Sir,

Verrucous carcinoma (VC) represents a distinct entity of well-differentiated squamous cell carcinoma (SCC) [1]. Its occurrence in the interdigital space is exceptional. Histologically, nonspecific changes are found, leading to false reassurances and diagnostic errors [2]. Herein, we report a case of VC in the interdigital space (IDS), which was diagnosed only after the second biopsy, occurring on a chronic interdigital intertrigo and in association with a duodenal stromal tumor.

A 75-year-old male, an imam by profession, with macerated interdigital intertrigo persistent for twenty years with iterative fissures (Fig. 1), presented with a painful, ulcerated, and verrucous lesion in the fourth interdigital space. The lesion had been evolving for two years and was resistant to antifungal treatment. A clinical examination revealed an ulceration with infiltrated borders, occupying the entire fourth right interdigital space and extending onto the dorsum of the foot without locoregional lymphadenopathy (Figs. 2a and 2b). The rest of the physical examination was unremarkable. The first skin biopsy showed features of keratoacanthoma, and the second revealed verrucous carcinoma. HPV identification was not performed. Extension assessment showed a tumoral process with underlying muscular infiltration without osteolysis. Additionally, a suspicious duodenal mass was revealed. Histology of the suspicious mass revealed a duodenal stromal tumor with positive CKIT and DOG-1 immunohistochemistry. Amputation of the two toes adjacent to the affected space was performed to ensure oncologic margin clearance (Fig. 3). As for the stromal tumor, the patient received chemotherapy.

	Figure 1: Macerated interdigital intertrigo with iterative fissures.
	Figure 2: (a and b) Ulcerated, nodular, and verrucous lesion with an infiltrated border in the fourth interdigital space.
	Figure 3: Amputation of the two toes adjacent to the affected space was performed to ensure oncologic margin clearance.

VC in the interdigital space is a rare entity particularly affecting the elderly. Inflammatory conditions or chronic maceration, including cultural factors such as ritual ablutions performed five times a day without drying the interdigital spaces, as well as domestic cleaning involving large amounts of water several times a week, favor this pathology [3]. In our patient, a profession as an imam and poorly dried religious ablutions were a major factor in interdigital maceration. The possible involvement of HPV in the pathogenesis of VC is known, although its investigation is rarely performed in published cases involving this location [2]. In our patient, this investigation was not conducted.

The clinical and histological presentation of VC is often misleading, leading to diagnostic delays, with the average delay ranging from 2 to 20 years [4], which was consistent with our case.

Clinically, it may present as erosive interdigital intertrigo refractory to treatment, a nodular tumor, or even an ulcerated and verrucous lesion [3,4].

Therefore, biopsies should be multiple, wide, and deep [3]. The treatment of this pathology is surgical, and distant metastases are rare.

No cases associating VC and a digestive tumor have been published in the literature, making our observation even more interesting.

We hypothesize that the potential cause explaining the association between VC and the digestive tumor is a probable HPV infection. Although HPV infection is mainly recognized as being associated with gynecological tumors, an increasing number of studies also suggest its association with gastrointestinal cancers [5].

HPV infection is highly likely to facilitate the worsening of the course of other concomitant infections, which, along with other coexisting infections by highly oncogenic bacteria and viruses, possibly including precancerous changes, ultimately leading to cancer [6].

Persistent HPV infection targets immune signaling as well as tumor suppressor pathways, ultimately leading to oncogenic promotion in the form of tumors [6].

Further research is needed to confirm our hypothesis regarding the association between VC and digestive tumors.

Screening could be implemented to identify HPV at the site of the VC surgical specimen.

Our observation is particular due to the exceptional location of VC in the IDS, the diagnostic difficulties, and the potential role of HPV causing VC and the duodenal stromal tumor.

REFERENCES

1. Lamchahab FE, Guerrouj B, Bourra H, Marot L, Zouaidia F, Lamzaf O, et al. [Aggressive course of intertoe verrucous carcinoma]. Ann Dermatol Venereol. 2012;139:510-3.

2. Lamchahab F-E, Guerrouj B, Bourra H, Marot L, Senouci K, Hassam B, et al. Difficultés diagnostiques d’un carcinome verruqueux de l’espace interorteil. Ann Dermatol Vénéréologie. 2011;1808:A1-A342.

3. Terrab Z, Azzouzi S, Benchikhi H, Chlihi A, Lakhdar H. [Intertoe space cutaneous epidermoid carcinoma]. Ann Dermatol Venereol. 2006;133(5 Pt 1):456-8.

4. Baptista AP, de Freitas CL, Lima Bastos A. [Interdigital spinocellular epitheliomas of the foot]. Ann Dermatol Syphiligr (Paris). 1975;102:491-8.

5. Bucchi D, Stracci F, Buonora N, Masanotti G. Human papilloma virus and gastrointestinal cancer:A review. World J Gastroenterol. 2016;22:7415-30.

6. Baj J, Forma A, Dudek I, Chilimoniuk Z, Dobosz M, Dobrzyński M, et al. The involvement of human papilloma virus in gastrointestinal cancers. Cancers. 2022;14:2607.