Neoplasms of the Hard Palate

SURGICAL ONCOLOGY AND RECONSTRUCTION

Neoplasms of the Hard Palate Utku Aydil, MD,* Yusuf Kızıl, MD,y Faruk Kadri Bakkal, MD,z Ahmet K€ oybas¸ıoglu, MD,x and Sabri Uslu, MDk Purpose:

Although the most common neoplastic lesion of the oral cavity is squamous cell carcinoma (SCC), primary neoplastic lesions of the hard palate have not been systematically reviewed to date. The aim of this study was to determine the histopathologic composition and characteristics of neoplasms of the hard palate.

Materials and Methods:

A retrospective analysis of 66 patients with a primary neoplasm of the hard palate managed at the authors’ institution from 1985 through 2012 was performed. Demographic features, malignancy rate, histopathologic characteristics and distribution, TNM staging results, metastasis patterns, and management strategies were investigated.

Results:

The sample was composed of 66 patients (mean age, 45.0 yr; 57.6% men). Neoplasms were benign in 57.6% of cases and malignant in 42.4%. Epithelial neoplasms and mesenchymal neoplasms were encountered in 52 patients (78.8%) and 14 patients (21.2%), respectively. Minor salivary gland tumors (MSGTs) were the most common histopathologic group (60.6%), followed by benign mesenchymal tumors (15.2%), SCCs (12.1%), malignant melanomas (6.1%), lymphomas (3.0%), and sarcomas (3.0%). Although 75.0% of malignant epithelial neoplasms were at an advanced stage, there were no pN+ SCC or malignant MSGT cases at presentation.

Conclusion:

The most common neoplasms of the hard palate were MSGTs. SCCs were relatively rare in this series. Although three-fourths of neoplasms were at an advanced stage, neck metastasis was not a characteristic of malignant epithelial neoplasms located in the hard palate. Ó 2014 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 72:619-626, 2014

The hard palate is 1 of 7 subsites of the oral cavity, together with the mobile tongue, floor of the mouth, alveolar ridges, lips, buccal mucosa, and retromolar trigon. This is a semilunar area bordered by the inner surface of the upper alveolar ridge anteriorly and the posterior edge of the palatine bone posteriorly. The palatine process of the maxillary bone and the horizontal plate of the palatine bone constitute the skeleton of the hard palate. The firm attachment of the mucosa of the hard palate to the underlying periosteum, the anatomic proximity of the mucosa to the bone, and the abundance

of minor salivary glands make the hard palate a unique anatomic region. Within this context, neoplastic lesions of the hard palate may show different characteristics and different histopathologic compositions compared with other anatomic regions. Many reports on hard palate neoplasms are case reports or series with a single histopathologic neoplastic type (eg, pleomorphic adenoma [PA]).1-4 In some other reports, the researchers have not considered the hard palate as a subsite of the oral cavity.5-8 In these studies, the hard palate has been evaluated with another subsite of the oral cavity, usually the upper alveolar

Received from the Department of Otorhinolaryngology, Head and

Address correspondence and reprint requests to Dr Aydil: Gazi € niversitesi Tıp Fak€ U ultesi KBB AD, 06500 Bes¸evler, Ankara, Turkey;

Neck Surgery, Gazi University, School of Medicine, Ankara, Turkey. *Associate Professor.

e-mail: [email protected]

yAssociate Professor.

Received February 26 2013

zChief Resident.

Accepted August 16 2013

xProfessor. kProfessor.

Ó 2014 American Association of Oral and Maxillofacial Surgeons

Presented at the 33th Turkish National Otorhinolaryngology and

http://dx.doi.org/10.1016/j.joms.2013.08.019

0278-2391/13/01107-5$36.00/0

Head and Neck Surgery Congress; Antalya, Turkey; October 26 to 30, 2011.

619

620

NEOPLASMS OF THE HARD PALATE

according to tissue origin (epithelial vs mesenchymal) and histopathologic type. All patients were treated surgically except for 2 with lymphoma. Preoperative evaluation included a history, detailed oral cavity, upper aerodigestive system, and neck examinations, and diagnostic imaging studies. Preoperative imaging studies included computed tomography or magnetic resonance imaging. Frozen biopsies were examined intraoperatively and surgical specimens and surgical margins were examined histologically postoperatively. Patients with an advanced stage malignant neoplasm also underwent postoperative adjuvant radiotherapy. Adjuvant radiotherapy was initiated 3 to 6 weeks after the operation. A total dose of 50 to 60 Gy within a 5- to 6-week period was administered using fractions of 2 Gy/day. Patients with a clinical N+ neck underwent simultaneous neck dissection.

Table 1. SUMMARY OF STUDY VARIABLES

Study Variables Sample size, n Age (yr), mean (range) Men, n (%) Malignant neoplasms, n (%)

Descriptive Statistics 66 45.0 (6-80) 38 (57.6) 26 (42.4)

Aydil et al. Neoplasms of the Hard Palate. J Oral Maxillofac Surg 2014.

ridge, or with the soft palate, which is a subsite of the oropharynx. Comprehensive studies analyzing various aspects of primary neoplastic lesions of the hard palate are not currently available in the literature.

Materials and Methods This study was conducted in complete agreement with the Declaration of Helsinki and the International Conference on Harmonization and Good Clinical Practice guidelines and was approved by the local ethics committee. A retrospective analysis of 66 patients with a primary neoplasm of the hard palate managed at the authors’ institution from 1985 through 2012 was performed. Demographic features, malignancy rate, histopathologic characteristics and distribution, TNM staging data, metastasis patterns, and management strategies were investigated. Neoplasms of the hard palate extending to the junction between the hard palate and soft palate were included. Non-neoplastic lesions, odontogenic neoplasms, and neoplasms invading the hard palate from an adjacent anatomic subsite (eg, the alveolar ridge) were excluded. Patients were staged according to the TNM (tumor stage, nodal stage, and distant metastasis) classification of the American Joint Committee on Cancer, seventh edition. Neoplastic lesions were grouped

Results The sample was composed of 66 patients with a mean age of 45.0 years (standard deviation, 19.3 yr; range, 6 to 80 yr) and 57.6% were men (Tables 1 and 2). Neoplasms were benign in 57.6% of cases and malignant in 42.4%. Fourteen neoplasms (21.2%) were mesenchymal and 52 (78.8%) were epithelial in origin. The most common neoplasms were minor salivary gland tumors (MSGTs), encountered in 40 cases (60.1%; Fig 1). Benign mesenchymal neoplasms, SCCs, malignant melanomas (MMs), lymphomas, and sarcomas were encountered in 10 patients (15.2%), 8 patients (12.1%), 4 patients (6.1%), 2 patients (3.0%), and 2 patients (3.0%), respectively (Fig 1). The most common histologic diagnosis was PA, which was found in 23 patients (34.8%; Table 3; Fig 2). In 28 patients with a malignant neoplasm, the most common pathologies were malignant minor salivary gland tumors

Table 2. GENDER AND AGE PREDILECTION

Pathology All benign Benign MSGTs Benign mesenchymal neoplasms All malignant SCCs Sarcomas Malignant melanomas Lymphomas Malignant MSGTs Total

Women, n

Men, n

Male-to-Female Ratio

Age (yr), Mean  SD

23 18 5

15 10 5

1.53 1.80 1.00

40.0  17.3 44.3  15.0 28.0  18.5

15 4 1 3 1 6 38

13 4 1 1 1 6 28

1.15 1.00 1.00 3.00 1.00 1.00 1.36

52.0  18.8 55.5  26.3 39.5  31.8 55.3  23.6 51.0  31.1 50.8  17.2 45.0  19.3

Abbreviations: MSGTs, minor salivary gland tumors; SCCs, squamous cell carcinomas; SD, standard deviation. Aydil et al. Neoplasms of the Hard Palate. J Oral Maxillofac Surg 2014.

621

AYDIL ET AL

FIGURE 1. Distribution of all neoplasms (n = 66). Aydil et al. Neoplasms of the Hard Palate. J Oral Maxillofac Surg 2014.

(MMSGTs), which were found in 12 patients (Table 3; Fig 3). SCCs were relatively rare and constituted only 12.1% of all neoplasms (Table 3; Fig 2). Eighteen malignant epithelial neoplasms (78.6%) were at advanced stages owing to palatal bone invasion (Table 4; Fig 4A, B). At presentation, neck metastases were detected clinically in 2 patients with SCC, 2 patients with MM, and 1 patient with sarcoma. Despite the preoperative clinical findings, pathologic examination of neck dissection specimens showed no metastases in the 2 cN+ SCC cases. As a result, there were no pN+ SCC or MMSGT cases at presentation in this series. Resection of the lesion with clear margins with underlying periosteum was performed for benign and early-stage malignant lesions (n = 44). For locally advanced malignant neoplasms (n = 20), composite

resection with underlying bone with consequent prosthetic rehabilitation was performed. A comprehensive therapeutic neck dissection was performed in 5 malignant cases owing to a clinical N+ neck. Elective neck dissection was not performed in any case. All patients with an advanced stage malignant neoplasm underwent adjuvant external radiotherapy. Two lymphoma cases were treated nonsurgically after a pathologic diagnosis of lymphoma based on the initial incisional biopsy material.

Discussion Approximately 25% of oral cancers occur in each of the 2 lateral alveololingual areas (corresponding to the posterior floor of the mouth and the adjacent lateral

Table 3. HISTOPATHOLOGIC COMPOSITION OF HARD PALATE NEOPLASMS

Pathology

n (%)

Benign salivary gland tumors

28 (42.4)

Benign mesenchymal tumors

10 (15.2)

Squamous cell carcinomas Sarcomas

8 (12.1) 2 (3.0)

Malignant melanomas Lymphomas Malignant salivary gland tumors

4 (6.1) 2 (3.0) 12 (18.2)

Total

66 (100.0)

Aydil et al. Neoplasms of the Hard Palate. J Oral Maxillofac Surg 2014.

Pathology pleomorphic adenoma myoepithelioma osteoma ossifying fibroma fibroma hemangioma giant cell tumor angiofibroma malignant fibrous histiocytoma osteosarcoma

adenocarcinoma mucoepidermoid carcinoma adenoid cystic carcinoma myoepithelial carcinoma total

n (%) 23 (34.8) 5 (7.6) 1 (1.5) 4 (6.1) 2 (3.0) 1 (1.5) 1 (1.5) 1 (1.5) 1 (1.5) 1 (1.5)

4 (6.1) 4 (6.1) 3 (4.5) 1 (1.5) 66 (100.0)

622

NEOPLASMS OF THE HARD PALATE

FIGURE 2. A, Classic view of pleomorphic adenoma of the hard palate. B, Computed tomographic view of the lesion. (Fig 2 continued on next page.) Aydil et al. Neoplasms of the Hard Palate. J Oral Maxillofac Surg 2014.

623

AYDIL ET AL

FIGURE 2 (cont’d). C, Surgical specimen excised with a small amount of surrounding normal mucosa. Aydil et al. Neoplasms of the Hard Palate. J Oral Maxillofac Surg 2014.

border of the tongue), 25% in the anterior floor of the mouth, and 25% in the rest of the mouth.9 The hard palate is 1 of the 2 least common neoplasm-harboring subsites in the oral cavity, in addition to the retromolar trigon.9 It is estimated that 1 to 3.5% of oral cancers are located at the hard palate, but studies and reports have generally reported data on SCC.9 SCC is relatively rare among hard palate neoplasms according to the present study. Conversely, it is well known that the hard palate is the most common location for MSGTs.10,11 In the present series, more than half the hard palate neoplasms were found to be benign and the most

common neoplasms were MSGTs; the most common histopathologic form was PA. In the literature, data regarding histopathologic distribution and clinical characteristics of hard palate neoplasms are not available, but the data are consistent in showing that PA is the most common benign MSGT located at the hard palate.10-12 The malignancy rate of hard palate MSGTs has varied in previous reports. In 3 large series reported by Beckhardt et al,13 Buchner et al,14 and Pires et al,15 the malignancy rates of palate neoplasms were 78%, 43%, and 47%, respectively. According to the largest published MSGT series, including 1,980 neoplasms, the ratio of benign to malignant palatal

FIGURE 3. Distribution of malignant hard palate neoplasms (n = 28). MM, malignant melanoma; MMSGT, malignant minor salivary gland tumor; SCC, squamous cell carcinoma. Aydil et al. Neoplasms of the Hard Palate. J Oral Maxillofac Surg 2014.

624

NEOPLASMS OF THE HARD PALATE

Table 4. CLINICAL T AND N STAGING OF MALIGNANT EPITHELIAL NEOPLASMS (N = 24)

T1 T2 T3 T4

N0

N1

N2

N3

2 4 1 15

— — — —

— — — 2

— — — —

Aydil et al. Neoplasms of the Hard Palate. J Oral Maxillofac Surg 2014.

MSGTs was equal.16 The same study also reported that adenoid cystic carcinoma (ACC) and mucoepidermoid carcinoma (MEC) were equally the most common malignant MSGT forms located at the hard palate.16 Other studies also have reported that ACC and MEC are the most common malignant MSGTs located at the hard palate.13-15 According to the present study, more than threefourths of malignant epithelial hard palate neoplasms are at the advanced stage at presentation; the main reason is palatal bone invasion. Data regarding T stages of isolated hard palate neoplasms are absent, but some studies have evaluated the maxillary alveolus and hard palate. Mourouzis et al7 reported that 71% of hard palate and alveolar SCCs were T4; despite this large proportion of neoplasms in advanced T stage, the neck involvement rate was 23% at presentation. These researchers reported a local recurrence rate as low as 18%. Beltramini et al17 also reported that T4 neoplasms constituted 60% of maxillary alveolar and hard palate SCCs. It is obvious that, like maxillary neoplasms, hard palate neoplasms can easily invade the underlying bone at an early period compared with other parts of the oral cavity. However, it is doubtful that bone invasion is really an important poor prognostic factor. In addition, unlike the mandible, the hard palate is not a mobile part of the maxillofacial skeleton and prosthetic rehabilitation is much easier and more effective in cases of bone resection. Bone invasion may not result in serious morbidity that is related to surgical treatment and may not have much impact on survival rates. As a result, the effect of bone invasion may be decreased for T staging of malignant hard palate neoplasms in the next edition of the TNM staging manual, as in the staging of maxillary cancer. Histopathologic diagnoses of hard palate neoplasms were performed before surgery. Although fine-needle aspiration biopsy (FNAB) is an option, the authors suggest that incisional biopsy has advantages over FNAB for the diagnosis of hard palate neoplasms. Aspirated material may be insufficient, and the sensitivity and specificity of FNAB may be variable owing to variations in aspiration technique, materials used for aspiration biopsy, and experience and familiarity of the cytologist.

FIGURE 4. A, B, Computed tomographic images of a low-grade mucoepidermoid carcinoma invading bone and extending into the right maxillary sinus. Aydil et al. Neoplasms of the Hard Palate. J Oral Maxillofac Surg 2014.

Because the overlying mucosa is excised to achieve safe margins in all cases with a hard palate neoplasm, contamination of the overlying healthy mucosa is not an actual risk for incisional biopsy. Whether benign or malignant, surgery is the treatment of choice for the management of hard palate neoplasms. In the authors’ opinion, radiotherapy should not be used as primary treatment for malignant MSGTs because they are relatively radioresistant and bone invasion is frequent. Enucleation of the benign neoplasms also should be avoided, and the neoplasm should be resected with a tissue cuff around the mass.

625

AYDIL ET AL

Although enucleation is avoided for major salivary gland neoplasms because of the high recurrence risk, it is not clearly known whether it is safe for benign minor salivary gland neoplasms. These lesions are submucosal and the overlying mucosa is usually very thin. It is known that benign minor salivary gland neoplasms may lack encapsulation and may have pseudopods or satellite nodule formations.18 During enucleation, rupture of the tumor capsule is more frequent. For these reasons, the authors routinely excise these lesions with some amount of surrounding healthy tissue and overlying mucosa. Excision with clear margins is also important to prevent recurrences of some other neoplasms, such as ossifying fibroma. For most benign cases, resection of the neoplasm with the periosteum would be sufficient. However, if the palatal bone is eroded, composite resection of the neoplasm with the palatal bone should be performed. Because bone invasion is frequent in malignant neoplasms, a composite resection is usually necessary. Cases of early malignant neoplasms without bone invasion can be removed, with resection of the periosteum. In such cases, preoperative evaluation should be performed very carefully. If there is any suspicion of bone invasion, the surgeon should not hesitate to resect the neoplasm with the underlying bone. Malignant neoplasms with an advanced T stage necessitate adjuvant radiotherapy. Almost all cases can be operated on transorally. An external approach is necessary for very advanced malignant neoplasms and neoplasms extending into the parapharyngeal space, pterygopalatine fossa, or masticator space, resulting in severe trismus. Because prosthetic rehabilitation is convenient, unlike neoplasms involving the mandible, the surgeon should not hesitate to resect the underlying bone, especially in malignant cases. If the surgeon has concerns about bone involvement in benign cases, the underlying bone can be partially removed using a surgical drill. In all malignant cases, clear surgical margins should be confirmed by intraoperative frozen biopsies. For posteriorly located malignant neoplasms, frozen biopsies also should be obtained from the palatine nerves, and, if positive, nerves should be traced proximally. SCCs and MMs should be resected more extensively. Although there are some clinical reports and studies on palate neoplasms, studies specifically focusing on soft or hard palate neoplasms are rare. The soft and hard palates are anatomically located within different parts of the upper aerodigestive system: the former is at the oral cavity and the latter is at the oropharynx. In addition to this anatomic difference, there are many other dissimilarities. Malignant neoplasms of the hard palate are prone to be at higher T stages because the underlying bone is nearby and can be easily invaded. Another important point may be the metastatic

patterns of malignant neoplasms located at these 2 different subsites. Although there are too few clues, it can be inferred that soft palate cancers metastasize more commonly, probably as a result of more abundant vascularization and the lymphatic system. Moreover, prosthetic rehabilitation of the hard palate is relatively easy. Surgical reconstruction and functional deficiencies, such as velopharyngeal insufficiency, are expected to be more common for soft palate neoplasms. Neoplasms extending to the junction between the hard palate and soft palate also share many features with hard palate neoplasms, so these neoplasms were included in the study group. The authors believe that their attempt to focus on hard palate neoplasms may encourage others to evaluate the clinical features and differences of hard palate and soft palate neoplasms separately. In consequence, increasing the number of studies on this topic may provide statistically more reliable results about malignancy rates, metastasis patterns, prognosis, functional treatment results, and other clinical features of neoplasms located at these 2 different anatomic subsites. In this study, the advanced stage owing to early invasion of the underlying bone and rare neck metastasis at presentation were the most remarkable features of malignant neoplasms of the hard palate. Survival rates and follow-up data were not presented owing to the high heterogeneity of the malignant neoplasms and variable follow-up periods of the cases. Multicenter studies may better identify the characteristics of neoplasms located at rare neoplasm-harboring anatomic sites such as the hard palate.

References 1. Erdem MA, Cankaya AB, G€ uven G, et al: Pleomorphic adenoma of the palate. J Craniofac Surg 22:1131, 2011 2. Daniels JS, Ali I, Al Bakri IM, et al: Pleomorphic adenoma of the palate in children and adolescents: A report of 2 cases and review of the literature. J Oral Maxillofac Surg 65:541, 2007 3. Becelli R, Frati R, Cerulli G, et al: Pleomorphic adenoma of the minor salivary glands of the palate. J Exp Clin Cancer Res 20: 25, 2001 4. Morris LG, Patel SG, Shah JP, et al: High rates of regional failure in squamous cell carcinoma of the hard palate and maxillary alveolus. Head Neck 33:824, 2011 5. Ural A, Livaoglu M, Bektas¸ D, et al: Approach to benign tumors of the palate: Analysis of 28 cases. Ear Nose Throat J 90:382, 2011 6. Tran L, Sadeghi A, Hanson D, et al: Salivary gland tumors of the palate: The UCLA experience. Laryngoscope 97:1343, 1987 7. Mourouzis C, Pratt C, Brennan PA: Squamous cell carcinoma of the maxillary gingiva, alveolus, and hard palate: Is there a need for elective neck dissection? Br J Oral Maxillofac Surg 48:345, 2010 8. Wang TC, Hua CH, Lin CC, et al: Risk factors affect the survival outcome of hard palatal and maxillary alveolus squamous cell carcinoma: 10-Year review in a tertiary referral center. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 110:11, 2010 9. Ganly I, Ibrahimpasic T, Patel SG, et al: Tumors of the oral cavity, in Montgomery PQ, Rhys Evans PH, Gullane PJ, (eds). Principles and Practice of Head and Neck Surgery and Oncology (ed 2). London, UK, Informa Helthcare, 2009, pp 160–191

626 10. Lopes MA, Kowalski LP, da Cunha Santos G, et al: A clinicopathologic study of 196 intraoral minor salivary gland tumours. J Oral Pathol Med 28:264, 1999 11. Subhashraj K: Salivary gland tumors: A single institution experience in India. Br J Oral Maxillofac Surg 46:635, 2008 12. Wang D, Li Y, He H, et al: Intraoral minor salivary gland tumors in a Chinese population: A retrospective study on 737 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 104:94, 2007 13. Beckhardt RN, Weber RS, Zane R, et al: Minor salivary gland tumors of the palate: Clinical and pathologic correlates of outcome. Laryngoscope 105:1155, 1995 14. Buchner A, Merrell PW, Carpenter WM: Relative frequency of intra-oral minor salivary gland tumors: A study of 380 cases from northern California and comparison to reports from other parts of the world. J Oral Pathol Med 36:207, 2007

NEOPLASMS OF THE HARD PALATE 15. Pires FR, Pringle GA, de Almeida OP, et al: Intra-oral minor salivary gland tumors: A clinicopathological study of 546 cases. Oral Oncol 43:463, 2007 16. Tian Z, Li L, Wang L, et al: Salivary gland neoplasms in oral and maxillofacial regions: A 23-year retrospective study of 6982 cases in an eastern Chinese population. Int J Oral Maxillofac Surg 39:235, 2010 17. Beltramini GA, Massarelli O, Demarchi M, et al: Is neck dissection needed in squamous-cell carcinoma of the maxillary gingiva, alveolus, and hard palate? A multicentre Italian study of 65 cases and literature review. Oral Oncol 48:97, 2012 18. Kuo YL, Tu TY, Chang CF, et al: Extra-major salivary gland pleomorphic adenoma of the head and neck: A 10-year experience and review of the literature. Eur Arch Otorhinolaryngol 268: 1035, 2011