CASE REPORT

Primary Gingival Squamous Cell Carcinoma: A Case Report of the Clinical Presentation and Management
David J. Meister,* Gregory R. Caldwell,* Lisa M. Masters,* Thomas W. Sterio, and Michael P. Mills*

Introduction: Oral squamous cell carcinoma is the eighth most common cancer in the world. In the United States, it is estimated that 41,380 people will be diagnosed with oral or pharyngeal cancer in 2013, with 7,890 deaths expected. Potentially malignant (premalignant/precancerous) oral lesions commonly present as areas of leukoplakia (white patch), erythroplakia (red patch), or a mixture of both. Early diagnosis is critical to the successful management of the lesion. Case Presentation: This case report documents the detection and management of a gingival squamous cell carcinoma in a 69-year-old white male who recently completed comprehensive periodontal and restorative therapy. Early detection and diagnosis were paramount in limiting the potential invasiveness and extent of the surgical resection for this patient. Conclusion: This case report illustrates the importance of maintaining vigilance and thoroughly evaluating the patient throughout all phases of therapy. Clin Adv Periodontics 2014;4:1-7.
Key Words: Carcinoma, squamous cell; erythroplasia; gingiva; leukoplakia; periodontitis.

Background
Oral squamous cell carcinoma is the eighth most common cancer in the world.1 In North America, the highest incidence of oral cancer is found in middle-aged AfricanAmerican males and in white males older than 65 years.2 The incidence in males is reported to be three times higher than in females.2 In the United States, it is estimated that 41,380 people will be diagnosed with oral or pharyngeal cancer in 2013, and, of these, 7,890 deaths are expected.3 The estimated 5- and 10-year relative survival rates for oral and pharyngeal cancers are 62% and 51%, respectively.3 In descending order of appearance, the most common locations for oral squamous cell carcinoma are: 1) the lower lip, 2) tongue, 3) floor of the mouth, 4) soft palate, 5) alveolar ridge and gingiva, and 6) buccal mucosa. Symptomatic
* Department of Periodontology, University of Texas Health Science Center at San Antonio Dental School, San Antonio, TX.

Private practice, San Antonio, TX. Private practice, Swampscott, MA.

Submitted March 1, 2013; accepted for publication May 28, 2013 doi: 10.1902/cap.2013.130021

oral squamous cell carcinomas are often not difficult to diagnose because patients may complain of pain, an ulcer, a swelling or growth, or difficulty in chewing or swallowing. However, early presentations of these lesions are often asymptomatic and can easily be overlooked. Oral potentially malignant lesions commonly present as areas of leukoplakia (white patch), erythroplakia (red patch), or a mixture of both.2 Other potentially malignant lesions include: 1) submucous fibrosis, 2) lichen planus, 3) actinic keratosis, 4) discoid lupus erythematosus, 5) keratosis congenita, and 6) epidermolysis bullosa.2 They may also present clinically as ulcers or nodular growths. The estimated global prevalence of oral potentially malignant lesions ranges from 1% to 5%.2 The subtle changes of gingival carcinoma may mimic candidiasis, denture stomatitis, reaction to an allergen, vesiculobullous disorders, periodontal disease (i.e., mobility of affected teeth), or a reactive epulis.2,4,5 This case report describes a patient who had received comprehensive periodontal and restorative therapy before the initial appearance of a leukoplakic lesion on the gingiva, detected during a periodontal maintenance visit. The lesion was subsequently biopsied and diagnosed as a gingival squamous cell carcinoma.
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Clinical Presentation, Management, and Outcomes

In September 2008, a 69-year-old white male was referred to the Graduate Periodontics Clinic at the University of Texas at San Antonio Health Science Center (UTHSCSA), San Antonio, Texas, for comprehensive periodontal and dental implant treatment. The patient reported a medical history of hypertension, hypercholesterolemia, low testosterone, and erectile dysfunction. Medications included valsartan, atorvastatin, testosterone injections, sildenafil, and 81 mg aspirin daily. He reported consuming two to three alcoholic beverages per week but denied use of any tobacco product or recreational drugs. Previous dental history included routine restorative treatment and nonsurgical periodontal therapy. Family medical history was negative for systemic illnesses or conditions. At his initial evaluation visit, extraoral findings were found to be unremarkable, and an intraoral screening for signs consistent with malignancy was negative. The comprehensive periodontal examination revealed poor oral hygiene with an OLeary plaque index6 (PI) of 60% (Fig. 1). Clinical parameters included: 1) probing depths ranging from 1 to 7 mm and clinical attachment loss from 2 to 7 mm; 2) gingival recession of 1 to 3 mm; 3) bleeding on probing at 22% of sites; 4) Glickman7 Class 1 and 2 furcation invasions on all remaining molars; and 5) a Miller mobility index8 of Class I for teeth #7 through #10 and #25. There were multiple failing restorations with carious lesions and a self-reported history of tooth grinding.

FIGURE 1 Initial clinical presentation in 2008.

Occlusal analysis revealed: 1) bilateral Angle Class I canine and molar relationships; 2) bilateral canine disocclusion in working excursions; 3) a non-working contact between teeth #5 and #28; and 4) crossbite of teeth #12 and #21. The intraoral radiographic survey revealed generalized moderate to localized severe horizontal bone loss (Fig. 2). The initial diagnoses included: 1) generalized moderate and localized severe chronic periodontitis; 2) gingival recession; 3) caries; 4) bruxism; 5) secondary occlusal trauma; and 6) partial edentulism. Over a 28-month period, the patient received both comprehensive periodontal and restorative therapy for which appropriate verbal and written informed consent was given and obtained. After the non-surgical phase of treatment, oral hygiene had improved to an OLeary PI of 20%. The periodontal surgical phase included three posterior sextants of osseous surgery, functional crown lengthening of teeth #6 through #11, and extractions of teeth #10 and #28 with subsequent dental implant placement at both sites. All surgical sites healed without sequellae. At 6.5 months after crown-lengthening surgery, the gingiva at teeth #6 through #11 appeared normal without signs of leukoplakia or erythroplasia (Fig. 3). Final restorations included full-coverage metal-ceramic crowns on teeth #6 through #9 and #11 and the implant crown at site #10 (Fig. 4). A protective occlusal guard was also made and delivered. At the completion of definitive therapy in January 2011, the patient was transferred to the private periodontal office of one of the authors (LMM) for maintenance care, where he was placed on a 4-month maintenance schedule. At his fourth maintenance appointment in March 2012, leukoplakic lesions were observed on the facial and palatal gingival margins of teeth #7 through #9 (Fig. 5). Periapical radiographs taken at that time were unremarkable (Fig. 6). On additional questioning, the patient denied a family history of cancer and reported that he had never been diagnosed and treated for cancer himself. A semilunar excisional biopsy of the marginal and papillary gingiva on the facial and palatal surfaces of teeth #7 through #9 was subsequently performed, fixed in 10% formaldehyde, and submitted to a local oral and maxillofacial pathology

FIGURE 2 Initial complete radiographic survey in 2008.

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FIGURE 3a and 3b Clinical presentation 6.5 months after crownlengthening surgery with provisional restorations.

FIGURE 5 Leukoplakia observed at the gingival and papillary margins on the facial (5a) and palatal (5b) surfaces of teeth #7 through #9.

FIGURE 4 Final restorations for teeth #6 through #11.

laboratory for histologic examination and diagnosis. Because some margins of this initial biopsy specimen were not distinct, a second more extensive excisional biopsy involving only the facial tissue from the same teeth was performed 1 week later. A final diagnosis of a superficially invasive, moderately differentiated squamous cell carcinoma was made (Fig. 7). The patient was notified of the diagnosis and referred to the UTHSCSA Department of Otolaryngology for additional evaluation and treatment. In May 2012, the otolaryngology report described the lesion as velvety gingival mucosa surrounding tooth #8 and extending to tooth #7 and #9. Leukoplakia was also noted along the gingival border of tooth #8. The lesion did not appear to extend into the vestibule. There was no evidence of peripheral lymphadenopathy, bone erosion, or metastatic disease to the neck. A partial en bloc maxillectomy from canine to canine was performed, and an interim dental prosthesis was fixated to the palate with one bone screw (Fig. 8). Intraoperative frozen sections of the specimen revealed superficially invasive, moderately differentiated squamous cell carcinoma of the maxillary gingiva around teeth #7 and #8
Meister, Caldwell, Masters, Sterio, Mills

FIGURE 6a and 6b Periapical radiographs of teeth #7 through #9 taken at the time of biopsy.

with clear margins. During the initial healing period, several small sequestra of bone were removed without consequence. A maxillary rotational path removable dental prosthesis was fabricated as the patients final prosthesis (Fig. 9). Currently, the patient is seen every 4 months in the office of the private periodontist (LMM) for periodontal maintenance and by the Department of Otolaryngology every 6 months.

Discussion
Squamous cell carcinoma develops from the epithelial lining of the oral cavity and accounts for >90% of malignant lesions in the mouth. The incidence for the most common locations for oral squamous cell carcinoma are reported as
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FIGURE 7 Hematoxylin and eosin histomicrographs of moderately differentiated squamous cell carcinoma demonstrating an abundant inflammatory cell infiltrate and nuclear atypia of the epithelial cells. 7a Original magnification 10. 7b Original magnification 40.

FIGURE 8a Prior to the maxillectomy. 8b After

removal of teeth #6 through #9 and #11 and dental implant for site #10. 8c Partial en bloc maxillectomy for teeth #6 through #11 completed. 8d Interim removable dental prosthesis fixated to the palate with one bone screw.

FIGURE 9 Facial and occlusal views after

maxillectomy (9a and 9b) and with the final prosthesis inserted (9c and 9d).

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35% for the lower lip, 25% for the ventral surface of the tongue, 20% for the floor of the mouth, 15% for the soft palate, 4% for the alveolar ridge and gingiva, and 1% for the buccal mucosa.9 The majority of gingival squamous cell carcinomas occur in the mandible, specifically in the posterior region (69%).10 Historically, the two major etiologic factors in squamous cell carcinoma in the oral cavity are the social habits of tobacco use and alcohol consumption. More recent epidemiologic data suggest that other risk factors may also be linked to the development of squamous cell carcinoma, including: 1) age, 2) sex, 3) human papilloma virus (HPV 16), 4) malnutrition, 5) weakened immune system, 6) betel quid, 7) solar radiation, 8) alcoholic mouthrinses, and 9) irritation from dentures.2 Fitzpatrick et al.11 reported that as many as 25% of 127 gingival squamous cell patients had received previous surgical treatment, of which 13 had recent periodontal surgical treatment and another 67 had recent extractions. More recently, Moergel et al.12 retrospectively investigated the occurrence of squamous cell carcinomas in the vicinity of dental implants in their own patient population and by a systematic review of published literature. Of the 15 patients identified in their population, six had no previous history of carcinoma. Data analyzed from 17 selected publications revealed 26 patients diagnosed with carcinomas around dental implants, 14 of which had no previous history of malignancy.12 Risk factors in this case report are identified as smoking, alcohol consumption, and a previous history of carcinoma.12 In the present case, the patient reported no tobacco use but did consume two to three alcoholic drinks per week, for which his relative risk might be calculated to be z3.5 according to Mashberg and Samit.13 He also falls within the age range, ethnicity, and sex categories for patients at higher risk for squamous cell carcinoma. In addition, he had received periodontal and dental implant surgical therapy in the maxillary anterior as part of his comprehensive care. What part this therapy may have had in the development of the carcinoma, if any, cannot be determined. Key factors in this patients treatment outcome were early

detection, biopsy, and timely referral. The presence of a suspicious leukoplakic lesion found during a routine periodontal maintenance visit prompted the immediate attention of the treating periodontist (LMM). The diagnosis rendered from the two biopsies performed was a superficially invasive, moderately differentiated squamous cell carcinoma. In a systematic review of 23 primary studies, Petti14 estimated the true global prevalence of leukoplakia to be from 1.7% to 2.7%. He further estimated the annual oral cancer incident rate attributable to leukoplakia to be 6.2 to 29.1 per 100,000 people.14 On referral to the Department of Otolaryngology, the lesion had transformed and was at that time clinically described as velvety gingival mucosa. This fits the description of erythroplakia, which is defined by the World Health Organization as any lesion of the oral mucosa that presents as bright red velvety plaques that cannot be characterized clinically or pathologically as any other recognizable condition.15 A review by Reichart and Philipsen16 reported the prevalence of erythroplakia to range from 0.02% to 0.83%. Persistent asymptomatic erythroplasia is the earliest and most consistent sign of oral carcinoma.13 If, after removal of all possible etiologic factors, these lesions persist for >14 days, they should be biopsied for histologic evaluation. Nine percent of erythroplastic lesions have shown dysplasia, another 40% presented as carcinoma in situ, and 51% were diagnosed as squamous cell carcinoma.16 Treatment for oral squamous cell carcinoma includes chemotherapy, radiation, and surgical resection along with possible radical neck dissection. Surgical resection is typically the primary mode of treatment but can be combined with radiation and/or chemotherapy.17 If the lesion is <1 cm in size, this potentially lethal disease can be treated in a more conservative manner with less morbidity.13 In the patient in this case report, early detection and diagnosis of a gingival squamous cell carcinoma allowed for a more conservative surgical intervention. Although the en bloc partial maxillectomy resulted in a significant anterior ridge defect, it was functionally and esthetically restored to the patients satisfaction with a removable dental prosthesis. n

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Summary
Why is this case new information? This is a case report of a primary gingival squamous cell carcinoma that appeared after comprehensive periodontal and restorative treatment. j Leukoplakic lesions are increasingly being associated with the development of oral squamous cell carcinoma. j This case emphasizes the periodontists and hygienists role as a first observer.
j

What are the keys to successful management of this case?

Continued vigilance and thorough examination of all oral tissues for aberrant changes are necessary. j There should be early detection, biopsy, and submission to pathology for histologic examination and diagnosis. j Timely referral to the appropriate health care specialty is necessary. j There must be interdisciplinary collaboration in all phases of treatment.
j j

What are the primary limitations to success in this case?

Subtle changes in the appearance of oral tissue may be difficult to detect or may even be masked during the course of comprehensive periodontal therapy.

Acknowledgments
The authors thank Dr. Juliana Robledo, Oral and Maxillofacial Pathologist at South Texas Oral Pathology, San Antonio, Texas, and Dr. Frank R. Miller, Department of Otolaryngology, University of Texas Medicine, University of Texas Health Science Center, San Antonio, Texas, for their expertise in diagnosis and treatment of the patients carcinoma. The authors report no conflicts of interest related to this case report.

CORRESPONDENCE: Dr. Michael Mills, 703 Floyd Curl, San Antonio, TX 78229. E-mail: millsm@uthscsa.edu.

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References
1. Marocchio LS, Lima J, Sperandio FF, Corre a L, de Sousa SO. Oral squamous cell carcinoma: An analysis of 1,564 cases showing advances in early detection. J Oral Sci 2010;52:267-273. 2. Johnson NW, Jayasekara P, Amarasinghe AA. Squamous cell carcinoma and precursor lesions of the oral cavity: Epidemiology and aetiology. Periodontol 2000 2011;57:19-37. 3. American Cancer Society. Cancer Facts and Figures 2013. Available at: http://www.cancer.org/research/cancerfactsstatistics/index. Accessed February 22, 2013. 4. Kim OS, Uhm SW, Kim SC, et al. A case of squamous cell carcinoma presenting as localized severe periodontitis in the maxillary gingiva. J Periodontol 2012;83:753-756. 5. Yoon TY, Bhattacharyya I, Katz J, Towle HJ, Islam MN. Squamous cell carcinoma of the gingiva presenting as localized periodontal disease. Quintessence Int 2007;38:97-102. 6. OLeary TJ, Drake RB, Nalor JE. The plaque control record. J Periodontol 1972;43:38. 7. Glickman I. The treatment of bifurcation and trifurcation involvement. In: Clinical Periodontology. Philadelphia: WB Saunders; 1958:693-704. 8. Miller SC. Textbook of Periodontia, 3rd ed. Philadelphia: Bakiston; 1950. 9. Sapp JP, Eversole LR, Wysocki GP. Epithelial Disorders. In: Sapp JP, Eversole LR, Wysocki GP, eds. Contemporary Oral and Maxillofacial Pathology, 2nd ed. St. Louis: CV Mosby Company; 2004:174-194.

10. Dahlstrom KR, Little JA, Zafereo ME, Lung M, Wei Q, Sturgis EM. Squamous cell carcinoma of the head and neck in never smoker-never drinkers: A descriptive epidemiologic study. Head Neck 2008;30:7584. 11. Fitzpatrick SG, Neuman AN, Cohen DM, Bhattacharyya I. The clinical and histologic presentation of gingival squamous cell carcinoma: A study of 519 cases. Oral Surg Oral Med Oral Pathol Oral Radiol 2012; 114:509-515. 12. Moergel M, Karbach J, Kunkel M, Wagner W. Oral squamous cell carcinoma in the vicinity of dental implants [published online ahead of print March 16, 2013]. Clin Oral Investig; doi:10.1007/s00784-0130968-5. 13. Mashberg A, Samit A. Early diagnosis of asymptomatic oral and oropharyngeal squamous cancers. CA Cancer J Clin 1995;45:328-351. 14. Petti S. Pooled estimate of world leukoplakia prevalence: A systematic review. Oral Oncol 2003;39:770-780. 15. Kramer IR, Lucas RB, Pindborg JJ, Sobin LH; WHO Collaborating Centre for Oral Precancerous Lesions. Definition of leukoplakia and related lesions: An aid to studies on oral precancer. Oral Surg Oral Med Oral Pathol 1978;46:518-539. 16. Reichart PA, Philipsen HP. Oral erythroplakia A review. Oral Oncol 2005;41:551-561. 17. Shaw RJ, Pace-Balzan A, Butterworth C. Contemporary clinical management of oral squamous cell carcinoma. Periodontol 2000 2011;57:89-101.

indicates key references.

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