Practice Essentials
Verrucous carcinoma is a relatively uncommon, locally aggressive, clinically exophytic, low-grade, slow-growing, well-differentiated squamous cell carcinoma with minimal metastatic potential.
Verrucous carcinoma may involve the oral cavity, larynx, anogenital region, plantar surface of the foot, and, less commonly, other cutaneous sites. See the image below.
Verrucous carcinoma; an exophytic and hyperkeratotic mass that discharged malodorous debris through several sinus tracts. Courtesy of J García-Gavín, D González-Vilas, L Rodríguez-Pazos, D Sánchez-Aguilar, and J Toribio, via Wikimedia Commons.
In 1948, Ackerman first described verrucous carcinoma in the oral cavity as a low-grade tumor that generally is considered a clinicopathologic variant of squamous cell carcinoma. [1] Aird et al first described cutaneous verrucous carcinoma (carcinoma cuniculatum) in 1954, and it was named as such because of its characteristic cryptlike spaces on histology. [2]
Pathophysiology
The pathogenesis of verrucous carcinoma is not yet fully elucidated. [3] Leading theories include human papillomavirus (HPV) infection (oral cavity, anogenital region, plantar foot, and a small subset of cutaneous verrucous carcinoma), [4] chemical carcinogenesis induced by smoking and chewing tobacco, [5] alcohol consumption and betel nut chewing (oral lesions), and chronic inflammation. Schistosomiasis is associated with verrucous carcinoma of the bladder. [6]
Signs and symptoms
Verrucous carcinoma manifests as a cauliflowerlike, exophytic mass that typically develops at sites of chronic irritation and inflammation. Verrucous carcinoma is slow growing, but may display locally aggressive behavior. Penetration into the skin, fascia, and even bone has been reported; however, verrucous carcinoma has low metastatic potential. [7]
Also see Physical Examination.
Diagnostics
Computed tomography or magnetic resonance imaging may be used to demonstrate the exact location and extent of the verrucous carcinoma for preoperative staging and surgical planning.
A skin biopsy is always required for definitive diagnosis of verrucous carcinoma, despite the fact that the diagnosis is suspected strongly on clinical grounds.
Biopsy is performed routinely in the physician's office using a local anesthetic.
All skin biopsy specimens obtained to diagnose verrucous carcinoma must reach at least the depth of the mid dermis to allow for determination of the presence or absence of invasive disease.
A deep (scoop) shave biopsy, a punch biopsy, an incisional biopsy, or an excisional biopsy may be performed.
Pathology readings preferably are made by a dermatopathologist who has extensive experience with verrucous carcinoma.
Histologic findings
Regardless of site of origin, verrucous carcinomas share the same histologic features. Verrucous carcinoma of all types may resemble a verruca superficially, with hyperkeratosis, parakeratosis, acanthosis, papillomatosis, and granular cell layer vacuolization. A characteristic feature is the blunt projections of well-differentiated epithelium surrounded by edematous stroma and chronic inflammatory cells that extend into the dermis, sometimes forming sinuses filled with keratin. Cutaneous verrucous carcinomas may be confused with warty carcinomas, but the higher-grade cytological atypia and the more infiltrative growth pattern of warty carcinomas can help to differentiate.
Also see Staging.
Treatment
See Surgical Care.
Long-term monitoring
Verrucous carcinoma usually is cured with appropriate therapy. However, recurrence of cutaneous carcinoma with clear surgical margins has been reported. In addition, patients with a history of verrucous carcinoma should be evaluated with regular skin examinations at 3- to 12-month intervals.
Prevention
Patients should be encouraged to refrain from tobacco use and excessive alcohol use. Patients in the appropriate age range (11 or 12 to 26 years) should receive human papillomavirus vaccination. [8]
Etiology
HPV may play a role in the development of verrucous carcinoma. HPV types 6 and 11 are most frequently associated with the Buschke-Löwenstein tumor. [9] In plantar lesions, HPV type 16 has been reported. [10] Finally, HPV type 33 has been reported in a verrucous carcinoma of the scalp. [4]
Despite the presence of HPV strains within some lesions of verrucous carcinoma, a causal relationship has not been proven and remains controversial. [11, 12]
Inflammation appears to sometimes play a role in the development of verrucous carcinoma. For instance, cutaneous verrucous carcinoma may develop at sites of inflammation or scarring such as decubitus ulcers or areas affected by hidradenitis suppurativa. [9, 13] In addition, lichen sclerosus may predispose patients to the development of penile verrucous carcinomas. [14] Similarly, verrucous carcinomas of the oral cavity have been reported to develop in patients with long-standing oral ulcerative lichen planus and chronic candidiasis.
Associations in oral verrucous carcinoma have been found in patients who chewed or inhaled tobacco and betel nuts, dipped snuff, and/or consumed alcohol. Lesions developed at the sites where tobacco was habitually placed in the mouth. [15]
Furthermore, oral verrucous carcinoma is associated with poor dental hygiene, ill-fitting dentures, and low socioeconomic status. Oral verrucous carcinoma has a higher incidence in males and in immunocompromised patients. [15]
Schistosomal infection often is coexistent with verrucous carcinoma of the bladder. [6]
Epidemiology
The incidence of verrucous carcinoma in the United States and worldwide is unknown. [16]
Verrucous carcinoma is reported predominantly in Whites. Verrucous carcinoma primarily affects men, except for tumors arising in the oral cavity, which are more common among women. [17]
Verrucous carcinoma generally occurs in middle-aged (50s) patients [16] ; however, the anogenital type of verrucous carcinoma has been reported to develop in men aged 18-86 years. [9]
Prognosis
Overall, patients with verrucous carcinoma have a favorable prognosis, although the course of verrucous carcinoma lesions is characterized by slow, continuous, local growth. Morbidity results from local skin and soft-tissue destruction and, occasionally, from perineural, muscle, and even bone invasion. The development of distant metastases is rare. Verrucous carcinoma mortality usually is due to local invasion rather than metastatic spread.
In most cases of verrucous carcinomas, regardless of the variant, the clinical outcome is rarely an aggressive course. Local verrucous carcinoma recurrence following definitive treatment is not uncommon. Regarding oral verrucous carcinoma, the reported recurrence rate ranges from 6-40%. If metastasis does occur, it is mainly at the regional lymph nodes. [15] There have been reports of metastases in distant sites, but this is considered rare. In long-standing lesions, occasional destruction of adjustment structures such as cartilage, tendons, and bones can occur. Patients with oral verrucous carcinoma may be at an increased risk of a second primary oral squamous cell carcinoma, which carries a poor prognosis.
Patient Education
Advise patients about the importance of receiving effective treatment for areas of chronic skin inflammation or trauma (eg, leg or decubitus ulcers) to prevent these problems from developing malignancies within them. Improved oral, genital, and perianal hygiene may help to prevent inflammatory conditions that predispose patients to verrucous carcinoma. Cessation of chewing tobacco use may help to prevent oral verrucous carcinoma.
-
Verrucous carcinoma; an exophytic and hyperkeratotic mass that discharged malodorous debris through several sinus tracts. Courtesy of J García-Gavín, D González-Vilas, L Rodríguez-Pazos, D Sánchez-Aguilar, and J Toribio, via Wikimedia Commons.
