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30 rev port estomatol med dent cir maxilofac . 2026;67(1):27-33

less common, particularly as proliferative verrucous leukopla- ithelial dysplasia and subsequently transform into convention-
kia is not typically associated with tobacco use. 21 al SCC, presenting more or less differentiated foci of SCC. In this
Another predisposing factor suggested in the etiopatho- context, the presence of at least one focus of SCC transformation
genesis of VC is the human papillomavirus (HPV), which has within a VC lesion characterizes a hybrid carcinoma. 30,37,38 In
24
been detected in tumor cells. 22,23 Greere et al. demonstrated fact, VC cases often present microinvasion, indicating that atyp-
the presence of HPV in approximately 20% of VC cases, espe- ical basal cells have acquired invasive properties. During his-
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cially subtypes 16 and 18. Although HPV’s influence on the topathological examination, it is mandatory to rule out SCC and
oncogenesis of VC is less significant compared to SCC, studies hybrid carcinoma, which require staging and treatment as con-
31
indicate that the pathogenesis of VC involves the abrogation ventional SCC due to the greater metastatic potential. To this
of a tumor suppressor gene by oncogenic HPV subtypes. 19,25 end, large and deep biopsies are essential, as invasion may be
Additionally, physical factors, such as irritation and repetitive missed in small and superficial specimens, making it unfeasible
31
mechanical trauma, may contribute to VC development, along- to exclude an underlying conventional carcinoma. Gokavarapu
40
side chronic inflammatory processes like osteomyelitis, fistu- et al. reported that approximately 50% of cases clinically diag-
las, ulcers, and lipoid necrobiosis. 25-27 In the cases presented nosed as oral VC or its benign precursors actually represented
herein, the only etiological factors identified were tobacco use hybrid carcinomas. Therefore, a thorough microscopic examina-
and poor oral hygiene, corroborating literature that smoking tion of the entire specimen, using serial sections to examine
and chewing tobacco represent the primary carcinogenic fac- deeper tissues, is crucial for identifying potential invasive com-
tors in VC. ponents. 9,40 If hybrid VC is identified, the pathologist must quan-
Regarding differential diagnosis, VC mimics several benign tify the tumor components, define the grade of differentiation
oral tumors; thus, lesions with a similar appearance must be of the conventional SCC foci, and determine the depth of inva-
considered in the clinical and histopathological differential sion, as well as evaluate lymphovascular and/or perineural in-
diagnosis, such as squamous papilloma, condyloma acumi- vasion, in order to assist clinicians in determining adjuvant
natum, focal epithelial hyperplasia, pseudoepitheliomatous therapeutic options. 41
hyperplasia, chronic hyperplastic candidiasis, verrucous hy- Several therapeutic approaches are employed for oral mu-
42
perplasia, and proliferative verrucous leukoplakia. 28-30 Fur- cosal VC, including surgery, chemotherapy, and radiotherapy.
thermore, a distinction should be made between VC and con- Among the therapeutic options, wide surgical excision is gen-
ventional SCC, especially with SCC that exhibits a “verrucoid” erally considered the treatment of choice, with recommended
appearance. The accurate diagnosis of VC can be challenging safety margins of at least 5 mm to minimize the risk of local
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and requires an adequate incisional biopsy, as well as close recurrence. 12,16,19,43,44 Neck dissection is typically not required
cooperation between the clinician and the pathologist. In this for VC, as the neoplasm tends to invade locally but rarely me-
context, superficial biopsies may microscopically display only tastasizes to lymph nodes. 19,45,46 In this context, cervical
benign features, such as hyperkeratosis, acanthosis, and pap- lymphadenopathy associated with VC represents, in most cas-
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illomatosis, leading to an erroneous diagnosis of benign squa- es, reactive changes rather than metastases. In cases involv-
mous proliferation. Therefore, a broad and deep biopsy is re- ing extensive lesions, surgery may not be feasible and lead to
16
quired to obtain an accurate microscopic diagnosis, avoiding unsatisfactory functional and cosmetic results. When resec-
the need for multiple biopsies and the misinterpretation of a tion is not indicated, therapeutic alternatives can be used,
malignant process as benign. 1,29,32,33 such as cytostatic drugs, imiquimod, α-interferon, and oral
4
The definitive diagnosis of VC is usually based on histo- retinoids. The use of high-dose cytostatic agents has shown
pathological examination of clinically suspicious oral lesions benefits in reducing VC size, while the complementary use of
and requires the identification of the histological criteria de- interferon (IFN) has the potential to slow tumor growth. Che-
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1
scribed by Ackerman. Histopathologically, VC typically pres- motherapy with bleomycin or methotrexate has demonstrated
ents with predominantly exophytic growth of well-differenti- success, used either as a monotherapy for inoperable cases or
ated hyperplastic epithelium, exhibiting a heavily keratinized as neoadjuvant therapy to reduce the size of extensive lesions
or parakeratinized surface and sharp or blunt epithelial projec- prior to surgery. 48,49
tions. In addition, scarce fibrovascular cores are noted, as well Regarding radiotherapy, some studies report the occur-
as numerous clefts between epithelial projections filled with rence of radiation-induced anaplastic transformation of VC,
keratin (keratin plugging). An intense subepithelial chronic in- which usually manifests 2−8 months after the end of treat-
flammatory infiltrate is often present. Other important histo- ment. 50,51 Although the potential for anaplastic transforma-
pathological features include an intact basement membrane, tion remains controversial, radiotherapy is considered a sal-
preservation of stratification, minimal or absent atypia, and vage option when surgery is not feasible or when
bulbous epithelial ridges, displaying an endophytic growth pat- histopathological findings indicate adverse risk features, such
tern that compresses the underlying connective tissue. 13,31,34,35 as positive lymph nodes or invasion of deeper vital structures
The abrupt transition between the adjacent normal epithelium (e.g., nerves and blood vessels). 8,13,52
and the endophytic growth of the lesion is considered a critical Regardless of the treatment modality, local recurrence
feature for distinguishing VC from benign verrucous process- rates are high, ranging from 30% to 50%, with a tendency to
32
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es. The cases presented herein showed microscopic findings recur in the form of less differentiated carcinomas. Never-
consistent with these aforementioned features. theless, the prognosis for oral VC is usually favorable com-
Several studies have demonstrated cases of SCC arising pared to other malignant tumors (7−8% mortality rate), except
within VC. It is suggested that VC may arise de novo or from ep- for hybrid carcinoma cases, which carry a worse prognosis and