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Introduction

A rare low grade and uncommon variant of a cutaneous squamous cell carcinoma (cSCC or SCC) is a verrucous squamous cell carcinoma (VSCC), also known as verrucous carcinoma (VC).^1,2 It gradually increases in size taking on a warty tumor like appearance.² Dr Ackerman, a professor of dermatology from Berlin, first described this type of lesion in two patients in 1896.³ Buschke, a professor of pathology, and his assistant Loewenstien described the lesions in the perianal or genital area in 1925.² In 1948 Dr Ackerman described these lesions in the oral cavity in 31 patients.⁴ He was the first to use the term verrucous carcinoma describing local exophytic SCC lesions that increased in size in the buccal mucosa, rarely bleeding. In 1954 Aird and colleagues⁵ published on three patients with lesions on their feet termed “epithelioma cuniculatum,” more commonly known as verucous carcinoma of the skin. The lesions can occur anywhere on the skin and mucosa, the most common sites being the soles of the feet, oropharynx and genitalia.^6,2 The name of the lesion varies according to the anatomical location, oral florid papillomatosis derives in the oropharynx, giant condyloma acuminata also known as Buschkle-Loewenstien occurs in the anorectal region and verrucous carcinoma on the plantar aspect of the foot.^2,7 Regardless of the name they all are representative of the same pathological condition.² The lesions slowly enlarge to take on a wart-like appearance. There is local invasion of the soft tissue which can be deep, however, bony involvement is rare.⁷ The incidence of metastases is also rare and, as such, the survival rate is high.^8,9,10 The reported incidence is most commonly in Caucasian males in their sixth to seventh decade.^8,11 Human papilloma virus (HPV) and abnormal expression of the p53 tumor suppressor protein are thought to be a potential cause for the pathogenesis of verrucous carcinoma.¹² People with diabetes and chronic foot ulceration are at risk of developing VC¹³. Although rare, VC is a known complication in the setting of a person with a high-risk foot and underlying diabetes and can occur in previous amputation sites.¹³ The challenge is that it can often be misdiagnosed as Verrucous hyperplasia (VH), as both lesions have a similar appearance. The only way to differentiate is by histopathology and this can lead to a delay in appropriate and definitive treatment.^6,13,14 Vigilance is required as the VC can reoccur if there has been insufficient excision of the neoplasm.⁷ Causative factors suggested including poor local hygiene, chronic infection, chronic diabetic foot ulcerations and multiple co-morbidities.^8,15 The authors present a challenging case of a verrucous carcinoma in a previously healed amputation site. Although there was a high index of suspicion for a VC, there was a delay in a definitive diagnosis. This was due to the lesion clinically having a similar appearance to VH. Earlier diagnosis may have negated the need for extensive debridement and preserved the function of his foot.

Case report

The patient was a 60-year-old Caucasian male with a history of type two diabetes mellitus, peripheral neuropathy, hypertension and gastroesophageal reflux disease. He was a smoker (15 per day for many years). He did not have underlying peripheral arterial disease (in an arterial duplex scan no stenosis was identified from the level of the common femoral to ankle). Three vessels run off to the ankle with palpable pedal pulses. His initial presentation was to the emergency department in April 2018 with right hallux osteomyelitis (OM), which required amputation (Figure 1). On discharge he was followed up in the Multidisciplinary Foot Ulcer Clinic (MDFUC). The MDFUC is situated within a large tertiary teaching hospital in Perth, Western Australia. The service consists of podiatrists, vascular surgeons, infections disease (ID) physicians, wound management nurse practitioners (WMNP), endocrinologists and an orthotist. When required, orthopedic and plastic surgeons are consulted on a case-by-case basis. The MDFU clinic has accreditation with the National Association of Diabetes Centres’ Centre of Excellence program for Interdisciplinary High Risk Foot Services. The team conducts two formal ward rounds together per week providing a comprehensive inpatient service.

On discharge the patient was treated for residual OM as his intraoperative proximal bone samples were positive for Enterobacter cloacae and Cornyebacterium, he was treated with a prolonged course of intravenous antibiotics via a peripherally inserted central catheter (PICC) and then oral antibiotics. The wound was slow to heal requiring ultrasonic debridement¹⁶ by the WMNP. The wound took eight months to heal. He developed callus over the first metatarsal head (MT) requiring regular sharp debridement by the podiatry team.

At a routine podiatry appointment in May 2019, he presented with dactylitis of his right second toe which required elective interphalangeal amputation for confirmed OM on X-ray. The amputated second toe site healed (Figure 2) however the area of callus over the first MT head ulcerated and became infected requiring surgical debridement and excision of the MT in June 2020 (Figure 3). This wound never healed and deteriorated to the point where in August 2020 he presented to the emergency department with a septic foot with a large collection of pus and necrotic tissue tracking along the plantar aspect and in between his first and second MT to the dorsum of his foot. He also had OM in the residual parts of the first and second MT requiring urgent surgical debridement and resection (Figure 4). He was septic with a disseminated multisite methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia and required intensive care unit (ICU) support. During his ICU admission he required an arthroscopic washout for a septic knee and incision and drainage of his left-hand dorsal infected tenosynovitis. He developed aortic valve endocarditis with severe aortic regurgitation and a left frontal lobe abscess. He was transferred to another facility for burrhole drainage of an intercranial abscess. He returned to theatre on five occasions for further drainage of a recurrent intracerebral abscess. In late September 2020 he had an aortic valve replacement with a trifecta bioprosthesis. Due to the frontal abscess, he needed cognitive retraining with an occupational therapist. He also developed sensorineural hearing loss (SNHL) and as a result had insertion of a cochlear implant. He eventually was able to return to work as an electrician.

 

Figure 4. August 2020

 

He returned to our MDFU clinic and was also regularly followed up by the podiatry team. The wound never fully healed with thick callus overlying the scar tissue regrowing significantly despite monthly podiatry appointments for sharp debridement. He also had a significant foot deformity, the third toe dislocated and medially deviated. Offloading modalities included a removeable cast walker (CAM boot) with custom orthosis, medical grade footwear by Darco^®. As this gentleman was living alone with stairs to his house and still driving, he declined higher level offloading. The wound at that point in time was reasonably superficial, he had palpable pedal pulses. In late 2022 he was developing repeated soft tissue infections and a white cell/bone scan demonstrated chronic OM for which the ID team continued long term oral antibiotics. During 2023 and early 2024 he was reviewed regularly, however, the wound deteriorated. To facilitate wound healing a trial of a total contact cast (TCC) was attempted. However, after one application he developed a soft tissue infection and significant friction from the cast and as result he required a brief hospital admission.

By July 2024 the wound was atypical in appearance (Figure 5). The wound bed was friable, and bled easily with unhealthy tissue, increase in exudate, and it was malodourous, demonstrating clinical signs of a soft tissue infection.¹⁷ There was a high index of clinical suspicion for malignant changes, and at his MDFU appointment a 3mm punch biopsy was performed. The results were inconclusive as the tissue sample was not deep enough. A repeat biopsy was performed late July 2024. Again this biopsy was also too superficial for histopathological diagnosis but was noted to be ‘clinically concerning’ with a ‘viral aetiology’. A white cell/bone scan demonstrated progression of the OM. Prior to any further surgery, he was counselled by his vascular surgeon that if the wound did not heal, he may require a major limb amputation. In August 2024 he had his right second MT shortening and completion forefoot amputation (Figure 6). Deep tissue was sent for histopathology and demonstrated VC, nevertheless the histopathological results showed that this was not f ully excised (Figure 7). He was, therefore,referred to a plastic surgeon for advice. This occurred in October 2024. The surgeon recommended more aggressive excision with at least 5mm wider than the suspected margins. Prior to the next procedure he was again readmitted from a routine MDFU appointment with a soft tissue infection despite being on oral antibiotics. This subsequent debridement and excision was performed in late November 2024 by a vascular surgeon, with clear margins confirmed on histopathology. He was discharged home (Figure 8) with negative pressure wound therapy (NPWT). He was closely monitored in a specialist wound clinic and MDFU clinic. In January 2025 the foot was well perfused with palpable pedal pulses, despite this the wound was stagnant not demonstrating clinical signs of wound healing. The possibility of a major limb amputation was rediscussed which he agreed to. While waiting for the amputation he continued to be monitored in a specialist wound clinic. The wound surprising granulated to the epidermal margin and in April 2025 he had a split skin graft (Figure 9). At the time of writing this paper, clinically the VC has returned (Figure 10 and 11) with the wound margins taking on a wart-like appearance. A major limb amputation has been rediscussed, and the  patient has agreed. At all times during the patient’s journey he was included in the decision-making process. The patient himself has expressed that he has always felt very supported both physically and psychologically and that he has confidence in the team caring for him.

 

Figure 5. July 2024

 

Figure 6. August 2024

 

Figure 7. November 2024

 

Figure 8. April 2025

 

Figure 9. June 2025

 

Figure 10. June 2025

 

Figure 11. June 2025

 

Discussion

Verrucous carcinoma is a rare, low-grade variation of a well differentiated squamous cell carcinoma.¹⁸ The tumor gradually increases in size and typically takes on a wart-like appearance, metastases is a rare occurrence, and the survival rate is high.^18-20 The most common anatomical location is on weight bearing areas such as the metatarsal region of the foot, areas exposed to trauma during ambulation and over previous amputation sites of the foot.^7,13,18,21­ The lesions can invade the plantar fascia and can cause destruction of the metatarsal bones, although this is a rare occurrence.^22,23 Plain film radiography should be performed to exclude bony involvement.²⁴ Chronic irritation and inflammation have a role in the pathogenies of VC, as does HPV and abnormal expression of the p53.^6,12,11 It predominantly affects Caucasian males aged 60–70 years.²⁵ Poor hygiene and tobacco use may also contribute to the pathogenesis.^8,20 Interestingly, the lesions can reoccur after attempts to excise the lesions.^7,11 There can be a delay in diagnosis as the lesions present like verruca plantaris, actinomycosis, pseudoepitheliomatous hyperplasia and plantar fibromatosis.^2,18,26 The lesions grow slowly with a wart-like appearance, therefore, there can be a low index of clinical suspicion for a malignant lesion.²¹ Clinicians need to be aware of the potential for malignant lesions and ensure a biopsy is taken in a timely manner. In our case the wound although unhealthy and atypical in appearance (Figure 5) and did not have a classical wart-like appearance, which may have led to a delay in investigation and subsequent surgical intervention. There is no clear linkage between the patient’s ICU admission and the development of VC as there was a four year time gap.

What is crucial is a biopsy taken correctly for histopathology to minimise false negative results, to avoid delays in diagnosis and appropriate treatment.^2,27 Having said this, there are no clear guidelines in the literature as to when a biopsy should be performed.^18,27 The biopsy must include the deep dermis and subcutaneous tissue including the wound edge. Tissue from the wound bed will not provide any useful information and will mainly show reparative and secondary findings. Verrucous vulgaris is also represented in superficial portions of tissue.¹⁸ The preferred biopsy technique is a incisional biopsy.²⁸ However, in an outpatient setting a 3mm punch biopsy can also be undertaken by an appropriately trained clinician.²⁶ If staff do not have the appropriate training in collecting a punch biopsy a referral to dermatology is recommended. The skin is prepared by cleansing with an antiseptic solution. If the patient does not have an insensate foot, then infiltration with a local anesthetic agent is recommended. The instrument is pressed onto the skin and rotated to ensure both dermal and subcutaneous tissue is taken. Remove the biopsy instrument and use forceps and scissors to gently remove the tissue. The sample is placed in formalin, each sample is labeled individually with the patient details, date, time and the site of each sample for transportation to the laboratory.²⁶ It is important to provide as much clinical information as possible including a description of the wound.²⁸ In deeper sections the histopathology results will demonstrate a mixed endo and exophytic squamoid growth pattern with broad blunted rete ridges with pushing margins, keratin filled crypts, keratin cores and minimal cytological atypia.² Biopsy is regularly performed in the outpatient setting. In our case two different clinicians performed the biopsy. Unfortunately, they were taken as you would a sample for microscopy, culture and sensitively (MC&S) which is performed in the center of the wound. As the VC is spongy unhealthy tissue the biopsy sample did not get deep enough into the dermal layer leading to a delay in diagnosis. When a punch biopsy is performed it must include tissue adjacent to the area of suspicion and be taken from multiple sites. Earlier diagnosis may have limited the extend of the debridement and resulted in a more functional limb.

Wide surgical excision and Mohs micrographic surgery is the primary treatment choice. Mohs surgery is considered the standard of care for skin cancers, as it allows for intraoperative complete circumferential peripheral and deep assessment. Although it has not been well studied in the instance of VC.²⁰ Non-surgical options include cryotherapy, photodynamic therapy, oral retinoids, laser therapy and intralesional chemotherapy.²⁰ The initial surgery was performed to preserve as much of the foot as possible to maintain functionality. Therefore, the VC was not initially fully excised requiring a second procedure. As is well documented, the lesions can reoccur.^7,11 Despite two surgical debridements, clinically the VC has returned. A major limb amputation has been discussed, and the patient has agreed to the procedure. The long-term sequelae of the wound never fully healing, repeated infections (including a life-threatening infection) and the need for multiple surgical debridements have affected the patient’s quality of life. Despite all he has endured, he has a positive attitude towards the future.

Conclusions

Our case highlights the complexity of managing patients with a high-risk foot. It is important to keep searching for a diagnosis when it is apparent wounds are not progressing towards a healing trajectory. This gentleman has had a seven-year struggle to preserve his limb. The impact on his quality of life is immeasurable. He is fortunate he survived a life-threatening infection that involved seeding to three different anatomical locations including a left frontal lobe abscess that required five burrhole drainage procedures. He classically was textbook for a VC. Caucasian, male aged 60. The lesion occurred over a previous amputation site. All in our department will be more mindful for the possible development of a VC and initiate early biopsy. This case highlights the need for vigilance and a proactive approach in non-healing wounds in high-risk foot patients.

Acknowledgements

Multimedia and design Royal Perth Hospital.

Conflict of interest

The authors declare no conflicts of interest.

Ethics statement

The patient provided written consent for clinical photography and for use of his images in this publication.

Funding

The authors received no funding for this study.

Author(s)

Donna E Larsen¹*, Rachel A Carle², Fernando P Pineda^3
1Nurse Practitioner, Royal Perth Hospital, Wellington Street, Perth, Australia
²Podiatrist, Royal Perth Hospital, Perth, Australia
³Consultant Vascular and Endovascular Surgeon, Royal Perth Hospital, and Adjunct Clinical Senior Lecturer at Curtin Medical School, Curtin University, Perth, Australia

*Corresponding author email donna.larsen@health.wa.gov.au

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