Shaheen MZ†, Sardar K†, Murtaza HG†, Safdar SS†, Hafeez A†, Mushtaq MA†, Hussain M†, Shahzad I†, Pervaiz A‡, Aslam M‡.

†Department of Pulmonology, Nishtar Hospital Multan.
‡Department of Radiology, Nishtar Hospital Multan

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ABSTRACT

INTRODUCTION:

Mediastinal and hilar mass lesions pose diagnostic problems due to their location and difficult access. Centrally located masses are not visible on routine ultrasound. There are limited facilities for mediastinoscopy and the availability of interventional radiologist in most teaching and district hospitals in Pakistan.  Presence of complex vascular structures in the Mediastinal and hilar areas demand precise location and route for needle aspiration cytology and biopsies (FNAC & FNAB). Computerized tomography (CT) has made it possible to better identify masses, determine their relationship to major vessels and plan the optimal approach.

METHOD: A total of 159 patients underwent CT guided FNAC & FNAB during 2003 and 2005. All patients presented with hilar or mediastinal mass lesions on chest X-rays and were referred for establishing the diagnosis. There was no evidence for distant metastasis and bronchoscopy was unremarkable.  The lesions were localized with a CT scan and the approach and distance determined by using the grid scale. Aspiration and biopsy needles were passed after application of local anesthesia and position confirmed via limited CT cuts before obtaining the tissue samples.

RESULTS: There were 159 patients, of them 104 were male and mean age was 52 years (range 39–76). Anatomical distribution of lesions was: hilar 46; anterior mediastinum 45; middle 28; and posterior 40. Histological diagnosis was confirmed in 143 patients, which was: adenocarcinoma 44; squamous cell carcinoma 41; small cell carcinoma 13; non Hodgkin’s lymphoma 5; Hodgkin’s disease 2; metastatic carcinoma 28; tuberculosis 8; and Thymoma 2. Among complications experienced, there was local pain in 25, mild haemoptysis in 14, large haemoptysis in 3, small pneumothorax in 31, large pneumothorax in 8 (6 patient required a small bore chest catheter for the drainage of pneumothorax). There was no death related to the procedure.  

CONCLUSION: CT guided FNAC and FNAB of mediastinal and hilar masses is a safe, accurate and well tolerated method. It is a speedy and cost effective method as compared to mediastinoscopy. In the absence of an interventional radiologist, this procedure can be done safely by the pulmonologists with low rates of acceptable complications.

Key:  FNAC – Fine needle aspiration cytology.  FNAB- Fine needle aspiration biopsy.
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INTRODUCTION
Image-guided percutaneous needle biopsy is a reliable technique for the diagnosis of thoracic lesions, particularly for assessment of mediastinal lesions1-3. Both ultrasonography and computed tomography have been used as imaging guides to direct the percutaneously administered biopsy needle towards the target lesion. Computed tomography (CT), however, has been established as the best imaging method for biopsy of deep seated lesions which ultrasound cannot visualize4. In addition, CT provides detailed anatomic and vascular details and can localize even smaller lesions located in any part of mediastinum. It helps in planning accurate trajectory of the needle while avoiding inadvertent puncture of vascular structures and vital organs5-8.
There are several alternative methods of obtaining tissue samples from mediastinal lesions for histopathological analysis. These include surgical techniques such as thoracoscopy, cervical mediastinoscopy, anterior mediastinotomy and other newer biopsy techniques like endoscopic ultrasound guided biopsy. Surgical techniques have limitations of being much more invasive than FNA, requiring general anesthesia, and having no access to retrotracheal, para-aortic or inferior mediastinal nodes. Percutaneous transthoracic biopsy is less invasive than mediastinoscopy, requires only local anesthesia and are cost effective because they shorten the period from admission to diagnosis, decrease the number of surgical procedures and shorten the time of hospital stay, which reduces overall treatment cost9. Furthermore, CT guidance allows precise localization of target lesion and access to virtually all mediastinal compartments including those that are inaccessible with alternative methods. The reported complications of transthoracic FNA include pneumothorax, bleeding (haemoptysis, hemothorax and hematoma) and, if the pericardium is penetrated, pericarditis and pericardial tamponade10-12.                     
AIMS:
In the absence of interventional radiologists we intended to develop local expertise and to evaluate the outcome and complications of percutaneous CT guided fine needle aspiration / biopsy procedure by the pulmonology team in collaboration with the department of radiology.
MATERIAL AND METHODS:
Study design:
A prospective study involving patients with hilar and mediastinal mass lesions who required tissue diagnosis for further management. Outcome analysis was performed on all the procedures carried out over a period of two years i.e.  between 2003 and 2005.  
Inclusion criteria:

1. All patients referred to the department of pulmonology with undiagnosed mediastinal or hilar mass lesion on chest X-ray.
2. CT scan of thorax confirming the hilar / mediastinal mass lesions.
3. Normal bronchoscopy or unyielding bronchoscopic sample  

Exclusion criteria:

1. Abnormal coagulation profile (INR>1.5)
2. Severe thrombocytopenia (platelet count < 50,000)
3. Bullous emphysema
4. Pulmonary hypertension
5. Accessible metastatic disease
6. Dyspnea at rest

Procedure details:
Recruitment into the study started after the approval from the hospital ethics committee. Written informed consent was taken from every patient. A full coagulation profile, hemoglobin level, platelet count and serum for cross-matching were made available before biopsy.
In each case, previous imaging studies were reviewed to determine the best approach for percutaneous biopsy. The approach for biopsy of mediastinal lesion was chosen according to the clinical circumstances, the location and size of the target lesion. Patients were placed supine, prone or in lateral decubitus position depending on the location of the lesion and safe approach for needle placement.
The lesions were localized by CT scan using contiguous 5 to 10 mm collimated images of the area of interest to map the most direct route to the lesion, thus avoiding unnecessary pleural puncture. The skin entry site was marked with pen by using the laser light from the CT gantry.
Local anesthesia (2% lidocaine) was administered through the needle guide. A small dermotomy was done by using No.11 surgical blade. Fine needle aspiration was performed by using 22 gauge spinal needle. Cores were obtained by using an 18 gauge Trucut biopsy needle. (Figure 1) The aspiration/ biopsy needle was advanced in a co-axial fashion through the needle guide into the lesion during suspended respiration. After the needle tip was confirmed to be in the desired location by taking the limited CT cuts, aspiration / biopsy was performed. (Fig 2 and 3) Each fine needle aspirate was immediately smeared onto glass slides; air dried, fixed with 95% ethyl alcohol and immediately sent for cytological analysis. The biopsy specimen were preserved in formalin and sent for histopathology. At the completion of the procedure, all patients underwent expiratory chest radiography to detect complications like pneumothorax and were monitored for 3 to 4 hours in the recovery area. The success of each procedure was established at review of the final pathology report.
RESULTS:
CT guided transthoracic FNA / biopsy was performed in a total of 159 patients out of which 104 (65.40%) were males and 55 (34.59%) were females. Mean age was 52.3 years, range 39 - 76. Out of total 159 patients, 46 (28.93%) patients had a hilar mass while 113 (71.06%) had a mediastinal lesion. Location details are given in Table 1.  

Table 1: Anatomical distribution of mass lesions.

Fine needle aspiration using 22G spinal needle alone was used in 42 cases, Trucut biopsy alone was done in 28 patients and combined aspiration and biopsy were undertaken in 89 patients. Diagnosis was established in 143 (89.93%) patients while in 16 (10.06 %) patients the procedure did not yield any diagnosis. Fine needle aspiration gave a diagnostic yield in 38 cases out of 42, with diagnostic accuracy of 90.4%. Trucut biopsy provided diagnosis in 23 out of 28 cases with diagnostic accuracy of 82.14%. With the combined FNA + biopsy procedure, diagnosis was achieved in 82 out of 89 cases ( 92.13% ).  Overall diagnostic yield in all 159 patients who underwent CT guided FNA / biopsy was 89.93% (Graph 1).
Graph 1: a) overall diagnostic accuracy of FNAC / biopsy in all patients.  b) Diagnostic accuracy of FNAC, FNAB and combined FNAC & FNAB 

Adenocarcinoma was most common pathological diagnosis seen in 44 (30.70%) patients, followed by Squamous cell carcinoma in 41 (28.6%). (See Table 2 and graph 2). 

Table 2: Frequencies and percentage of various histological diagnoses established.

Graph 2: Numbers of various histopathological diagnoses confirmed on CT guided percutaneous fine needle aspiration / biopsy of mediastinal / hilar masses

No mortality was recorded during or after the procedure and no blood transfusion required. Regarding complications, local pain was experienced by 25 (15.72%) patients, small pneumothorax developed in 31 (19.49%) patients requiring no intervention, large pneumothorax was encountered in 8 (5.03%), of which two required close chest aspiration and 6 required small bore chest drains, mild haemoptysis was seen in 14 (8.80%) cases and moderate to severe haemoptysis was encountered in 3 cases (1.88%).
Table 3: Frequencies and percentage of complications observed.

DISCUSSION:
In mediastinal and hilar lesions, early diagnosis, separation of malignant from benign lesions and early medical treatment are the main goals to decrease morbidity and mortality. The possibility of severe complications such as respiratory or circulatory compression mandates fast and sometimes urgent diagnosis and treatment of mediastinal masses. Anatomically critical location poses difficulties and risk for establishing tissue diagnosis.            
Procedures for obtaining tissue samples for cytology or histopathology of hilar / mediastinal lesions include mediastinoscopy or thoracotomy. Compared to these procedures, CT guided   transthoracic biopsies are cost-effective because they shorten the period from presentation to diagnosis, decrease the number of surgical procedures and shorten the time of hospital stay, which reduces overall treatment costs9. There are only few contraindications that preclude the use of percutaneous biopsies. Absolute contraindication being suspicion of hydatid cyst, whereas relative contraindications are bleeding diathesis, Dyspnea at rest, bullous emphysema and pulmonary hypertension13, 16.       
Mediastinoscopy is used widely by thoracic surgeons in staging lung cancer and diagnosing hilar / mediastinal mass lesions. Diagnostic yield of this procedure is reported to be 83% to 89%7, 17. However, it is more invasive than FNA, requires general anesthesia and has no access to retrotracheal, para-aortic or inferior mediastinal nodes. The reported complication rates with mediastinoscopy range from 1 to 3%. Although the reported complication rate of transthoracic FNA (especially pneumothorax) is higher than that of mediastinoscopy, complications associated with mediastinoscopy may be immediately life-threatening. Arrhythmias as well as death from stroke or reactions to general anesthesia have also been reported with mediastinoscopy18. Moreover, very limited availability of thoracic surgeons means this option is not available to a majority of chest physicians in Pakistan.                           
The best approach to percutaneous biopsy of a hilar / mediastinal lesion depends on the location and size of target lesion. CT scan provides a safe and shortest route for FNA / biopsy needle to avoid vessels and other vital structures, therefore minimizing complications and enhancing diagnostic yield3, 13. Reported accuracy rates of CT guided percutaneous needle aspiration / biopsy ranges from 64%-97% with a small risk of complications1-6. The diagnostic accuracy of the mediastinal and hilar lesions approached 89.93% in our study which is in concordance with the diagnostic success rate of other studies14, 15. Out of 159 biopsies performed, pathological diagnoses included adenocarcinoma (n=44), squamous cell carcinoma (n=41), small cell carcinoma (n=13), metastatic carcinoma (n=28), tuberculosis (n=8), Non Hodgkin’s lymphoma (n=5), Hodgkins lymphoma (n=2) and Thymoma (n=5). There is high rate of neoplastic lesions in our study which may be because the study was conducted in a tertiary referral centre for lung cancer.
CT guided FNA/biopsy of mediastinal and hilar masses carry a risk of complications due to close proximity of major vessels.  Small haemoptysis is common immediately after the procedure, 8.8 % in our study. However, severe bleeding is rare11, 12; only 1.8 % in our study. This settled with out requiring blood transfusion.  Pneumothorax has been reported in 10 to 60 % of procedures; however, chest tube placement is needed in 5 to 25% of such cases10. Risk of pneumothorax depends on multiple factors, including depth and size of the lesion, number of needle passes and the presence of emphysema or blebs. In our study the rate for minor complications was slightly on the higher side but major complications were low and overall complications were acceptable. Local pain (15.72%) was mostly relieved by post procedure simple analgesia. Small pneumothorax developed in 19.49% patients but they were mostly asymptomatic, detected on post procedure chest radiograph and was relieved by conservative management within 24 hours. Mild haemoptysis was seen in 14 (8.80%) cases which also settled spontaneously. Moderate to severe haemoptysis was encountered in 3 cases (1.88%). Moderate to large pneumothorax was encountered in 8 (5.03%) patients, 2 of them were managed by closed chest aspiration and  6 patients needed intubations. The risk of developing pneumothorax and major haemoptysis was linked directly with number of needle passes made during the procedure. All 3 cases of major haemoptysis were those who had 2 or more needle passes during the procedure. Similarly 7 cases with large pneumothorax had more than one needle passes, as compared to only 1 case with single needle pass that developed large pneumothorax requiring aspiration.  No mortality related to the procedure was recorded during our study making it a safe procedure. Similar outcome has been reported by other studies19.
Conclusion:
Our study shows that computed tomography guided percutaneous biopsy of mediastinal and hilar masses is highly effective and relatively safe procedure. Keeping its safety and high diagnostic yield in our study, we suggest that in the absence of interventional radiologists, this technique can be learnt and safely provided by the pulmonologists in collaboration with the department of radiology. 

                   
Figure 1: Trucut biopsy needle and spinal needle used in the procedure

Figure 2: CT guided biopsy of a hilar mass in a 40 years old man.

Figure 3: CT guided Percutaneous FNAC in a 56 years old male with mediastinal mass.

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