CC

A 68- year-old male farmer is referred to you. He complains, “I’m worried about this growth on my cheek. It just won’t seem to go away.” (Verrucous carcinoma is more commonly seen in the older adult male population, those older than 60 years of age.)

HPI

The patient reports a 6-month history of a rough, corrugated area on his right buccal mucosa and mandibular gingiva. He was seen by his dentist and was referred to you for evaluation of possible “oral cancer.” (Verrucous carcinoma cannot be distinguished clinically from squamous cell carcinoma [SCC].) The area has not been painful but has recently become more irritated. (Pain is not characteristically seen with neoplastic processes.) He has been inadvertently chewing on the area, with occasional bleeding. He denies any weight loss or constitutional symptoms. (These may be seen with metastatic disease.)

PMHX/PDHX/medications/allergies/SH/FH

The patient has a positive history of chronic obstructive pulmonary disease (COPD; secondary to chronic tobacco use). He sees his local dentist only when he develops a problem. (He does not have routine oral cancer screening.) He has used smokeless tobacco for 30 years and consumes three or four alcoholic beverages per week.

Many patients with verrucous carcinoma are reported to chew tobacco, but this association is not consistent. Both tobacco use and chronic alcohol consumption are risk factors for the development of SCC. The association with verrucous carcinoma is uncertain.

Examination

General. The patient is a thin, older adult White male who appears older than his stated age; this is most apparent by his sun-damaged skin and extensive facial rhytids. (Chronic tobacco and sun exposure both contribute to early signs of aging secondary to changes in collagen synthesis.)

Maxillofacial. The patient has deeply tanned skin with many rhytids (secondary to prolonged sun exposure). There are no skin lesions in the sun-exposed areas (it is important to look for early signs of basal cell carcinoma and actinic keratosis), and there is no facial or cervical lymphadenopathy. (Enlarged lymph nodes would be suggestive of a malignant disease process.)

Intraoral. The patient has significant occlusal wear on his teeth, enamel staining (secondary to smokeless tobacco use), and moderate generalized periodontal disease. There is a heterogeneous, multifocal growth that involves the right buccal mucosa and right mandibular gingiva (the most common site of verrucous carcinoma is the buccal mucosa), measuring 4 cm × 5 cm ( Fig. 73.1 ). On the posterior buccal mucosa, the lesion is a cauliflower, exophytic mass. On the anterior buccal mucosa, the lesion has leukoplakia with surrounding erythema, as well an exophytic pink mass inferior to this leukoplakia. On the right mandibular gingiva, there is a cauliflower exophytic growth measuring 8 mm × 8 mm (can be seen on final specimen on Fig. 73.2 ). The entire buccal mucosa is firm to palpation.

Multifocal verrucous carcinoma of the right buccal mucosa.

The final specimen after wide local excision of right buccal mucosa and rim mandibulectomy was performed.

Imaging

A panoramic radiograph should be obtained to screen for any bony erosion or infiltration and to evaluate the dentition. Although verrucous carcinoma has a low tendency to metastasize, it does represent a malignancy; therefore, formal oncologic staging should be considered. A routine oncologic workup includes an assessment of the extent of locoregional disease using clinical and radiographic modalities (panoramic radiograph, computed tomography [CT] scan of the head and neck, nasopharyngeal laryngoscopy, and chest radiograph or CT). The likelihood of distant disease is remote and can be addressed based on system-driven findings.

In the current patient, a panoramic radiograph demonstrated normal bony anatomy of the jaws. The maxillary sinuses appear clear and have no evidence of widening of the periodontal ligaments or localized resorption of teeth (signs of infiltrative disease processes). A contrast-enhanced CT scan (contrast enhances visualization of soft tissue) of the head and neck was obtained. This showed a mass of the right buccal mucosa. There was no evidence of infiltration or extension of the lesion, and no enlarged lymph nodes (signs of metastatic disease) were noted. Because of the risk of occult malignancy, nasopharyngoscopy was performed. No abnormalities were detected. An anteroposterior chest radiograph revealed mild cardiomegaly and lung hyperinflation (secondary to COPD) but no focal lung lesions indicative of metastatic disease.

Labs

Routine laboratory tests are indicated in the routine workup of verrucous carcinoma as dictated by the medical history. A hemoglobin or hematocrit level may be obtained before the removal of larger lesions. Liver function tests are typically not required because the risk of liver metastasis is extremely low.

Differential diagnosis

Based on the history and clinical examination, verrucous carcinoma can be confused with SCC, as well as a number of white lesions. These different lesions may represent a spectrum of similar diseases. Proliferative verrucous leukoplakia is a diagnosis for lesions that begin as simple hyperkeratosis and spread to other sites, become multifocal, and progress slowly through a spectrum of dysplasia to frank invasive carcinoma. Histologically, the associated dense inflammatory infiltrate may contribute to the occasional misdiagnosis as pseudoepitheliomatous hyperplasia or chronic hyperplastic candidiasis. Small lesions can resemble focal epithelial hyperplasia (Heck disease).

Biopsy

When a diagnosis of verrucous carcinoma is considered, a full-thickness biopsy sample, down to the periosteum or submucosa, must be taken to minimize the possibility of misdiagnosis. Appropriate treatment relies on a good biopsy technique, with attention to including the base of the lesion as part of the specimen. The key in differentiating between benign and malignant lesions is to take a biopsy sample that is both deep (full thickness) and large enough to allow examination of the relationship between the tumor and the underlying connective tissue. On occasion, multiple biopsies may be necessary to diagnose verrucous carcinoma.

Assessment

This is a 68-year-old male with COPD presenting with a multifocal cT3N0 verrucous carcinoma of the right buccal mucosa. For the current patient, under local anesthesia, a full-thickness wedge biopsy sample, including normal tissue, was taken from center of the cauliflower lesion on the posterior buccal mucosa. The tissue was sent for permanent hematoxylin and eosin staining, which showed a thick surface layer of orthokeratinized squamous epithelium with occasional parakeratosis. There were exaggerated, blunt rete pegs extending into the lamina propria, with an intact, well-polarized basal layer and a “pushing border” appearance. The suprabasilar cells were well differentiated. Lymphocytic inflammation was seen throughout the lamina propria with a high degree of keratinization and minimal pleomorphism.

Treatment

Surgical resection is the mainstay of management of verrucous carcinoma of the oral cavity. For treatment planning purposes, preexisting comorbidities; the site, grade, and stage of the tumor; and the effectiveness of the particular therapy and its associated complications should be taken into account.

Because of the superficial, cohesive growth pattern and sharply demarcated margins of this lesion, a number of authors recommend surgical excision as the treatment of choice. Surgery involves wide excision of the primary lesion and surrounding tissues, including bone and muscle when invasion is suspected. Wide surgical excision with 0.5- to 1-cm margins is the recommended treatment for verrucous carcinoma. With adequately treated tumors, the recurrence rate is low. Neck dissections can be performed for clinically N+ necks. However, verrucous carcinoma rarely exhibits regional or distant metastasis, and enlarged lymph nodes, if present on initial examination, tend to be reactive in nature.

Postoperative radiation therapy can be performed for close or positive margins. However, recent studies in oral cavity verrucous carcinoma show no clear survival benefit with postoperative radiation therapy. Palliative radiation may be used in unresectable tumors or in patients not amenable to surgical excision because of comorbidities. Surgery alone with negative margins appears to show optimal survival benefit for patients with oral verrucous carcinoma. Patients should be aware of the risks of mucositis, xerostomia, radiation caries, and osteoradionecrosis of the jaws.

For the current patient, general anesthesia was induced, and nasal endotracheal intubation was performed. The lesion was excised with wide margins (0.5–1 cm) of uninvolved surrounding tissue. A rim mandibulectomy was also performed, which included a rim of the right mandibular bone as well as teeth #28 and #29. The final specimen measured 3.5 cm × 5 cm (see Fig. 73.2 ). The depth of the specimen measured less than 2 mm relative to the surrounding normal mucosa, which included excision to the level of the buccinator fascia. After complete hemostasis was obtained, the wound bed was covered with a 0.015-inch, split-thickness skin graft harvested from the thigh. On the final pathology, the tumor did not invade the bone. Lymphovascular invasion and perineural invasion not identified. The final stage of the specimen was pT3Nx (multifocal) verrucous carcinoma.

Complications

The prognosis is excellent after adequate excision. Complications relate mainly to local destructive effects caused by the tumor itself and its surgical removal. Large lesions can be locally destructive, with invasion or erosion of adjacent tissue and bone. Regional and distant metastasis is exceedingly rare, and clinically, N+ necks are typically reactive on final pathology. Focal areas of invasive SCC are sometimes found within an excised specimen. Those with hybrid features (verrucoid SCC) should be treated similar to conventional SCC.

Discussion

The terms verrucous carcinoma of Ackerman and oral florid papillomatosis have been used to describe verrucous carcinomas occurring within the aerodigestive tract. This is an uncommon tumor; it is diagnosed in 1 to 3 individuals per 1 million people each year and accounts for 2% to 9% of oral cancers. Most patients with verrucous carcinoma are older than age 50 years. (The average age at the time of diagnosis is 65 years.) Males are affected more often than females. Verrucous carcinoma is typically associated with a favorable prognosis, with 5-year survival rates up to 85% (compared with slightly greater than 50% for SCC). Radiation can be used as adjuvant therapy for close or positive margins or unresectable lesions; however, long-term survival rates drop to about 57.6%.

The most common site of verrucous carcinoma is the oral cavity. Verrucous carcinoma most commonly involves the buccal mucosa, the mandibular gingiva alveolar ridge, or the tongue. It typically presents as a nonulcerated, slow-growing, exophytic, “papulonodular” or “warty,” fungating gray or white mass. Less frequently, the roughened, pebbly surface can be inconspicuous, and the tumor can present as a flattened white lesion. It can vary in size from a small patch to a confluent, extensive mass. Verrucous carcinoma can superficially invade the soft tissues and underlying bone structures, becoming fixed to the periosteum. Distant metastasis is exceedingly rare.

The etiology of verrucous carcinoma remains unclear, but tobacco is thought to play a significant role for lesions of the aerodigestive tract. Tobacco smoking and excess alcohol are known risk factors for the development of SCC of the mouth, and they may play a role in the pathogenesis of verrucous carcinoma. Similarities between the morphologic features of verrucous carcinoma and virally infected epithelial lesions suggest a possible etiologic link with human papillomavirus (HPV) infection. HPV types 6, 11, 16, and 18 have been detected to varying degrees in verrucous carcinoma of the oral cavity.

The hallmark of this tumor is the discrepancy between the histologic pattern and the clinical behavior. Microscopically, verrucous carcinoma appears as a papillary or verrucous, low-grade (i.e., well-differentiated) SCC. Verrucous carcinomas typically present clinically as exophytic lesions; they can also present with a mixed or an endophytic growth pattern. Squamous cells display minimal or no dysplasia, with infrequent mitoses localized to the invading (pushing) front. There is an overlying hyperorthokeratosis or parakeratosis, resulting in keratin-filled clefts of the surface epithelium with prominent, bulbous rete processes extending to a uniform distance into the underlying connective tissue; this creates a “pushing border” rather than an infiltrating quality at the base of this tumor. The basement membrane is intact, with little evidence of connective tissue invasion. An intense, mixed inflammatory infiltrate may surround and blend with the tumor, sometimes obscuring the epithelium–connective tissue interface.

As mentioned, verrucous carcinoma is an uncommon tumor that can be seen in the oral cavity. Excision of the tumor should be followed by frequent follow-up evaluations for recurrence and for new-onset SCCs of the upper aerodigestive tract.