Multiple synchronous verrucous carcinomas of the scalp in the background of generalized verruca vulgaris.

Verrucous carcinoma (VC) is a clinicopathologic entity which is defined as a locally aggressive, clinically exophytic, slow-growing, well-differentiated, squamous cell carcinoma with negligible metastatic potential. The cutaneous form of VC is typically known to arise from the palmoplantar and the genitocrural areas. Involvement of the scalp is extremely rare. Multiple synchronous involvement of the scalp by VC along with associated generalized verruca vulgaris has possibly never been reported before. We present this unique report of VC in a 38-year-old male patient with emphasis on its atypical clinical presentation and the resultant challenges in management. Interestingly, the tumor cells of our patient were confirmed to be positive for human papillomavirus infection by polymerase chain reaction and by p16 immunohistochemistry.

What was known?

The cutaneous form of VC is typically known to arise from the palmoplantar and the genitocrural areas. Involvement of the scalp is extremely rare. The exact relationship between cutaneous VC at other sites and HPV infection remains obscure and so is the role of adjuvant radiotherapy.

Introduction

Verrucous carcinoma (VC) is an uncommon, exophytic, low-grade, well-differentiated variant of squamous cell carcinoma. This neoplasm has been reported to typically involve the oral cavity, larynx, genitalia, and the esophagus.[1] Cutaneous lesions are typically known to arise in the palmoplantar and the genitocrural areas. Involvement of the scalp is extremely rare. Multiple synchronous involvement of the scalp by VC along with associated generalized verruca vulgaris has possibly never been reported before. We present a unique case of VC in a 38-year-old male patient with an association with human papillomavirus (HPV).

Case Report

A 38-year-old male, an agricultural laborer by occupation, presented to us with a history of multiple warts (verruca vulgaris) all over his body for the past 25 years and a recent increase in the size of four, cauliflower like hyperkeratotic fleshy lesions; the first, arising from the skin of the right post-auricular region measuring 6 × 3 cm; the second from the right parietal region of the scalp measuring 8 × 6 cm; the third lesion 4 × 2 cm in the vertex of the scalp 2 cm medial to the second lesion; and the fourth, a 5 × 3 cm lesion in the left temporal region of the scalp [Figure 1]. He was a diabetic (type 2) controlled on oral hypoglycemic drugs and was seropositive to hepatitis B surface antigen, but was otherwise well-preserved. He had attempted various native topical remedies for the same, despite which the lesions continued to progressively increase and worsen over the past 10 months, with associated foul smelling discharge and occasional bleeding episodes. There were multiple warts of various sizes and shapes scattered all over his body, predominantly involving his trunk, palmoplantar regions, and genitalia which had been static over time. There was no significant cervical adenopathy. He has no significant past medical or family history. A computed tomography (CT) scan of the head and neck revealed the extent of the lesions and also found all four of them to be confined to the skin of the scalp [Figure 2]. The patient was taken up for a wide excision of all the four lesions of the scalp lesions after a biopsy confirmation of VC. The extensive skin defects following the wide excision were reconstructed with large split skin grafts. Despite a macroscopic clear margin of 0.8-1 cm, the final histopathology of the right parietal lesion and the left temporal region lesions showed microscopic tumor to be extending up to the resected margins. The tumor cells were found to be positive for HPV infection as was confirmed by polymerase chain reaction (PCR) and by immune-positivity to p16 [Figure 3a–d]. The patient refused a repeat surgery and was hence offered adjuvant radiotherapy for better local control. He received 60 Grey of external beam radiotherapy to the entire scalp using intensity-modulated radiotherapy technique. He tolerated the treatment well with dramatic resolution the warty lesions as well [Figure 4] and continues to be disease free for close to 2 years following completion of treatment.

Figure 1

(a and b) Clinical picture at presentation

Figure 2

Reconstructed image of the computed tomography (CT) scan of the head and neck showing the cutaneous verrucous carcinomas in the scalp alongside the warts.

Figure 3

(a and b) Tumor composed of marked verrucous hyperplasia of squamous epithelium with reduplication, down growths, pushing borders, and mild nuclear atypia; the clinicopathological picture was suggestive of a verrucous carcinoma (hematoxylin and eosin (H and E), ×20). (c) Verrucous carcinoma showing mild focal immunopositivity for p16 (H and E, ×10). (d) Figure showing the polymerase chain reaction (PCR) amplification of the sample deoxyribonucleic acid (DNA) showing human papillomavirus (HPV) infection using consensus primer GP5+ and GP6+ showing lane 1-7 in the PCR ladder; Lane 3 - positive control (HeLa cells), lane 4 - tumor sample; and lane 6 - negative control

Figure 4

Clinical photograph of the patient 1 month post-surgery and radiotherapy

Discussion

Ackerman in 1948 first described VC in the oral cavity, cutaneous VC was first described in Aird et al., in 1954 and he named as carcinoma cuniculatum because of the characteristic histologic appearance showing crypt like spaces. The etiopathogenesis of VC is unclear; the leading theories include chemical carcinogenesis due to oral tobacco, betel nut and alcohol consumption, and chronic inflammation.[2] The carcinogenic nature of certain subtypes of the HPV has been recognized now, the cervix in the female genital tract is most prone to the carcinogenic effect of these viruses, although any part of the glabrous skin can also be potentially affected. The exact relationship between cutaneous VC at other sites and HPV infection remains obscure, many studies showing contrasting results.[3456] The initial link of HPV infection to the development of cutaneous malignancies was to the development of the disease epidermodysplasia verruciformis (EV).[7] EV is a rare inherited dermatological condition, which is characterized by an increased susceptibility to infection from certain HPV subtypes, resulting in both benign and malignant skin lesions (typically seen in infection with HPV subtypes 5, 8, and 14d) which often clinically manifests as verruca plana-type lesions. Acquired EV has been described as a syndrome which resembles congenital EV, but is more often associated with immunocompromised patients. EV was in fact earlier believed to be a model for HPV associated skin cancers,[7] but subsequent new data from virological studies by the same authors showed that the association was not specific. They demonstrated EV HPVs in non-EV populations as well.[8] The authors suggested that HPVs are most likely indirectly involved by facilitating ultraviolet (UV)-related carcinogenesis (by preventing UV-induced apoptosis). Infection with HPV never the less has been proposed as a causative factor for VC involving the oral, plantar, and anogenital regions. A combination of HPV infection, relative immunosuppression, and sunlight exposure may have contributed to the pathogenesis of VC in our patient.

VCs are well-known for its local aggressiveness; these lesions however have an indolent clinical behavior with negligible metastatic potential. VC is a clinicopathological entity, the pathological diagnosis is extremely difficult and it is more often exclusionary. It has been reported that multiple biopsies are often required before diagnostic histological features supporting an appropriate interpretation of VC is identified. The differential diagnosis of VC should include verrucous hyperplasia, proliferative verrucous leukoplakia, reactive keratosis with epithelial hyperplasia, and pseudoepitheliomatous hyperplasia. It is imperative to rule out hybrid carcinoma including conventional squamous cell carcinoma alongside VC.[9]

Surgical excision with negative margins or Mohs micrographic surgery represents the treatments of choice for cutaneous VC and is curative in a great majority of cases.[10] It is generally accepted that primary definitive radiotherapy is not as effective as surgery in the initial treatment of VC, the effectiveness of adjuvant radiation therapy in advanced VCs continues to remain a topic of debate. It was traditionally believed that adjuvant radiation therapy for VC increased the chances of dedifferentiation and hence the risk of distant metastasis.[6] More recent reports have not confirmed these concerns of anaplastic transformation.[1112] Extrapolating the benefit of adjuvant radiotherapy from studies involving VC of the larynx, many authors[11] have found it reasonable to offer radiotherapy for patients of VC with gross or microscopic positive margins as was done for our patient. Another setting for the use of radiotherapy can be for palliative in advanced cases. Patients with VC tend to have a favorable prognosis; the mortality in these cases is usually due to extensive local invasion rather than metastatic spread.

In conclusion, a close coordination between a surgeon and the pathologist is crucial to the timely and accurate diagnosis of VCs, the role of HPV infection in the etiopathogenesis of VC is definitely worth further exploring.

What is new?

Multiple synchronous involvement of the scalp by VC along with associated generalized verruca vulgaris has possibly never been reported before. Adjuvant radiotherapy can be safely used as was seen in our patient, who is loco regionally controlled for nearly two years following the completion of treatment.