When Pedal Verruca Vulgaris is Actually Verrucous Carcinoma

Verruca vulgaris, commonly known as a cutaneous wart, is an epidermal proliferation that forms firm rough papules, or nodules, that are benign in nature. These cutaneous warts are caused by human papillomavirus (HPV), a group of non-enveloped, double-stranded DNA viruses that specifically target and invade human epithelial cells and mucosal membranes.^1-5 Clinically, patients may present with hyperkeratotic warts with thrombosed capillaries, disrupting the normal skin lines/folds. Histopathologic findings of warts include hyperkeratosis of stratum corneum, koilocytotic changes of the superficial epidermal layers, and thickening of epidermis, forming fingerlike projections of epidermal layer, also known as papillomatosis, which serves as a hallmark histological feature of verruca vulgaris.^1-5
 
Generally, warts are benign. However, reports describe infrequent malignant transformation of these lesions to verruca carcinoma. Given the rarity of this carcinoma, it is frequently misdiagnosed and initially treated as a benign verruca vulgaris lesion. In previous case reports, there was an average 6-year delay in diagnosis of the malignant lesion.⁶ In this article, we share a relevant case and aim to provide insight into to a multidisciplinary approach for a proper diagnosis and treatment for this malignant tumor.

Evaluating a Rapidly Growing Interdigital Mass

A 36-year-old male with no significant past medical history initially presented to the hospital with left fifth-digit pain secondary to a rapidly growing mass (see Figure 1A and Figure 1B). He first noticed a fissure in the left fourth interspace about 6 months prior to initial evaluation, and with time, he noted a rapidly growing soft tissue mass extending circumferentially along the plantar aspect of the fifth digit, measuring 2.3 x 1.6 x 1.8 cm. He had difficulty with certain shoe gear and increased pain with ambulation. Initial radiographs were negative for osseous involvement (see Figure 2). Our initial diagnoses included either verruca vulgaris or verruca carcinoma. Given the patient’s lack of insurance, outpatient follow up with podiatry and dermatology were recommended for further evaluation.
 
The patient followed up as an outpatient with continued pain. Given the suspicion for malignancy, magnetic resonance imaging (MRI) was recommended; however, the MRI could not be performed due to a retained bullet, so a computed tomography (CT) scan was ordered. The CT scan demonstrated an attenuating, fungating, exophytic mass along the medial base of the fifth digit at the level of the proximal interphalangeal joint that abuts the underlying flexor tendon, and the tendon was not separable from the mass. There was no osseous destruction or periosteal reaction adjacent to the aforementioned mass. Based on the concern for malignancy, two 4-mm skin-punch biopsies were performed in the outpatient setting. The initial pathology reading was verruca vulgaris without carcinoma. However, due to the superficial nature of the biopsy, verrucous carcinoma cannot be ruled out.
 
The patient also followed up with a dermatologist who performed a deeper shave biopsy, which again suggested verruca vulgaris. Based on these findings, we were still not satisfied with the biopsy results. Therefore, we recommended the patient see surgical oncology, who also felt that the lesion was malignant. Thus, we made a joint decision to surgically excise the mass. A left partial fifth ray amputation was performed with a 1 cm margin of skin between the soft tissue mass and healthy skin (see Figure 3). Intraoperatively, a fresh-frozen specimen was obtained, which revealed clean, soft tissue margins with no evidence of tumor. The pathology report revealed verrucous carcinoma with no osseous involvement and no further visible tumors or malignant lesions in the soft tissue margins surrounding the lesion. Given these results, surgical oncology determined that the patient would require no further surgical excision and recommended close follow-up for skin cancer surveillance with a PET/CT scan to evaluate for metastasis.

Verrucous Carcinoma: What You Should Know

Verrucous carcinoma is a slow-growing, locally destructive tumor of the epidermis and is classified as a well-differentiated, squamous cell malignancy. Clinically, this malignancy appears as an irregularly shaped, exophytic, well-demarcated soft tissue mass.^1-6 Risk factors for developing verrucous carcinoma include: chronic exposure to ultraviolet light, radiation, tobacco use, and presence of plantar warts secondary to human papilloma virus.^1-3,7-10 If a verrucous carcinoma is suspected, then first-line treatment should include a punch biopsy of the lesion with an adequate depth to into the basal layer of the epidermis.^1-3,7-10 If the biopsy is too superficial, a false negative could result. The literature cites MRI as an aid in differentiating benign and malignant lesions; however, this imaging study could not be ordered for the patient due to a retained metallic foreign body.^8,9 The gold standard of treatment includes wide local excision of the lesion with clean margins, possibly supplemented with a reconstructive skin flap or skin grafting for soft tissue coverage. Extensive soft tissue compromise may require a partial or total amputation of the foot.⁷

Our case report highlights the importance of accurate diagnosis along with a high index of clinical suspicion for malignancy, regardless of negative skin biopsies, as seen in the case of this healthy, 36-year-old male. Given the ambiguous pathology results and the clinical appearance of the lesion, a multidisciplinary team of surgical services determined that the best course of treatment for the patient was a wide, local excision of the lesion with 1 cm of safety margins. Due to the extensive nature of the lesion, and significant soft tissue defect of the fifth digit that remained after lesion excision, a left partial fifth ray amputation was performed. The pathology results confirmed the presence of verruca carcinoma that was previously missed during outpatient biopsies. Surgical services such as podiatry, dermatology, and surgical oncology provided multidisciplinary care to ensure prompt treatment for the patient’s challenging case. We hope this case report adds to the body of knowledge in the literature.

Dr. Fils-Aime is a second-year resident at the Temple University Hospital Podiatric Surgical Residency Program in Philadelphia.

Dr. Mateen is a fellow in Foot and Ankle Deformity Correction and Orthoplastics at the Rubin Institute Advanced Orthopedic International Center for Limb Lengthening in Baltimore.  

Dr. Pontious is a Clinical Professor in the Department of Podiatric Surgery at Temple University School of Podiatric Medicine in Philadelphia.

References
1.     Al Aboud AM, Nigam PK. Warts. In: StatPearls. NCBI Bookshelf version. StatPearls Publishing: 2022. Accessed October 13, 2022. https://www.ncbi.nlm.nih.gov/books/NBK431047/
2.     Goldstein B, Goldstein A, Morris-Jones R. Cutaneous warts (common, plantar, and flat warts). UpToDate. https://www.uptodate.com/contents/cutaneous-warts-common-plantar-and-flat-warts. October 29, 2021. Updated May 24, 2022. Accessed April 13, 2022.
3.     Muršić I, Vcev A, Kotrulja L, et al. Treatment of verruca vulgaris in traditional medicine. Acta Clin Croat. 2020;59(4):745-750. doi:10.20471/acc.2020.59.04.22
4.     Ural A, Arslan S, Ersoz S, Deger B. Verruca vulgaris of the tongue: A case report with a literature review. Bosn J Basic Med Sci. 2014;14(3):136. doi:10.17305/bjbms.2014.3.29
5.     Witchey DJ, Witchey NB, Roth-Kauffman MM, Kauffman MK. Plantar warts: Epidemiology, pathophysiology, and clinical management. J Am Osteopath Assoc. 2018;118(2):92. doi:10.7556/jaoa.2018.024
6.     Wright PK, Vidyadharan R, Jose RM, Rao GS. Plantar verrucous carcinoma continues to be mistaken for verruca vulgaris. Plast Reconstr Surg. 2004;113(3):1101-1103. doi:10.1097/01.prs.0000107744.60818.e9
7.     Potter BK, Pitcher JD, Adams SC, Temple HT. Squamous cell carcinoma of the foot. Foot Ankle Int. 2009;30(6):517-523. doi:10.3113/FAI.2009.0517
8.     Chen CK, Wu HT, Chiou HJ, et al. Differentiating benign and malignant soft tissue masses by magnetic resonance imaging: Role of Tissue Component Analysis. J Chin Med Assoc. 2009;72(4):194-201. doi:10.1016/S1726-4901(09)70053-X
9.     Chung WJ, Chung HW, Shin MJ, et al. MRI to differentiate benign from malignant soft-tissue tumours of the extremities: A simplified systematic imaging approach using depth, size and heterogeneity of signal intensity. Br J Radiol. 2012;85(1018):e831-e836. doi:10.1259/bjr/27487871
10.  Knackfuss I, Giordano V, Goody-Santos A, Fernandes NC, Camargo O. Squamous cell carcinoma in the foot: Case series and literature review. Acta Ortop Bras. 2018;26(2):108-111. doi:10.1590/1413-785220182602187183