|Year : 2015 | Volume
| Issue : 4 | Page : 593-597
Verrucous carcinoma on pre-existing oral submucous fibrosis
Sourav Malhotra, Vijay Raghavan, Abhishek Kumar, Abhishek Kumar Singh
Department of Oral Medicine and Radiology, Seema Dental College and Hospital, Rishikesh, Uttarakhand, India
|Date of Submission||05-Jun-2015|
|Date of Acceptance||22-May-2016|
|Date of Web Publication||19-Aug-2016|
Dr. Sourav Malhotra
Department of Oral Medicine and Radiology, Seema Dental College and Hospital, Rishikesh - 249 203, Uttarakhand
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Verrucous carcinoma (VC) is a variant of squamous cell carcinoma. It most commonly affects the oral cavity with buccal mucosa being the most common site affected. Clinically it has proliferative finger-like projections or a cauliflower-like appearance which is a significant factor in its diagnosis. It is more common in tobacco user males. The histopathological diagnosis of VC is difficult and requires immense experience to report a case of VC. Though VC is described as a benign lesion with minimum aggressive potential but long-standing cases have shown transformation into squamous cell carcinoma. Therefore, early diagnosis and surgical excision of the lesion are the most appropriate treatment modality of VC.
Keywords: Carcinoma, hyperplasia, papillomatosis, verrucous
|How to cite this article:|
Malhotra S, Raghavan V, Kumar A, Singh AK. Verrucous carcinoma on pre-existing oral submucous fibrosis. J Indian Acad Oral Med Radiol 2015;27:593-7
|How to cite this URL:|
Malhotra S, Raghavan V, Kumar A, Singh AK. Verrucous carcinoma on pre-existing oral submucous fibrosis. J Indian Acad Oral Med Radiol [serial online] 2015 [cited 2022 Oct 1];27:593-7. Available from: https://www.jiaomr.in/text.asp?2015/27/4/593/188770
| Introduction|| |
Oral verrucous carcinoma (VC) is a rare tumor first described by Lauren V. Ackermann in 1948. It is a special form of well-differentiated squamous cell carcinoma with specific clinical and histological features. Various names are used in the literature to describe this entity, including Ackerman's tumor, Buschke-Loewenstein tumor, florid oral papillomatosis, epithelioma cuniculatum, and carcinoma cuniculatum. The tumor grows slowly and locally, is invasive in nature and unlikely to metastasize.  It appears as a painless, thick white plaque resembling a cauliflower. The most common sites of oral mucosal involvement include the buccal mucosa, followed by the mandibular alveolar crest, gingiva, and tongue. Shear and Pindborg described a condition termed verrucous hyperplasia (VH) in 1980. Both lesions closely resemble each other clinically and pathologically. VH has been considered an antecedent stage or early form of VC and is believed to have the same biological potential. While histopathology is the gold standard in diagnosis, it is a subjective assessment of tissue, with inter- and intra-rater variability.  Surgery has been the first choice of treatment for these lesions, and radiotherapy is controversial; however, surgery combined with radiotherapy is the next most preferable treatment and may have benefits, particularly in cases of extensive lesions. If left untreated for years, a focus within VC may progress to invasive squamous carcinoma and release metastases. Recurrence rate is high in cases in which either irradiation or surgery alone is performed. 
| Case Report|| |
A 45-year-old female patient reported to the Department of Oral Medicine and Radiology with the chief complaint of white patch present in the mouth from last 9 to 10 months. Patient's dental history revealed extraction under local anesthesia 15 years back. There was a history of reduced mouth opening since last 2 years and her past medical history, including her family history was unremarkable. The patient gave a history of pan chewing from last 17 years but has quit the habit completely since last 1 year.
Extraoral examination revealed right and left submandibular lymphadenopathy, which were nontender, firm with limited mobility. Intraoral examination revealed alteration in the texture of the entire mucosa that was pale in color. Fibrous bands were palpable on the left and right buccal mucosa posteriorly and on the labial mucosa. Mouth opening was limited with maximum interincisal opening of 3.5 cm. The floor of the mouth was firm with a lack of normal flexibility. The tongue was completely bald with restricted movement. White lesions were multifocal and seen at least in three locations:
- Red and white lesion extending from the left commissure to the region of the third molar. It was slightly raised with rough surface and was at the level of occlusal plane [Figure 1]
- Exophytic white lesion involving the buccal sulcus extending onto the adjacent alveolar mucosa and gingiva, in the region between 43 and 47. The surface was rough with numerous finger-like projections [Figure 2]
- Right retromolar area region.
|Figure 2: Lesion present on the right labial and vestibule area with white papillary growth|
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Exophytic white lesions were present with irregular surfaces and had a finger-like projection in the region of 31-36. A complete hemogram was performed and all the values were within the normal range. An incisional biopsy [Figure 3] was performed at the right alveolus and labial mucosal region, and the excised tissue was sent for histopathological analysis.
Hematoxylin and eosin stained section of lower right labial and alveolar mucosa showed hyperkeratotic stratified squamous epithelium overlying the connective tissue stroma. The epithelium was well differentiated and showed both exophytic and endophytic growth. The epithelial cells showed mild pleomorphism and hyperchromasia. Mitotic activity was evident in the basal layers. The papillary exophytic proliferations of the heavily keratinized epithelium were separated by deep clefts-like spaces [Figure 4]. Keratin plugging could be seen within these clefts. The endophytic growth of the epithelium into the connective tissue showed blunt rete processes, tending to be on the same level, giving "pushing margin" of tumor [Figure 5]. The basement membrane was intact. The connective tissue papillae showed intense inflammatory lymphocytic infiltrate. The deeper connective tissue showed the presence of loosely arranged collagen fibers, spindle-shaped fibroblasts, and moderate amount of chronic inflammatory infiltrate. Mucous salivary glands could also be seen within the connective tissue.
|Figure 4: Photomicrograph showing broad and bulbous rete ridges which seemed to push the adjacent connective tissue (×40)|
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|Figure 5: Photomicrograph showing stratified squamous epithelium with parakeratotic plugging (×10)|
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| Discussion|| |
VC is slow-growing and spreads laterally rather than deeply.  VC represents <1-10% of all oral squamous cell carcinomas (OSCCs), depending on the local popularity of smokeless tobacco use. VC can be described clinically as papillary, verrucoid, fungating, or cauliflower-like. VC may develop from the progression of proliferative verrucous leukoplakia (PVL) and progress to carcinoma.  The only epidemiologic assessment of this tumor in a Western culture reported an average annual incidence rate of one to three oral lesions per 1 million populations each year. These typically present as extensive, white, warty lesions. 
The etiology of VC is not well defined. Human papillomavirus has been considered one of the causative factors. Smoking seems highly associated with the development of mucosal VC of the neck and head. Poor oral hygiene, presence of oral lichenoid, and leukoplakic lesions may act as predisposing factors.  Smokeless tobacco habits include tobacco-lime quid placement in buccal vestibule, pan with or without tobacco, areca nut mixed with tobacco and other ingredients to form kharra, gutkha, and mava, while smoked form includes bidi and cigarette. 
A distinction should be made between VH and VC. VH was described by Shear and Pindborg in 1980. It is more superficial and does not extend deeper than the surrounding normal epithelium. It shows dysplasia and can later develop into VC or squamous cell carcinoma. VC, on the other hand, extends more deeply, pulling the adjacent normal epithelium at its margin. , Oral submucous fibrosis (OSMF) is a precancerous condition associated with chronic betel nut chewing. The development of squamous cell carcinoma is seen in one-third of the OSMF patients, but the development of VC is rare in such patients. 
The pathogenesis of OSMF is not well established, although a number of possible mechanisms have been suggested. Pathogenesis is believed to involve juxta-epithelial inflammatory reaction and fibrosis in the oral mucosa, probably due to increased cross-linking of collagen through upregulation of lysyl oxidase activity. Fibrosis results from the effects of areca nut, which increases collagen production and decreases collagen degradation. The initial pathology of OSMF is characterized by juxta-epithelial inflammation which initially composes of neutrophils and then plasma cells and lymphocytes. In more advanced stages, OSMF is characterized by the formation of thick bands of collagen and hyalinization extending into the submucosal tissues and decreased vascularity. 
OSMF may cause atrophy in the epithelium, increasing carcinogen penetration. Studies suggest that dysplasia is seen in about 25% of biopsies of OSMF cases, and the rate of transformation to malignancy varies from 3% to 19%. The evidence supporting the malignant potential of OSMF includes:  (i) higher prevalence of leukoplakia among OSMF patients, (ii) high frequency of epithelial dysplasia, (iii) histologic diagnosis of carcinoma without the clinical signs of carcinoma, (iv) concurrent finding of OSMF among patients with oral cancer, and (v) incidence of oral cancer among patients with OSMF. 
Although the development of squamous cell carcinoma is seen in one-third of OSMF patients, this occurrence is said to be extremely rare. OSMF, a potentially malignant disorder, may also give rise to VC. Alternatively, VC may develop de novo or from an existing PVL. Due to very few cases reported in literature, a definite conclusion cannot be established as to whether the OSMF in this case has caused the development of VC or if it is just an incidental finding. Moreover, in the present case, the patient is a gutkha chewer and has no other habits commonly associated with VCs. Hence, it can be inferred that here OSMF could be the cause for the development of VC. 
Most of the VC that develops in smokeless tobacco users occurs in older individuals who have practiced the habit for several years. The tumor occurring in younger individuals has been rarely documented. Friedell and Rosenthal in 1941 reported eight cases of VC; all were men over 60 years. Ackerman in 1948 reported 31 cases of VC in old men with many years of duration of tobacco chewing. Sorger in 1960 reported four cases of VC in men above 70 years.  In VC, regional lymph nodes are often tender and enlarged because of inflammatory involvement, simulating metastatic tumor. 
The most common sites of occurrence in the oral cavity are buccal mucosa and gingiva. Emel Bulut's study showed mandibular posterior alveolar crest and retromolar region to be the most common sites of involvement, followed by buccal mucosa, palate, and floor of the mouth.  The tumor may also be found on different sites including skin, paranasal sinus, bladder and anorectal region, male and female genitalia, sole of the foot, and ear. 
Ferlito et al. (1980) emphasized on the following classic description for the diagnosis of VC: 
- 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.
The deceptively benign microscopic pattern and the absence of significant cellular atypia are important.  Only biopsy can differentiate between true VC and a clinically verrucoid-appearing squamous cell carcinoma.  VC typically has a heavily keratinized or parakeratinized, irregular clefted surface with parakeratin extending deeply into the clefts.  Microscopically, the uniform cells show none of the mitoses or dysplastic features expected with squamous carcinoma. The surface shows characteristic "church spire" formations due to extensive keratinization. 
A distinction should be made between VC and other verrucous lesions, especially PVL. PVL is an uncommon progressive form of multifocal leukoplakia with high rate of malignant transformation to either OSCC or VC and a high probability of recurrence. Although the lesions typically begin as simple, flat hyperkeratosis that is indistinguishable from ordinary leukoplakic lesions, PVL exhibits persistent growth eventually becoming exophytic and verrucous in growth. VH is an antecedent or early form of VC and should be treated as VC. VH may develop from leukoplakic lesions. 
VH is best distinguished from VC in biopsies taken at the margins of the lesions. In the former, the verrucous processes and greater part of the hyperplastic epithelium are superficial to adjacent normal epithelium. Whereas in the latter, the verrucous processes are superficial, but the broad rete processes extend considerably deeper than the adjacent normal epithelium, often pulling a margin of normal epithelium down with them into the underlying connective tissue.  The definitive diagnosis obviously requires concurrence between the clinician's appreciation of the tumor and the pathologist's identification of the microscopic criteria described by Ackerman. 
Surgery is considered the primary mode of treatment for oral VC.  Oral VC has an excellent prognosis with surgical management. Surgical excision and primary grafting with regular long-term follow-up for recurrence can be considered as a feasible option for the treatment of oral VC. The treatment of OSMF has been concentrated on attempts to improve opening of the mouth by medical or surgical means. Surgical excision and skin grafting are applicable where the areas of fibrosis are localized and access is unrestricted.  Thus, surgery has not always been attempted in severe and diffuse cases of OSMF. Attempts to improve the opening of the mouth by merely surgically dividing the fibrous bands may make matters worse by increasing scarring.  Split thickness skin grafting following bilateral temporalis myotomy or coronoidectomy has been advocated. Prognosis of VC is excellent after complete surgical removal. Local recurrence may occur with incomplete excision of the tumor. 
| Conclusion|| |
Several studies have shown that VC can develop de novo or from preexisting leukoplakia but in our case, VC developed over a preexisting OSMF in a 45-year-old female patient which is a rare and unique. Etiology, clinical features, histopathological appearance, and differential diagnosis were discussed. Treatment modalities for VC were reviewed.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]