Verrucous Carcinoma of the Foot: A Retrospective Study of 19 Cases and Analysis of Prognostic Factors Influencing Recurrence
This study sought to evaluate a cohort of patients with verrucous carcinoma of the foot with special focus on 5 cases of locally recurrent tumors despite negative margins. Nineteen cases of verrucous carcinoma of the foot were identified through the University of Michigan (Ann Arbor, Michigan) pathology database from 1995 to 2019 and were included in demographic and clinical presentation analyses. Sixteen cases were treated at the University of Michigan and are included in the treatment analyses. A review of medical records was conducted to characterize clinical, surgical, and pathologic features. Recurrent cases were found to have a predilection for nonglabrous skin of the foot and great toe. Otherwise, there was little to differentiate outcomes between recurrent and nonrecurrent groups based on demographic, clinical, surgical, or histopathologic data. Recurrent tumors regrew locally and were not associated with histologic progression to conventional squamous cell carcinoma. Verrucous carcinoma of the nonglabrous surface of the foot should have a higher suspicion for possible local recurrence. Recurrence occurs within months of treatment, deserves early biopsy, and warrants aggressive re-treatment. Future directions should include greater examination of pathologic features and genetic markers to improve management of verrucous carcinoma of the foot.
Practice Points
- Clinicians should have a high suspicion for verrucous carcinoma in the setting of a chronic ulceration or warty lesion that is resistant to traditional treatment. Early biopsy with tissue collection of the raised ulcer borders and the deep dermis layer of warty lesions is imperative for diagnosis.
- Verrucous carcinoma originating on the nonglabrous surface of the foot may have a higher rate of recurrence often occurring within months of previous treatment. Patients presenting with nonhealing surgical sites in this area should be treated with a high level of suspicion for recurrence.
Pathology was rereviewed for selected cases, including 2 cases with recurrence and matched primary, 2 cases with recurrence (for which the matched primary was unavailable for review), and 5 representative primary cases that were not complicated by recurrence. Pathology review was conducted in a blinded manner by one of the authors (P.W.H) who is a board-certified dermatopathologist for approximate depth of invasion from the granular layer, perineural invasion, bone invasion, infiltrative growth, presence of conventional squamous cell carcinoma, and margin status.
Statistical analysis was performed when appropriate using an N1 χ2 test or Student t test.
Results
Demographics and Comorbidities—The median age of the patients at the time of diagnosis was 55 years (range, 34–77 years). There were 12 males and 7 females (Table 1). Two patients were Black and 17 were White. Almost all patients had additional comorbidities including tobacco use (68%), alcohol use (47%), and diabetes (47%). Only 1 patient had an autoimmune disease and was on chronic steroids. No significant difference was found between the demographics of patients with recurrent lesions and those without recurrence.
Tumor Location and Clinical Presentation—The most common clinical presentation included a nonhealing ulceration with warty edges, pain, bleeding, and lowered mobility. In most cases, there was history of prior treatment over a duration ranging from 1 to 8 years, with a median of 5 years prior to biopsy-based diagnosis (Table 1). Six patients had a history of osteomyelitis, diagnosed by imaging or biopsy, within a year before tumor diagnosis. The size of the primary tumor ranged from 2.4 to 6 cm, with a mean of 4 cm (P=.20). The clinical presentation, time before diagnosis, and size of the tumors did not differ significantly between recurrent and nonrecurrent cases.
The tumor location for the recurrent cases differed significantly compared to nonrecurrent cases. All 5 of the patients with a recurrence presented with a tumor on the nonglabrous part of the foot. Four patients (80%) had lesions on the dorsal or lateral aspect of the great toe (P=.002), and 1 patient (20%) had a lesion on the low ankle (P=.09)(Table 1). Of the nonrecurrent cases, 1 patient (7%) presented with a tumor on the plantar surface of the great toe (P=.002), 13 patients (93%) presented with tumors on the distal plantar surface of the foot (P=.0002), and 1 patient with a plantar foot tumor (Figure 1) also had verrucous carcinoma on the thumb (Table 1 and Figure 2).
Histopathology—Available pathology slides for recurrent cases of verrucous carcinoma were reviewed alongside representative cases of verrucous carcinomas that did not progress to recurrence. The diagnosis of verrucous carcinoma was confirmed in all cases, with no evidence of conventional squamous cell carcinoma, perineural invasion, extension beyond the dermis, or bone invasion in any case. The median size of the tumors was 4.2 cm and 4 cm for nonrecurrent and recurrent specimens, respectively. Recurrences displayed a trend toward increased depth compared to primary tumors without recurrence (average depth, 5.5 mm vs 3.7 mm); however, this did not reach statistical significance (P=.24). Primary tumors that progressed to recurrence (n=2) displayed similar findings to the other cases, with invasive depths of 3.5 and 5.5 mm, and there was no evidence of conventional squamous cell carcinoma, perineural invasion, or extension beyond the dermis.
Treatment of Nonrecurrent Cases—Of the 16 total cases treated at the University of Michigan, surgery was the primary mode of therapy in every case (Tables 2 and 3). Of the 11 nonrecurrent cases, 7 patients had wide local excision with a dermal regeneration template, and delayed split-thickness graft reconstruction. Three cases had wide local excision with metatarsal resection, dermal regeneration template, and delayed skin grafting. One case had a great toe amputation
