (organising pneumonia, eosinophilicpneumonia, diffuse alveolar damage with or withouteosinophils, alveolar haemorrhage with or withoutcapillaritis, alveolar proteinosis) [18, 19] are easilyidentifiable in small lung fragments but they are moreor less non-specific and are considered diagnostic on-ly in agreement with clinical, radiological and otherlaboratory data. Specimens obtained through TBLBshould be serially sectioned and immunohistochemi-cal investigations should be encouraged for example,Langerhans cell histiocytosis, lymphangioleiomy-omatosis, sarcoidosis, carcinomatous or malignantsoft tissue metastases, and lymphoproliferative disor-ders are better defined using specific monoclonal an-tibodies (CD1a, Langerhin, HMB-45, CD68, TTF-1or CDX-2 immunohistochemical expression). Thetiny specimens obtained by TBLB may not be suffi-cient in cases in which the morphological features arecharacteristic only in large volumes of tissue (usualinterstitial pneumonitis, desquamative interstitialpneumonitis, nonspecific interstitial pneumonitis, fi-brosing type). Usually, TBLB specimens are usuallyconsidered too small and non-representative to allowthe diagnosis of the usual interstitial pneumonia(UIP) pattern, although recently [22] the presence ofpatchwork fibrosis along with honeycomb changesand/or the presence of fibroblastic foci were shown tobe present in TBLB specimens in 32% of patientswith histologically proved UIP. Furthermore, wehave also shown [8] that the characteristic histologi-cal features of diffuse parenchymal lung disease/IIPmay be identified on TBLB specimens more oftenthan previously appreciated using more large flexibleforceps (as modified gastroenterological forcepscalled “Jumbo” forcep) via rigid bronchoscopy. Gen-erous TBLB may provide good specimens for a mor-phological diagnosis of pattern called nonspecific in-terstitial pneumonia (NSIP), cellular variant. Thispathological diagnosis is acceptable in specific clini-cal settings (polymyositis-dermatomyositis-relatedinterstitial lung disease, drug toxicity) but it might al-so be of clinical value in cases of unknown aetiology.ContraindicationsEvaluation of the patient before the procedureis crucial. TBLB is contraindicated in the presenceof bleeding abnormalities. An international nor-41TRANSBRONCHIAL PULMONARY BIOPSIESmalised ratio (INR) greater than 1.5 is an absolutecontra-indication; successful TBLB can be carriedout if the INR is less than 1.5. If a patient is takingwarfarin, it can usually be withheld for 4 to 5 daysto allow the INR to slowly decrease to a saferrange. TBLB is also contraindicated if the plateletcount is less than 50000/µL but the platelet countcan be increased relatively quickly with platelettransfusions prior to the procedure. Also, plateletdysfunction is a relative contra-indication to biop-sy. There is insufficient data on antiplatelet agentssuch as clopidogrel, but most bronchoscopists arehesitant to perform a TBLB if the patient is usingthis agent. Other contra-indications for bron-choscopy and TBLB are severe hypoxemia, un-controlled cardiac arrhythmias, unstable angina,and severe asthma or exacerbation of chronic ob-structive pulmonary disease.Recommendations• The main indications for performingTBLB are the evaluation of periph-eral nodular lung lesions or diagno-sis of diffuse parenchymal lung dis-ease (Grade B).• TBLB may be considered as the firstchoice for diagnosis of diffuseparenchymal lung disease. Histologi-cal examination should be routinelyperformed. HRCT is very useful inpredicting the yield of TBLB based onthe anatomic distribution and appear-ance of any abnormalities (Grade B).• The HRCT has demonstrated usefulto increase the diagnostic accuracy ofTBLB in presence of some HRCTpatterns as nodular, alveolar consoli-dations, ground glass, tree in bud,thickening of the interlobular septa(peri-lymphatic pattern) and pres-ence of broncus sign (Grade B).• In order to obtain a satisfacory diag-nostic yield it is reasonable to carryout 7-8 biopsies (fragments of validtissue!) for examination (Grade B).• The size of lung nodules (especially ifit is <2 cm) is the limiting factor inthe diagnostic yield of TBLB. The useof endoscopic ultrasound (EBUS) sig-nificantly improves the diagnosticyield of TBLB in the presence of a pe-ripheral pulmonary nodule with a di-ameter less than 3 cm (Grade B).References1. Andersen HA, Fontana RS, Harrison EG. Transbron-choscopic lung biopsy in diffuse pulmonary disease.Dis Chest 1965; 48: 187-192.2. Poletti V, Patelli M, Ferracini R, Simonetti M, Spiga L.Transbronchial lung biopsy in infiltrative lung disease.The importance of the pathologic approach. Sarcoidosis1988; 5: 43-50.3. Descombes E, Gardiol D, Leuenberger P. Trans-bronchial lung biopsy: An analysis of 530 cases withreference to the number of samples. Monaldi ArchChest Dis 1997; 52: 324-329.4. Hopkins PM, Aboyoun CL, Chhajed PN, et al. Prospec-tive analysis of 1,235 transbronchial lung biopsies inlung transplant recipients. J Heart Lung Transplant2002; 21: 1062-7.5. Curley FJ, Johal JS, Burke ME, Fraire AE. Trans-bronchial lung biopsy: Can specimen quality be predict-ed at the time of biopsy? Chest 1998; 113: 1037-1041.6. Loube DI, Johnson JE, Wiener D, Anders GT, BlantonHM, Hayes JA: The effect of forceps size on the ade-quacy of specimens obtained by transbronchial biopsy.Am Rev Respir Dis 1993; 148: 1411-1413.7. Becker HD, Shirakawa T, Tanaka F, Muller KM, HerthF. Transbronchial (transbronchoscopic) lung biopsy inimmunocompromised patient; in Strausz J (ed): Pul-monary Endoscopy and Biopsy Techniques. Eur RespirMonogr 1998, vol 3, pp 193-208.8. Casoni GL, Gurioli C, Chhajed PN, et al. The value oftransbronchial lung biopsy using jumbo forceps viarigid bronchoscope in diffuse lung disease. MonaldiArch Chest Dis 2008; 69: 59-64.9. Prakash UB, Offord KP, Stubbs SE. Bronchoscopy inNorth America: the ACCP survey. Chest 1991; 100:1668-75.10. Baaklini WA, Reinoso MA, Gorin AB, Sharafkaneh A,Manian P. Diagnostic yield of fiberoptic bronchoscopyin evaluating solitary pulmonary nodules. Chest 2000;117: 1049-1054.11. Paone G, Nicastri E, Lucantoni G, et al. EndobronchialUltrasound-Driven Biopsy in the diagnosis of peripher-al lung lesions. Chest 2005; 128: 3551-3557.12. Herth FJ, Eberhardt, Becker HD and Ernst A. Endo-bronchial ultrasound-guided transbronchial lung biopsyin fluoroscopically invisible solitary pulmonary nod-ules. Chest 2006; 129; 147-150.13. Gaeta M, Pandolfo I, Volta S, et al. Bronchus sign on CTin peripheral carcinoma of the lung: value in predicting re-sults of transbronchial biopsy. AJR 1991; 157: 1181-1185.14. Zompatori M, Sverzellati N, Poletti V, et al. High-res-olution CT in diagnosis of diffuse infiltrative lung dis-ease. Semin Ultrasound CT MR 2005; 26: 332-347.15. Colby TV, Swensen SJ. Anatomic distribution andhistopathologic patterns in diffuse lung disease: corre-lation with HRCT. J Thorac Imaging 1996; 1: 1-26.16. Poletti V, Costabel U, Semenzato G. Pulmonary com-plications in patients with haematological disorders:pathobiological bases and practical approach. SeminRespir Crit Care Med 2005; 26: 439-444.17. Poletti V, Trisolini R, Tura S. Pulmonary disease in pa-tients with hematologic malignancies. Sarcoidosis VascDiffuse Lung Dis 2002; 19: 29-45.18. Poletti V, Cazzato S, Minicuci N, et al. The diagnosticvalue of bronchoalveolar lavage and transbronchiallung biopsy in cryptogenic organizing pneumonia. EurRespir J 1996; 9: 2513-2516.19. Lacasse Y, Fraser RS, Fournier M, Cormier Y. Diag-nostic accuracy of transbronchial biopsy in acutefarmer’s lung disease. Chest 1997; 112: 1459-1465.20. Mayaud C, Cadranel J. A persistent challenge: the di-agnosis of respiratory disease in the non-AIDS im-munocompromised host. Thorax 2000; 55: 511-517.21. Rano A, Agusti C, Benito N, et al. Prognostic factors ofnon-HIV immunocompromised patients with pul-monary infiltrates. Chest 2002; 122: 253-261.22. Berbesku EA,Katzenstein AL, Snow JL, et al. Trans-bronchial biopsy in usual interstitial pneumonia. Chest2006; 129: 1126-1131.

Transbronchial Pulmonary Biopsies

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Transbronchial Pulmonary Biopsies

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