Contribution of transthoracic lung biopsy in the diagnosis of organizing pneumonia


Introduction :

The organizing pneumonia (PO), formerly known as bronchiolitis obliterans with organizing pneumonia or BOOP, is an inflammatory disease and fibroproliferative lung whose diagnosis remains difficult. The presumptive diagnosis is based on clinical and radiological criteria.Contribution of transthoracic lung biopsy in the diagnosis of organizing pneumonia

However, nor the unspecific clinical picture (cough, dyspnea, fever mimicking an infectious process) or the varied radiological presentation (opacities bilateral migratory alveolar, diffuse infiltrative forms mimicking ILD isolated nodule or suspicious for malignancy) do not allow a definitive diagnosis. This requires histological samples for the detection of connective endoalvéolaires buds forming the elementary lesion of OP. This diagnosis requires an invasive procedure that allows the collection of a fragment of lung tissue. It can be obtained conventionally by either transbronchial lung biopsy (BTB), either by surgical lung biopsy (BC).

Nevertheless BTB provides samples of varying quality and general anesthesia required for BC is not always possible. It is not uncommon, especially in frail patients, we renounce histological evidence for the diagnosis of OP and one test corticosteroids are established based on radiological criteria, assisted by a bronchoalveolar lavage. Such an attitude should be avoided as much as possible because the probability of diagnostic error is significant because of the many PO differential diagnoses. This can have serious consequences, either by ignorance of malignancy, the adverse effects of corticosteroids on a neglected disease such as mycobacteriosis, or by the risk of prolonged corticosteroid therapy in elderly patients. To limit the presumptive diagnoses, it seems interesting to discuss the interest of transthoracic lung biopsy (BTT) guided by scanner in the histological diagnosis of PO. For it, six personal observations are reported and discussed based on the literature on the subject and comparing the advantages and disadvantages of each diagnostic technique.

Methods :

Six observations of patients, followed in two pulmonology services Franche Comté between September 2005 and April 2007, having presented a radiological features compatible with PO and in which was conducted a BTT scanoguidée referred to diagnostic, are reported.

Results :

Observation n° 1 :

A man was hospitalized for rest dyspnea,fever 38,5 ° C and hemoptysis. He had a PaO 2 to 65 mmHg in 4 L / min of oxygen (1 mmHg = 7,5 kPa) and a CRP 273 mg / L.

thoracic CT uninjected in parenchymatous window viewing transthoracic biopsy

Fig. 1.
A) thoracic CT uninjected in parenchymatous window viewing transthoracic biopsy needle coaxially in
lobar average alveolar condensation.
B) optical microscopy, magnification × 100, Hématoxilline-Eosine-Safran staining. Buds connective endoalvéolaires rich in collagen
with characteristic appearance butterfly wing connective bud communicating between two cells by a pore Köhn.

The CT scan revealed bilateral interstitial syndrome in the predominant form of reticular lesions in the right lung field and lower lobes, associated with a lobar average alveolar condensation. Clavulanic acid and amoxicillin antibiotic ofloxacin was started. Under this treatment, hypoxemia worsened and radiological lesions have spread. General anesthesia was required for BC-cons indicated by the precarious respiratory status of the patient but BTT under scanner of the middle lobar consolidation was achieved. There was no complication gesture. Histological examination concluded to a PO.

A corticosteroid 0,75 mg / kg / day was continued and gradually reduced over a total period of six months. Treatment with atorvastatin and amiodarone were arrested in the case of a drug-induced OP. A clinical and radiological cure was obtained after two months of corticosteroid therapy. One year after discontinuation of corticosteroids, no relapse was observed.

Observation n° 2 :

thoracic CT injected parenchymatous window
Fig. 2. chest CT injected parenchymal window showing the disappearance of the alveolar-interstitial syndrome after steroid therapy ; Persistence of lesions known emphysema.

A man was hospitalized for rest dyspnea despite antibiotic therapy with ceftriaxone and ofloxacin for five days. He was afebrile but had crackles in the lung field right to auscultation. The PaO 2 was 45 mmHg in air and CRP 43 mg / L.

A new antibiotic therapy with ceftriaxone and spiramycin was conducted during 12 days, without improvement. Fiberoptic bronchoscopy was normal. A BTT under CT was performed in a lobar parenchyma average condensation. The suites were simple gesture. Histological examination concluded to a PO.

After consulting the literature, simvastatin has been implicated and arrested. Corticosteroid therapy was initiated at 0,75 mg / kg / day and then gradually reduced over six months. The patient has recovered its basic respiratory status and chest radiography was normalized, relapse nine months after discontinuation of corticosteroids.

Observation n° 3 :

A carpenter has consulted for cough and fever loss 8 kg in a month. La PaO 2 was at 63 mmHg in air and CRP 275 mg / L. CT scan showed parenchymal condensations bilateral clods. Symptoms and radiological appearance did not change after 10 days of antibiotic treatment with ceftriaxone and ciprofloxacin.


Fig. 3.
A) thoracic CT injected parenchymatous window ; confluent alveolar opacities in clumps all the right lung,
associated with an aspect of frosted glass and pleural effusion right mean abundance.
B) optical microscopy, magnification × 200, Hématoxilline-Eosine-Safran staining. loose connective endoalvéolaires Buds, infiltrated
Inflammatory interstitium and the presence of eosinophils evoking a drug-induced.

Endoscopy with biopsies of spurs was normal, bronchoalveolar lavage showed alveolitis neutrophils and bronchial aspiration was Haemophilus influenzae sensitive to antibiotics skill. A BTT scano-guided was performed in a parenchymatous condensation lower left lobar. The gesture is complicated immediate minimal left pneumothorax, not increased control five minutes, spontaneous resolution. Histological analysis of biopsies concluded the diagnosis of OP. sildenafil, whose responsibility was not excluded, has been arrested. Corticosteroid therapy was initiated at 0,75 mg / kg / day and then gradually decreased, enabling complete resolution of lung injury. After six months of follow up, no relapse was observed.

Observation n° 4 :

A woman treated with amiodarone for atrial fibrillation was hospitalized for acute bronchitis, quickly evolving into a febrile respiratory distress. In the absence of improvement after 10 days of antibiotic therapy, a BTT under scanner referred diagnosis was made at the left upper lobe, uncomplicated. The successful histological diagnosis was extensively PO. Corticosteroid therapy was continued at a dose of 1 mg / kg / day and gradually decreased over four months, allowing a return to the usual clinical condition.

Observation n° 5 :


Fig. 4.
A) thoracic CT injected parenchymatous window ; parenchymal bilateral extended with bronchogramme
air ; frosted glass within interstitial thickening performing one aspect of micromesh.

B) optical microscopy, magnification
× 100, Hématoxilline-Eosine-Safran staining. Many connective endoalvéolaires buds with architectural destruction of the beginning
pulmonary fibrotic process by. alveolar hemorrhage areas.


bi-basal fibrotic lesions
Fig. 5. thoracic CT injected parenchymatous window ; some bi-basal fibrosis of bronchial lesions with distortions and aspect of micromesh.

A woman treated with simvastatin for hypercholesterolemia consulted for dry cough and dyspnea effort for three months, little improved by several successive antibiotic. The under air oxygen saturation was 94 %, There was no fever but crackles lung auscultation right field. CRP was 118 mg / L. CT scan showed a lobar alveolar condensation lower right with air bronchogramme, Extensive despite antibiotic therapy. Bronchoscopy with bronchoalveolar lavage neither evoked an infectious etiology or neoplastic. A BTT was performed in the right pulmonary condensation, uncomplicated.

Histological analysis concluded the diagnosis of OP. Simvastatin has been implicated and arrested. corticosteroid therapy 0,3 mg / kg / day was started and gradually reduced over three months, allowing the disappearance of cough and the normalization of the CXR. Three weeks after discontinuation of corticosteroids, the patient presented with dyspnea increase of fever 38 ° and CRP 188 mg / L. Alveolar syndrome lobar top right appeared. These symptoms were not improved by antibiotic therapy 10 days PO relapse diagnosis was retained. Corticosteroid therapy was resumed at 0,5 mg/kg/j, which resulted in the disappearance of radiological injuries a month later. Corticosteroid treatment was decreased to 0,3 mg / kg / day for a month without clinical relapse or radiological.

patient in the prone positionFig. 6.
thoracic CT uninjected in parenchymatous window
(patient in the prone position) ; biopsie transthoracique
in lobar alveolar condensation lower right.



Observation n° 6 :

minimal alveolar hemorrhage
Fig. 7. thoracic CT uninjected in parenchymatous window (patient in the prone position) : transthoracic biopsy in a cellular condensation with air lower left lobar bronchogramme ; minimal alveolar hemorrhage around the puncture site ; frosted glass RLL.

A man presented during a trip to Asia a cough with purulent sputum and slimming 3 kg 10 days. CT scan showed bilateral parenchymal lesions condensations with frosted glass. After several antibiotic, the clinical condition had improved but the radiological lesions persist. Bronchoscopy with bronchoalveolar lavage and biopsies of spurs was normal histologically and microbiological. A BTT under CT was performed in a lobar alveolar condensation lower left.

This was complicated by minimal alveolar hemorrhage around the puncture area and a small left pneumothorax, asymptomatic, spontaneous resolution. Histological analysis found a PO. At the same time, under a new antibiotic by imipenem and ciprofloxacin, and in the absence of steroid treatment, the patient had a clinical and radiological improvement, with three months to complete disappearance of alveolar damage to the scanner, which persisted only a few glass frosted beaches. The diagnosis of OP satellite infectious pneumonitis was finally accepted and no further treatment was conducted. The patient had no recurrence after 11 months of surveillance.

Note that for these six observations, BTT was always performed by the same radiologist or control, with a coaxial needle size 20 G and sampling four biopsies and an aspirate. These samples have been analyzed by the same pathologist, specializing in lung disease.

Discussion :

Based on these personal observations, BTT seems to be a possible alternative to the BTB for the histological diagnosis of OP. To support this hypothesis, both current diagnostic methods PO will be described and their advantages and disadvantages discussed. Comparing literature data on reported observations, BTT interest in the diagnosis of OP will be discussed.

current diagnostic methods PO :

So far PO certainty of the diagnosis is based on BTB or BC, that highlight connective alveolar buds, elementary lesion of OP. The BTB is often the first-line diagnostic method ; the choice of secondary use, or sometimes immediately, CB depends on the degree of suspicion radiological PO and the risk of misdiagnosis. There are indeed many clinical and radiological differential diagnosis of OP and some diseases may be associated with identical histological lesions.

This is the case for example of Wegener's granulomatosis, where one can find endoalvéolaires connective buds periphery granulomatous lesions or even as main histological abnormality. These connective buds can also be an incidental histological lesions around lung cancer, pneumonia, in hypersensitivity pneumonitis, nonspecific interstitial pneumonia or chronic eosinophilic pneumonia. To account for these multiple differential diagnoses, BC and BTB have advantages but also disadvantages.

BC has the advantage of being oriented (pathological lung zones being macroscopically visible to the surgeon) and therefore associated with excellent profitability, a percentage of usable sampling 98 at 100 % in the litterature. It provides large samples (the order of a few cubic centimeters), containing bronchioloalveolar vascular centro-acinar structures to better appreciate the topography of the lesions and to ensure the absence of other histological lesion that endoalvéolaires buds. BC is the gold standard for the diagnosis of OP ; it is indispensable when clinicoradiological table is atypical or the BTB is noncontributory.

However, it is an invasive procedure, the heavy postoperative, qu'allégées well by the development of
thoracoscopy video-assisted. It requires the availability of medical and paramedical personnel and therefore an operating theater and above all it requires general anesthesia, which can indicate the against-in frail patients or severely affected the respiratory map.

The BTB is to place the tip of the endoscope as far as possible in a bronchus sub-segmental pulmonary territory whose histology is desired. A biopsy forceps is inserted into the endoscope and then pushed until it is in abutment, out of sight of the operator ; it is then removed from 1 or 2 centimeters, opened, then delayed until abutment, closed and removed from the endoscope. The fragment thus collected corresponds theoretically to the lung parenchyma. The BTB has the advantage of being made during a bronchoscopy "classic", local anesthetic, without involving human or technical means. For this reason, it is often the first line examination on a suspected PO. However, samples are inconstant exploitable. Indeed, conducted blind with only endpoint the abutment of the clamp, only 77 at 86 % BTB contain the lung parenchyma and those that contain, there is no certainty that the biopsy was performed in a pathological lung area. The diagnostic value of BTB (the number of diagnoses made by BTB and finally selected) varies depending on the type of lesion : from 26 at 55 % for localized lesion and 66 at 75 % to diffuse lesions.

She lowers for peripheral lesions, it increases with the number of biopsies and their size, which can be significantly increased if the BTB are performed under general anesthesia by rigid bronchoscopy. Clair et al. assess the sensitivity of the BTB for the diagnosis of PO to 64 %. The size of the BTB is lower than samples obtained by BC, the order of a few cubic millimeters, not having at better than 50 at 100 alveolar walls but often less. The main complications of BTB are severe pulmonary hemorrhage and pneumothorax.

Bibliography :

A literature search was conducted on PubMed search engine with the keywords "BOOP, COP and organizing pneumonia "successively associated with" CT-guided biopsy ", « percutaneous biopsy », « needle biopsy », "Transthoracic biopsy" and "Tru-cut lung biopsy" to study.

We must add an article examining the clinical features and radiological PO, in which the authors claim to have obtained the histological diagnosis of PO by BTT and / or BTB home 18 of their 26 patients. Note that for references, it is not clear whether the BTT was performed under CT guidance, other guidance methods are described, such as ultrasound.

Clinical factors motivating the BTT are the same in our observations and for the case of literature, that is to say a dyspnea table, fever and cough, antibiotic resistant, This corresponds to the most common clinical presentation of OP.

The radiological characteristics are also the same : bilateral cellular condensations in 2/6 If literature and 4/6 personal cases, unilateral alveolar condensation in 2/6 If literature and 2/6 personal cases, interstitial syndrome being associated with the condensation in one case. These elements are part of the most common formats of OP. The only cases in the literature where the diagnosis of OP initially retained by the BTT is default set is where the radiological presentation is unusual, in the form of cavitation.

A surgical biopsy, performed because of unfavorable corticosteroids, corrects in this case the diagnosis. In the case of literature, a BTB was conducted in first-line in only one case and was not contributory. In our observations, BTT was the only histological examination referred performed and the diagnosis was considered retrospectively confirmed before a favorable outcome with corticosteroids and / or stopping the offending drug, This justifies that no other invasive investigation has been carried. In our observations, a majority of PO there is probable drug-induced (83 %) while cases in the literature are presented as cryptogenic except one, where bucillamine is incriminated.

Regarding treatment, the exact terms of corticosteroids are not specified in the case of literature. In our observations, corticosteroids was conducted according to the recommendations of the GERM”O”P based on several studies for case No. 1, 2 and 3. In case No. 4 the duration of corticosteroids was reduced to four months but the initial dose was increased. In case No. 5, a PO relapse was observed due to a likely underdosing initial corticosteroid and too short a treatment period compared to recommendations.

Technique, advantages and disadvantages of BTT-guided scano :

The scano-guided BTT is to provide a lung biopsy through the chest wall under local anesthesia and CT control. Thin sections scanner (2 at 5 mm) are performed to locate the lesion to be biopsied and optimize patient positioning. The procedure is currently the most used uses coaxial hands : a needle carrier is first placed percutaneously into contact with the lesion and is left in place during the entire gesture, its positioning being regularly checked by the scanner snapshots.

Through this guide, semi-automatic needle-like "Trucut" is introduced repeatedly and biopsies are performed immediately downstream of the needle carrier, two centimeters. With a single pleural break, several biopsies and aspiration of the lesion are performed, providing samples for analysis at both histological and cytological. The levy rates deemed adequate by pathologists in the literature is the order of 92 at 100 %, even for nodules of diameter less than 20 mm, with needle sizes varying between 18 G 25 G. Lawrence et al. report a levy rates exploitable 98,9 % during a study 202 biopsies of lung nodules formed with a coaxial needle 20 G same as our practice.

The diagnostic value of the BTT is between 88 and 97 %, best for malignant lesions as benign. These data are valid for lung nodule biopsies, Studies on the use of the BTT in interstitial pneumonitis being few. An article from 1981 was a diagnostic value only 42 % for BTT but sampling techniques have evolved since.

Several recent articles report an etiologic diagnosis of ILD obtained by BTT in 79 at 100 % cases. In one of the studies 23 patients and where a diagnosis was obtained by BTT in all cases, the authors state that a BTB had previously been carried out in 20 case, without contributory result.

Complications are mainly represented by pneumothorax (8 at 61 % according to studies but usually in the range of 20 at 30 %, requiring a chest tube in 3 at 15 % cases). The risk depends on the type of needle used, the number of break-ins pleural and the distance between the pleura and the lesion. The pneumothorax is most often detected early on cuts scanner end of the procedure. Minimal alveolar hemorrhage around the sampled area is common and may cause some minor sputum hémoptoïques.

Other complications are rare : hémothorax, severe alveolar hemorrhage, embolism, tumor spread over the puncture path in case of malignancy of the lesion and cardiopulmonary arrest.

The absolute cons-indications are bleeding disorders or, on lesion, vascular kind or resembling a hydatid cyst. The cons-indications are the history of pneumonectomy (risk of pneumothorax on single lung), pulmonary hypertension (increased risk of vascular wound), severe chronic respiratory failure (FEV less than 1 L) and grounds increasing the risk of pneumothorax, that is to say the severe airway obstruction with lung hyperinflation or the presence of bubbles emphysematous juxta-lesional or the puncture path. The patient's clinical status should enable it to remain in the same position for 30 minutes.

The location of the lesion can also be a limiting factor : a lesion located behind a coast may be technically difficult to achieve. The lesions located in the posterior part of a large bronchus are inaccessible due to the presence at this level of the bronchial artery Satellite, hence the high risk of vascular wound.

A puncture requires crossing several fissures carries an increased risk of pneumothorax.

However the nature of the lung lesion is not a limiting factor since studies describe for BTT under scanner profitability (number of usable samples) et une valeur Diagnostique identiques he let de lesions alvéolaires, nodules localized or integrating into a diffuse interstitial pathology.

Square BTT scano-guided in the diagnosis of OP :

It is under these considerations it seems interesting to consider the interest of the BTT under scanner for diagnosing OP. This gesture has the advantage of being performed under local anesthesia and be feasible even in patients with precarious respiratory status. Thanks to the accuracy of CT guidance, it has better profitability than the BTB and provides lung levies referred histological and cytological oriented, larger than those obtained by BTB, which reduces the risk of misdiagnosis by ignorance satellite pathology PO home. The TTO has a higher diagnostic value than the BTB, and this whatever the presentation of lesions (alveolar, Focal nodular or diffuse), which is known to vary in the PO. Complications are rare and usually benign.

The pneumothorax rate of BTT is higher than that of the BTB but it is usually of low abundance pneumothorax, not requiring drainage, early detected on CT snapshot end procedure. If scalability, they are then immediately drained under CT guidance.

The article Safadi et al. illustrates, however, that diagnostic error is possible with BTT because the samples are smaller than those obtained by BC, remains therefore the reference method for the diagnosis of OP. On the other hand the results of the BTT should always be interpreted in connection with clinical, as shown in our sixth observation, the diagnosis is questionable. If we stick to the result of the BTT, this is the diagnostic PO which is retained and the treatment is to establish a corticosteroid.

However there may PO lesions in the periphery of a lung infection site and favorable antibiotics in the case of this patient is rather retain this hypothesis and only antibiotic therapy is justified, corticosteroids may instead be harmful because of the infectious context. The BTT-scano guidéedevrait be evaluated by replacing the BTB in the diagnostic process of PO in hospitals with a radiologist experienced in this technique and a histologist specializing in lung disease.

It is important to know the limits of implementation and interpretation of this technique. In case of diagnostic uncertainty, either immediately on the initial radiological presentation, or especially in case of unfavorable corticosteroids, must be used, if the patient's condition allows, to BC. This will reinforce a diagnosis of PO hesitant, or, conversely, to correct the final diagnosis to BTT.

Conclusion :

The BTT under scanner seems to find a rightful place in the diagnostic process of PO. Far from claiming to usurp the place and qualities of BC, which is undoubtedly the diagnostic method of reference against a suspected PO, BTT under scanner should be a replacement assessment of BTB in this indication because it provides, with improved profitability, lung specimens larger than the BTB, This limits the risk of misdiagnosis in a disease with many differential diagnoses.


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