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��ࡱ�>��	���������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������{�	��	ibjbjBrBr	4  �`.�������`	`	������������8,2��Ŗ"�������� h�j�j�j�j�j�j�����2j�� ��  j�����H��$�$�$ ^����h��$ h��$�$�Pp�x������'�qZ������f#��rHT���0Ŗ0s�˛`$�˛�xxx˛����  �$     j�j��$   Ŗ    ��������������������������������������������������������������������˛         `	 �:	Ultrasound guided Fine needle aspirate and Core biopsy in head and neck lesions
First Author: 		Ryan DE FREITAS MBBS, BMedSci, MRCS
Second Author: 	Truong An PHAM MBBS, BMedSci
Third Author: 		John STUCKEY MBBS FRACP FRANZCR	
Fourth Author: 	Nazmoon LAILA MBBS
Fifth Author:		Eric HU MBBS FRCPA
Sixth Author:		Neil VALLANCE MBBS FRACS

Department of Otorhinolaryngology, Head and Neck Surgery, Monash Medical Centre, Victoria, Australia

This study was presented at the 2011 Australian Society of Otolaryngology and Head and Neck Surgery meeting in Melbourne

Key words: core biopsy, FNA, head, neck, lesion, ultrasound
Word count: abstract 222 words, body of text 1768 words

CORRESPONDING AUTHOR:
DR TRUONG AN PHAM
34 SPRINGVALE RD, NUNAWADING 3131, VICTORIA AUSTRALIA
PHONE: 61- 401686257
E MAIL: an.pham@live.com.au
ABSTRACT
Objective: To evaluate the accuracy of ultrasound (US) guided fine needle aspiration (FNA) and core biopsy (CBX) in head and neck lesions. 
Study design: Retrospective analysis of large population database.
Setting: Tertiary referral hospital.
Subject and Methods: A retrospective review was undertaken of all patients who had had US guided FNA or CBX of head and neck lesions through Monash Cancer Centre between March 2006 and July 2010. All FNA and CBXs were performed by the third author. Accuracy of FNA and CBX was determined from definitive surgical histology where available. 
Results: There were 81 FNAs and 98 CBXs performed in 140 patients.  Excision biopsy was performed in 39 patients.  Both FNA and CBX were performed on the same lesion in 24 patients.  The diagnostic rate for FNA and CBX was 88% and 98% respectively. The accuracy of FNA and CBX in detecting neoplasms was 90% and 91% respectively. The accuracy of detecting malignancy with FNA and CBX was 95% and 96%.  These results are comparable with the literature. There were no complications or cases of tumour seeding.
Conclusions: US guided FNA and CBX are acceptable diagnostic tools in head and neck lesions. Addition of CBX may change management.  There may be an expanding role for CBX in evaluation of head and neck lesions.
INTRODUCTION
Fine needle aspiration cytology (FNA) has been the traditional workhorse in the initial investigation of head and neck lesions. The advantages are that of high diagnostic accuracy for benign (95%) and malignant (87%) head and neck lesions (1). It is a safe, quick and minimally invasive test, which is performed at low cost, with reduced complications compared with core biopsy (CBX) (1).
The benefit of ultrasound (US) guidance over palpation in FNA, is that it improves the diagnostic rate, especially in the case of small or non-palpable lesions (84% vs 58%) (2).
The disadvantages of FNA are that there are inadequate samples in 10-15% of cases (1,3,4), false negative interpretations in sclerotic carcinomas and small lesions, inabilities in distinguishing invasive from in situ lesions and incomplete classification of lymphoma (1).
FNAs are most accurate when experienced cytologist are available, and for on-site evaluation of adequacy of specimen.
The gold standard for diagnosis of head and neck lesions is surgical excision, which is often performed under a general anaesthetic. Risks from this, although rare in experienced hands, include significant neurovascular injury as well as attendant general anaesthetic risks.  An alternative to surgical excision is CBX. The benefits of CBX over FNA include a larger tissue sample and preservation of tissue architecture, therefore the potential for use of histopathologic and immunohistochemical stains. This improves differentiation of low grade lymphoma from reactive hyperplasia and allows grading and typing of lymphoma and poorly differentiated carcinoma (3). There is also the theoretical increased risk of tumour seeding related to increased needle diameter (5).
METHODS
This is a retrospective review of ultrasound guided FNA or CBX of head and neck lesions performed by a single consultant radiologist at a tertiary referral hospital. Patient details were collected from the radiologist�s logbook over a 52 month period (March 2006 to July 2010). This same radiologist performed the majority of ultrasound guided FNA and CBX of head and neck lesions at this centre. 
FNA and CBX were evaluated separately in the following 3 situations: to supply a specific diagnosis, to differentiate neoplastic from non-neoplastic lesions and to distinguish between malignant and benign lesions. The sensitivity, specificity and accuracy of FNA and CBX for diagnosis of neoplasm and malignancy were compared with the gold standard of surgical histology where available. The diagnostic rate was also calculated for FNA and CBX.
Patients were excluded if the specimen was sent to an external pathology site or if they had less than 6 months follow-up.
FNA was performed with a 22G or 25G needle with a minimum of 3 three passes. For thyroid lesions, a 25G needle was used, with a non-aspiration capillary technique. CBX was performed using a Bard Magnum gun and 18G needle using a 15mm throw with two passes. A small incision was made prior to the passes, and the patient would apply compression for 2-3 minutes after the procedure.  For both FNA and CBX, an onsite consultant pathologist confirmed the adequacy of the sample.
If an FNA was inadequate or inconclusive (as determined by the onsite pathologist), or if there was suspicion of lymphoma, the radiologist would proceed to CBX if the site was deemed safe and easily accessible.  CBX was generally only performed on thyroid lesions after 2 inconclusive FNAs, and only if deemed safe by the radiologist. Generally a larger, more superficial lesions that was not adjacent to the common carotid artery was considered a safe site.
Ethics approval was not required as determined by the Research Directorate, Monash Medical Centre.
RESULTS
There were 140 patients in the study. 44% were males and 56% were females. There were 81 FNAs done (27 thyroid, 16 parotid and 38 other head and neck lesions, of which 35 were lymph nodes). There were 98 CBXs performed (13 thyroid, 12 parotid and 73 other head and neck lesions, of which 66 were lymph nodes.  Any FNA or CBX performed on the same patient but on a different head lesion was counted separately.
There were 9 FNAs and 4 CBXs excluded due to the specimen being analysed by an external pathology department.
The diagnostic rate for FNA was 88%. All of the 10 inconclusive FNAs subsequently went on to have CBX or excision biopsy. The diagnostic rate for CBX was higher at 98%, with only 2 inconclusive CBXs. One was in a patient who had a cervical mass who went on to have biopsy of the primary, a supraglottic SCC. This patient was disease free at 2 year follow up with PET-CT, and at 3 years on clinical exam after treatment with radiotherapy. The other CBX was in a patient who subsequently had a mediastinal lymph node biopsy positive for recurrent lymphoma. This patient underwent treatment with monoclonal antibody therapy and is remission free at 5 year follow up.
Thirty-nine patients went on to have surgical excision.  Diagnosis in 33% was a non-neoplastic lesion, either benign (7 thyroid and 2 lymph node) or inflammatory (1 parotid gland, 1 submandibular gland and 2 lymph node). Of the 39, the definitive result was neoplastic in 67% of which 9 were benign neoplasms: 1 follicular adenoma of the thyroid, and 8 benign parotid neoplasms (6 pleomorphic adenomas, 1 Warthin�s tumour and 1 lipoma). The 17 malignancies comprised 9 SCCs (2 parotid, 1 laryngeal, 6 lymph node), 1 anaplastic carcinoma parotid, 1 basaloid carcinoma lymph node, 1 follicular carcinoma thyroid, 1 medullary cancer thyroid, 1 papillary carcinoma thyroid, 1 metastatic breast cancer lymph node, 1 metastatic melanoma parotid and 1 lymphoma lymph node.
From the 39 cases of surgical excision which were compared to previous FNA, CBX or both, 8 of 21 FNAs performed were inadequate. In comparison of the 39 cases of surgical excision, 23 had had prior CBX and of those only 1 was inadequate for diagnosis. Using the gold standard of excision biopsy, the sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of FNA and CBX for \diagnosing neoplasms and malignancy was calculated (see Table 1 and 2).




DISCUSSION
This study is unique in that there is a high number of FNA and CBX included (81 and 98 respectively), with 39 cases also undergoing the gold standard of surgical excision, and also because all FNAs and CBXs were performed by a single consultant radiologist. The results are consistent with the literature of FNA giving inadequate sample in 10-15% and CBX having a higher diagnostic rate (1,3,4). Both US guided FNA and CBX have similar sensitivity and specificity, which is also consistent with the literature (3). Screaton et al (6) found a sensitivity of 98%, and a specificity of 100% with CBX for the detection of malignancy lymphadenopathy in the 260 patients, a larger group than this present study. However only 23% of their patients were compared against the gold standard of surgical excision; the remaining had their CBX results compared with clinical examination or other laboratory tests, yet all patients were used for statistical analysis. This present study only included FNA and CBXs that could be compared against the gold standard of surgical excision for the calculation of sensitivity and specificity.  The fact a single radiologist performed all FNAs and CBXs, and all pathology was assessed at the same tertiary centre, reduced inter-observer variability.
Ultrasound has been proven to increase precision of the needle passes and adequacy of the sample and in doing so decrease the number of passes needed to obtain an adequate sample when compared with palpation technique (2). Complications such as bleeding, infection and nerve injury are not higher than that of FNA when CBX is performed under US guidance (3). CBX is usually contraindicated in parotids because of the risk of facial nerve injury, although Wan et al (7) and Howlett et al (8) followed 53 and 135 patients respectively who had US guided CBX of the parotid and had no incidences of facial nerve palsy.
The current practice in our tertiary centre is that FNA is the first line method of investigation for all head and neck lesions. For salivary gland or thyroid lesions, CBX would be second line after two inconclusive or insufficient FNAs. For other head and neck lesions such as lymph node where there was a suspicion of lymphoma, the radiologist would proceed to CBX after only one inconclusive FNA. Although the value of FNA for metastatic carcinoma and recurrent lymphoma is accepted, its role in the initial diagnosis of lymphoma remains controversial (1). A negative diagnosis must be placed in clinical context as false negatives occur and a negative FNA does not rule out a lymphoma. CBX on the other hand can differentiate between lymphoid hyperplasia and malignant lymphoma, and give a subtype and grading, obliterating the need for open surgical excision and potentially general anesthesia. It is the experience of the pathologists at our centre that a CBX compared to a FNA is more likely to produce enough specimen for a cell block for p16 testing, another advantage of CBX over FNA.
Tumour seeding with CBX and FNA is extremely rare and its true incidence is unknown. Studies suggest that the larger the bore of the needle, and the higher the number of needle passes, the higher the chances of tumour seeding (5). There were no recorded cases of tumour seeding or other more immediate complications such as haematoma after any of the FNA or CBXs performed in this study.
In regards to seeding, experimental studies suggest that dissemination of malignant cells during biopsy are not as uncommon as thought, despite the lack of evidence in the literature. Animal studies have shown tumour implantation occurs in 65 to 83% of FNAs of solid tumour, and that 103 to 104 tumour cells may be seeded during the process (9,10). This result, however, rarely results in clinically identifiable metastases, presumably because the cells are physically damaged, nonviable, and the host immune system destroys the rest (11). In addition, tumour seedings may be excised with the main specimen (9). There are case reports of tumour seeding in head and neck lesions after FNA and CBX (see table 3). 





CONCLUSION
FNA and CBX are complementary tests, although CBX is considered superior for diagnosing lymphoma and has a higher diagnostic rate (98% vs 88% in this study). CBX may avoid open surgical excision and the risks from general anesthesia.  US guidance is important in targeting the biopsy and avoiding complications, and an on-site experienced pathologist can reduce the non-diagnostic rate. Using surgical excision as the gold standard of diagnosing head and neck lesions, FNA and CBX have similar sensitivity, specificity, accuracy, positive predictive and negative predictive values. FNA is still a first line investigation and the practice at our institution, especially with thyroid lesions and the risk of bleeding. There have been no reported complications of haematoma, nerve injury or seeding in our study.
CONFLICTS OF INTERESTS
None of the authors had any financial or personal gains from being involved in this study.
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TABLE 1. DETECTION OF NEOPLASMS
Detection of Neoplasm in adequate CBX or FNA specimens (95% confidence interval in brackets)Biopsy site N= Sensitivity Specificity Accuracy PPV NPV Thyroid CBX 4 100 100 100 100 100 Thyroid FNA 7 0 100 71 N/A 71 Parotid CBX 8 86 100 88 100 50 Parotid FNA 10 100 N/A 100 100 N/A Other CBX 11 83 100 90 100 80 Other FNA 4 100 N/A 100 100 N/A Total CBX 23 87% 
(60-98)100% 
(63-100) 91% 
(72-99)100% 
(75-100)80%
 (44-98)Total FNA 21 88% 
(62-98) 100% 
(48-100)90%
 (70-00) 100%
 (77-100) 71% 
(29-96)





TABLE 2. DETECTION OF MALIGNANCY
Detection of Malignancy in adequate CBX or FNA specimens (95% confidence interval in brackets)Biopsy site N= Sensitivity Specificity Accuracy PPV NPV Thyroid CBX 4 100 100 100 100 100 Thyroid FNA 7 0 100 86 N/A 86 Parotid CBX 8 100 100 100 100 100 Parotid FNA 10 100 100 100 100 100 Other CBX 11 83 100 90 100 80 Other FNA 4 100 N/A 100 100 N/A Total CBX 23 91%
(59-100)100% 
(74-100) 96% 
(78-100)100% 
(69-100)92% 
(64-100)Total FNA 21 90%
(56-100)100%
 (72-100)95% 
(76-100) 100 %
(66-100)92% 
(62-100)




TABLE 3. CASE REPORTS OF TUMOUR SEEDING
FNASalivary
Pleomorphic adenoma parotid � case report (11)Adenoid cystic carcinoma submandibular gland � case report (12) ThyroidFollicular carcinoma seeding � case report seeding 5 years after FNA (13)Papillary carcinoma � case series 4912 patients with 5 cases of implantation (14) Anaplastic carcinoma � case report (15)CBXParotidParotid carcinoma � case report (16)SkinMelanoma � one case of seeding from lymph node from CBX immediately prior to neck dissection (3)








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