Tumors of the Hard Palate and Upper Alveolar Ridge April 22, 201= 1

= TITLE: Tu= mors of the Hard Palate and Upper Alveolar Ridge
SOURCE: Grand Rounds Presentation,
The University of Texas Medical Branch (UTMB), Dept. of Otolaryngology
DATE: April 22, 2011
RESIDENT PHYSICIAN: Regina Rodman, MD
FACULTY PHYSICIAN: Tammara L. Watts, MD, PhD
DISCUSSANT: Tammara L. Watts, MD, PhD
SERIES EDITOR: Francis B. Quinn, Jr., MD
ARCHIVIST: Melinda Stoner Qui= nn, MSICS

"This material was prepared by resident physicians in partial fulfillment of educational requirements established for the Postgraduate Training Program = of the UTMB Department of Otolaryngology/Head and Neck Surgery and was not intended for clinical use in its present form. It was prepared for the purp= ose of stimulating group discussion in a conference setting. No warranties, eit= her express or implied, are made with respect to its accuracy, completeness, or timeliness. The material does not necessarily reflect the current or past opinions of members of the UTMB faculty and should not be used for purposes= of diagnosis or treatment without consulting appropriate literature sources and informed professional opinion." =

Introduction:

The need for this paper ari= ses from a lack of clinically useful information written specifically about manageme= nt of tumors of the hard palate and upper alveolar ridge. Much research has be= en published about oral cancer, and many of these papers discuss palatal tumor= s in a subsection, but a distinction is not drawn between hard and soft palate tumors, although the etiology, presentation, histology, and subsequent treatment is quite different between the two. Tumors of the soft palate ten= d to be similar to other tumors of the oral cavity, with 69.7% of these tumors b= eing squamous cell carcinoma.

In contrast, the tumors of = the hard palate have much more varied histology with non-squamous cell tumors, inclu= ding minor salivary gland tumors, causing a greater portion of the tumors seen in the hard palate, as well as rare cases of melanoma, sarcoma and malignant lymphomas. Similarly, multiple papers have been written about tumors of minor salivary glands, but there is rarely specification that details the distribution of these tumors within t= he oral cavity. The purpose of t= his paper is to describe clinical recommendations for evaluation and management= of tumors specifically of the hard palate and upper alveolar ridge.

Anatomy:

The palate forms the roof o= f the mouth and intervenes between the nasal and oral cavities. It consists of the palatine proces= s of the maxilla, the horizontal plates of the palatine bone, and the pterygoid = plate. It is covered by thick mucosa bound tightly to the underlying periosteum. The mucosa is covered by keratinizing stratified squamous epithelium which shows regional variations and may be ortho- or parakeratinized. This keratinization may explain the decreased incidence of squamous cell carcinoma in the hard palate as compar= ed to other areas of the oral cavity. <= /span>The submucosa in the posterior half of the hard palate contains minor salivary glands of the mucous type.

The palate derives its bloo= d supply principally from the greater palatine artery, a branch of the third part of= the maxillary artery. The greater palatine artery descends with its accompanying nerve in the palatine canal.= The greater palatine emerges on th= e hard palate from the greater palatine foramen, runs forward in a groove on the inferior surface of the bony palate almost to the incisor teeth and supplies the gums and the mucosa and glands of the hard palate. The nasopalatine nerves are branch= es of the maxillary division of the trigeminal nerve. They enter the palate at the incis= ive foramen and are branches of the maxillary nerve which pass through the pterygopalatine ganglion to supply the anterior part of the hard palate beh= ind the incisor teeth. Parasympat= hetic postganglionic secretomotor fibres from the pterygopalatine ganglion run wi= th the nerves to supply the palatine mucous glands. Tumors spreading by perineural ext= ension can be discovered by radiographic enlargement of the palatine foramina or widening of the palatine canals or the foramen rotundum.

The upper alveolar ridge co= nsists of mucosa overlying the alveolar process of the maxilla and extends from the gingivobuccal sulcus laterally to the junction of the hard palate medially.=

Etiology:

There is a well-established= link between lifestyle factors such as tobacco, alcohol, and diet lacking in antioxidants and squamous cell carcinoma of the oral cavity. Other factors, such as infection with the HPV 16 virus, have been shown have shown an increased odds ratio of 2.2 for squamous cell CA in individuals who were seropositive for HPV 16, but the exact role of HPV in oral carcinogenesis is still not entirely defined. Tobacco, particularly cigarettes, and alcohol remain the primary factors in the etiology of squamous cell oral cancer in = the United States.

In parts of India and south= -east Asia, chewing betel quid with tobacco and areca nuts is the primary risk fa= ctor for oral cancer. Those who use tobacco and alcohol simultaneously are thought to have a significantly incr= eased risk of oral cancer relative to using either one alone, likely because the combined use of nicotine and ethanol significantly increases the penetratio= n of N-Nitrosonornicotine (NNN), a known carcinogen, across the oral mucosa. This link between smoking and drink= ing is not so clear in cases of tumors of the hard palate and upper alveolar ridge, however. Squamous cell tumors occur most frequently on the ventral surface = of the tongue, and the floor of the mouth.&nb= sp; The likely reason for the increased incidence of cancer in these are= as is due to the histology of the region. The majority of the oral cavity mucosa (including the hard palate) consists of a thick layer of squamous cells with well-developed rete pegs a= nd a prominent superficial keratin layer, whereas the floor of the mouth and the ventral surface of the tongue are lined by thin, atrophic mucosa with shall= ow rete pegs and little surface keratin. This phenomenon, together with the fact that this area is constantly bathed by a pool of saliva containing potential carcinogens, is a possible reason for the high incidence of oral carcinoma in these areas.

A large portion of palatal = tumors are minor salivary gland tumors, and the etiology of these tumors is less clear. One study found that t= here showed that smoking, alcohol consumption did not independently or jointly increase the risk of salivary gland cancer. Another study demonstrates that th= ere is a possible increased risk for salivary gland tumors in patients who received radiation treatment to the head and neck, ultraviolet light treatment or fu= ll mouth dental x-rays before 1955, when the exposure dose was substantially higher. Still, this does not account for all patients with minor salivary gland tumors, and more research needs to be done regarding the etiology of such neoplasms.

Melanoma of the oral mucosa= is a rare tumor, but when it does occur the most common locations are the palate= and maxillary gingiva. The etiology of these tumors is unclear, but possible etiologic mechanisms include solar irradiation, mechanical trauma, ill-fitt= ing dentures, oral habits, self medication and exposure to formaldehyde. One cl= ear etiology for hard palate tumors is seen in areas of India where the practic= e of chutta, or reverse smoking, is practiced.&= nbsp; This practice of holding the lit end of the cigarette in the mouth causes smoke to hit the hard palate directly, and it has been demonstrated = that there is a close correlation between reverse smoking, nicotine stomatitis a= nd carcinoma or the hard palate. Other possible etiologic mechanisms include poor oral hygiene, mechanical irritat= ion from ill fitting dentures, syphilis, and vitamin deficiencies.&nb= sp;

Evaluation:

Most patients will present = with pain and discomfort as the most common presenting symptom. If the tumor has ulcerated, they m= ay present with foul odor and bleeding (if not submucosal). In minor salivary gland tumors, pa= tients may be asymptomatic, smooth, and mucosa covered. The only symptom the patient may n= otice is fit of dentures changes.

A Study from Pittsburg show= ed that there was a delay in diagnosis of months to years in many patients. It is not entirely uncommon for th= ese tumors to present late. If th= is is the case, the symptoms depend on the areas invaded. Extension superiorly in= to the maxillary antrum and nasal cavity will present with nasal obstruction.<= span style=3D'mso-spacerun:yes'> Posterior extension into the struc= tures of the oropharynx, into pterygoid muscles will present with trismus, malocclusion.

Once patients do present, evaluation includes a history and thorough head and neck exam including lym= ph nodes in neck. The middle ear= must be evaluated for middle ear effusion, which may be caused by extension into nasopharynx or invasion of the tensor veli palatini m. or eustachian tube.<= span style=3D'mso-spacerun:yes'> An absent trigeminal blink reflex = or palatal hypesthesia may be due to involvement of maxillary division of trigeminal nerve in the sphenopalatine fossa. Masseter or temporalis wasting may indicate involvement of the mandibular division of the trigeminal nerve= .

Imaging for these patients = must include a CT scan, including axial views to define the anterior-posterior dimension, assess bone destruction, especially of erosion of pterygoid plas= tes and skull base. It should also include coronal views to evaluate superior extension and paranasal sinus involvement. An MRI may be us= eful in evaluating cranial base and CNS.

After imaging, a biopsy nee= ds to be performed. In the case of ulc= erated, exposed lesions, transoral pu= nch or cup foreceps can be used. For= mucosa covered lesion, incisional biopsy is preferred. Small, well circumscribed covered with intact mucosa may require complete excision, leaving the defec= t to granulate. If nodes are present, they require an FNA.

Treatment:

The treatment of tumors of = the hard palate is surgical excision. = Small lesions may be excised transorally. Large tumors requiring partial maxillec= tomy can be approached through lateral rhinotomy incision or midface degloving. = If cancer extends through the palate require total maxillectomy.

Adjuvant Therapy:

An area where much has been published is the area of adjuvant therapy, and the prognosis/survival compared across treatment modalities including surgery vs. radiation treatment vs. combination therap= y. A few papers have been written that specifically focus adjuvant therapy for tumors of the hard palate and upper alveolar ridge. In these papers, it is determined = that radiation is effective for both squamous cell tumors and salivary gland tumors, = and that while surgery has a role in management of hard palate tumors, so does radiation therapy. It is beli= eved that some patients may receive more benefit from radiotherapy alone, includ= ing patients who have very early lesions, those unfit for surgery, and those with post-operative margins. When reflecting on data comparing treatment modalities, several problems arise; = papers published on this subject thus far are retrospective studies, and the treat= ment modality chosen was based on factors that affect prognosis, and skew the ability to equally compare treatment modalities. Patients who receive only radiatio= n are either poor surgical candidates with unressectable disease or have neoplasm= s so small they can be treated without surgery. To date, we know of no studies w= hich have created a forward facing matched pair analysis. Another difficulty that arises is = the small sample size included in most reviews due to the relative rarity of tu= mors in this location. Small sampl= e size may show a discrepancy between that which is clinically significant and what proves to be statistically significant.

There have also been numero= us studies published about adjuvant therapy in minor salivary tumors, and it is believed that most minor salivary gland tumors are radioresponsive, with a = dose response relationship, and that combination therapy showed better local control, however did not improve overall survival due to the better salvage rate in the surgery only group. However, in the case of adenoid cystic carcinoma, combination therapy has been shown to increase overall survival = likely because radiation controls f= or the adenoid cystic tumors propensity for perineural invasion. Until a substantial conclusion can= be reached regarding the role of radiotherapy as a stand alone treatment, we recommend radiation therapy as adjuvant therapy only, to be used in patients with demonstrated cervical metastasis, adenoid cystic carcinoma, and high g= rade tumors, particularly high grade mucoepidermoid carcinomas.

Neck Dissection:

The palate is a midline structure.<= span style=3D'mso-spacerun:yes'> The areas at risk for metastatic d= isease include the retropharyngeal lymphatics and the jugular lymphatics bilaterally. The question of whether or not to perform an elective neck dissection in an N0 neck is answ= ered differently depending on the type of tumor. There is recent literature that su= ggests that selective elective neck dissection should be offered to patients with = squamous cell cancer of the hard palate and the maxillary alveolus due to the significant rates of occult cervical metastasis, both locally and regionall= y.= = [1] Elective selective neck dissection should also be performed in tumors occurring on t= he lateral and buccal surfaces of the alveolar ridge. In the majority of tumors not fitti= ng the above qualifications, elective neck dissection is not routinely advocated.<= /p>

Defect/Reconstru= ction/Prosthesis:

There is much debate over w= hether to reconstruct the defect with tissue reconstruction vs. an obturator. Comp= ared to mandible, the residual maxilla does not move, making a prosthesis a good option for functional recovery. Because of this, the Obturator was the “gold standard” for years.&nbs= p; However, advancements in reconstructive surgery have lead to multiple publications in recent years advocating tissue reconstruction.

Evaluation of reconstructive options requires a multi disciplinary approach, involving a Dental oncologi= st, Endodontist, Maxillofacial prosthedontist, Head and Neck Surgeon, Reconstru= ctive Surgeon, Patient, and Patient’s Family/Caregivers. Factors that need to be considered= are 1) Disease Biology, 2) Oral Anatomy and Physiology, 3) Patient Factors, 4)D= efect Analysis.

When considering disease bi= ology, it has been suggested by some authors that= some tumors have potential of rapid regrowth and need cavity surveillance. In these cases = an obturator is an ideal choice, as it can be easily removed for physical exam. Examples of these include, but are not limited to Ameleoblastoma, Myxoma, M= ucosal Melanoma. Some authors disagr= ee, however, a study by Moreno et al showed there was no significant difference= in local recurrence detection between groups.

In patients with severe tri= smus, a free flap is better as it will not require daily removal and maintenance th= at obturator does. The status of= the teeth of the patients may also alter the decision, as the presence of teeth may help plan osteotomy planes through the existing tooth sockets. It is important to preserve the su= pport of adjacent teeth (abutments), as they may be strategic for retentio= n of a prosthesis. - Edentulous or partially edentulous patients have difficulty with retention of obturator and, in some cases, difficulty with support as well. In these cases, osseointegrated implants can anchor and support the obturator prosthesis, usually with bone graft s/p radiation.

When considering oral anato= my and physiology, one needs to keep in mind that the patient needs to be able to remove prosthesis BID. The pa= tient needs to be able to clean the prosthesis as well as perform irrgation of the defect with baking soda and salt. Therefore, the following are NOT good candidates for obturator: patients with trismus, decreased manual dexterity= , decreased vision, altered mental status, patient preference, and those unwilling to l= ive with defect.

There are many papers argui= ng success and failure of obturators and free tissue transfer. A paper by Okay et al, in 2001 giv= es summary of how to assess the defect and plan for reconstruction. The idea i= s based on 4 Pillars of stability: 1) Molars 2) Canines

Please see slides for illustration of defects. Essentially, Class I, where none o= r one pillar is removed can be reconstruceted with soft tissue or a local flap, or with prosthesis. A Class II, which= is 2 pillars, can be reconstructed with a prosthesis or a Vascularized Bone Free Flap. Class III, which is >3 pillars = absent needs reconstruction with a vascularized bone free flap.

Conclusions:

1.&n= bsp; Think outside the squam when you see a tumor of the hard palate

2.&n= bsp; Etiology is less clear in these tumors. The patient may not be our typical “head and neck patient”

3.&n= bsp; Work up: imaging, biopsy

4.&n= bsp; Surgical excision (except very small and too large tumors)

5.&n= bsp; Neck Dissection in N+, all squamous cell, and later= al tumors

6.&n= bsp; Adjuvant therapy for N+ neck, Adenoid cystic, High grade mucoepidermoid

7.&n= bsp; Reconstruction depends on Okay criteria and resourc= es available to you and the patient.

<= /o:p>

____________
Discussant̵= 7;s Comments on Tumors of the Hard Palate and Upper Alveolar Ridge
Tammara L. Watts, MD, PhD

Reconstruction = of the palate is a challenging endeavor. Dr. Urkin’s palatomaxillary defect classification provides a useful scheme to conceptually organize these defects and the available opti= ons for reconstruction. As with a= ny defect, thinking about the goals of reconstruction from both a functional a= nd aesthetic point of view will further tailor which approach is most suitable= for the patient. Each defect will= be as unique as the patient and therefore the breath of one’s surgical armamentarium is critical. Wi= th that being said, these tumors are somewhat rare and a multi-disciplinary multispecialty approach often times is warranted.

Soft tissue def= ects of the hard palate are essentially a non-issue, as the hard palate can be l= eft to granulate with relatively little patient morbidity. Bony defects in a dentate patient = can be treated conservatively with an obturator provided a skilled prosthodonist is available. Bony defects of the upper alveolar ridge will cause a significant cosmetic and functional deformity, and therefore free tissue transfer techniques will augment the anterior projection of the face and the soft tissue can be used to seal the oral cavity from the nose. Ob= turators can also be employed provided the contralateral hemi-maxilla remains.<= /o:p>

<= /span>

Each technique = has its advantages and disadvantages. The goal of maintaining speech, swallowing and anterior facial projection should be kept at the forefront of every surgeons mind when approaching this difficult cases.

____________

REFERENCES=

1. Oral Cancer Facts, The Oral Cancer Foundation. http://oralcancerfoundation.org 2011

2. Krutchkoff DJ, Chen J, Eisenberg E= , Katz R.. Oral Cancer: A survery of= 566 cases from the Universtiy of Connecticut Oral Pathology Biopsy Service, 1975-1986. Oral Surgery, Oral Medicine, Oral Pathology, 1990; 70:192-8.

3. Lopez-Graniel CM, Ochoa-Carrillo F= J, Meneses-Garcia A. Malignant Melanoma of the Oral Cavity:Diagnosis and Treatment. Oral Oncology, 35:4, pp.425-430, 1999.

4. Ratech H, Burke J, Blayney D, Shei= bani K, Pappaport H. A clinicopath= ologic Study of Malignant Lymphomoas of the Nose, Paranasal Sinuses, and Hard Pala= te, Including Cases of Lethal Midline Granuloma. Cancer 64:2525-2531, 1989.<= span style=3D'color:#B83D68'>

5. Cummings , Flint et al. Cummings Otolaryngology Head and N= eck Surgery. Mosby Elsevier, Philadelphia PA, 2010.

6. Moore KL, R. Agur AM “Oral Region&= #8221; Essential Clinical Anatomy” Lippincott Williams and Wilkins, New York, NY, 2002

7. Gluckman JL, Savoury LW. “Carcinoma of the Oral Cavity” Otolaryngology, Volume III, Head and Neck Surgery. Ed by Paparella, Shumrick, Glukman, Meyerhoff. WB Saunders Co, Philadelphia, PA 1991.

8. Mork, et al. Human Paillomavirus Infection as a Risk Factor for Squamous Cell Carcinoma of the Head and Neck. New England Journal of Medicine 344 No. 15, April 12, 2001.

9. Reichart, Peter A. Identification of Risk Groups for = Oral Precancer and Cancer and reventative Measures. Clinical Oral Investigation 5:207-213. 2001

10. Sciubba, James J. Oral Cancer: The Importance of Ear= ly Diagnosis and Treatment. Amer= ican Journal of Clinical Dermatology: 2 (4) 239-251. 2001.

11. Baral RN, Patanaik S, Das BR. Co-overexpression of p53 and c-myc proteins linked with advanced stages of betel and tobacco related oral squa= mous cell carcinomas from eastern India. European Journal of Oral Science 106:907-913. 1998.

12. Sri Lanka Socio-Economic = Data 1998; Report on Consumer Finances and Socio Economic Survey 1996/1997 Part = 1, 1999

13. Du X, Squler CA, Kremer M= J, Wertz PW. Penetration of N-nitrosonornicotine (NNN) across oral mucosa in the presence of ethanol and nicotine. J Oral Pathol Med 2= 00:29: 80-5.

14. Robbins and Cotran. Pathologic Basis of Disease. Elsevier Inc, Philadelphia, PA 200= 5.

15. Petruzzelli G, Myers E. Malignant Neoplasms of the Hard Pa= late and Upper Alveolar Ridge. Onc= ology 1994:April:43-53.

16. Gluckman JL, Savoury LW.<= span style=3D'mso-spacerun:yes'> “Carcinoma of the Oral Cavit= y” Otolaryngology, Volume III, Head and Neck Surgery. Ed by Paparella, Shumrick, Glukman, Meyerhoff. WB Saunders Co, Philadelphia, PA 1991.

17. Muscat JE, Wynder EL. A Case Control Study of Risk Facto= rs for Major Salivary Gland Cancer. Otolaryngology Head and Neck Surgery 1998 Feb; 118(2):195-8.<= span style=3D'color:#B83D68'>

18. Horn-Ross PL, Ljung BM, M= orrow M Enviornmental Factors and t= he Rish of Salivary Gland Cancer. Epidemiology 1997 July;8(4):414-9.

19. Martinez EA, Alonso FC, S= iles MS, Jornet PL. Melanoma of th= e oral mucosa with cerebral metastasis: a clinical case. Oral Oncology Extra 41,

30-33, 2005

20. Ulusal BG, Karatas O, Yil= diz AC, Oztan Y. Primary Malignant Melanoma of the Maxillary Gingiva. Dermatologic Surgery 2003; 29:304-307.

21. Ramulu C, Raju MVS, Venkatarathnam G, Reddy CRRM Reddy. Nicotine Stomatitis and Its Relation to Carcinoma in Reverse Smokers= of Chuttas. Journal of Dental Re= search 52(4) 711-718, 1973.=

22. Johnson, JT. “Surgery of the Hard Palate&= #8221;

23. Guggenheimer J, Verbine RS, Johnso= n JT, et al: Factors delaying the diagnosis of oral and oropharyngeal ca. Cancer 64:932-935 1989.

24. Simental AA, Johnson JT, = Myers EN. Cervical Metastasis From Squamous Cell Carcinoma of the Maxillary Alveolu and Hard Palate. Laryngoscope 116: September 2006.<= /span>

25. Inagi K, Takahashi H, Oka= moto M, Nakayama M, Makoshi T, Nagai H. Treatment Effects in Patients with Squamous Cell Carcinoma of the Or= al Cavity. Acta Otolaryngology 2= 002; Supplement 547: 25-29.

26. Shibuya H, Horiuchi I, Su= zuki S, Amagasa M, and Mashima K. = Oral Carcinoma of the Upper Jaw: r= esults of Radiation Treatment. Acta Radiologica Oncology 23, 331-335. 1984.

27. Yorozu A, Sykes AJ, Slevin NJ. Carcinoma of the Hard Palate Treat= ed with Radiotherapy: A Retrospective Review of 31 cases. Oral Oncology 37 493-497; 2001.

28. Jenkins DW, Cynthia SA, Constable = WC, Cantrell R. Minor Salivary Gl= and Tumors: The Role of Radiotherapy. American Journal of Otolaryngology 10: 250-256, 1989.

29. Kovalic Jj, Simpson JR. Carcinoma of the Hard Palate. Journal of Otolaryngology 1993 22(2):118-20.

30. Chung CK, Johns ME, Cantrell RW, e= t al: Radiotherapy in the management in primary malignancies of the hard palate.<= span style=3D'mso-spacerun:yes'> Laryngoscope 1980 90:576-584, 1980.

31. Le QT, Birdwell S, Terris= D, Gabalski E, Varghese A, Fee Jr WE, Goffinet D. Postoperative Irradiation of Minor Salivary Gland Malignancy of the = Head and Neck. Radiotherapy and On= cology 52 (1999) 165-171

32. Garden AS, Weber RS, Morrison W, A= ng KK, Peters L. The Influence of Po= sitive Margins and Nerve Invasion in Adenoid Cystic Carcinoma of the Head and Neck Treated with Surgery and Radiation. International Journal of Radiation Oncology, Biology and Physics. Vol 32, No 3, pp619-626, 1995.

33. Urken M. Functional Palatomaxillary Reconstruction. Mastery of Ad= vanced Head-Neck Reconstruction and Skull Base Surgery, February 2011.

34. Moreno MA, Skoracki RI, H= anna EY, Hanasono MM. Microvascula= r free flap reconstruction versus palatal obturation for maxillectomy defects. Head and Neck 2010 Jul:32(7):860-8.

35. Genden EM, Wallace DJ, Okay D, Urk= en ML. Reconstruction of the hard palate using the radial forearm free fla: indications and outcomes. Head and Neck, 2004 Sep:26(9):808-14

36. Okay DJ, Genden E, Buchbinder D, U= rken M. Prosthetiic guidelines for surgical reconstruction of the maxilla: a classification system of defects. J Prosth= etic Dent 2001 Oct:86(4) 352-63