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Int. J. Oral Maxillofac. Surg. 2014; xxx: xxx–xxx http://dx.doi.org/10.1016/j.ijom.2014.01.002, available online at http://www.sciencedirect.com

Clinical Paper Head and Neck Oncology

Fine needle aspiration cytology and frozen section in the diagnosis of malignant parotid tumours

N. Fakhry, L. Santini, A. Lagier, P. Dessi, A. Giovanni Service d’ORL et Chirurgie Cervico-Faciale, Centre Hospitalier Universitaire La Timone, Aix-Marseille Univ, 264 rue Saint Pierre, 13385 Marseille Cedex 05, France

N. Fakhry, L. Santini, A. Lagier, P. Dessi, A. Giovanni: Fine needle aspiration cytology and frozen section in the diagnosis of malignant parotid tumours. Int. J. Oral Maxillofac. Surg. 2014; xxx: xxx–xxx. # 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved. Abstract. The aim of this study was to determine the value of fine needle aspiration cytology (FNAC) and frozen section (FS) in the diagnosis of malignant parotid tumours. One hundred and thirty-eight patients who underwent FNAC and FS of a parotid tumour between 2006 and 2011 were analyzed retrospectively. The sensitivity, specificity, and positive and negative predictive values of FNAC and FS were determined using final histological diagnosis as the gold standard. Of the 138 tumours assessed in our study, 30 were malignant and 108 benign. For FNAC, the sensitivity was 73%, specificity 87%, positive predictive value 61%, and negative predictive value 90%. For FS, the sensitivity was 80%, specificity 98%, positive predictive value 92%, and negative predictive value 94%. Four false-negative results by FNAC were corrected by FS, and surgery was completed. Two falsepositive results were identified by both FNAC and FS. FNAC is an important examination that provides valuable information for the preoperative diagnostic work-up and alerts the surgeon to the possible presence of malignancy. However, FNAC cannot be used alone, and FS has a very important place in the intraoperative management of parotid tumours.

Parotid tumours are malignant in 26–32% of all reported cases. Specific symptoms of malignancy are absent in two-thirds of cases, which makes the clinical diagnosis of a malignant parotid tumour difficult.1 The preoperative investigation of a parotid tumour is based on clinical and paraclinical evaluations. Magnetic resonance imaging (MRI) is the standard imaging method used for the diagnosis of parotid 0901-5027/000001+04 $36.00/0

tumours. Fine needle aspiration cytology (FNAC) is another potential paraclinical examination. These two methods are used to confirm the presence of malignancy in the preoperative stage and allow the surgeon to perform a parotidectomy with an accurate preoperative diagnosis.1–3 Frozen section (FS) is used by surgeons to obtain information on the nature of the tumour during the parotidectomy.

Keywords: salivary glands; parotid gland; head and neck tumour; surgery. Accepted for publication 6 January 2014

The aim of this study was to determine the value of FNAC and FS in the diagnosis of malignant parotid tumours in order to evaluate the use of these examinations in the care of patients with parotid tumours. Materials and methods

Between January 2006 and March 2011, 300 parotidectomies were performed at

# 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Please cite this article in press as: Fakhry N, et al. Fine needle aspiration cytology and frozen section in the diagnosis of malignant parotid tumours, Int J Oral Maxillofac Surg (2014), http://dx.doi.org/10.1016/j.ijom.2014.01.002

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the study institution. All patients underwent radiological (MRI) and histological (FS and final histological analysis) examinations. FNAC, with a contributory result, was performed in 138 patients (46%). These 138 patients were included in the study. Fine needle aspiration cytology (FNAC)

All patients had a palpable parotid mass, allowing palpation-guided FNAC. A 25gauge needle was introduced into the mass, and rotation movements associated with to-and-fro vertical movements were applied to the needle. The histological material was collected by capillarity without aspiration. A syringe containing 5 ml of air was then attached to the needle and the collected material was expelled onto three glass slides by placing the tip of the syringe on the slide. The material was then smeared and dried in air before being sent to the cytology laboratory. Three aspirations were performed for each tumour in order to optimize the cytological examination and reduce the number of noncontributory slides due to insufficient material. All examinations were performed and interpreted by the same experienced pathologist. Data were obtained from the pathology reports. Frozen section (FS)

Just after removal, the tumour specimen was sent to the pathology laboratory for macroscopic examination (with annotated schema) and the FS procedure. The surgical specimen was placed on a metal chuck and frozen rapidly to about 20 to 30 8C. The specimen was embedded in a gel-like medium. After it had become frozen it was cut with the microtome portion of the cryostat. The section was then placed on a glass slide and stained (usually with haematoxylin and eosin, H&E stain). The report delivered by the pathologist was usually limited to a diagnosis of ‘benign’ or ‘malignant’, with the most probable histological diagnosis, and communicated to the operating surgeon via intercom with a maximum delay of 30 min. All results (cytological diagnosis and FS diagnosis) were analyzed and labelled as ‘positive’ or ‘negative’ in order to determine the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of each technique. Malignant diagnoses were considered as positive. Benign diagnoses were considered negative. All cases of a suspicious diagnosis were considered as positive

because they did not exclude the possibility of malignancy. A comparison to the definitive histological examination was done to determine statistical values. Results

Of the 138 tumours assessed, 30 were malignant (22%) and 108 were benign (78%). The final diagnosis for the benign tumours was pleomorphic adenoma in 52, Warthin’s tumour in 26, benign cyst/ inflammatory process in 14, adenoma in nine, and reactive lymphoid tissue in seven. The final diagnosis for the malignant tumours was mucoepidermoid carcinoma in 11, adenoid cystic carcinoma in five, acinic cell carcinoma in four, malignant

pleomorphic adenoma in two, lymphoma in four, and metastasis in four cases. No complication of FNAC was observed. Among the 138 FNAC samples analyzed, a correct diagnosis was obtained for 116 cases (84%). A false-negative result was obtained in eight cases (6%) and a false-positive result was obtained in 14 cases (10%). The calculated sensitivity for the diagnosis of malignancy was 73%, with a specificity of 87%. The PPV was 61% and NPV was 90%. Results are shown in Tables 1–3. For FS, a correct diagnosis was obtained in 130 cases (94%). The calculated sensitivity for the diagnosis of malignancy was 80%, with a specificity of 98%. The PPV was 92% and NPV was 94%. Results are

Table 1. Value of fine needle aspiration cytology and frozen section. FNAC (%) Sensitivity Specificity Positive predictive value Negative predictive value

FS (%)

73 87 61 90

80 98 92 94

FNAC, fine needle aspiration cytology; FS, frozen section. Table 2. False-positive results from fine needle aspiration cytology (n = 14). Cytological diagnosis

Final histological diagnosis

Squamous cell carcinoma (n = 3) Squamous cell carcinoma (n = 1) Mucoepidermoid carcinoma (n = 1) Mucoepidermoid carcinoma (n = 2) Adenoid cystic carcinoma (n = 3) Acinic cell carcinomas (n = 2) Acinic cell carcinomas (n = 1) Acinic cell carcinomas (n = 1)

Necrotizing sialometaplasia Warthin’s tumour Canalicular adenoma Warthin’s tumour Basal cell adenoma Warthin’s tumour Oncocytoma Lymphoid hyperplasia

Table 3. False-negative results from fine needle aspiration cytology (n = 8). Cytological diagnosis Warthin’s tumour (n = 1) Warthin’s tumour (n = 1) Warthin’s tumour (n = 1) Warthin’s tumour (n = 1) Lymphoid hyperplasia (n = 2) Adenomas (n = 2)

Final histological diagnosis Lymphoma Malignant pleomorphic adenoma Acinic cell carcinoma Mucoepidermoid carcinoma Lymphomas Acinic cell carcinoma

Table 4. False-positive results from frozen section (n = 2). Frozen section diagnosis

Final histological diagnosis

Squamous cell carcinoma (n = 1) Adenoid cystic carcinoma (n = 1)

Necrotizing sialometaplasia Basal cell adenoma

Table 5. False-negative results from frozen section (n = 6). Frozen section diagnosis Pleomorphic adenoma (n = 1) Lymphoid hyperplasia (n = 3) Benign cyst (n = 1) Fibrosis (n = 1)

Final histological diagnosis Malignant pleomorphic adenoma Lymphomas Mucoepidermoid carcinoma Malignant pleomorphic adenoma

Please cite this article in press as: Fakhry N, et al. Fine needle aspiration cytology and frozen section in the diagnosis of malignant parotid tumours, Int J Oral Maxillofac Surg (2014), http://dx.doi.org/10.1016/j.ijom.2014.01.002

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Diagnostic management of parotid tumors shown in Tables 1, 4 and 5. Two falsepositive results were found (both by FNAC and FS): in one case, FNAC and FS gave a result of squamous cell carcinoma while the final diagnosis was necrotizing sialometaplasia; in the other case, FNAC and FS gave a result of adenoid cystic carcinoma while the final diagnosis was a basal cell adenoma. The falsenegative results for FS consisted of the following: three cases where lymphoid hyperplasia was in fact lymphoma; one case where a cystic lesion was diagnosed as a low-grade cystic mucoepidermoid carcinoma upon definitive analysis; and one case where a benign pleomorphic adenoma was revealed to be malignant after definitive analysis. In these last two cases the correct diagnosis was made by FNAC. In one case the FS examination was conducted in an area of cicatricial fibrosis (related to a previous surgery) and not the tumour area (malignant pleomorphic adenoma). In four cases, the false-negative result of FNAC was corrected by FS and the surgical procedure was then modified. If we analyze the patients with a nontumour as one specific group (i.e., the 21 patients with a cyst/inflammatory process or reactive lymphoid tissue), a false-positive result was obtained in four cases (19%) for FNAC and in only one case for FS (5%). Among the four false-positive cases by FNAC, FS allowed a correct diagnosis in three. Discussion

The use of FNAC to assess parotid tumours is controversial. This examination is simple to conduct, can be performed during the consultation, causes almost no pain, and can be performed without the use of local anaesthesia. In most cases the procedure is guided by palpation.1 In certain cases where it is difficult or not possible to palpate the tumour (deep lobe tumour or small tumour), an ultrasound is needed to guide the needle.2,3 For these cases, close collaboration is needed between surgeons, radiologists, and pathologists. When a pathologist conducts FNAC, as was the case in the current study, the clinical and paraclinical elements presented by the patient can be examined. This information may help in the histological analysis.4 Potential complications of FNAC are haemorrhages, the development of hematomas, and infection at the site of needle insertion.5 None of these complications was observed in the current study. Other reported criticisms of FNAC concern the

risk of neoplastic cell dissemination along the path of the needle.6 There are also studies that have demonstrated the risk of lesions to the adjacent anatomic structures and the breaking of tissue; however the use of needles with small diameters reduces these risks.5 We could find no article in the literature that has reported cases of neoplastic cell dissemination along the path of the needle. In the recent literature, the sensitivity of parotid FNAC in the diagnosis of malignancy has been reported to be in the range of 54–92%, with specificity in the range of 86–100%.1,5,7 The false-negative rate ranges from 2% to 31% and the falsepositive rate from 0% to 7%.8 Our results are comparable to those presented in the recent literature. According to Fathallah et al.9 FNAC errors can be classed into four large categories: (1) those in the taking of the sample (taken from a non-tumour zone); (2) errors of triage (where a pathologist fails to direct appropriate secondary studies); (3) mistakes due to cytological material (hypocellularity of the material); and (4) errors in interpretation. With regard to histological types, two large categories of lesion cause problems: hypercellular tumours and cystic tumours. In the case of hypercellular tumours, such as lymphomas, the cytological material, which is sometimes abundant, appears as small round cells lacking major morphological characteristics, making the cytological diagnosis particularly difficult.10,11 In the case of cystic or necrotic tumours, the cytological material is often abundant but poorly cellular and does not allow for a reliable cytological analysis. Traditionally, teams treating parotid tumours have commonly used FS. FS allows for a fast intraoperative diagnosis, which guides the continuation or interruption of the surgical procedure. FS does not expose the patient to complications.12,13 In the literature, few studies have examined the sensitivity and specificity of FS for parotid surgery. In a study by Seethala et al., which included 220 patients, the sensitivity was determined to be 77% and specificity 100%.4 Zba¨ren et al., in a study that examined malignancy by FS in 110 parotidectomies, found a sensitivity of 93% and specificity of 95%.14 The results of the first study are comparable to those of our study; we found a sensitivity of 80% and specificity of 98% for the diagnosis of malignant parotid tumours. In the study by Zba¨ren et al., 62% of the cohort had malignant tumours, which makes it difficult to compare the

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results of their study with ours in terms of sensitivity. It has been reported in the literature that knowing that a parotid tumour is malignant during the preoperative phase improves the treatment of parotid cancer. This diagnosis may be used to help counsel patients and improve the quality of surgical management. This preoperative diagnosis also allows for better management of the operating rooms (more accurate scheduling of the duration of the intervention).7,10,15 FNAC and MRI are the only examinations, at this time, that are able to provide the diagnostic orientation of the malignancy during the preoperative phase. FS, even though it is a reliable examination, comes late in the diagnostic process; however, this procedure has better sensitivity and specificity than FNAC and allows the surgeon to information intraoperatively. gather Nevertheless it is important to emphasize the fact that the majority of parotid tumours, both benign and malignant, are not homogeneous and this can lead to misdiagnosis of the FS. Therefore careful analysis of the entire tumour specimen is required before a final diagnosis can be established.8,12,13,15,16 In conclusion, FNAC is an important examination that provides valuable information for the preoperative diagnostic work-up and can alert the surgeon to the possible presence of malignancy. FNAC cannot be used alone, and FS, which has better sensitivity and specificity, has a very important place in the intraoperative management of parotid tumours. Funding

None. Competing interests

None. Ethical approval

None. References 1. Fakhry N, Antonini F, Michel J, Penicaud M, Mancini J, Lagier A, et al. Fine-needle aspiration cytology in the management of parotid masses: evaluation of 249 patients. Eur Ann Otorhinolaryngol Head Neck Dis 2012;129:131–5. 2. Pratap R, Qayyum A, Ahmed N, Jani P, Berman LH. Ultrasound-guided core needle biopsy of parotid gland swellings. J Laryngol Otol 2009;123:449–52.

Please cite this article in press as: Fakhry N, et al. Fine needle aspiration cytology and frozen section in the diagnosis of malignant parotid tumours, Int J Oral Maxillofac Surg (2014), http://dx.doi.org/10.1016/j.ijom.2014.01.002

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3. Wan YL, Chan SC, Chen YL, Cheung YC, Lui KW, Wong HF, et al. Ultrasonographyguided core-needle biopsy of parotid gland masses. Am J Neuroradiol 2004;25:1608– 12. 4. Seethala RR, LiVolsi VA, Baloch ZW. Relative accuracy of fine-needle aspiration and frozen section in the diagnosis of lesions of the parotid gland. Head Neck 2005;27:217– 23. 5. David O, Blaney S, Hearp M. Parotid gland fine-needle aspiration cytology: an approach to differential diagnosis. Diagn Cytopathol 2007;35:47–56. 6. Aversa S, Ondolo C, Bollito E, Fadda G, Conticello S. Preoperative cytology in the management of parotid neoplasms. Am J Otolaryngol 2006;27:96–100. 7. Lin AC, Bhattacharyya N. The utility of fine needle aspiration in parotid malignancy. Otolaryngol Head Neck Surg 2007;136: 793–8. 8. Fundakowski C, Castan˜o J, Abouyared M, Lo K, Rivera A, Ojo R, et al. The role of indeterminate fine needle biopsy in the diagnosis of parotid malignancy. Laryngoscope

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2013. http://dx.doi.org/10.1002/lary.24341. [Epub ahead of print]. Fathallah L, Tulunay OE, Feng J, Husain M, Jacobs JR, Al-Abbadi MA. Histopathologic and cytopathologic diagnostic discrepancies in head and neck region: pitfalls, causes, and preventive strategies. Otolaryngol Head Neck Surg 2006;134:302–8. Zbaren P, Schar C, Hotz MA, Loosli H. Value of fine-needle aspiration cytology of parotid gland masses. Laryngoscope 2001;111:1989–92. Cohen EG, Patel SG, Lin O, Boyle JO, Kraus DH, Singh B, et al. Fine-needle aspiration biopsy of salivary gland lesions in a selected patient population. Arch Otolaryngol Head Neck Surg 2004;130:773–8. Wong DS. Frozen section during parotid surgery revisited: efficacy of its applications and changing trend of indications. Head Neck 2002;24:191–7. Arabi Mianroodi AA, Sigston EA, Vallance NA. Frozen section for parotid surgery: should it become routine? ANZ J Surg 2006;76:736–9. Zba¨ren P, Gue´lat D, Loosli H, Stauffer E. Parotid tumors: fine-needle aspiration and/or

frozen section. Otolaryngol Head Neck Surg 2008;139:811–5. 15. Zba¨ren P, Nuyens M, Loosli H, Stauffer E. Diagnostic accuracy of fine-needle aspiration cytology and frozen section in primary parotid carcinoma. Cancer 2004;100:1876– 83. 16. Schmidt RL, Hunt JP, Hall BJ, Wilson AR, Layfield LJ. A systematic review and metaanalysis of the diagnostic accuracy of frozen section for parotid gland lesions. Am J Clin Pathol 2011;136:729–38.

Address: Nicolas Fakhry Assistance Publique – Hoˆpitaux de Marseille Universite´ Aix-Marseille Centre Hospitalier Universitaire La Timone Service ORL et Chirurgie Cervico-Faciale 264 rue Saint Pierre 13385 Marseille Cedex 05 France Tel.: +33 4 91 38 60 71; Fax: +33 4 91 38 77 57 E-mail: [email protected]

Please cite this article in press as: Fakhry N, et al. Fine needle aspiration cytology and frozen section in the diagnosis of malignant parotid tumours, Int J Oral Maxillofac Surg (2014), http://dx.doi.org/10.1016/j.ijom.2014.01.002

Fine needle aspiration cytology and frozen section in the diagnosis of malignant parotid tumours.

The aim of this study was to determine the value of fine needle aspiration cytology (FNAC) and frozen section (FS) in the diagnosis of malignant parot...
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