Sarcoidosis is a multisystem disorder of unknown etiology with pulmonary involvement seen in ∼95% of patients. Pulmonary involvement usually manifests as hilar and/or mediastinal adenopathy (stage 1) with or without pulmonary parenchymal lesions (stages 2, 3, and 4). Extrapulmonary involvement can be seen in skin, liver, spleen, heart, CNS, parotid and thyroid gland, and other tissues.1 Clinical diagnosis of sarcoidosis can be made based on constellation of signs and symptoms and radiographic findings but biopsy is needed for pathologic confirmation and exclusion of other causes of lymphadenopathy, most importantly malignancy. Bronchoscopy with transbronchial needle aspiration (TBNA), transbronchial lung biopsy (TBLB), and endobronchial lung biopsy (EBB) can be used to obtain tissue for pathology. Over the last decade, endobronchial ultrasound (EBUS) is being increasingly used to accomplish TBNA with reported diagnostic yield higher than conventional blind TBNA.2,3 Mediastinoscopy is usually reserved for nondiagnostic cases due to the more invasive nature of the procedure. EBUS-guided TBNA has also increased the diagnostic yield of flexible bronchoscopy with reported pooled diagnostic yield of 79%.4 Almost all of the published data about diagnostic yield of EBUS-TBNA is using 21- or 22-G needle. There is conflicting evidence if larger needle offers an increase in diagnostic yield.5–7 Olympus introduced a new 19-G needle in 2015 (ViziShot FLEX 19-G needle; Olympus America, Redmond, WA) and there is limited published data about diagnostic yield using this needle for sarcoidosis.8 This study reports the first case series and diagnostic yield using this needle for clinically suspected sarcoidosis.
MATERIALS AND METHODS
Electronic medical record system was retrospectively reviewed for all bronchoscopies performed between July 2016 and July 2017. Patients who underwent bronchoscopy with EBUS were identified. Medical charts of these patients were studied to identify indication and to ascertain if patient was being evaluated for clinical suspicion of sarcoidosis. Procedure report and pathology report was reviewed to identify needle gauge, sampling location, diagnosis, and any immediate complication from the procedure. This study was approved by Institutional Review Board (Maine General Medical Center, Augusta, ME).
All patients were intubated for the procedure. Written consent was obtained from all patients before the procedure. All procedures were done as outpatient in the bronchoscopy suite with general anesthesia with intravenous anesthetics (propofol infusion with or without remifentanil). Anesthesiology services were utilized for all bronchoscopies with EBUS. All bronchoscopies were performed by 2 staff pulmonologists. White light bronchoscopy (using Olympus BF-1TH190, BF-1THQ190; Olympus America) was performed in all patients before EBUS. Convex probe EBUS was used in all patients (Olympus BF-UC180F and ultrasound image processor EU-ME1; Olympus America). The 19-G Olympus Vizishot needle was preferentially used in patients with clinical suspicion of sarcoidosis, suspicion of lymphoma, or cancer restaging. The needle was aligned to the biopsy channel as per manufacturer’s recommendation. The lymph node station was identified according to the International Association for Study of Lung Cancer lymph node map.9 The designated lymph node was punctured under direct EBUS guidance. Suction was used with all passes unless significant bleeding and/or vascularity was noted with the preceding passes. At least 6 passes were done at each station. An additional pass was done if no visible aspirate was obtained on any of the attempted aspiration. Part of the aspirated material from first +/− second pass was smeared on to glass slides. Remainder of the aspirate was discharged into 95% ethanol for cell block preparation by using stylet or blowing air. Smears were air-dried and fixed in 95% ethanol. Rapid on-site evaluation was used in all cases to ensure sampling adequacy. Adequate cell material was defined as presence of lymphoid tissue of adequate cellularity or sufficient for a specific diagnosis, such as the presence of noncaseating granulomas. TBNA was terminated if later was reported and subsequent biopsies performed at discretion of bronchoscopist. Bronchioalveolar lavage, TBLB (fluoroscopy guided), and EBB were performed in a standard manner. The size of biopsy forceps (2.0 vs. 2.8 mm) was at the discretion of the bronchoscopist. TBLB and EBB specimens were fixed in formalin and sent for histopathologic examination. Postprocedure chest x-ray was performed to exclude pneumothorax in all patients undergoing TBLB.
Eighty-six bronchoscopies with EBUS were performed during the review period. Sixty-two bronchoscopies were done with suspected diagnosis of malignancy and subsequently had a confirmed diagnosis of malignancy or a true negative lymph node, 9 patients received alternate benign diagnosis [polyangitis with granulomatosis (1), coccidiomycosis (1), hypersensitivity pneumonitis (1), necrotizing pneumonia (1), interstitial lung disease (1), diastolic heart failure (1), and incidental benign lymph node (3)]. Needle selection was at discretion of bronchoscopist for these patients. Fifteen patients underwent bronchoscopy with clinical suspicion of sarcoidosis and 19-G needle was used for all of these patients. Average age was 49 years (range, 26 to 73 y). Majority of patients were female (n=10, 66.6%) (Table 1). On-site evaluation report was available for 14 patients. Initial rapid on-site evaluation was positive for granulomatous inflammation in 3 patients and equivocal in 1. Diagnosis of sarcoidosis was confirmed in 14 of 15 patients based on clinical, pathologic, and radiographic findings. One patient with nondiagnostic bronchoscopy was empirically started on low-dose steroid with rapid clinical improvement and lost to follow-up. None of the patients required mediastinoscopy for diagnosis. Flow cytometry and culture data were available for 10 patients. These tests help exclude other diagnosis in these patients. Diagnostic yield for sarcoidosis was 93% for bronchoscopy with EBUS-TBNA. EBB was performed in 14 patients and was positive in 6 patients (43%), TBLB was performed in 13 patients, and was positive in only 5 patients (38%) (Table 2). In patients with parenchyma l involvement (stage II), TBLB, and EBB had a yield of 50% (4/8) and 60% (6/10), respectively. Median number of passes for TBLB and EBLB was 6 (3 to 12) and 4 (3 to 6), respectively. Diagnostic yield of EBUS-TBNA+TBLB; EBUS-TBNA+EBB or EBUS-TBNA+EBB+TBLB was not different than EBUS-TBNA alone as all diagnostic cases had a diagnostic TBNA sample. Thirty-three lymph nodes were sampled in these patients, 32 aspirates had evidence of lymph node sampling with 1 aspirate deemed inadequate. Median number of lymph node stations punctured was 2 (range, 1 to 3). Twenty-eight lymph node aspirates were positive for granuloma or pathologic finding suggestive of sarcoidosis (87.5%, 28/32). Station 7 lymph node was sampled most frequently (13/15) followed by station 11L (8/15) and station 11R (6/15) (Table 3). No immediate complications or clinically significant adverse effects were noted in this group. One patient had breakage of the needle sheath during the procedure and a small plastic sheath (see Figure, Supplemental Digital Content 1, http://links.lww.com/LBR/A154) was retrieved from bronchus without any untoward events. None of the patients required hospital admission or escalation in level of care. No major anesthesia-related complications were reported in the sarcoidosis subgroup.
Over the last decade, EBUS-TBNA has emerged as a useful diagnostic tool for diagnosis of sarcoidosis with reported diagnostic yield from 50% to 96%.4 Over the last few years, new TBNA needles have become available. In this study, a clinical decision was made to use the larger 19-G needle for patients with suspected sarcoidosis as it theoretically provides larger tissue sample. This is the largest series reporting diagnostic yield for clinically suspected sarcoidosis using 19-G EBUS needle and other bronchoscopic modalities. Diagnostic yield using this needle in this series was noted to be comparable or higher than most published literature using TBNA. The decision was made to perform 6 passes at each station based on prior experience with other devices. This number was chosen based on pathologist feedback indicating a preference for more tissue in cell blocks. Sufficient tissue could likely be obtained with a fewer number of passes but this review cannot comment on same. There is also a possibility that a high number of passes with a larger needle might lead to more contamination with blood. The best number of passes should be decided based on feedback from the institutional pathologist.
Few published studies suggest that addition of TBLB and EBB can increase the diagnostic yield of bronchoscopy for sarcoidosis when used in conjunction with TBNA.3,10,11 However, in this case series and other studies yield of TBLB +/− EBB has been lower than TBNA with EBUS with no significant difference in yield with addition of TBLB or EBB.12–14 The diagnostic yield of TBLB can be increased by obtaining additional biopsies but this increases the risk of pneumothorax and bleeding.11 In this series, TBLB or EBB did not add to the diagnostic yield recognizing that no patients had stage 3 or 4 sarcoidosis. It is fair to assume that most patients undergoing EBUS-TBNA will likely have stages 1 and 2 sarcoidosis. Therefore, future studies are needed to provide a definitive answer to additional utility of TBLB and EBB. On occasion, granulomatous inflammation on TBLB and EBB does add to the diagnostic certainty in patients as granulomatous inflammation in lymph nodes is not exclusive to sarcoidosis.
One of the major limitations of this retrospective study is small sample size and lack of comparison group. This in part is due to the relatively recent introduction of the needle in the market. This case series does not establish advantage of the larger 19-G needle but does provide diagnostic yield data comparable to the highest reported diagnostic yields with other needles and safety data for use of this larger needle. Unfortunately, a diagnosis of sarcoidosis could not be confirmed or refuted in the only patient with nondiagnostic bronchoscopy as she was lost to follow-up. No other patient in this series required additional tissue sampling for diagnosis as the diagnosis was established through bronchoscopy. In addition, it is acknowledged that there was a lower diagnostic yield of TBLB as compared with some published literature3 and this might have been confounded by the preliminary pathologist impression of granulomas obviating the necessity of aggressive transbronchial biopsy approach. Transbronchial biopsy carries a risk of bleeding and pneumothorax and in the author’s opinion, might not be necessary in all cases if it does not add to the diagnostic yield. Cultures, acid-fast, and fungal stains can be performed on the TBNA or bronchoalveolar lavage specimens. It should be highlighted that this series was done in a community hospital setting. Most of the available literature is from larger institutions with likely higher volume. Operator experience is one of the possible factors that can influence the diagnostic yield for EBUS-TBNA15 but the author has seen a higher yield with this instrument compared with the author’s prior anecdotal experience with 21- and 22-G needles. Similar yield is reported in the only other series published about initial experience with this needle.8
Additional studies are needed to compare the sample quality, diagnostic yield, and number of passes needed with other available needle products in the market. It might be possible to decrease the procedure time, anesthesia time, fluoroscopy time, and overall safety profile of the procedure by obviating need for TBLB and EBB using better biopsy instruments or techniques to sample the lymph nodes.
The author thanks the colleagues and endoscopy staff who provided clinical care for patients in this data set.
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