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Year : 2016  |  Volume : 12  |  Issue : 1  |  Page : 142-145

Oral verrucous carcinoma: A retrospective analysis for clinicopathologic features

Department of Oral and Maxillofacial Pathology, Hitkarini Dental College and Hospital, Jabalpur, Madhya Pradesh, India

Date of Web Publication13-Apr-2016

Correspondence Address:
Wanjari G Sonalika
Department of Oral and Maxillofacial Pathology, Hitkarini Dental College and Hospital, Jabalpur - 482 001, Madhya Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-1482.172709

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 > Abstract 

Aim: To study the clinicopathological features of oral verrucous carcinoma (VC).
Methods: Archives of the department were retrieved for verrucous lesions. After thorough histopathologic examination, 10 cases were confirmed as VC. Age, sex, site, tobacco habit, clinical presentation, and histologically, the presence of dysplasia and koilocytic changes were studied.
Results: Oral VC showed a distinct male preponderance with male:female ratio of 8:2 and occurring predominantly in sixth and seventh decade. Tobacco association in the form of chewing (50%), smoking (40%) or both (10%) was found in all the cases. In chewers, the site of lesion corresponded to the site of tobacco placement that is gingivobuccal sulcus. In smokers, the posterior part of the oral cavity was affected, and the lesions were extensive. Painless, exophytic, cauliflower-like growth was the most common presentation with surrounding whitish (leukoplakic) mucosa. Fifty percentage of the cases showed human papilloma virus-induced changes in the epithelium. Dysplasia was seen in two cases.
Conclusion: Oral VCs are invariably associated with tobacco habits. In smokers, the lesions are extensive, affecting the posterior parts of the oral cavity. Although evidence of viral infection was seen but its role as an etiological agent is still controversial. Site and depth of the biopsy along with thorough histopathological sampling is essential to avoid erroneous diagnosis.

Keywords: Habits, human papilloma virus, oral verrucous carcinoma, tobacco

How to cite this article:
Sonalika WG, Anand T. Oral verrucous carcinoma: A retrospective analysis for clinicopathologic features. J Can Res Ther 2016;12:142-5

How to cite this URL:
Sonalika WG, Anand T. Oral verrucous carcinoma: A retrospective analysis for clinicopathologic features. J Can Res Ther [serial online] 2016 [cited 2021 Jan 20];12:142-5. Available from: https://www.cancerjournal.net/text.asp?2016/12/1/142/172709

 > Introduction Top

The papillary or verrucous-type lesions are quite common in the oral region, representing 3% of all the biopsied oral lesions. They are characterized by a unique proliferation of the stratified squamous epithelium.[1] The lesions included in this spectrum ranges from benign lesions like papilloma, premalignant lesions like verrucous hyperplasia (VH) to malignant verrucous carcinoma (VC).[2] Most of them are clinically benign, but they are removed and subjected to microscopic evaluation for ruling out early malignancy.[1]

VC and VH are clinically indistinct but can be differentiated based on careful gross and microscopic correlation.[1] VC is a diffuse, largely exophytic, superficial spreading highly keratinized warty from of well-differentiated squamous cell carcinoma (SCC) that is unlikely to metastasize.[3] It occurs commonly in elderly male and can be quite extensive at the time of presentation. It occurs at various extraoral sites such as larynx, vagina, rectal mucosae and skin from the breast, axilla, ear canal, and soles of the feet where it is associated with human papillomavirus (HPV) subtypes 16 and 18. Oral VC is far more common than extraoral VC and is distinctly linked to tobacco use.[4] The role of HPV in oral VC is controversial. Within the oral cavity, buccal mucosa and gingiva are the most frequently involved sites.[1]

A 5 years institutional review was undertaken to determine the incidence of oral VC with clinicopathological correlation.

 > Methods Top

Archives of the institution from 2010 to 2014 were reviewed for all the verrucous lesions reported. A total of 27 cases were found included under this category. Out of these 27 cases, ten cases were confirmed as VC based on the characteristic histological feature of the proliferation of well-differentiated stratified squamous epithelium with exophytic growth forming surface projections and endophytic growth pattern of broad bulbous rete ridges with pushing margin. The clinical and histopathological details of VC were assessed [Table 1].
Table 1: Clinical and histological data for verrucous carcinoma

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 > Results And Observations Top

We evaluated ten cases of VC for clinical and histopathological details. Each lesion was examined by two oral pathologists. The collected data is depicted in [Table 1]. Males (eight cases) were commonly affected than females (two cases). Most patients (80%) were in a sixth and seventh decade and the remaining two cases were below 40 years of age. Tobacco habits were invariably associated with all the cases, most commonly in the form of chewing (50%) followed by smoking (40%) and the remaining (10%) had a habit of smoking and chewing both. The most common presentation was a verruciform patch/growth with a whitish adjacent mucosa. Lymph node involvement was seen in two cases as soft and tender enlargement. Within the oral cavity, gingivobuccal sulcus (40%) was most frequently involved followed by retrocommisural region with the adjoining buccal mucosa (30%), palate (20%) and lower lip (10%).

Histopathologically, all the cases were typified by the proliferation of well-differentiated epithelium without or with minimal atypia and lymphoplasmocytic infiltration at the epithelial-connective tissue interface [Figure 1]. Two cases showed distinct dysplasia. HPV-induced changes identified as pyknotic nuclei and perinuclear clear halo was seen in 50% of the cases [Figure 2]. All the cases were treated by wide surgical excision, and none recurred after a follow-up of variable period ranging from 1 to 5 years.
Figure 1: Photomicrograph showing exophytic and endophytic proliferation of well-differentiated epithelium with chronic inflammatory cell infiltration at the epithelial-connective tissue interface (H and E, ×4)

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Figure 2: Photomicrograph showing pyknotic nuclei and perinuclear clear halo (Koilocytes) indicating human papilloma virus infection (H and E, ×10)

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 > Discussion Top

VC belongs to a distinct group of lesions characterized by unique proliferation of the epithelium [1] which gets heaped above the surface,[5] termed as verrucous-papillary lesions. VC was found to be the most common verrucous lesion in our study followed by VH.

VC represents a variant of epidermoid carcinoma which typically evolves slowly, expands persistently and is extremely reluctant to metastasize.[6] It occurs at various sites like skin, cervix, larynx [4],[6] but 75% of all cases of VC occur in the oral cavity.[7] It is typically observed in older males.[7] Similarly, our series also showed a distinct male preponderance with a male:female ratio of 8:2 and commonly in the older age groups.

Tobacco chewing habit is accepted as the primary etiological factor for oral VC.[4],[7] This was very well-observed in our study too, where all of the cases were associated with the habit. Tobacco smoking and alcohol are known chemical carcinogen, but their association with VC is feeble. The etiology of VC is not well-defined. HPV has been considered one of the causative factors.[8] HPV subtypes 16 and 18 have been identified in up to 40% of oral VC.[7] The viral oncoproteins E6 and E7 binds to the proteins regulating cell division cycle p53 and Rb, inducing proliferative changes that are responsible for the malignant phenotype.[8] The role of HPV in oral VC is still controversial. Some authors hypothesized the synergistic action between chemical carcinogen and viral carcinogen.[9] Sequential combined effect of HPV 16 and tobacco related carcinogen can lead to malignant transformation of oral keratinocytes.[10] On the contrary, experiments have also shown that even though a minority of VC were positive for p16 and HPV DNA, but the uniform absence of transcriptionally active high-risk HPV has led to the conclusion that these are not HPV-driven tumors.[11] Poor oral hygiene and chronic irritation which were consistently present in our cases also support their etiologic role, although not as a primary factor. One case was seen in lower lip which suggests the role ultraviolet exposure too.[9]

All the cases showed adjacent mucosal abnormalities supporting the view of VC developing from a benign precursor.[7] Initially, thin white keratotic plaque is formed which progressively thickens and develop surface projections (papillary/verruciform).[7] Histologically, this concept is very well-supported by the finding of hyperkeratotic epithelium with dysplasia seen adjacent to the VC [Figure 3]. Further, it is conceptualized that such epithelium becomes acanthothic, the superficial cells distant from the nutrition supply becomes edematous and necrotic which eventually desquamates and forms clefts at the surface resulting in epithelial projections between two clefts [12] [Figure 4].
Figure 3: Photomicrograph showing abnormal mucosa at the periphery of verrucous carcinoma identified as hyperkeratosis with dysplasia (H and E, ×4)

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Figure 4: Photomicrograph showing edematous and necrotic superficial cells which are exfoliating resulting in cleft formation. Clefts get filled by thick layer of keratin forming parakeratin plugging (H and E, ×10)

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VC can become extensive by lateral spread. Despite its histologically benign appearance, it may cause substantial destruction by local invasion.[1],[7] The characteristic bulbous rete ridges comprising the pushing margin of the tumor invasion front tends to compress the surrounding structures including bone rather than infiltration. Lymph node involvement is uncommon if present is usually due to reactive hyperplasia secondary to inflammatory reaction seen at the invasive front of the tumor.[6]

Special emphasis should be given for the evaluation of areas of ordinary SCC present in the vicinity of VC. Batsakis et al. introduced the term “hybrid VC” and defined it as “A nonverrucous SCC (of varying degree and differentiation) that arises synchronously with the VC and in the same microscopic fields.”[13] Hybrid VC is clinically indistinct but have a higher tendency for local recurrence. As these areas of SCC will be the decisive factor for prognostication, hence hybrid tumors are treated as SCC.[1]

VH is clinically indistinct from VC. Epithelial proliferation in VH is predominantly above the surface, not invading below the level of adjacent rete ridges of the normal epithelium. Whereas in VC, the epithelium grows downward, retracting the margin of the adjacent normal epithelium.[1] However, as VH are considered irreversible precursors of VC, same treatment is recommended for both.[14] VH has been considered an antecedent stage or early form of VC and is believed to have the same biological potential, VH, verrucous keratosis, and VC may not be distinguished clinically or may coexist. It should be kept in mind that VH may also develop from leukoplakic lesions, and it may transform into VC or SCC, acting as a potential precancerous lesion.[15]

Wide surgical excision is the treatment of choice, as there is risk of anaplastic transformation of the tumor after radiotherapy.[5]

 > Conclusion Top

In our study we found VC accounting for the highest number of verrucous-papillary lesion reported. Oral VC differs from extraoral VC in its association with tobacco habits. In chewers, the involved site corresponds to the site of tobacco placement but interestingly in smokers the posterior part of the oral cavity was affected with extensive lesions. However, this observation needs confirmation by a study on larger number of samples. The most ideal site of biopsy is the periphery of VC where the surrounding epithelium dips downward. An adequate incisional biopsy is mandatory to arrive at a final diagnosis owing to the benign histomorphic appearance of the epithelium. The excised specimen needs extensive histologic sectioning for identification of coexisting SCC, which influences the treatment plan. Thus, the ideal site and depth of biopsy along with thorough microscopic evaluation is the key to avoid erroneous diagnosis.

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Conflicts of interest

There are no conflicts of interest.

 > References Top

Gnepp DR. Diagnostic Surgical Pathology of the Head and Neck. 2nd ed. Philadelphia: WB Saunders; 2001.  Back to cited text no. 1
Thomas GJ, Barrett AW. Papillary and verrucous lesions of the oral mucosa. Diagn Histopathol 2009;15:279-85.  Back to cited text no. 2
Sapp JP, Eversole LR, Wysocki GP. Contemporary Oral and Maxillofacial Pathology. 2nd ed. St. Louis: Mosby; 2004.  Back to cited text no. 3
Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and Maxillofacial Pathology. 2nd ed. New Delhi: Saunders; 2002.  Back to cited text no. 4
Koch BB, Trask DK, Hoffman HT, Karnell LH, Robinson RA, Zhen W, et al. National survey of head and neck verrucous carcinoma: Patterns of presentation, care, and outcome. Cancer 2001;92:110-20.  Back to cited text no. 5
Kraus FT, Perezmesa C. Verrucous carcinoma. Clinical and pathologic study of 105 cases involving oral cavity, larynx and genitalia. Cancer 1966;19:26-38.  Back to cited text no. 6
Barnes L, Eveson JW, Reichart P, Sidransky D, editors. World Health Organization Classification of Tumors. Pathology and Genetics of Head and Neck Tumors. Lyon, France: IARC Press; 2005.  Back to cited text no. 7
Eversole LR. Papillary lesions of the oral cavity: Relationship to human papillomaviruses. J Calif Dent Assoc 2000;28:922-7.  Back to cited text no. 8
Schwartz RA. Verrucous carcinoma of the skin and mucosa. J Am Acad Dermatol 1995;32:1-21.  Back to cited text no. 9
Kim MS, Shin KH, Baek JH, Cherrick HM, Park NH. HPV-16, tobacco-specific N-nitrosamine, and N-methyl-N'-nitro-N-nitrosoguanidine in oral carcinogenesis. Cancer Res 1993;53:4811-6.  Back to cited text no. 10
Patel KR, Chernock RD, Zhang TR, Wang X, El-Mofty SK, Lewis JS Jr. Verrucous carcinomas of the head and neck, including those with associated squamous cell carcinoma, lack transcriptionally active high-risk human papillomavirus. Hum Pathol 2013;44:2385-92.  Back to cited text no. 11
Shear M, Pindborg JJ. Verrucous hyperplasia of the oral mucosa. Cancer 1980;46:1855-62.  Back to cited text no. 12
Batsakis JG, Hybels R, Crissman JD, Rice DH. The pathology of head and neck tumors: Verrucous carcinoma, part 15. Head Neck Surg 1982;5:29-38.  Back to cited text no. 13
Batsakis JG, Suarez P, el-Naggar AK. Proliferative verrucous leukoplakia and its related lesions. Oral Oncol 1999;35:354-9.  Back to cited text no. 14
Alkan A, Bulut E, Gunhan O, Ozden B. Oral verrucous carcinoma: A study of 12 cases. Eur J Dent 2010;4:202-7.  Back to cited text no. 15


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

  [Table 1]


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