Journal of Otology & RhinologyISSN: 2324-8785

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Review Article, J Otol Rhinol Vol: 3 Issue: 6

Verrucous Carcinoma Variant of Squamous Cell Carcinoma: Review of Literature

Amit Gupta1*, Sweety Gupta2 and Sarika Bansal3
1Assistant Professor, UCMS & GTB Hospital, Delhi, India
2Consultant, Galaxy Cancer Institute, Pushpanjali Crosslay Hospital Ghaziabad,Delhi NCR, India
3Assistant Professor DSCI, GTB Hospital Campus Delhi, India
*Corresponding author : Amit Gupta
Assistant Professor, Department of Surgery, UCMS & GTB Hospital, Delhi, India
Tel: +91-9891981331
E-mail: [email protected]
Received: April 28, 2014 Accepted: June 09, 2014 Published: December 05, 2014
Citation: Gupta A, Gupta S, Bansal S (2014) Verrucous Carcinoma Variant of Squamous Cell Carcinoma: Review of Literature. J Otol Rhinol 3:6. doi:10.4172/2324-8785.1000194


Verrucous Carcinoma Variant of Squamous Cell Carcinoma: Review of Literature

Verrucous Carcinoma is a infrequent variant of well differentiated squamous cell carcinoma and has some distinctive characteristics clinically and histologically diverse from a archetypal oral squamous cell carcinoma. Verrucous carcinoma grows gradually, has a tendency of local invasion, and seldom metastasizes. In the present article we discuss about etiology, pathogenesis and the management of this uncommon tumor with a detailed review of literature.

Keywords: Verrucous; Squamous cell carcinoma; Invasion

Verrucous; Squamous cell carcinoma; Invasion


Verrucous carcinoma (VC) is a variant of well differentiated squamous cell carcinoma first described by LV Ackerman in 1948 [1]. The oral cavity is one of the predilection sites for VC and constitutes 2-4.5% of all forms of squamous cell carcinomas [2]. This carcinoma has also been reported in the nasal cavity, larynx and esophagus. In the oral cavity, the buccal mucosa and lower gingiva is the common site. Although the mucous membranes of the head and neck are the most common sites of VC development, this tumour may also be found on other cutaneous surfaces including the anorectal region, external genitals and skin of the extremities, particularly the sole of the foot. There are four clinicopathological types. It has been known by several different names, usually related to anatomic sites:
• Anourogenital: giant condyloma acuminatum, Buschke- Loewenstein tumor, giant malignant condyloma, verrucous carcinoma of the anogenital mucosa, carcinoma-like condyloma, and condylomatoid precancerosis
• Oroaerodigestive: Ackerman tumor, verrucous carcinoma of Ackerman, oral florid papillomatosis
• Feet: epithelioma cuniculatum, carcinoma cuniculatum
• Other cutaneous sites: cutaneous verrucous carcinoma, papillomatosis cutis carcinoides, papillomatosis cutis [2].


The ages range from 50 to 80 years with a male predominance and the median age is 67 years.
The pathogenesis of this neoplasm has been associated with benign verrucous lesions and tobacco carcinogenic factors, especially those related to tobacco chewing. Lesions often develop at the site where the tobacco was placed habitually. However, there are also reports of patients who developed oral VC without a history of smoking [3]. A probable relation between oral VC and human papillomavirus has also been suggested. Studies have further confirmed the association between HPV and OVC by detecting HPV– DNA types 6, 11, 16 , and 18 by polymerase chain reaction (PCR), restriction fragment analysis, and DNA slot–blot hybridization [4,5]. A more acceptable hypothesis is that opportunist viral activity associated with chronic tobacco and alcohol consumption may be involved in the pathogenesis of this neoplasm.

Clinical Presentation

The macroscopic appearance depends on several factors like duration of lesion, degree of keratinization and the changes in adjacent mucosa.VC in the oral cavity is characterized by a cauliflower-like exophytic growth with a cleft, warty, whitish-to-gray surface which may have erythematous areas.


Microscopically, VC is a predominantly exophytic growth of welldifferentiated stratified squamous epithelium with deep bulbous rete ridges that exhibit little or no cytologic atypia and deep surface invaginations filled with parakeratin or orthokeratin. Despite exaggerated rete pegs, the associated basement membrane appears intact The lesion’s margins show a compressive growth pattern and local destruction of connective tissue can occur in advance of the deep epithelial (“pushing”) border [2]. The term “Verrucous” is used because of its fine, finger like surface projections. The cells are arranged in an orderly maturation towards the surface, with abundant surface keratosis (orthokeratosis; called ‘church-spire’ keratosis. Parakeratotic crypting is a common feature.
The cell kinetics of verrucous carcinoma are distictive, containing a thick zone of non-proliferating, non keratinizing cells between the basal germinative layer of normal squamous mucosa, lacking the Sphase cells [6]. In contrast, non-verrucous sqamous cell carcinoma manifests S-phase cells distribution throughout non kerantinized zones. Because of deceptive benign appearance of neoplastic cells, an accurate pathological diagnosis requires a sufficient biopsy specimen that contains infiltrative features of verrucous carcinoma.
In the most advanced stages, bone, salivary glands, muscles and cartilage involvement can be seen. Regional lymph node metastasis is rare and distant metastasis has not been reported. Most enlarged lymph nodes at presentation are often reactive to a secondary infection or inflammation rather than true metastasis.
The establishment of a clinical or histopathologic diagnosis of VC in the oral cavity may be difficult. It depends heavily on close collaboration between clinician and pathologist and the availability of a sufficiently large biopsy specimen. Some investigators have described “hybrid” lesions, seen when tumours present the dominant microscopic features of VC, but also contain small areas of tumour invasion, which are common in conventional SCCs. However, others consider that the presence of tumour invasion demands a histopathologic diagnosis of SCC, because this indicator will dictate clinical treatment.
Ferlito et al. [7] emphasized on the following classic description for the diagnosis of verrucous carcinoma:
• Fungating warty tumor
• Thickened club shaped, papillomatous projections which push rather than infiltrate into the underlying tissue.
• Deeply projecting cleft like spaces with degenerating keratin and later cystic degeneration of central portion of the filiform projections.
• High degree of cellular differentiation with absence of features of malignancy.
• Considerable inflammatory response in invaded tissues.
• Rare regional lymph node and distant metastasis.

Differential Diagnosis

Differential diagnosis includes, SSC, viral verruca, amelanotic melanoma, histoplasmosis, secondary syphilis, Darrier's disease, white spongy nevus and erythematous lupus [8,9]. The main histopathological differential diagnosis of VC is from leukoplakia, papilloma, pseudoepitheliomatous hyperplasia, verrucous hyperplasia and highly differentiated squamous cell carcinoma [10].
In a 1980 study, Shear and Pindborg [11] emphasized that verrucous hyperplasia is clinically indistinguishable from verrucous carcinoma with Olu careful histologic examination. According to them, carcinoma is characterized by extension of the lesion into the underlying connective tissue deep to the adjaccnt normal epithelium. They believed that both lesions can exist concurrently, and that verrucous hyperplasia can progress either to SCC or VC.
Rajendran et al. [12] agreed that verrucous hyperplasia is an intermediate lesion, often arising in areas of leukoplakia, which can in tum lead to VC and then invasive carcinoma. Emphasizing that clinical and histologic diagnosis can be difficult; these authors cite pseudocpitheliomatous hyperplasia, well-differentiated squamous carcmoma, chronic candidiasis, and condyloma accuminatum as lesions that must be distinguished from VC. This distinction obviously requires concurrence between the clinician's appreciation of the typical verrucous appearance of the tumor and the pathologist's identification of the microscopic criteria described by Ackerman.
Saito et al. [13] reported that expression of the cell cycle-associated proteins p16, pRb, p53, p27 and Ki-67 by immunohistochemistry in precancerous and cancerous oral lesions, including verrucous carcinomas (VCs). Generally, expression of pRb, p53 and Ki-67 increased according to the cell proliferative activity or tumor progression, but p27 expression showed an inverse relationship. Comparing squamous cell carcinomas (SCCs) with VCs, there was a great difference in expression levels of p27, Ki-67 and p53, which seemed to reflect the different cell proliferative activities of these two tumors. Expression of p16 was low in both dysplasia and SCCs, whereas p16 expression was high in VCs.


Surgical excision remains the treatment of choice for the oral VC [14]. The aggressive clinical presentation of the tumor often sways clinical judgment in favor of performing lymph node dissection, especially in the presence of clinical lymphadenopathy. This sentiment is reinforced by the fact that OVC is an extremely challenging pathological diagnosis and often even an adequate biopsy may miss areas of squamous differentiation. However, data from various studies suggest that lymph node dissection in OVC should be confined to immediately adjacent lymph node groups only and in cases, where any possibility of increased morbidity or mortality may arise from inclusion of neck dissection with surgical excision, it could be omitted entirely [15]. Given the low incidence of pathological bone involvement; more conservative surgical options such as marginal mandibular resection may be considered while planning surgical therapy in these patients chemotherapy, alone or in combination with radiotherapy, has also been employed as initial treatment [16]. There is a considerable controversy in the literature regarding ‘anaplastic transformation of verrucous carcinoma following irradiation therapy in 10-20 percent cases [17]. Following irradiation small proportion of verrucous carcinoma are reported to have changed their biological behaviour from indolent low grade locally destructive lesion to a highly malignant, metastasizing and fatal tumor, with extremely short latent period of transformation. other authors don’t believe in this ‘dedifferentiation’ phenomenon and account this observation due to presence of ‘hybrid tumors’, i.e. presence of foci of less differentiated squamous cell carcinoma within verrucous carcinoma. Because of reported incidence of anaplastic transformation following radiotherapy, many centres recommend wide field surgical resection with good clearance as preferred treatment modality While others recommend that verrucous carcinoma should be treated as other squamous cell carcinomas with the treatment modality determined by effectiveness of control without regarding the potential risk of its developing into a far more aggressive lesion after irradiation. The local recurrence of oral VC has been reported frequently.


VC of the oral cavity is a different clinicopathologic tumor distinguished from the usual squamous cell carcinoma because of its local invasiveness, non metastasizing behavior, and special clinical appearance. It has an excellent prognosis with surgical management. The follow up of verrucous carcinoma is particularly deceptive, and radiologic imaging should be employed as indicated.


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