Yujiro Fukuda1,2, Hidenori Suzuki2, Nobuhiro Hanai2, Hitoshi Hirakawa2, Taijiro Ozawa2, Eiichi Sasaki3, Yasushi Yatabe3, Hiroshi Yamashita1 and Yasuhisa Hasegawa2*
1Department of Otolaryngology, Yamaguchi University Graduate School of Medicine, 1-1-1, Minamikogushi, 755-8505 Ube, Japan
2Department of Head and Neck Surgery, Aichi Cancer Center Hospital, 1-1, Kanokoden, Chikusa-Ku, 464-8681 Nagoya, Japan
3Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, 1-1, Kanokoden, Chikusa-Ku, 464-8681 Nagoya, Japan
Received: 30 September, 2016; Accepted: 12 October, 2016; Published: 13 October, 2016
Yasuhisa Hasegawa, Aichi Cancer Center Hospital, 1-1, Kanokoden, Chikusa-Ku, 464-8681 Nagoya, Japan, Tel: +81 52 762 6111; (x3104); Fax: +81-52-764-2944; E-mail:
Fukuda Y, Suzuki H, Hanai N, Hirakawa H, Ozawa T, et al. (2016) Prediction of Positive Surgical Margins in Sinonasal Tract Squamous Cell Carcinoma. Arch Otolaryngol Rhinol 2(1): 056-060. DOI: 10.17352/2455-1759.000026
© 2015 Fukuda Y, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Sinonasal tract; Squamous cell carcinoma; Positive surgical margin; Clinical N stage; Total maxillectomy
Background: In patients with clinical T4 (cT4) squamous cell carcinoma (SCC) of sinonasal tract who received surgery, the relationship between positive surgical margins and positive clinical N stage as diagnosed by the presence of cervical lymph node metastasis has not been investigated so far. Therefore, we investigated the relationship between positive surgical margins and preoperative parameters in patients with cT4 SCC of the sinonasal tract following surgery.
Methods: Forty-one patients who underwent surgery for cT4 SCC of the sinonasal tract were investigated and survival rates were calculated using the Kaplan-Meier method. The relationship between surgical margins and preoperative parameters was analyzed.
Results: Both positive surgical margins and clinical N stage were significantly correlated with shorter survival rate by log-rank test.
Conclusion: Positive surgical margins can be predicted based on clinical N stage in patients with cT4 SCC of the sinonasal tract.
Squamous cell carcinoma (SCC) of the sinonasal tract with clinical T4 (cT4) classification, including paranasal sinuses and nasal cavity, usually has a worse prognosis than that with clinical T1 to T3. The 5-year overall survival (OS) rate of patients with cT4 SCC of the sinonasal tract who receive radical therapies, such as surgery and chemoradiotherapy, generally ranges from 32.0% to 75.0% [1-7]. However, a number of investigators has attempted to develop an accurate prognosis of SCC of the sinonasal tract using several approaches, such as clinical and pathological parameters [1-5].
Positive clinical N stage diagnosed based on the presence of cervical lymph node metastasis from clinical findings pre-surgery for SCC of the sinonasal tract leads to reduced rates of OS, and the rate of patients with SCC of the sinonasal tract and positive clinical N stage ranges from 3.3% to 36.7% [8-11]. Similarly, having positive surgical margins diagnosed by pathological findings following surgery for SCC of the sinonasal tract also leads to reduced rates of OS [2,5,12-16] and the rate of positive surgical margins in patients with SCC of the sinonasal tract ranges from 10.5% to 63.5% [14-17]. Of note, among patients with SCC of the sinonasal tract, the 5-year OS rate among those with positive surgical margins (0% - 32.8%) was significantly shorter than among those with negative surgical margins (65.7% - 81.8%) [13,15,18].
The relationship between positive surgical margins and preoperative parameters before surgery has been investigated in several cancers other than SCC of the sinonasal tract [19,20]. Age can predict positive surgical margins patients in cutaneous melanoma of the head and neck, and the rate of positive clinical N stage among patients with positive surgical margins is greater than that among those with negative surgical margins in subjects with SCC of the oral cavity [19,20]. To our knowledge, however, the relationship between positive surgical margins and positive clinical N stage in patients with cT4 SCC of the sinonasal tract following surgery has not been investigated.
Here, we investigated the relationship between positive surgical margins and preoperative parameters in patients with cT4 SCC of the sinonasal tract following surgery and determined whether or not positive clinical N stage can predict positive surgical margins using univariate and multivariate analyses with adjustments for clinical parameters.
Materials and Methods
Patients and treatments
Between January 2001 and December 2011, 52 patients underwent surgery for malignant neoplasms of the sinonasal tract, including SCC and non-SCC with cT4, at the Department of Head and Neck Surgery in Aichi Cancer Center Hospital. We excluded 11 patients who did not have pathologically diagnosed SCC, resulting in enrollment of 41 patients with pathologically diagnosed cT4 SCC of the sinonasal tract. All patients gave informed consent for each examination and treatment.
Routine clinical examinations and blood chemistry were performed on the first visit to our institution. Clinical T and N classifications were diagnosed by physical examination, nasopharyngoscopy, and enhanced cervical computed tomography (CT) or magnetic resonance imaging (MRI). Positive clinical N stage was defined as findings on enhanced cervical CT of ringed enhancement or short distance of lymph node ≥ 10 mm. As no patients showed evidence of either distant metastasis or second primary cancers on chest CT, we performed positron emission tomography (PET) or PET/CT when possible. Diagnoses were made according to the clinical TNM classification of the Union for International Cancer Control (6th edition) .
Unresectable disease was defined by the presence of distant metastasis or the involvement of the sphenoid sinus, clivus, cavernous sinus, both orbits, and internal carotid artery. Resectable disease was defined as a tumor that could be resected in an en bloc fashion . All patients underwent both en bloc resection of primary tumors and free-flap reconstructive procedures, as previously described . Total maxillectomy was conducted for 11 patients and extended total maxillectomy for 30 (5 with orbital exenteration and 25 with skull base resection). Thirty-seven of the 41 patients received induction chemotherapy (ICT), with the majority of regimens consisting of 5-fluorouracil (800mg/m2/day, day1-5) and cisplatin (80mg/m2/day, day6), before surgery for tumor shrinkage and distant metastasis suppression. ICT has been received to nearly all patients. However, some of the patients did not receive the ICT for its rejection or other reasons.
Thirty-two (78.1%) of the 41 patients were clinically diagnosed with no lymph node metastasis before surgery, and 10 of the 41 patients underwent prophylactic neck dissection while 9 (21.9%) who were N-positive underwent neck dissection. Prophylactic neck dissection was performed at the discretion of the attending physician.
Resected specimens consisted of 5-mm thick sections cut from the tumor by a head and neck surgeon that were then fixed with 10% formalin for several days. After macroscopic evaluation of surgical margins by both an experienced pathologist and head and neck surgeon, sections were stained with hematoxyline and eosine (H&E). Pathological diagnoses were made by two experienced pathologists who then compiled all reports. Surgical margins were defined as follows . free margin, tumor at least 5 mm from the surgical margin; closed margin, tumor less than 5mm from the surgical margin; and involved margin, tumor present in the surgical margin. In this study, involved margins were categorized as positive surgical margins, and both free and closed margins as negative surgical margins.
Thirty-four (82.9%) of the 41 patients had negative surgical margins while 7 (17.1%) had positive surgical margins. When possible, we planned postoperative radiation therapy (PORT) at a total dose of 60 Gy with or without chemotherapy for patients with positive surgical margins. However, 24 patients did not receive PORT due to prolonged wound healing after surgery or lack of patients consent. Clinical characteristics of patients are shown in Table 1. Preoperative enhanced CT images and H&E stains of one randomly selected patient with positive surgical margins and one with negative surgical margins are shown in Figure 1.
- Mendenhall WM, Amdur RJ, Morris CG, Kirwan J, Malyapa RS, et al. (2009) Carcinoma of the nasal cavity and paranasal sinuses. Laryngoscope 119: 899-906 .
- Mine S, Saeki N, Horiguchi K, Hanazawa T, Okamoto Y (2011) Craniofacial Resection for Sinonasal Malignant Tumors: Statistical Analysis of Surgical Outcome over 17 Years at a Single Institution. Skull Base 21: 243-248 .
- Dirix P, Nuyts S, Geussens Y, Jorissen M, Vander Poorten V, et al. (2007) Malignancies of the nasal cavity and paranasal sinuses: long-term outcome with conventional or three-dimensional conformal radiotherapy. Int J Radiat Oncol Biol Phys 69: 1042-1050 .
- Guntinas-Lichius O, Kreppel MP, Stuetzer H, Semrau R, Eckel HE, et al. (2007) Single modality and multimodality treatment of nasal and paranasal sinuses cancer: a single institution experience of 229 patients. Eur J Surg Oncol 33: 222-228 .
- Mirghani H, Mortuaire G, Armas GL, Hartl D, Aupérin A, et al. (2013) Sinonasal cancer: Analysis of oncological failures in 156 consecutive cases. Head Neck 36: 667-674 .
- Dalal AJ, McLennan AS (2013) Cervical metastases from maxillary squamous cell carcinoma: retrospective analysis and of the literature. Br J Oral Maxillofac Surg 51: 702-706 .
- Kano S, Hayashi R, Homma A, Matsuura K, Kato K, et al. (2013) Effect of local extension sites on survival in locally advanced maxillary sinus cancer. Head Neck 36: 1567-1572.
- Cantù G, Bimbi G, Miceli R, Mariani L, Colombo S, et al. (2008) Lymph node metastases in malignant tumors of the paranasal sinuses: prognostic value and treatment. Arch Otolaryngol Head Neck Surg 134: 170-177 .
- Homma A, Sakashita T, Yoshida D, Onimaru R, Tsuchiya K, et al. (2013) Superselective intra-arterial cisplatin infusion and concomitant radiotherapy for maxillary sinus cancer. Br J Cancer 109: 2980-2986 .
- Rinaldo A, Ferlito A, Shaha AR, Wei WI (2002) Is elective neck treatment indicated in patients with squamous cell carcinoma of the maxillary sinus? Acta Otolaryngol 122: 443-447 .
- Kruse AL, Grätz KW (2009) Cervical metastases of squamous cell carcinoma of the maxilla: a retrospective study of 9 years. Head Neck Oncol 1: 28 .
- Eldeeb H, Macmillan C, Elwell C, Hammod A. (2012) The effect of the surgical margins on the outcome of patients with head and neck squamous cell carcinoma: single institution experience. Cancer Biol Med 9: 29-33 .
- Mücke T, Loeffelbein DJ, Hohlweg-Majert B, Kesting MR, Wolff KD, et al. (2009) Reconstruction of the maxilla and midface-surgical management, outcome, and prognostic factors. Oral Oncol 45: 1073-1078 .
- Bobinskas AM, Wiesenfeld D, Chandu A (2014) Influence of the site of origin on the outcome of squamous cell carcinoma of the maxilla-oral versus sinus. Int J Oral Maxillofac Surg 43: 137-141 .
- Patel SG, Singh B, Polluri A, Bridger PG, Cantu G, et al. (2003) Craniofacial surgery for malignant skull base tumors: report of an international collaborative study. Cancer 98: 1179-1187 .
- Bristol IJ, Ahamad A, Garden AS, Morrison WH, Hanna EY, et al. (2007) Postoperative radiotherapy for maxillary sinus cancer: long-term outcomes and toxicities of treatment. Int J Radiat Oncol Biol Phys 68: 719-730 .
- Janjua OS, Ahmed W, Qureshi SM, Khan TS, Ahmed A, et al. (2013) Assessment of margins in resection specimens for head and neck malignancies. J Coll Physicians Surg Pak 23: 265-268 .
- Yang Z, Deng R, Sun G, Huang X, Tang E (2013) Cervical metastases from squamous cell carcinoma of hard palate and maxillary alveolus: A retrospective study of 10 years. Head Neck 36: 969-975.
- Christophel JJ, Johnson AK, McMurry TL, Park SS, Levine PA. (2013) Predicting positive margins in resection of cutaneous melanoma of the head and neck. Laryngoscope 123: 683-688 .
- Girardi FM, Zanella VG, Kroef RG. (2013) Correlation between clinical and pathological data and surgical margins in patients with squamous cell carcinoma of the oral cavity. Braz J Otorhinolaryngol 79: 190-195 .
- Sobin LH, Wittekind Ch. (2002) International Union Against Cancer (UICC): TNM classification of malignant tumors, 6th edition. Wiley-Liss, New York .
- Okada T, Saito K, Takahashi M, Hasegawa Y, Fujimoto Y, et al. (2008) En bloc petrosectomy for malignant tumors involving the external auditory canal and middle ear: surgical methods and long-term outcome. J Neurosurg 108: 97-104 .
- Sagheb K, Sagheb K, Taylor KJ, Al-Nawas B, Walter C (2013) Cervical metastases of squamous cell carcinoma of the maxilla: a retrospective study of 25 years. Clin Oral Investig 18: 1221-1227.
- Sanghvi S, Khan MN, Patel NR, Yeldandi S, Baredes S, et al. (2014) Epidemiology of sinonasal squamous cell carcinoma: a comprehensive analysis of 4994 patients. Laryngoscope 124: 76-83 .
- Sutton DN, Brown JS, Rogers SN, Vaughan ED, Woolgar JA (2003) The prognostic implications of the surgical margin in oral squamous cell carcinoma. Int J Oral Maxillofac Surg 32: 30-34 .