Original Research

Verrucous Carcinoma of the Foot: A Retrospective Study of 19 Cases and Analysis of Prognostic Factors Influencing Recurrence

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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.



Verrucous carcinoma is a rare cancer with the greatest predilection for the foot. Multiple case reports with only a few large case series have been published. 1-3 Plantar verrucous carcinoma is characterized as a slowly but relentlessly enlarging warty tumor with low metastatic potential and high risk for local invasion. The tumor occurs most frequently in patients aged 60 to 70 years, predominantly in White males. 1 It often is misdiagnosed for years as an ulcer or wart that is highly resistant to therapy. Size typically ranges from 1 to 12 cm in greatest dimension. 1

The pathogenesis of plantar verrucous carcinoma remains unclear, but some contributing factors have been proposed, including trauma, chronic irritation, infection, and poor local hygiene.2 This tumor has been reported to occur in chronic foot ulcerations, particularly in the diabetic population.4 It has been proposed that abnormal expression of the p53 tumor suppressor protein and several types of human papillomavirus (HPV) may have a role in the pathogenesis of verrucous carcinoma.5

The pathologic hallmarks of this tumor include a verrucous/hyperkeratotic surface with a deeply endophytic, broad, pushing base. Tumor cells are well differentiated, and atypia is either absent or confined to 1 or 2 layers at the base of the tumor. Overt invasion at the base is lacking, except in cases with a component of conventional invasive squamous cell carcinoma. Human papillomavirus viropathic changes are classically absent.1,3 Studies of the histopathology of verrucous carcinoma have been complicated by similar entities, nomenclatural uncertainty, and variable diagnostic criteria. For example, epithelioma cuniculatum variously has been defined as being synonymous with verrucous carcinoma, a distinct clinical verrucous carcinoma subtype occurring on the soles, a histologic subtype (characterized by prominent burrowing sinuses), or a separate entity entirely.1,2,6,7 Furthermore, in the genital area, several different types of carcinomas have verruciform features but display distinct microscopic findings and outcomes from verrucous carcinoma.8

Verrucous carcinoma represents an unusual variant of squamous cell carcinoma and is treated as such. Treatments have included laser surgery; immunotherapy; retinoid therapy; and chemotherapy by oral, intralesional, or iontophoretic routes in select patients.9 Radiotherapy presents another option, though reports have described progression to aggressive squamous cell carcinoma in some cases.9 Surgery is the best course of treatment, and as more case reports have been published, a transition from radical resection to wide excision with tumor-free margins is the treatment of choice.2,3,10,11 To minimize soft-tissue deficits, Mohs micrographic surgery has been discussed as a treatment option for verrucous carcinoma.11-13

Few studies have described verrucous carcinoma recurrence, and none have systematically examined recurrence rate, risk factors, or prognosis.3,9,14 In our retrospective review of 19 new cases of verrucous carcinoma of the foot, we examined 5 recurrent tumors despite negative margin surgical resection and report risk factors and surgical management of these lesions.


Patient cases were identified through the University of Michigan (Ann Arbor, Michigan) pathology database from 1995 to 2019 based on the primary diagnosis of verrucous carcinoma located on the foot. Nineteen cases were identified and were included in demographic and clinical presentation analyses. Medical records were reviewed to abstract selected clinical data and outcomes of analysis.

Of the 19 cases, 16 were treated at the University of Michigan and are included in the treatment analyses. Specific attention was then paid to the cases with a clinical recurrence despite negative surgical margins. We compared the clinical and surgical differences between recurrent cases and nonrecurrent cases.


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