|Year : 2017 | Volume
| Issue : 4 | Page : 265-268
Contribution of cell block obtained by endobronchial ultrasound-guided transbronchial needle aspiration in the diagnosis of malignant diseases and sarcoidosis
Onur Fevzi Erer1, Serhat Erol1, Ceyda Anar1, Zekiye Aydoğdu2, Serir Aktoğu Özkan1
1 Deparment of Chest Diseases, Izmir Dr. Suat Seren Chest Diseases and Surgery Training Research Hospital, Izmir, Turkey
2 Deparment of Pathology, Izmir Dr. Suat Seren Chest Diseases and Surgery Training Research Hospital, Izmir, Turkey
|Date of Submission||28-Mar-2015|
|Date of Acceptance||08-May-2015|
|Date of Web Publication||21-Apr-2016|
Deparment of Chest Diseases, Izmir Dr. Suat Seren Chest Diseases and Surgery Training Research Hospital, Izmir
Source of Support: None, Conflict of Interest: None
Aim: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a safe and minimally invasive procedure that can be performed in outpatient settings. Several studies have demonstrated the usefulness of EBUS-TBNA in the diagnosis of sarcoidosis and malignant diseases. This study focused on the role of cell block (CB) analysis in determining the diagnostic yield of EBUS-TBNA in malignant diseases and sarcoidosis. Materials and Methods: The study was conducted at a training and research hospital. Records of patients who underwent EBUS-TBNA between March 2011 and December 2014 for diagnosed sarcoidosis or malignancy were retrospectively analyzed. Results of all EBUS-TBNA smears and CB were separately evaluated to determine the diagnostic value of each. Results: There were 84 sarcoidosis and 179 malignancy patients. In the malignancy group, CB contributed to cancer diagnosis in 15 (8.3%) patients and subclassification in 19 (10.6%) patients. In the sarcoidosis group, for 45.2% of patients (38/84), smears were not diagnostic but CB showed granulomatous inflammation. Conclusion: CB significantly increases the diagnostic yield of EBUS-TBNA for sarcoidosis. In our study, in the malignancy group the diagnostic yield was low but it was helpful for subclassification, especially for adenocarcinoma.
Keywords: Cell block (CB), endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), malignant diseases, sarcoidosis
|How to cite this article:|
Erer OF, Erol S, Anar C, Aydoğdu Z, Özkan SA. Contribution of cell block obtained by endobronchial ultrasound-guided transbronchial needle aspiration in the diagnosis of malignant diseases and sarcoidosis. Endosc Ultrasound 2017;6:265-8
|How to cite this URL:|
Erer OF, Erol S, Anar C, Aydoğdu Z, Özkan SA. Contribution of cell block obtained by endobronchial ultrasound-guided transbronchial needle aspiration in the diagnosis of malignant diseases and sarcoidosis. Endosc Ultrasound [serial online] 2017 [cited 2020 Aug 14];6:265-8. Available from: http://www.eusjournal.com/text.asp?2017/6/4/265/180763
| Introduction|| |
Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a safe and minimally invasive procedure that allows the bronchoscopist to see beyond the airway and to evaluate mediastinal and hilar pathology. Current guidelines recommend EBUS-TBNA before mediastinoscopy for the mediastinal staging of lung cancer., EBUS-TBNA has also been performed to diagnose enlarged mediastinal nodes detected by computed tomography (CT) and/or hypermetabolic lymph node(s) (LNs) detected by positron emission tomography/computed tomography (PET/CT).
The material obtained using EBUS-TBNA can also be processed as a cell block preparation (CB) for additional diagnostic procedures. Recent studies have shown that a combination of CB and smear preparation increases the diagnostic yield of EBUS-TBNA., CB preparations are, however, not yet widely used in EBUS-TBNA samples and there is little information about its contribution to the diagnostic process. Therefore, the aim of this study was to evaluate the contribution of CB in the diagnostic yield of EBUS-TBNA in sarcoidosis and malignancy.
| Materials and Methods|| |
This is a retrospective study of prospectively followed-up cases in which the diagnostic value of CB prepared from cytological specimens of hilar and mediastinal lymphadenopathies was obtained by EBUS-TBNA.
Case selection and inclusion criteria
The medical database of our hospital was searched. Patients who were diagnosed with sarcoidosis or malignancy with EBUS-TBNA between March 2011 and March 2014 were included.
This study was approved by the local Ethical Committee.
EBUS-TBNA and evaluation of specimens
EBUS-TBNA was performed using an EBUS-guided TBNA bronchoscope (7.5 MHz, BF-UC160F; Olympus Optical Co., Tokyo, Japan) by the oral route under topical anesthesia and conscious sedation (midazolam). Mediastinal and hilar LNs were examined systematically. Mediastinal LNs with short axis ≥5 mm were aspirated. EBUS-TBNA was performed for diagnosing enlarged and/or hypermetabolic mediastinal or hilar LNs. Informed consent was obtained from every patient.
LNs were aspirated with dedicated 22-gauge needles (NA-201SX-4022-C; Olympus, Tokyo, Japan). At least three consecutive aspirates were obtained from each LN station. Some amount of the aspirate was smeared onto glass slides, air-dried, fixed immediately with 95% alcohol, and stained with hematoxylin and eosin (H&E). The rest of the aspirate was placed into a mixture of formalin and alcohol in order to obtain a CB for histological examination. Rapid onsite cytological examination (ROSE) was not available. CBs were embedded in paraffin, and 6-μm thick sections were obtained and stained as deemed necessary by the cytopathologist. Routine H&E staining was used on CB sections and immunohistochemical staining (IHCS) was applied for the identification or phenotyping of malignant cells in all of the patients. Somatic mutations of the genes coding the tyrosine kinase domain of epithelial growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) were not examined on CB samples in our pathology laboratory. All aspirates were also sent for acid-fast staining, mycobacterial cultures, and polymerase chain reaction (PCR).
Tissue obtained by EBUS-TBNA was considered malignant when the aspirated material contained malignant cells. Tumor-positive findings from EBUS-TBNA samples were not surgically validated, but tumor-negative findings were validated by mediastinoscopy, video-assisted thoracoscopic surgery (VATS), or thoracotomy. If a patient rejected these procedures, radiological follow-up was done. During the follow-up period, if LNs enlarged as a result of clinical radiological evaluation, it was accepted as “false negative.”
IHCS was performed for all patients to confirm diagnosis and determine the subtype of cancer.
Sarcoidosis was diagnosed when all of the following criteria were fulfilled:
- Demonstration of necrotizing or nonnecrotizing granulomas on EBUS with negative acid-fast bacilli,
- No growth of mycobacteria on culture, and
- Clinical and radiological presentation consistent with sarcoidosis.
All analyses were carried out using the SPSS statistical package (ver. 16.0). Descriptive statistics were expressed as mean ± standard deviation for continuous variables and as frequency (percentage) for categorical variables.
Diagnostic value of CB
- Cytological examination of smears was not diagnostic, but CB found granulomatous inflammation or malignancy, it was defined as “contribution to diagnosis by CB.”
- Cytological examination of smears was reported as only malignancy, but CB or IHCS reported the subtype of cancer; it was defined as “contribution to subclassification by CB.”
| Results|| |
Between March 2011 and December 2014, 514 patients underwent EBUS-TBNA. Sensitivity and negative predictive value of EBUS-TBNA in malignancy and sarcoidosis group were 81.3% and 87.7%, and 84.8% and 96.5%, respectively.
Eighty-four (24 male, 60 female) sarcoidosis and 179 malignancy (147 male, 32 female) patients diagnosed with EBUS-TBNA were included in the study. The mean ages of the patients were 44.8 ± 13.5 years for sarcoidosis and 61.3 ± 9.4 years for the malignancy group. In total, 580 LNs were sampled. The subcarinal LN (station 7) was most commonly sampled, followed by the right lower paratracheal LN (station 4R) [Table 1].
|Table 1: The characteristics of patients and frequency of LNs diagnosed by EBUS-TBNA|
Click here to view
In the malignancy group, 362 LNs were sampled in 179 patients. In 29 patients (16.2%), smear cytology was malign, but there was no malignancy in CB. Examination of CB was reported as benign in 12 (41.3%), anthracosis in 7 (24.1%), and insufficient tumor tissue in 10 (34.4 %) of these patients. Because IHCS were not performed in these patients. Malignancy was determined in the CB of 150 (83.7 %) patients, and IHCS was performed for all of the patients.
In the malignancy group, smears of 15 (8.3%) patients were nondiagnostic or benign, but examinations of CB were diagnostic. For 19 (10.6%) patients, both smear and CB were diagnostic but histologic subtype was determined with CB. One of these 19 patients was diagnosed as squamous cell carcinoma with cytomorphological examination. However, IHCS reported adenocarcinoma. As a result, CB contributed to the diagnosis of malignancy in 8.3% of patients and subtype in 10.6% of patients [Table 2] and [Table 3].
|Table 2: The frequency of smear and CB in patients with sarcoidosis and malignancy diagnosed by EBUS-TBNA|
Click here to view
|Table 3: The frequency of malignancy patients and contribution of CB diagnosed by EBUS-TBNA|
Click here to view
Somatic mutations of the genes coding the tyrosine kinase domain of EGFR and ALK were not examined on CB samples.
In 46 (54.7%) patients, both smears and CB examinations found granulomatous inflammation. In 38 (45.2%) patients, smears were nondiagnostic but the examination of CB reported granulomatous inflammation. There was no patient for whom smear was diagnostic and CB was not [Table 2].
| Discussion|| |
This study showed that CB improved the diagnostic yield of EBUS-TBNA for diagnosis of sarcoidosis. Von Bartheld et al. have emphasized the importance of CB in fine-needle aspiration (FNA)-based diagnosis of sarcoidosis, as among 18 smear negative patients in their study, CB analysis detected the presence of a nonnecrotizing granuloma in 6 (33%). Similarly, Iwashita et al. found that the diagnosis of sarcoidosis increased from 77.8% to 94.4% when CBs were used. Navani et al. reported that in patients with sarcoidosis, the sensitivity of EBUS-TBNA in detecting noncaseating granulomas was 85%. They mostly used air-dried cytological smears, but noted that in some cases, formalin-fixed histological cores were obtained.
The improved diagnostic yield in granulomatous diseases when CBs are used is due to the fact that when the specimen is allowed to clot, recognition of granulomas is easier than with smear preparations., Wang et al. found that in 37 patients who underwent EBUS-TBNA, 100% of CBs showed nonnecrotizing granulomas, compared to only 27% in smears. This may be because the smearing of samples between two slides disrupts the epithelioid groups in the FNA samples; this does not tend to occur during CB preparation as sedimentation and paraffin embedding do not disrupt the histological structure.
Although CB is accepted as a standard procedure for diagnosis of granulomatous diseases such as sarcoidosis, it has yet to be cleared for malignancy.
Nathan et al. reported the importance of CB for the diagnosis and categorization of tumors. Previous studies on CBs obtained with EBUS-TBNA showed that CB contributed to diagnosis when combined with smear, but it is more important for subtyping.,,
Additionally, as a previous study revealed, CB provides material suitable for genetic analysis. Targeted therapies are becoming more important in lung cancer treatment and the current guidelines recommend their subclassification and genetic analysis, especially for non-small cell lung cancer. Thus, CBs should be obtained in all cases of suspected malignancy. Consistent with the previous studies, in our study CB slightly increased the diagnostic yield of EBUS-TBNA for malignancy. However, CBs obtained during EBUS-TBNA provided additional information for subtyping of cancer with IHCS, as in other studies.,,
| Conclusion|| |
In conclusion, we showed that CBs increase the diagnostic yield of EBUS-TBNA in sarcoidosis and enable subclassification of malignancy. Therefore, all efforts should be made to obtain sufficient samples for CB preparation in all patients with suspected granulomatous diseases or malignancy.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Gu P, Zhao YZ, Jiang LY, et al
. Endobronchial ultrasound-guided transbronchial needle aspiration for staging of lung cancer: A systematic review and meta-analysis. Eur J Cancer
Detterbeck FC, Jantz MA, Wallace M, et al
.; American College of Chest Physicians. Invasive mediastinal staging of lung cancer: ACCP evidence based clinical practice guidelines (2nd
Gauchotte G, Vignaud JM, Ménard O, et al
. A combination of smears and cell block preparations provides high diagnostic accuracy for endobronchial ultrasound-guided transbronchial needle aspiration. Virchows Arch
Alici IO, Demirci NY, Yılmaz A, et al
. The combination of cytological smears and cell blocks on endobronchial ultrasound-guided transbronchial needle aspirates allows a higher diagnostic yield. Virchows Arch
von Bartheld MB, Veseliç-Charvat M, Rabe KF, et al
. Endoscopic ultrasound-guided fine-needle aspiration for the diagnosis of sarcoidosis. Endoscopy
Iwashita T, Yasuda I, Doi S, et al
. The yield of endoscopic ultrasound-guided fine needle aspiration for histological diagnosis in patients suspected of stage 1 sarcoidosis. Endoscopy
Navani N, Booth HL, Kocjan G, et al
. Combination of endobronchial ultrasound-guided transbronchial needle aspiration with standard bronchoscopic techniques for the diagnosis of stage I and stage II pulmonary sarcoidosis. Respirology
Nathan AN, Narayan E, Smith MT, et al
. Cell block cytology: Improved preparation and its efficacy in diagnostic cytology. Am J Clin Pathol
Wang H, Rao A, Lafranco A, et al
. Cell block examination is critical for sarcoidosis diagnosis by endobronchial ultrasound guided mediastinal lymph node fine needle aspiration. N A J Med Sci
Lourido-Cebreiro T, Leiro-Fernández V, Tardio-Baiges A, et al
. The contribution of cell blocks in the diagnosis of mediastinal masses and hilar adenopathy samples from echobronchoscopy. Arch Bronconeumol
Sanz-Santos J, Serra P, Andreo F, et al
. Contribution of cell blocks obtained through endobronchial ultrasound-guided transbronchial needle aspiration to the diagnosis of lung cancer. BMC Cancer
Tennant DA, Durán RV, Gottlieb E. Targeting metabolic transformation for cancer therapy. Nat Rev Cancer
[Table 1], [Table 2], [Table 3]
|This article has been cited by|
||Correlation between clinical risk factors and tracheal intubation difficulty in infants with Pierre-Robin syndrome: a retrospective study
| ||Yanli Liu,Jiashuo Wang,Shan Zhong |
| ||BMC Anesthesiology. 2020; 20(1) |
|[Pubmed] | [DOI]|
||Cell blocks in cytopathology: An update
| ||Aruna Nambirajan,Deepali Jain |
| ||Cytopathology. 2018; |
|[Pubmed] | [DOI]|
||Cell block is a valuable adjunct to conventional smear for thyroid fine needle aspiration: 2395 cases with histological correlation
| ||Ke Jiang,Junyi Zhou,Jianyong Lei,Ying Liu,Jinnan Li,Xueying Su,Zhihui Li,Tao Wei,Yong Jiang,Jingqiang Zhu |
| ||Cytopathology. 2018; 29(6): 525 |
|[Pubmed] | [DOI]|
||Contribution of cell blocks obtained through endobronchial ultrasound-guided transbronchial needle aspiration for the determination of lung cancer subtypes
| ||Nilgün Yilmaz Demirci,Asiye Ugras Dikmen,Zarife Abdullayeva,Can Öztürk |
| ||The Clinical Respiratory Journal. 2017; |
|[Pubmed] | [DOI]|