Potential For Malignant Transformation Research Articles

Malignant Transformation and Treatment Recommendations of Chronic Hyperplastic Candidiasis-A Six-year Retrospective Cohort Study.

Oral chronic hyperplastic candidiasis (CHC) is the most uncommon type of oral candidiasis with diverse manifestations. Up to date the diagnosis, long-term management and prognosis of this oral potentially malignant disorder remain obscure. The aim of this study was to provide the recommendations guiding the diagnostic procedure, clinical management and prognosis assessment of CHC. A retrospective cohort study was performed during January 2015 to April 2021 involving patients with a definite diagnosis of CHC in the Department of Oral Medicine of Peking University School and Hospital of Stomatology. Demographic features, clinical and histopathological features, treatment protocols and follow-ups including malignancy transformation were analysed. Fourty eight CHC patients were collected and reviewed, with a male-to-female ratio of 2.69:1. The average age at diagnosis was 54.92±9.79 (36-80) years old. Clinically, the multiform oral lesions were diverse and frequently presented as white plaque and erythematous lesions. As a result, the initial diagnostic accordance rate was only 54.17%, and the most common presumptive initial diagnoses were oral lichen planus (22.92%), oral leukoplakia (20.83%) and traumatic lesion (2.08%). Histopathologically, ten (20.83%) patients had varying degrees of epithelial dysplasia, and two (4.17%) patients had malignant transformation with a mean transformation time of 6.5±6.36months. Among the 28 patients who underwent fungal culture, 24 patients were exclusively infected by Candida albicans, with two patients each mixed infected by Cglabrata and Ctropicalis, respectively. Notably, treatment with fluconazole had the lower recurrence rate compared with topical nystatin. The diagnosis and management of CHC remain a challenge due to its polymorphic clinical presentations, chronic progression and potential of malignant transformation.

Burden of Renal Cysts Imaging: A Survey of Patients among the Greater Plains Collaborative

Purpose: Renal cysts are a frequent incidental finding on cross-sectional radiographic imaging. While most cysts are indolent, individuals with such cysts are frequently monitored for interval growth and potential malignant transformation, which is ultimately rare. In this study, we aimed to assess patients’ values and preferences (believes and attitudes) about renal cysts. Methods: We deployed a cross-sectional survey to a random sample of patients with a diagnosis of renal cysts who were identified by billing code and self-identification. We collected data about demographics, insurance status, family history and overall health, and characteristics of patients with renal cysts. We performed a binary regression analysis (adjusted for age, gender, family history of cancer and kidney disease, and treatment plan for renal cysts) to determine anxiety predictors in patients with renal cysts. Results: We included 301 respondents in whom billing code and self-identification corresponded; of these, 138 had renal cysts and 163 did not. In an adjusted regression analysis, there was a suggestion that a clear management plan (OR = 0.49, 95% CI [0.22–1.11]) (p value 0.08) may be associated with less anxiety and a family history of renal disease may be associated with more anxiety (OR = 1.94 [0.76–4.94]) (p value 0.17). Family history of cancer also did not significantly predict anxiety (OR = 0.54 [0.24–1.19]) (p value 0.13). All these results were not statistically significant and had wide confidence intervals of the effect estimates make the results imprecise. Conclusion: Findings of this pilot study suggest a clear management plan for the renal cyst(s) management may be associated with a lower level of anxiety, thereby by emphasizing the importance of good communication, patient engagement and evidence-based guidance. More definitive, adequately powered studies are needed to evaluate this finding further. In addition, further studies exploring differences in imaging practices, patient symptomatology and patient engagement by different provider types would be insightful. Ultimately, tools to improve shared decision-making are needed to provide more patient-centered care.

Bladder Substitution: The Role of Tissue Engineering and Biomaterials

Tissue engineering could play a major role in the setting of urinary diversion. Several conditions cause the functional or anatomic loss of urinary bladder, requiring reconstructive procedures on the urinary tract. Three main approaches are possible: (i) incontinent cutaneous diversion, such as ureterocutaneostomy, colonic or ileal conduit, (ii) continent pouch created using different segments of the gastrointestinal system and a cutaneous stoma, and (iii) orthotopic urinary diversion with an intestinal segment with spherical configuration and anastomosis to the urethra (neobladder, orthotopic bladder substitution). However, urinary diversions are associated with numerous complications, such as mucus production, electrolyte imbalances and increased malignant transformation potential. In this context, tissue engineering would have the fundamental role of creating a suitable material for urinary diversion, avoiding the use of bowel segments, and reducing complications. Materials used for the purpose of urinary substitution are biological in case of acellular tissue matrices and naturally derived materials, or artificial in case of synthetic polymers. However, only limited success has been achieved so far. The aim of this review is to present the ideal properties of a urinary tissue engineered scaffold and to examine the results achieved so far. The most promising studies have been highlighted in order to guide the choice of scaffolds and cells type for further evolutions.

Targeted gene expression profiling of inverted papilloma and squamous cell carcinoma

Inverted papilloma (IP) is a sinonasal tumor with a well-known potential for malignant transformation. The purpose of this study was to identify the genes and pathways associated with IP, with progression to carcinoma-in-situ and invasive carcinoma. To determine genes and molecular pathways that may indicate progression and correlate with histologic changes, we analyzed six IP without dysplasia, five IP with carcinoma-in-situ, and 13 squamous cell carcinoma ex-IP by targeted sequencing. The HTG EdgeSeq Oncology Biomarker Panel coupled with next-generation sequencing was used to evaluate 2560 transcripts associated with solid tumors. Progressive upregulation of 11 genes were observed (CALD1, COL1A1, COL3A1, COL4A2, COL5A2, FN1, ITGA5, LGALS1, MMP11, SERPINH1, SPARC) in the order of invasive carcinoma>carcinoma-in-situ>IP without dysplasia. When compared with IP without dysplasia, more genes are differentially expressed in invasive carcinoma than carcinoma-in-situ samples (341 downregulated/333 upregulated vs. 195 downregulated/156 upregulated). Gene set enrichment analysis determined three gene sets in common between the cohorts (epithelial mesenchymal transition, extracellular matrix organization, and coagulation). Progressive upregulation of genes specific to IP malignant degeneration has significant clinical implications. This panel of 11 genes will improve concordance of histologic classification, which can directly impact treatment and patient outcomes. Additionally, future studies on larger tumor sets may observe upregulation in the gene panel that preceded histologic changes, which may be useful for further risk stratification.

Eficacia del ácido hialurónico tópico para el liquen plano oral sintomático: Revisión Sistemática

Background: Oral lichen planus (OLP) is a chronic inflam-matory disorder with a potential of malignant transformation. Despite the extensive research on the topic, the management of OLP is still quite challenging, with no definitive cure. Objective: The present systematic review assessed the efficacy of topical hyaluronic acid in the management of OLP. Material and Methods: A comprehensive search of PubMed, Scopus, Web of Science and Google Scholar was carried out by two independent investigators. All randomized clinical trials that compared the efficacy of hyaluronic acid with other interventions and/or placebo in the management of OLP and fulfilled the following criteria were included: 1) OLP diagnosis was confirmed clinically and histopathologically, 2) the study included systemically healthy patients aged 15 years and older, 3) a minimum sample size of 10, and 4) reporting the main outcomes including pain, erythema, and ulcer size. Case reports, case series, reviews, animal studies, uncontrolled trials were excluded. Results: Four clinical trials involving 234 patients were included. Two studies compared hyaluronic acid with a topical corticosteroid, and two studies compared it with placebo. Only one of the four included studies was at low risk of bias. Overall, topical hyaluronic acid showed good efficacy in alleviating the signs and symptoms of OLP. Two studies found hyaluronic acid significantly more effective in reducing pain and improving clinical signs of OLP compared to placebo. Compared to topical corticosteroids, one study reported comparable results; and one study found hyaluronic acid to be superior to triamcinolone in reducing pain but inferior to triamcinolone in improving the healing time. Conclusion: The limited available evidence suggests that hyaluronic acid may have some benefits in the management of OLP. Further well-designed studies with adequate follow-up periods are highly recommended.

Systematized Epidermal Nevus Syndrome Involving the Upper and Lower Eyelids Bilaterally

A 29-year-old woman presented with dark-colored raised lesions on both eyelids since early childhood. Ophthalmological examination revealed pigmented verrucous lesions on her upper and lower eyelids bilaterally. The patient had a history of generalized tonic-clonic seizures. Dermatological examination revealed hyperpigmented verrucous plaques arranged along lines of Blaschko on the neck, trunk, and arms. On the basis of these findings, the diagnosis of epidermal nevus syndrome (ENS) was made. She had surgery for debulking of the lesions. Histological analysis revealed hyperkeratosis with foci of parakeratosis, acanthosis, and papillomatosis, consistent with linear verrucous epidermal nevus. Postoperative residual lesions did not respond to oral acitretin therapy (10 mg/kg/day for 2 months). Systematized ENS can rarely cause linear verrucous nevi on the upper and lower eyelids on both sides. These patients should be investigated for accompanying systemic anomalies and followed for potential malignant transformation of the skin lesions.

A machine-learning algorithm for the reliable identification of oral lichen planus.

Oral lichen planus (OLP) is a relatively common oral disorder which shares clinical and histopathological features with other lichenoid lesions, leading to considerable inter-observer disagreement. This negatively impacts understanding of the pathogenesis and malignant transformation potential of this condition. Artificial intelligence was employed to create a machine-learning artificial neural network to identify and quantify mononuclear cells and granulocytes within the inflammatory infiltrates in digitized hematoxylin and eosin microscopic slides. Twenty-four regions of interest were extracted from OLP cases for learning purposes and validated on a retrospective cohort of 130 cases. All cases were related to patients with confirmed diagnoses of OLP, oral lichenoid lesions (OLLs), or oral epithelial dysplasia (OED) with lichenoid host response. The number of inflammatory cells was statistically significantly higher in OLP compared to OLLs or OED with lichenoid host response (p<0.0005). The proposed machine-learning method was reliably capable of detecting OLP cases based on the number of inflammatory cells and the number of mononuclear cells with an area under the curve of 0.982 and 0.988, respectively. Identifying a cut-off point between OLP and other lichenoid conditions based on the number of mononuclear cells showed a sensitivity of 100% and an accuracy of 94.62%. Artificial intelligence has shown promising outcomes and provides a robust approach to enhance the accuracy of anatomical pathologists in accurately diagnosing OLP using features of disease pathogenesis.

28521 Frequency of procedural and medical treatments for actinic keratosis

Actinic keratosis (AK) is a common dermatologic diagnosis with the potential of malignant transformation. Treatment options include destructive therapies, such as cryotherapy, and topical medications, such as 5-fluorouracil (5-FU), imiquimod, and ingenol mebutate. Historically, destructive procedures have remained the standard of care. There have been limited updates on AK management practices; we determined the frequency of procedural and medical treatments of AK. We assessed visits from the 2009 to 2016 National Ambulatory Medical Care Survey to quantify the use of cryotherapy, topical 5-fluorouracil, imiquimod, ingenol and topical aminolevulonic acid (as a proxy for photodynamic therapy). There were an estimated 11.5 (10.6, 12.4) million visits with a primary diagnosis of AK. One or more of the studied treatments were identified at 47.1% (42.5, 51.6) of visits. Of visits with some kind of AK treatment, cryotherapy was used in 90.6% (81.5, 99.7) of visits, while 5-fluorouracil, imiquimod, and ingenol were prescribed at 4.06% (2.20, 5.92), 5.00% (1.65, 8.36) and 0.16% (0, 0.33) of all visits (respectively). Photodynamic therapy was used at 0.90% (0.25, 1.55) of all visits with treatment. Despite the expansion of treatment options, cryotherapy remains the standard of care. Future development of therapies with improved tolerability and patient compliance as well as alternate payment models have the potential to change the standard of practice.

Basal cell carcinoma developed from an epidermal cyst: A case report and review of the literature.

Cutaneous epidermal cysts are common benign cysts derived from the epidermis or epithelium of hair follicles, and malignancy originating from epidermal cysts is uncommon. When a cutaneous epidermal cyst turns malignant, it is mostly squamous cell carcinoma, and basal cell carcinoma is rare.We present the case of a 58-year-old man with basal cell carcinoma originating from an epidermal cyst on the buttocks. Histopathological analysis with hematoxylin- eosin (H&E) staining showed the presence of the cyst, the wall of which was partially replaced by a malignant tumor. Moreover, the cyst was filled with malignant tumor cells in some areas. The tumor cells were basaloid, and extended through the dermis down to the subcutaneous tissue in a solid pattern. Immunoperoxidase staining for Ber-EP4 was positive.To our knowledge, there are 11 reported cases of BCC originating from epidermal cysts in English, and we reviewed these reports and examined potential trends. We estimate that some longstanding epidermal cysts may have the potential of malignant transformation, and chronic and repeated irritation might trigger malignancy from epidermal cysts. We emphasize that benignlooking cystic lesions showing progressive growth should be examined histopathologically.

ZNF582 hypermethylation as a prognostic biomarker for malignant transformation of oral lesions.

This hospital-based cohort study evaluated whether ZNF582 and PAX1methylation levels at baseline can be used as biomarkers to identify lesions with a high potential for malignant transformation in patients with normal mucosa and oral potentially malignant disorders. We recruited 171 adult patients with normal mucosa and oral potentially malignant disorders in 2012-2014. They were followed until 2017. Outcomes, including advanced histopathological findings and oral cancer occurrence, were obtained from medical charts, the Taiwan Cancer Registry, and cause-of-death data. Kaplan-Meier analysis and Cox proportional hazards regression models were used to examine the association of ZNF582 and PAX1methylation levels at baseline with subsequent outcome occurrences. After 260,192days of follow-up, 11 cases of oral cancer and 4 cases of advanced histopathological progression occurred. Patients with higher ZNF582 and PAX1methylation levels at baseline had a higher incidence of disease progression. After adjustment for all studied factors using Cox proportional hazards regression models, ZNF582m level (adjusted hazard ratio, 11.41; 95% CI, 2.05-63.36; p=0.005) was the only significant and independent predictor of disease progression. ZNF582hypermethylation can be an effective and noninvasive biomarker for identifying oral lesions with a high potential for malignant transformation.

PROLIFERATIVE VERRUCOUS LEUKOPLAKIA—AN OBSTINATE PATHOLOGY

<h3>Objective</h3> Proliferative verrucous leukoplakia (PVL) is a unique form of oral leukoplakia that has a high risk of becoming dysplastic and transforming into oral squamous cell carcinoma. The purpose of this study was to review and analyze institutional data on PVL. <h3>Material and Methods</h3> This was a hospital-based study, performed in the Department of Oral Pathology & Microbiology, Goverment Dental College & Hospital, Nagpur. The total number of PVL cases from January 2003 to April 2016 was calculated based on clinicopathologic correlation. They were further analyzed based on their demographic data, habits, clinical presentation, histopathologic diagnosis, and malignant transformation. <h3>Results</h3> Twelve cases were diagnosed as PVL on the basis of clinicopathologic correlation. Among these patients, 3 were female (25%) and 9 were male (75%). The average age of these patients was 48.5 years. Ten patients had a habit of chewing tobacco in various forms (83%) and 2 patients did not (17%). PVL lesions in 4 patients out of 12 were transformed into malignancy (33%). <h3>Conclusion</h3> PVL is rare, highly aggressive form of oral leukoplakia that requires special attention on the part of clinician. The earliest possible diagnosis and treatment is recommended. Proper long-term follow-up of these patients should be done even after surgical management because PVL has a higher recurrence rate and owing to its malignant transformation potential.

Assembling a consensus on actinic cheilitis: A Delphi study.

To discuss the terminology to define and classify actinic cheilitis (AC) and to build a consensus on the diagnostic and therapeutic approaches to AC. Two-round Delphi study using a questionnaire including 34 closed sentences (9 on terminology and taxonomy, 5 on potential for malignant transformation, 12 on diagnostic aspects, 8 on treatment) and 8 open questions. Experts' agreement was rated using a Likert scale (1-7). A consensus was reached on 24 out 34 statements (73.5%) and on 5 out of 8 (62.5%) close-ended questions. The response rate was identical in both rounds (attrition of 0%). AC is the term with the highest agreement (median of 7 (strongly agree; IQR: 6-7)) and the lowest dispersion (VC=21.33). 'Potentially malignant disorder' was the preferred classification group for AC (median of 7) and 85.6% of participants showing some level of agreement (CV<50). Experts (66.75%) consider AC a clinical term (median: 7; IQR: 4-7) and believe definitive diagnosis can be made clinically (median: 6; IQR: 5-7), particularly by inspection and palpation (median: 5; IQR: 4-6). Histopathological confirmation is mandatory for the management of AC (median: 5; IQR: 2.5-7), even for homogeneous lesions (median: 5; IQR: 3.5-6). Consensus was reached on all treatment statements (VC<50). AC is a potentially malignant disorder with a significant lack of agreement on diagnostic criteria, procedures, biopsy indications and the importance of techniques to assist in biopsy. A consensus was reached on nomenclature and management of this disorder.

Benign biliary neoplasms and biliary tumor precursors.

SummaryBenign biliary tumor are common lesions that are often an incidental finding in subjects who undergo medical imaging tests for other conditions. Most are true neoplasms while few result from reactive or malformative proliferation. Benign tumors have no clinical consequences, although the premalignant nature or potential for malignant transformation is of concern in some cases. The main practical problem for pathologists is the need to differentiate them from malignant biliary tumours, which is not always straightforward.Premalignant lesions of the bile duct have been described, although their incidence has been poorly characterized. These lesions include biliary mucinous cystic neoplasms, intraductal papillary neoplasms of the bile duct, and biliary intraepithelial neoplasia. In this article, histopathology of benign biliary tumors and biliary tumor precursors is discussed, with a focus on the main diagnostic criteria.

Clinical characteristics of sinonasal inverted papilloma associated with recurrence and malignant transformation

ObjectiveSinonasal inverted papilloma is a benign tumor but has a potential for recurrence and malignant transformation. The aim of this article is to analyze the clinical characteristics of sinonasal inverted papilloma associated with recurrence and malignant transformation. Material and MethodsA retrospective study was performed in all patients with sinonasal inverted papilloma diagnosed between in our hospital during May 2013 and May 2018. ResultsA total of 151 patients were enrolled in this study. The average age of these patients was 52.24 years, with a male-to-female ratio of 2.775:1, and the most frequent clinical symptom was nasal obstruction. The recurrence rate was 39.07% (59/151), the mean time of recurrence was 35.8 months and most recurrences occur within the first three years after surgery. There was no significant difference in recurrence rate between all four stages and between after endoscopic surgery and a combined endoscopic and external approach. The malignant transformation rate was 5.96% (9/151) and the mean time of malignant transformation was 9.06 months. ConclusionsBecause of its high recurrence rate and the potential of malignant transformation, so it is important to determine the primary site of the tumor and to make a complete removal and a follow-up of at least five years after surgery is recommended.

HPV infection upregulates the expression of ZNT-1 in condyloma acuminatum.

Condyloma acuminata (CA) are benign anogenital warts caused by human papillomavirus (HPV) infection with a high recurrence rate. Despite its high contagiousness, high recurrence rate and potential for malignant transformation, effective treatments for CA have not yet been developed. Accordingly, it is necessary to clarify the mechanisms underlying CA development. Zinc (Zn) is stably maintained in the weight of human body. Skin is the third most Zn-abundant tissue in the body. Zn is present as a divalent ion (Zn2+) in cells and does not need a redox reaction upon crossing the cellular membrane. Zn transporters (ZnTs; SLC30A) and Irt-like proteins (ZIPs; SLC39A) are involved in Zn2+ efflux and uptake, respectively. ZnT1 is one of the ZnTs, which associates with the development of HPV. However, the role of ZnT1 regulation in the CA caused by HPV infection remains unknown. A multigroup case-control study was designed to investigate the expression and significance of the ZnT1 in patients with CA infected with HPV and in normal vulva controls. ZnT1 was assessed by immunohistochemistry in 44 patients with CA at Zhongnan Hospital of Wuhan University 2019-2020. Samples were analyzed by paraffin embedding and sectioning and hematoxylin-eosin and immunohistochemical staining. Immunohistochemical methods detected specific, dark brown, positive staining of ZnT1 in the keratinocytes of epidermis. We verified that the expression levels of ZnT1 that interact with HPV were upregulated in the CA groups independently of genotype compared with the control group. And then we found that the HPV risk grade in CA patients has a certain correlation with ZnT1 expression. These findings showed that HPV infection upregulated the expression of ZnT1 in CA. Additionally, there were obvious differences in the expression of ZnT1 between the different HPV risk grade infection groups. The higher the HPV risk grade, the stronger the ZNT1 protein expression. This study provided new insights into the sign pathway to HPV infection.

Pattern of Tumor-Infiltrating Lymphocytes in Mixed Epithelial and Stromal Tumor of the Kidney: A Review of Five Cases.

Mixed epithelial and stromal tumor of the kidney (MESTK), a benign rare tumor with malignant transformation potential, is thought to be derived from fetal or immature cells originating from the mesonephric and Müllerian ducts. However, due to its rarity, little is known about the anti-tumor immune responses in MESTK. Herein, we present five cases of MESTK and evaluate the population of tumor-infiltrating lymphocytes (TILs) using a freshly obtained MESTK sample. Microscopically, TILs were scattered or clustered in large aggregates in the stroma in all five cases; furthermore, three cases exhibited heavy, large lymphocytic aggregates with no well-organized tertiary lymphoid structures with germinal centers. Flow cytometric analysis of TILs in one freshly obtained MESTK sample revealed that >40% of CD3+ T cells were effector memory Fas+CD28− γδ T cells expressing high levels of programmed cell death protein 1 and inducible T-cell co-stimulator, but low levels of CD44 and CD27. Most αß T cells exhibited a naïve phenotype. Additionally, we detected many activated class-switched CD21+CD27+ B cells as well as CD11chighIgMhigh marginal zone B-like and CD27−CD21−CD23− immunoglobulin (Ig)DhighIgMlow age-associated B-like cells. Collectively, for the first time, we report the immune microenvironment pattern of MESTK to oncogenic stress.

Surgical solution of the extensive post-radiation defect developped 33 years after radiotherapy for breast carcinoma − case report

Introduction: Damage of the skin and its underlying structures is a common side effect of radiotherapy. These conditions limit further treatment and dealing with these complications is a routine practice of clinical oncologist. The majority of the complications are immediate, with a perspective of healing ad integrum within a few weeks. Less frequently, but sometimes with severe manifestations, chronic toxicity occurs belatedly after months, or even many years after irradiation, in form of post-radiation ulcer, for instance with potential of secondary malignant transformation. Regarding surgery, it might be one of the most challenging chronic wounds to treat. In extreme cases, extensive resection of the entire affected area is needed, inevitably ending with demanding reconstruction of the resulting defect. Case report: This case report presents a female patient with rapidly progressive post-radiation chest wall defect 33 years after the irradiation, when relatively insignificant skin injury occured. Prior to this sudden deterioration, only long-term, non-progressive changes, without a cutaneous defect, were described during the dispensarisation. After a protracted outpatient treatment with unsatisfactory results, when the patient repeatedly refused mastectomy, the condition inevitably led to the complex surgical procedure with necessary cooperation of breast, plastic and thoracic surgeons. Conclusion: Although changes of the similar severity rarely occur even after many years following the treatment, we haven‘t found such a dramatic change of the patient’s condition three decades after the therapy with urgency of this type of complex, surgical intervention in current literature.

Observer agreement in the diagnosis of oral lichen planus using the proposed criteria of the American Academy of Oral and Maxillofacial Pathology.

Oral lichen planus (OLP) is a common chronic inflammatory condition with an undefined malignant transformation potential. There have been many attempts at providing a specific definition of OLP without conclusive outcomes. A new set of diagnostic criteria was proposed in 2016 by the American Academy of Oral and Maxillofacial Pathology (AAOMP) in an endeavour to resolve this issue, and this has not yet been evaluated. This study aimed to assess the utility of AAOMP proposed criteria for the diagnosis of OLP. Five pathologists blindly assessed a cohort of 215 digital whole slide images (WSI) obtained from haematoxylin and eosin-stained microscopic slides. Forty-six WSI were included twice to assess the intra-observer agreement. Included cases were diagnosed clinically as either OLP or oral lichenoid reaction. Each pathologist was asked to utilize the AAOMP histopathological criteria while assessing slides. The variations in diagnoses were assessed by unweighted kappa statistics. The level of intra-observer agreement was very good (0.801 to 0.899). The level of inter-observer agreement among the observers varied from good (0.658) to very good (0.842) when the responses were categorized as evident/compatible OLP versus no OLP and was good (0.62 to 0.725) when the responses were categorized as evident OLP, versus compatible OLP, versus no OLP. The clinico-pathological correlation was 87.6%. A reliable level of agreement can be achieved by pathologists for the diagnosis of OLP using the AAOMP criteria for differentiation between lichenoid and other conditions. There are still limitations in discriminating OLP from oral lichenoid lesions microscopically.

Small Molecule "Silmitasertib" Repurposed as Inhibitor of Transforming Growth Factor Beta 1 for the Development of Therapeutics for Oral Submucous Fibrosis.

Oral submucous fibrosis (OSMF) is considered a premalignant condition characterized by aggressive fibrosis of the submucosal tissues of the oral cavity reflecting its malignant transformation potential. Activation of transforming growth factor beta (TGF-β) signaling has been reported to lead increased collagen production and fibrosis. Recently, significant upregulation of TGF-β1 has been reported in OSMF as compared to normal tissues. Therefore, inhibition of the TGF-β1 may pave for the development of therapeutics of OSMF. Based on the structure-assisted drug designing, we found “silmitasertib” as potent inhibitor of TGF-β1. We suggest that this molecule can be validated and implemented for the treatment of OSMF.

Expression and Localisation of CD44 Antigen as a Prognostic Factor of Oral Leukoplakia

Abstract It is essential to identify markers that could indicate the presence of early molecular changes in premalignant tissues like oral leukoplakia (OL). CD44 adhesion molecule is not only a stem cell marker, but also determines cell proliferation and migration in malignant processes. The aim of our study was to assess the amount and pattern of CD44 antigen expression by epithelial and mononuclear cells in the lamina propria under OL and their role in premalignant lesions. The current study included 102 cases of OL and ten biopsies from healthy oral mucosa. Immunohistochemical CD44 antigen expression was determined in 34 cases by a standard EnVision imaging system in three points of OL: both edges and centre. Statistical analysis was done using GraphPad Prism software version 8.4.0. In OL, statistically significant overexpression of membranous CD44 was demonstrated compared to healthy mucosa (p &lt; 0.0001). The intra-cytoplasmatic CD44 expression of epithelium together with characteristic nuclear changes may be used as a predictive factor for potential malignant transformation of non-homogenous leukoplakia. CD44 expression in mononuclear cells under the basal membrane in OL (p &lt; 0.05) possibly influences the process of premalignant lesion transformation into intraepithelial cancer. Further study of CD44 antigen expression in intra-cytoplasmatic structures is required for better explanation of the role of this glycoprotein.