The Value Of TBNA And EBUS-TBNA In The Diagnosis Of Ⅰand Ⅱ Sarcoidosis

BackgroundSarcoidosis is termed as a systemic granulomatous disease characterised by affecting several organs and tissues. The etiology and pathogenesis are not yet entirely clarified. The most easily affected organs are lung and lymph nodes. The chest radiography showed hilar or mediastinal lymph nodes enlargement in nearly90%of the patients.In1958, a German radiologist, Wurm classified sarcoidosis into five stages according to X-ray manifestations:0stage:normal chest X-ray. I stage:bilateral hilar lymph node enlargement with no lesion in the lung fields. II stage:bilateral hilar lymph node enlargement with lesions in lung fields. III stage:pulmonary interstitial lesions. IV stage:pulmonary fibrosis. O stage accounts for5%-10%of newly diagnosed cases, I stage accounts for50%, II stage accounts for25%, III stage accounts for25%, IV stage accounts for about5%-10%。There is no effective and specific non-invasive examination to get definite diagnosis of sarcoidosis.30to80percent of sarcoidosis patients·serum angiotensin converting enzyme (SACE) increase, but there is no specificity, because diseases such as tuberculosis and diabetes could appear a similar increase. Gallium67(67Ga) isotope scanning can contribute to the diagnosis, but the specificity was bad, and could’t replace the pathological diagnosis. Sarcoidosis antigen (Kveim) test, also known as Kveim-Siltzbach test, with the positive rate of75-85%, the false positive rate of2%-5%, has been rarely used in clinic at present due to the lack of sources of antigen preparation.According to diagnostic standards of sarcoidosis jointly formulated by ATS/ERS/WASOG in1999, the diagnosis of sarcoidosis should be established in presence of compatible clinicoradiographic findings and histologic evidence of noncaseating epithelioid cell granulomas after exclusion of other diseases capable of producing a similar histologic or clinical picture, so it is essential to get histopathological diagnosis for diagnosing sarcoidosis. Mediastinoscopy is the "gold standard" of I and II stage sarcoidosis for capabling of get larger specimen,with the positive rate of about90%, but mediastinoscopy is performed under general anesthesia and can only reach Staion2.4and7lymph nodes,while sarcoidosis patients often suffer from hilar lymph node enlargement, besides the patients have to be hospitalized, and costs a lot of money,with larger wounds, so it is not widely used. Therefore, Clinicians have been looking for ways to obtain a histological diagnosis with less trauma.Endobronchial biopsy (EBB):In Bilaceroglu and others’research, EBB diagnostic rates were45%and50%for I and II stages respectively. However, some scholars find low EBB diagnostic rates, in Tournoy and others’research the diagnostic yield was26%. In Ishii and others study only one out of the18patients was diagnosed with sarcoidosis by EBB, therefore, it is not recommended routinely to use EBB on Japanese sarcoidosis patients. One research from the domestic find sole EBB get the positive rate of38%.From the research above we could find the positive rate is very low using EBB alone in the Asian population,besides with the risk of bleeding, so it could not be used as a routine method of diagnosing sarcoidosis.Because both the I and II phase sarcoidosis patients exist enlarged hilar lymph nodes,so transbrochial needle aspiration(TBNA)and endobronchial ultrasound-guided transbronchial needle aspiration(EBUS-TBNA)is ofen employed to get histopathological specimen.Recent research find that TBNA and EBUS-TBNA can get higher diagnostic yield than TBLB in I stage sarcoidosis, and the probability of pneumothorax and hemoptysis decreased.Transbrochial needle aspiration (TBNA):TBNA is a technology to get biopsy specimens by puncturing swelling mediastinum or hilar lymph nodes outside the trachea through the biopsy channel of bronchoscope with specialized flexible puncture needles. For I stage sarcoidosis, TBNA has a higher diagnostic rate than TBLB and EBB. In Trisolini and others’study, TBNA and TBLB had diagnostic rates of82.3%and52.9%for I stage sarcoidosis, and another study showed diagnostic rates of TBNA, TBLB and EBB for I stage sarcoidosis were61%,52%and45%respectively. Differences among TBNA positive rates may have something to do with the size of lymph nodes, the number of punctured lymph nodes and the number of punctures on each lymph node besides sarcoidosis staging, the operators skill and the capabilities of pathology department at local hospital.Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA):EBUS-TBNA is a way to use ultrasound probe entering the trachea through bronchoscopy to perform ultrasound detection and get pathology specimen. In the retrospective study by Nakajima, the diagnostic yield of EBUS-TBNA and TBLB to I stage sarcoidosis were90.3%and32.3%respectively, and the diagnostic yield of EBUS-TBNA and TBLB to II stage sarcoidosis was both100%.In the prospective study by Masahide and his colleagues the diagnostic yield of EBUS-TBNA and TBLB to I stage sarcoidosis is97%and31%respectively, and the diagnostic yield of EBUS-TBNA and TBLB to II stage sarcoidosis were88%and50%. So the diagnostic yield of EBUS-TBNA is superior to TBLB whether it is I stage or II stage sarcoidosis.To sum up, Although the TBLB had higher diagnostic rate to II phase sarcoidosis, but the diagnostic rate of TBLB to I stage intrathoracic sarcoidosis was low, and the incidence of pneumothorax and hemoptysis was higher. While TBNA and EBUS-TBNA were effective methods for the diagnosis of stage I and II sarcoidosis with less trauma, fewer complications, and higher diagnostic yield. EBUS-TBNA was not popularized due to the cost and learning cure, on the contrary TBNA could be easily developed as long as the conventional bronchoscopy and TBNA puncture needle were provided, but the diagnostic yield of TBNA was influenced greatly by the lymph node size and lymph node location because of "blind puncture". Therefore, when TBNA shoud be the first choice, and when EBUS-TBNA should be the first choice in the diagnosis of I and II stage sarcoidosis is inconclusive. There was rare research in this field at home and abroad. Althoug the diagnostic yield of EBUS-TBNA was higher than TBNA using a standard19-gauge needle in patients suspected stage I and II sarcoidosis in the research by Tremblay and his colleagues, Whether the superiority of EBUS-TBNA is resulted from the greater average number of lymph node stations sampled could not be answered. There was no report to compare the diagnostic yield of TBNA and EBUS-TBNA in the case of the same number of needle aspiration lymph nodes and the same lymph nodes needle aspiration times.ObjectiveThe aim of this study was to compare the diagnostic yield of TBNA and EBUS-TBNA in the patients with suspected stage I and II sarcoidosis in the case of the same number of needle aspiration lymph nodes and the same lymph nodes needle aspiration times. And the diagnostic yield was analysed according to lymph node size and lymph node location as subgroup, so as to explicit the value of TBNA and EBUS-TBNA in the diagnosis of I and II sarcoidosis, promoting the standardization of diagnosis process of sarcoidosis.MethodsBetween October2009and December2012, a total of62patients were enrolled in this study in respiratory department of Shandong Provincial Hospital, suspected sarcoidosis on the basis of the clinical details and radiological findings. Chest CT showed bilateral hilar or mediastinal lymph nodes enlargement with or without pulmonary infiltrates in these patients. The patients were randomly divided into TBNA group and EBUS-TBNA group, biopsy specimens of each patient in both groups were taken from two lymph nodes with two needle passes per lymph node. The decion as to whether or not to proceed to EBB and TBLB was left to the discretion of the operator in the TBNA group. The same operator punctured the easily accessible lymph nodes for the both groups. Station7and4were preferred if patient had more than2enlarged nodes, otherwise the largest2was the preference. Rapid on-site cytologic evaluation(ROSE) was not performed. All procedures were conducted without an anaesthetist being present. TBLB and EBB specimens were fixed in formalin for histopathologic examination after bronchoscopy was completed(HE stain). TBNA and EBUS-TBNA biopsy fragment was directly transferred onto the glass slides, air-dried, fixed in95%alcohol for cytological examination(Wright Giemsa stain). The visible tissue fragment on the glass slide was then collected and transferred into separate containers filled with formalin for histologic examination(HE stain). The residual specimen stored at the lumen of the needle and catheter was then washed and flushed into the saline for microbiologic analysis culture including microscopic fungi, acid-fast staining, fungal culture, and mycobacterial culture. A chest radiograph was routinely obtained to identify the pneumothorax2hours after the procedures.The EBUS-TBNA was performed another time if TBNA did not confirm the diagnosis. If necessary, mediastinoscopy or video-assisted thoracoscopic surgery (VATS) was performed for further diagnosis. The mediastinoscopy or VATS was considered to be the surgical pathological sampling if EBUS-TBNA did not confirm the diagnosis. The mediastinoscopy or VATS was considered to be the surgical pathological sampling if EBUS-TBNA did not confirm the diagnosis. If the families do not agree to perform mediastinoscopy or VATS, the second EBUS-TBNA could be performed when the first EBUS-TBNA is negative.All the patients were clinically radiologically followed-up for at least six months.The final diagnosis of sarcoidosis was based on the clinical and radiographic manifestation compatibility, the histologic findings of noncaseating epithelioid cell granulomas, with negative microbiology examination and no evidence of malignancy. If the pathological and microbiological tests were negative, it was interpreted as "indefinite".The primary endpoint was the diagnostic yields of TBNA and EBUS-TBNA for sarcoidosis, The secondary endpoint were the diagnostic yields of TBNA and EBUST-TBNA of subgroup including the4th and7th lymph nodes (referred to as group A), in other stations (group B), greater than15mm and less than15mm in the shortest diameter. Additional secondary outcome included the diagnostic yield of TBNA combined with TBLB, bronchial biopsy, and the incidence of complications. The ratio of finding "epithelioid cell clusters" or "cellosilk" in the cytology specimen in the patients of confirmed with sarcoidosis was simultaneously calculateed.ResultsFrom among62patients,57had sarcoidosis, three had tuberculosis, and two had lymphoma. All patients were clinically followed up for at least six months and the diagnosis was not modified.The diagnostic yields of TBNA and EBUS-TBNA were64%(18/28) and93%(27/29), respectively (Χ2=7.12, P<0.05). The diagnostic yield of TBNA and EBUS-TBNA in group A was79%(30/38) and95%(40/42), respectively. The diagnostic yield of TBNA and EBUS-TBNA in group B was17%(4/24) and90%(18/20), respectively (Χ2=23.47, P<0.05).The diagnostic yields of TBNA and EBUS-TBNA in lymph nodes greater than15mm were78%(28/36) and94%(30/32), respectively. However, the difference was not statistically significant (Χ2=2.29, P>0.05). The diagnostic yields of TBNA and EBUS-TBNA in in lymph nodes less than15mm were15%(4/26) and90%(27/30), respectively (x2=31.38, P<0.01).In TBNA group,18cases were diagnosed with sarcoidosis by TBNA, eight cases by TBLB (8/22), and one case by bronchial biopsy (1/20). The combination of TBNA, TBLB, and EBB for sarcoidois diagnosed a total of26cases. Compared with EBUS-TBNA, there was no statistically significant difference (x2=0.000, P>0.05).Four cases of moderate mucosal bleeding occurred during TBNA. One case of pneumothorax resulted from TBLB. In another case, a hemoptysis of about50ml occurred after TBLB. Two cases of moderate mucosal bleeding occurred during EBUS-TBNA.Among the cytological specimens of49patients confirmed with sarcoidosis by TBNA and EBUS-TBNA,"epithelioid cell clusters" were found in34cases and "cellosilk" could be find in32cases.Conclusions1. Both TBNA and EBUS-TBNA has high value in diagnosing stage I and II sarcoidosis.The overall diagnostic yield of EBUS-TBNA was higher than TBNA, and the diagnostic yieald could be evalated by EBUS-TBNA when TBNA got the negative results.2. TBNA has very high diagnostic yield, similar to EBUS-TBNA, if the lymph nodes located on the4th and7th group or the shortest diameter was greater than15mm. TBNA should be the first choice when the lymph nodes was located on4th and7th group or the shortest diameter was greater than15mm.3. EBUS-TBNA should be the first choice when the lymph nodes was not located on4th and7th group or the shortest diameter was less than15mm.4. Finding "epithelioid cell clusters" or "cellosilk"in the cytological specimens may contribute to the diagnosis of sarcoidosis if the histological specimen is negative, but needs further study.