Oral Mucosa and Saliva Alterations Related to Vape.

OBJECTIVES: Electronic nicotine delivery systems (e-cigarette, pod, and vape) are currently among the tobacco consumption of adolescents and young adults. The aim is to show oral mucosa and saliva alterations related to vape. MATERIAL AND METHODS: A vape-user patient, presenting a white plaque in the posterior region of the hard palate, underwent clinical examination, sialometry, pH evaluation, and excisional biopsy of the white lesion. Molecular changes in saliva and vape liquid were analyzed by vibrational spectroscopy. RESULTS: The histopathological analyses showed hyperparakeratosis without dysplasia. Formaldehyde, ketones, and aromatic hydrocarbon species were identified in e-cig liquid by the FTIR. CONCLUSIONS: The use of vape may be related to the development of hyperkeratotic lesions in the oral mucosa as well as significantly modify the patient's salivary patterns as the vape liquid presents carcinogenic and cytotoxic components in its composition.

Associations between the keratinized mucosa width and the underlying alveolar bone dimensions at partial edentulous molar sites: a retrospective cross-sectional study.

BACKGROUND: The assessment of hard and soft tissue at edentulous sites is important for subsequent implant treatment design. The aim of the present study was to explore the associations between the keratinized mucosa width (KMW) and the underlying alveolar bone dimensions at partial edentulous molar sites. METHODS: In this retrospective study, a total of 110 patients with at least one missing molar were selected. The buccal KMW of the edentulous molar sites was evaluated. Cone-beam computed tomography scans were collected, and the height discrepancy between the alveolar crest and the buccal bone plate (HC-B) as well as the alveolar bone height (ABH) were measured. The KMW was compared among the HC-B and ABH groups at both maxillary and mandibular sites. Linear regression and generalized estimation equations (GEEs) were used to explore the associations between the KMW and alveolar bone dimensions at α = 0.05. RESULTS: Among the 110 patients, 158 edentulous molar sites were analyzed. The average HC-B and ABH were significantly lower at the maxillary sites (1.26 ± 1.62 mm, 11.62 ± 3.94 mm) than at the mandibular sites (3.67 ± 2.85 mm, 14.91 ± 3.01 mm, p < 0.001). The KMW was significantly lower at sites with HC-B > 2 mm than at sites with HC-B ≤ 2 mm both in the maxilla and mandible (p < 0.001). No significant differences were found between the KMW at sites with ABH < 10 mm and sites with ABH ≥ 10 mm (p > 0.05). Linear regression and GEEs analyses revealed that the HC-B was significantly associated with the KMW (B = -0.339, p < 0.001), while the association between the KMW and the ABH was not statistically significant (B = -0.046, p = 0.352). CONCLUSIONS: The buccal KMW at edentulous molar sites was significantly associated with the HC-B. Alveolar ridges presenting with a sloped configuration were more prone to possess a narrower band of keratinized mucosa. Both hard and soft tissue augmentation should be considered for implant treatment at these sites. The correlations of dynamic changes between the KMW and alveolar bone dimensions after tooth extraction should be further investigated.

[Clinicopathological features of primary mucosal CD30-positive T-cell lymphoproliferative disorders].

Objective: To investigate the clinicopathological features and differential diagnosis of primary mucosal CD30-positive T-cell lymphoproliferative disorders (pmCD30+TLPD). Methods: Eight cases of pmCD30+TLPD diagnosed from 2013 to 2023 at the Department of Pathology, Beijing Friendship Hospital Affiliated to Capital Medical University and Beijing Ludaopei Hospital were retrospectively collected. The immunophenotype, EBV infection status and T-cell receptor (TCR) clonability of tumor cells were examined. The clinicopathological features were analyzed and related literatures were reviewed. Results: There were 5 females and 3 males, aged 28 to 73 years, without B symptoms, lack of trauma and autoimmune diseases. Seven cases occurred in oral mucosa and one in anal canal mucosa. Submucosal nodules with ulcerations were presented in all cases except one, which only submucosal nodule. Morphologically, there was different distribution of allotypic lymphocytes in inflammatory background. Four cases showed "kidney-shaped", "embryonic" and "horseshoe-shaped" cells, and one case resembled Hodgkin and Reed/Sternberg (HRS) cells. Allotypic lymphocytes expressed CD3 (7/8), CD4+/CD8-(7/8) and CD4-/CD8-(1/8). CD30 was uniformly strongly positive while ALK and CD56 were negative. In situ hybridization of EBER was negative in five cases (5/5). Clonal TCR gene rearrangement was positive in two cases. Four patients did not receive radiotherapy or chemotherapy. All the seven patients survived without disease except one died due to concurrent leukopenia. Conclusions: pmCD30+TLPD had a broad morphological spectrum and could be easily confused with primary cutaneous CD30+TLPD and systemic ALK-negative anaplastic large cell lymphoma involving mucosa, which may lead to misdiagnosis. Although the majority of the cases had a favorable prognosis, a few cases relapsed or progressed to lymphoma.

A case of larva migrans representing a pitfall in oral diagnosis.

The present work reports a case of a female patient complaining of itching and painful lesions affecting the oral mucosa for 7 months. Buccal and lip mucosa showed swelling and erythema, with serpiginous tracks. The patient was diagnosed with oral larva migrans, and the lesions resolved after ivermectin administration. At 18-month follow-up, no sign of recurrence was observed. Larva migrans can represent a pitfall in oral diagnosis and a stressful condition for the patient. Oral health care providers should be aware of this and keep this disease in mind as a possible differential diagnosis in oral mucosa lesions.

Evaluation of Turkish dentists' knowledge about oral cancer and oral mucosal lesions.

BACKGROUND/PURPOSE: Oral cancer, including malignancies of the tongue, lips, floor of the mouth, cheek mucosa, gums, palate, and oropharynx, is life-threatening. Early diagnosis and appropriate treatment are crucial for long-term survival. Dentists frequently encounter oral cancers due to the nature of their work. This study aimed to evaluate the knowledge and experience of dentists in Turkey regarding oral cancers. MATERIALS AND METHODS: A total of 361 participants were included in the study, and survey questions were sent via email. The survey consisted of 16 questions measuring demographic data and knowledge about oral cancerous lesions. Participants were grouped based on their specialization and knowledge level, and differences in responses among groups were examined. RESULTS: Only 21.3% of the participants felt they had sufficient knowledge and experience about oral cancerous lesions. Overall, the correct answer rates indicated a moderate level of knowledge and experience. When grouped by specialization, oral surgeons had the highest accuracy in their responses (p < 0.05). CONCLUSION: Dentists are the professional group that most frequently encounters clinically oral cancerous lesions. Therefore, it is critically important for them to be knowledgeable and experienced to reduce morbidity and mortality through early diagnosis. This study evaluated the knowledge status of dentists in Turkey regarding oral cancer and highlighted the need for improved education.

Association of Peri-Implant Mucosa Dimensions With Emergence Profile Angles of the Implant Prosthesis.

OBJECTIVES: The primary aim of this cross-sectional study was to investigate the association between prosthesis design and peri-implant mucosa dimensions and morphology. The secondary aim was to investigate associations between mucosal dimensions and the presence of mucositis. MATERIALS AND METHODS: Forty-seven patients with 103 posterior bone level implants underwent clinical and radiographic examination, including cone beam computer tomography and intraoral optical scanning. Three-dimensional models for each implant and peri-implant mucosa were constructed. Vertical mucosa height (TH), horizontal mucosa width at implant platform (TW), and 1.5 mm coronal of the platform (TW1.5), as well as mucosal emergence angle (MEA), deep angle (DA), and total contour angle (TA) were measured at six sites for each implant. RESULTS: There was a consistent correlation between peri-implant mucosa width and height (ß = 0.217, p < 0.001), with the width consistently surpassing height by a factor of 1.4-2.1. All three angles (MEA, DA, TA) were negatively associated with mucosa height (p < 0.001), while DA was negatively associated with mucosa width (TW1.5) (p < 0.001, ß = -0.02, 95% CI: -0.03, -0.01). There was a significant negative association between bleeding on probing (BoP) and mucosa width at platform (OR 0.903, 95% CI: 0.818-0.997, p = 0.043) and 1.5 coronal (OR 0.877, 95% CI: 0.778-0.989, p = 0.033). Implants with less than half sites positive for BoP (0-2/6) had significantly higher mucosa height (OR 3.51, 95% CI: 1.72-7.14, p = 0.001). CONCLUSIONS: Prosthesis design can influence the dimensions of the peri-implant mucosa, with wider emergence profile angles associated with reduced peri-implant mucosa height. In particular, a wider deep angle is associated with reduced mucosa width in posterior sites. Reduced peri-implant mucosa height and width are associated with more signs of inflammation. TRIAL REGISTRATION: Registered in Thai Clinical Trials Registry: http://www.thaiclinicaltrials.org/show/TCTR20220204002.

Establishment of Canine Oral Mucosal Melanoma Cell Lines and Their Xenogeneic Animal Models.

Canine oral melanoma is the most prevalent malignant tumor in dogs and has a poor prognosis due to its high aggressiveness and high metastasis and recurrence rates. More research is needed into its treatment and to understand its pathogenic factors. In this study, we isolated a canine oral mucosal melanoma (COMM) cell line designated as COMM6605, which has now been stably passaged for more than 100 generations, with a successful monoclonal assay and a cell multiplication time of 22.2 h. G-banded karyotype analysis of the COMM6605 cell line revealed an abnormal chromosome count ranging from 45 to 74, with the identification of a double-armed chromosome as the characteristic marker chromosome of this cell line. The oral intralingual and dorsal subcutaneous implantation models of BALB/c-nu mice were successfully established; Melan-A (MLANA), S100 beta protein (S100ß), PNL2, tyrosinase-related protein 1 (TRP1), and tyrosinase-related protein 2 (TRP2) were stably expressed positively in the canine oral tumor sections, tumor cell lines, and tumor sections of tumor-bearing mice. Sublines COMM6605-Luc-EGFP and COMM6605-Cherry were established through lentiviral transfection, with COMM6605-Luc-EGFP co-expressing firefly luciferase (Luc) and enhanced green fluorescent protein (EGFP) and COMM6605-Cherry expressing the Cherry fluorescent protein gene. The COMM6605-Luc-EGFP fluorescent cell subline was injected via the tail vein and caused lung and lymph node metastasis, as detected by mouse live imaging, which can be used as an animal model to simulate the latter steps of hematogenous spread during tumor metastasis. The canine oral melanoma cell line COMM6605 and two sublines isolated and characterized in this study can offer a valuable model for studying mucosal melanoma.

[Verruciformes Xanthom an der linken Wange bei einer 56-jährigen Patientin - Diagnostik, Therapie und Nachsorge].

The oral verruciform xanthoma (OVX) is a rare, benign lesion that occurs predominantly in the masticatory region of the oral cavity. The OVX is small, slow growing, and mostly free of clinical symptoms. The exact pathogenesis is unknown, and a viral etiology such as from a human papillomavirus (HPV) infection has not been proven. Although primarily observed in healthy individuals, there have been cases in patients with autoimmune diseases and with chronic graft-versus-host disease (GvHD). The treatment of choice is complete excision of the lesion. This case report showcases a successful surgical removal of an oral verruciform xanthoma on the left buccal mucosa in a 56-year-old patient with GvHD 14 years after allo-genic stem cell transplantation due to a Non-Hodgkin lymphoma.

Case Report: Recalcitrant oral lichen planus involving bilaterally buccal mucosae treated with a combination of photodynamic and photobiomodulation therapies.

Background: Managing recalcitrant oral lichen planus (OLP) can be challenging. Laser therapy has been suggested as an alternative to corticosteroids for treatment. Photodynamic therapy (PDT) is a non-invasive technique that enables the removal of lesions without surgery. Photobiomodulation therapy (PBMT) can promote healing and recovery of the lesions. Case presentation: The objective was to treat unresponsive bilateral OLP of the whole buccal mucosae with a combination of PDT and PBMT. Results: A 43-year-old Thai male presented with the severe painful reticular type of OLP of bilateral buccal mucosae involving upper and lower vestibular areas. The lesions were not remitted with either prednisolone systemic steroids or fluocinolone topical corticosteroids. After undergoing ten sessions of PDT with 10% 5-Aminolevulinic acid (5-ALA) in the form of thermoplastic gel and a 635 nm diode laser at 100 to 400 mW with an energy density of 20 to 30 J/cm 2 in continuous wave mode, combined with five interim-sessions of PBMT using a 635 nm diode laser at 200 to 300 mW with an energy density of 6 to 10 J/cm 2 in continuous wave, the patient reported relief of burning sensation beside remission of lesions without any complications. Conclusion: The wide-spreading recalcitrant OLP with burning sensation can be managed by combining PDT and PBMT.

The features of the reparative regeneration of an oral mucosa wound created under the exposure of a laser at a wavelength of 445 nm (a pilot study).

In clinical practice, an innovative laser technology that provides contactless preparation of soft tissues with a wavelength of 445 nm has been introduced. This study aimed to investigate the morphological changes in the oral mucosa when exposed to laser radiation at a wavelength of 445 nm in the ablation mode.An experimental study was conducted to analyze the dynamics of reparative regeneration in the wound caused by that particular type of radiation, utilizing the procedure of lower lip frenuloplasty as an illustration. 48 sexually mature male laboratory rats were chosen as the research object. The procedure of preparing the oral vestibule was executed by employing a contactless laser beam with a wavelength of 445 nm and a power of 0.7 W in continuous mode (CW) and an uninitiated fiber.Histological examination showed that 25 min after the surgery, there were large areas of coagulation necrosis in the oral mucosa in the area affected by the blue laser. In 48 h, the area of necrosis decreased both in size and depth. By the 7th day after the surgery, the necrotic masses had grown into the connective tissue, while marginal regeneration of the epithelium was noted. By the 14th day, the wound surface was completely epithelialized, represented by fibrous scar tissue. Clinically, around the mandibular incisors, there was a wide area of attached keratinized gingiva.The findings of histological examination indicate a necrosis of coagulation type in the region of tissue ablation and also show the absence of phase II of the inflammatory response (the stage of exudation), which expedites the process of epithelialization of the oral mucosa wound.

Molecular histopathology of matrix proteins through autofluorescence super-resolution microscopy.

Extracellular matrix diseases like fibrosis are elusive to diagnose early on, to avoid complete loss of organ function or even cancer progression, making early diagnosis crucial. Imaging the matrix densities of proteins like collagen in fixed tissue sections with suitable stains and labels is a standard for diagnosis and staging. However, fine changes in matrix density are difficult to realize by conventional histological staining and microscopy as the matrix fibrils are finer than the resolving capacity of these microscopes. The dyes further blur the outline of the matrix and add a background that bottlenecks high-precision early diagnosis of matrix diseases. Here we demonstrate the multiple signal classification method-MUSICAL-otherwise a computational super-resolution microscopy technique to precisely estimate matrix density in fixed tissue sections using fibril autofluorescence with image stacks acquired on a conventional epifluorescence microscope. We validated the diagnostic and staging performance of the method in extracted collagen fibrils, mouse skin during repair, and pre-cancers in human oral mucosa. The method enables early high-precision label-free diagnosis of matrix-associated fibrotic diseases without needing additional infrastructure or rigorous clinical training.

Evaluation of micronuclei, cytomorphometric and cytologic changes of the oral mucosa in hookah and cigarette smokers.

OBJECTIVE: To analyze the effect of hookah and cigarettes on the oral mucosa of smokers through the use of exfoliative cytology. STUDY DESIGN: Smear samples were collected by exfoliative cytology from the tongue of 33 hookah smokers, 22 cigarette smokers, and 30 non-smokers. The selected analyses include micronuclei (MN), metanuclear anomalies, epithelial maturation, and cytomorphology (nuclear area [NA], cytoplasmic area [CA], and NA/CA ratio). RESULTS: The largest differences observed for MN and metanuclear anomalies were between cigarette smokers and the control group (notably 1 MN P = .04; total cells with MN P = .039; total MN P = .042; karyorrhexis and binucleation, P = .0001). The hookah group, compared with the control group, showed the greatest differences for karyolysis (P = .0023), binucleation (P = .0003), and broken egg (P = .008). Significant differences were found between the smokers and the control groups regarding changes in the superficial cell without nucleus, perinuclear halo, vacuolization, color change, mucus, and keratohyalin granules. There was a significant increase in the NA and NA/CA ratio in the smoker groups. CONCLUSION: This study showed that a combined analysis of exfoliative cytology associated with other diagnostic methods is a useful tool for studying oral carcinogenesis. Hookah and cigarettes showed similar effects in terms of displaying substantial cytogenetic and cytotoxic damage.

Ocular Cicatricial Pemphigoid in Young Patients.

PURPOSE: The purpose of this study is to report ocular cicatricial pemphigoid (OCP) occurring in young patients. Relevant literature is also reviewed. METHODS: Medical records of patients aged 30 years or younger who were treated for OCP between August 2021 and May 2023 at a tertiary care eye institute were reviewed. The most common differential diagnoses of cicatrizing conjunctivitis, such as Stevens-Johnson syndrome sequelae, chemical injury, chronic topical/systemic drug use, autoimmune connective tissue disorders, or allergic eye diseases, were ruled out based on clinical history, examination, and the Cicatrizing Conjunctivitis Score described by Shanbhag et al. The diagnosis of OCP was confirmed by positive direct immunofluorescence of oral mucosal and/or conjunctival biopsy in a majority of the patients. RESULTS: Seven patients fulfilled the criteria for a diagnosis of OCP. The mean age at presentation was 21.86 ± 5.25 years (13-28 years). Some of the patients presented with relatively atypical features for OCP such as corneal immune ring infiltrate and bilateral corneal perforation. Six patients exhibited systemic mucosal lesions, and the direct immunofluorescence yield was 85.71%. All patients required aggressive immunosuppressive treatment. CONCLUSIONS: OCP is classically described as a rare disease that occurs in old age. This case series highlights the importance of a higher index of suspicion for diagnosing OCP at a younger age. Early administration of immunosuppressive agents can potentially control severe ocular surface inflammation and its sequelae.

An Update on the Use of Artificial Intelligence in Digital Pathology for Oral Epithelial Dysplasia Research.

INTRODUCTION: Oral epithelial dysplasia (OED) is a precancerous histopathological finding which is considered the most important prognostic indicator for determining the risk of malignant transformation into oral squamous cell carcinoma (OSCC). The gold standard for diagnosis and grading of OED is through histopathological examination, which is subject to inter- and intra-observer variability, impacting accurate diagnosis and prognosis. The aim of this review article is to examine the current advances in digital pathology for artificial intelligence (AI) applications used for OED diagnosis. MATERIALS AND METHODS: We included studies that used AI for diagnosis, grading, or prognosis of OED on histopathology images or intraoral clinical images. Studies utilizing imaging modalities other than routine light microscopy (e.g., scanning electron microscopy), or immunohistochemistry-stained histology slides, or immunofluorescence were excluded from the study. Studies not focusing on oral dysplasia grading and diagnosis, e.g., to discriminate OSCC from normal epithelial tissue were also excluded. RESULTS: A total of 24 studies were included in this review. Nineteen studies utilized deep learning (DL) convolutional neural networks for histopathological OED analysis, and 4 used machine learning (ML) models. Studies were summarized by AI method, main study outcomes, predictive value for malignant transformation, strengths, and limitations. CONCLUSION: ML/DL studies for OED grading and prediction of malignant transformation are emerging as promising adjunctive tools in the field of digital pathology. These adjunctive objective tools can ultimately aid the pathologist in more accurate diagnosis and prognosis prediction. However, further supportive studies that focus on generalization, explainable decisions, and prognosis prediction are needed.

Local intralesional talimogene laherparepvec therapy with complete local response in oral palatine mucosal melanoma: a case report.

BACKGROUND: Mucosal melanoma, an aggressive type of malignancy different from the cutaneous melanomas commonly seen in the head and neck region, represents < 1% of all malignant melanomas. The pathogenesis of mucosal melanoma is unknown. Targetable mutations commonly seen in cutaneous melanoma, such as in the BRAF and NRAS genes, have a lower incidence in mucosal melanoma. Mucosal melanoma carries a distinct mutational pattern from cutaneous melanoma. Surgery with negative margins is the first-line treatment for mucosal melanoma, and systemic therapy is not well defined. Talimogene laherparepvec, an oncolytic viral immunotherapy, is United States Food and Drug Administration approved for the treatment of advanced malignant cutaneous melanoma, with local therapeutic benefits. Mucosal melanoma was initially excluded from talimogene laherparepvec's initial phase III clinical trial. CASE PRESENTATION: We present the case of a white female patient in her 40s with past medical history of systemic lupus erythematous, scleroderma, and estrogen-receptor-positive invasive ductal breast carcinoma. Following a bilateral mastectomy, the patient was found to have BRAF-negative mucosal melanoma of her hard palate with a soft palate skip lesion. Owing to the presence of a skip mucosal lesion as well as the anticipated defect and need for free-flap reconstructive surgery, nonsurgical management was considered. The patient was referred to medical oncology, where-based on the patient's complicated medical history and the risk of immunotherapy possibly worsening her prior autoimmune diseases-local talimogene laherparepvec injections were chosen as the primary therapy for her mucosal lesions. Though talimogene laherparepvec is approved for the treatment of cutaneous melanoma, there are limited data available on the use of talimogene laherparepvec in mucosal melanomas. CONCLUSION: The patient had a complete local tumor response at both the primary lesion as well as the skip lesion with the local injections. She had no side effects and maintained a high quality of life during treatment.

Novel Histopathological Findings of Micro Bone Fragments and Epithelial Response in the Oral Mucosa in Bisphosphonate-Related Osteonecrosis of the Jaw.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) occurs in the jawbone and interfacing oral mucosa of patients treated with bisphosphonates. Herein, we report novel histopathological findings in the oral mucosa of a surgical specimen obtained from a 61-year-old man with BRONJ. The resected jawbone and adjacent oral mucosa were separated for histological examination. The mucosal tissue was examined using Von Kossa staining and immunohistochemical (CK5/6, p63) staining of non-decalcified paraffin sections. Pseudoepitheliomatous hyperplasia (PEH), a microscopic feature of the mucosal epithelium in BRONJ, was observed in soft tissue specimens, concomitant with inflammatory cell infiltration. Von Kossa staining revealed small fragments of necrotic bone, tens to hundreds of micrometers in size, scattered within the connective tissues; the PEH forefront contacted some of the bone fragments. Immunohistochemical staining demonstrated that occasionally, the PEH not only contacted but also encompassed the bone fragments. To our knowledge, this is the first report of presence of micro bone fragments and their association with PEH in the oral mucosa in BRONJ.

Fixed drug eruption secondary to etoricoxib.

Fixed drug eruptions (FDE) are adverse cutaneous drug reactions and a form of delayed type 4 hypersensitivity reaction characterised by recurrent lesions at the same site each time a specific drug is taken. They most commonly result in cutaneous lesions presenting as an erythematous round or oval macule or plaque. FDEs have rarely been reported to affect oral mucous membranes and tend to have a bullous or aphthous-like appearance with erythema. Almost half of patients report an increase in the severity of symptoms with prolonged exposure to the offending medication. The most commonly attributed classes of drug are antibiotics (tetracyclines and sulphonamides) alongside non-steroidal anti-inflammatory drugs. Cutaneous adverse reactions to etoricoxib, a highly selective COX-2 inhibitor, have been reported. Here we describe an adverse reaction restricted to the oral mucosa.

Tumor budding is an optimal indictor of occult cervical metastasis in clinical early-stage buccal mucosa squamous cell carcinoma.

BACKGROUND: Buccal mucosa squamous cell carcinoma (BMSCC) is an aggressive disease. This study investigated the clinicopathological significance of tumor budding (TB), depth of invasion (DOI), and mode of invasion (MOI) on occult cervical metastasis (CM) of BMSCC. METHODS: Seventy-one cT1-2N0 BMSCC patients were included in this retrospective study. TB, DOI, MOI, and other clinicopathological features were reviewed. Risk factors for occult CM, locoregional recurrence-free survival (LRRFS), and overall survival (OS) were analyzed using logistic regression and Cox's proportional hazard models, respectively. RESULTS: Multivariate analysis with the logistic regression model revealed that MOI, DOI, and TB were significantly associated with occult CM in early-stage BMSCC after adjusting for variates. However, multivariate analysis with the Cox's proportional hazard model found only TB to be a prognostic factor for LRRFS (hazard ratio 15.03, 95% confidence interval [CI] 1.94-116.66; p = 0.01; trend test p = 0.03). No significant association was found between MOI, DOI, or TB and OS. CONCLUSIONS: The optimal predictor of occult CM and prognosis of early-stage BMSCC is TB, which may assist clinicians in identifying patients at high risk of cervical metastasis.

Malignant transformation of white sponge nevus: a case report of a novel keratin 4 mutation.

BACKGROUND: White Sponge Nevus (WSN) is traditionally considered a benign genetic disorder affecting the oral mucosa, primarily caused by pathogenic mutations in keratin 4 (KRT4) or keratin 13 (KRT13). Despite its benign nature, recent evidence has begun to question the malignant potential of WSN. CASE PRESENTATION: We report a case involving a 70-year-old man who presented with a white lesion on the right floor of his mouth. Initial diagnostic evaluations confirmed the lesion as WSN. Over a one-year follow-up, the lesion underwent malignant transformation, evolving into local epithelial moderate-to-severe dysplasia. Exome sequencing identified a novel insertion mutation in exon 1 of the KRT4 gene, resulting in a deletion-insertion amino acid mutation involving glycine. Single-cell RNA sequencing further revealed altered epithelial proliferation and differentiation dynamics within the lesion. CONCLUSIONS: This case not only expands the known genetic spectrum of KRT4 mutations associated with WSN but also provides preliminary evidence suggesting the malignant potential of WSN. The novel pathogenic mutation in KRT4 is postulated to alter epithelial proliferation and differentiation, thereby raising concerns about the malignant transformation of WSN. Further studies are warranted to confirm these findings.