Epithelioma Cuniculatum (Plantar Verrucous Carcinoma): A Systematic Review of Treatment Options
Epithelioma cuniculatum (EC) is a subtype of verrucous carcinoma (VC) that affects the feet. Treatment involves complete tumor removal by wide local excision (WLE) or Mohs micrographic surgery (MMS). Extensive local destruction may require amputation. We sought to compare reported treatment methods for EC and determine their efficacy by assessing for tumor recurrence and treatment-associated complications. A systematic review of the literature spanning multiple databases was performed. To date, surgical excision is recommended as the standard of care for treatment of EC, with amputation considered in more advanced cases. Mohs micrographic surgery appears to be a promising treatment modality for EC and may have lower recurrence rates than WLE but requires further investigation.
Practice Points
- Because of its slow-growing nature and propensity for local invasion and recurrence, diagnosis of epithelioma cuniculatum (EC) often is delayed and therefore can be associated with notable morbidity.
- Wide local excision with 5-mm to 1-cm margins is considered standard of care and is the most commonly reported treatment of EC. Amputation may be required in cases with extensive local destruction.
- Mohs micrographic surgery is a viable option for treatment of EC, with more recent cases suggesting favorable outcomes regarding recurrence rates.
Other Treatment Modalities—Three cases utilized imiquimod, with 2 cases of imiquimod monotherapy and 1 case of imiquimod in combination with electrodesiccation and WLE.37 One of the cases of EC treated with imiquimod monotherapy recurred and required WLE.61
There were reports of other treatments including curettage alone (2% [2/115]),40,62 debridement alone (1% [1/115]),40 electrodesiccation (1% [1/115]),37 and radiation (1% [1/115]).43 Recurrence was found with curettage alone and debridement alone. Electrodesiccation was reported in conjunction with WLE without recurrence. Radiation was used to treat a case of VC that had metastasized to the lymph nodes; no follow-up was described.43
COMMENT
Epithelioma cuniculatum is an indolent malignancy of the plantar foot that likely is frequently underdiagnosed or misdiagnosed because of location, sampling error, and challenges in histopathologic diagnosis. Once diagnosed, surgical removal with margin control is the first-line therapy for EC. Our review found a number of surgical, systemic, and other treatment modalities that have been used to treat EC, but there remains a lack of evidence to provide clear guidelines as to which therapies are most effective. Current data on the treatment of EC largely are limited to case reports and case series. To date, there are no reports of higher-quality studies or randomized controlled trials to assess the efficacy of various treatment modalities.
Our review found that WLE is the most common treatment modality for EC, followed by amputation and MMS. Three cases43-45 that reported metastasis to lymph nodes also were treated with fine-needle aspiration or biopsy, and it is recommended that sentinel lymph node biopsy be performed when there is a history of radiation exposure or clinically and sonographically unsuspicious lymph nodes, while dissection of regional nodes should be performed if lymph node metastasis is suspected.53 Additional treatments reported included acitretin, interferon alfa, topical imiquimod, curettage, debridement, and electrodesiccation, but because of the limited number of cases and variable efficacy, no conclusions can be made on the utility of these alternative modalities.
The lowest rate of reported recurrence was found with amputation, followed by MMS and WLE. Amputation is the most aggressive treatment option, but its superiority in lower recurrence rates was not statistically significant when compared with either WLE or MMS after Yates correction. Despite treatment with radical surgery, recurrence is still possible and may be associated with factors including greater size (>2 cm) and depth (>4 mm), poor histologic differentiation, perineural involvement, failure of previous treatments, and immunosuppression.63 No statistically significant difference in recurrence rates was found among surgical methods, though data trended toward lower rates of recurrence with MMS compared with WLE, as recurrence with MMS was only reported in 2 cases.25,56
The efficacy of MMS is well documented for tumors with contiguous growth and enables maximum preservation of normal tissue structure and function with complete margin visualization. Thus, our results are in agreement with those of prior studies,54-56,64 suggesting that MMS is associated with lower recurrence rates for EC than WLE. Future studies and reporting of MMS for EC are particularly important because of the functional importance of the plantar foot.
It is important to note that there are local and systemic risk factors that increase the likelihood of developing EC and facilitate tumor growth, including antecedent trauma to the lesion site, chronic irritation or infection, and immunosuppression (HIV related or iatrogenic medication induced). These risk factors may play a role in the treatment modality utilized (eg, more aggressive EC may be treated with amputation instead of WLE). Underlying patient comorbidities could potentially affect recurrence rates, which is a variable we could not control for in our analysis.
Our findings are limited by study design, with supporting evidence consisting of case reports and series. The review is limited by interstudy variability and heterogeneity of results. Additionally, recurrence is not reported in all cases and may be a source of sampling bias. Further complicating the generalizability of these results is the lack of follow-up to evaluate morbidity and quality of life after treatment.
CONCLUSION
This review suggests that MMS is associated with lower recurrence rates than WLE for the treatment of EC. Further investigation of MMS for EC with appropriate follow-up is necessary to identify whether MMS is associated with lower recurrence and less functional impairment. Nonsurgical treatments, including topical imiquimod, interferon alfa, and acitretin, may be useful in cases where surgical therapies are contraindicated, but there is little evidence to support these treatment modalities. Treatment guidelines for EC are not established, and appropriate treatment guidelines should be developed in the future.
