Risk Factors For Malignant Transformation Research Articles

Architectural dysplasia in surgical margins and the risk of local relapse in oral cancer

AbstractBackgroundA major challenge in the clinical management of oral cavity squamous cell carcinoma is local relapse. Even when surgical margins are tumor‐free, local relapses occur frequently, and relapse prediction by histology remains suboptimal. In leukoplakia, an oral potentially malignant disorder, the presence of architectural dysplasia is a critical risk factor for malignant transformation. This study aimed to investigate whether the presence of architectural dysplasia in oral cavity squamous cell carcinoma surgical margins is a risk factor for local relapse.MethodsHematoxylin and eosin‐stained slides of resection margins from a consecutive cohort of surgically treated patients diagnosed with stage I–IV oral cavity squamous cell carcinoma between 2008 and 2014 were assessed for the presence of architectural dysplasia (N = 311). Five‐year local relapse‐free survival rates of oral cavity squamous cell carcinoma with architectural dysplasia were compared to those of oral cavity squamous cell carcinoma without architectural dysplasia.ResultsIn total, 92 of 311 (29.6%) of oral cavity squamous cell carcinoma displayed architectural dysplasia in the margins. The presence of architectural dysplasia was associated with higher patient age, female sex, less pack years, lower cT‐stage, and a cohesive tumor growth pattern. In oral cavity squamous cell carcinomas with architectural dysplasia, postoperative (chemo)radiotherapy was less often indicated compared with oral cavity squamous cell carcinoma without architectural dysplasia (19.5% vs. 36.1%, p = 0.009). Five‐year local relapse‐free survival was significantly lower in oral cavity squamous cell carcinoma with architectural dysplasia than in oral cavity squamous cell carcinoma without architectural dysplasia (83.1% vs. 94.9%, p = 0.017).ConclusionsOral cavity squamous cell carcinoma arising in the background of architectural dysplasia displays relatively favorable clinical and histopathological characteristics. Nonetheless, the presence of architectural dysplasia in oral cavity squamous cell carcinoma surgical margins is associated with a higher risk of local relapse, indicating its clinical relevance.

LGG-32. MALIGNANT TRANSFORMATION OF PEDIATRIC LOW-GRADE GLIOMA TO SECONDARY HIGH-GRADE GLIOMA - REPORT FROM THE GERMAN BRAIN TUMOR STUDIES

Abstract BACKGROUND Malignant transformation (MT) of pediatric low-grade glioma (pLGG) to secondary high-grade glioma (sHGG) is a rare but momentous event. We explored its clinical, epidemiologic, and molecular characteristics and risk factors. METHODS Forty-eight pediatric patients with histology-based or radiological (n=4) diagnosis of primary LGG (median age 10.2 years [range, 0.7–16.9]) and subsequent sHGG were identified within registries of the HIT-network from 1996-2019. For 29 patients, tumor specimens of both pLGG and corresponding sHGG were available for neuropathological review and studied genetically. RESULTS MT occurred after median 4 years (range, 0.5-14) following LGG diagnosis. Its 15-year cumulative incidence was 1.6±0.4% (23/1586 SIOP-LGG-2004 patients), but 11.7±4.1% (9/100) for diffuse pLGG WHO-grade 2 (DG2). Clinical risk factors for MT were spinal location and prior dissemination. MT was accompanied by an increment of nuclear p53 accumulation (20/29 tumors), cytogenetic and molecular alterations. CDKN2A/B homozygous deletions (7/12 tumors), 1p/1q alterations (4/12) and ATRX loss (3/12) were the most common acquired alterations detected in sHGG. 8/16 tumors were unclassifiable by methylation profiling. DG2s (n=19), harboring IDH-1 mutation in 3/9 cases, progressed to diffuse WHO-grade 3 (n=8) or grade 4 HGG (n=9), two developed gliomatosis cerebri. Circumscribed LGG (PA, n=13; GG, n=7; PXA, n=4; DNET, n=1) typically harbored MAPK/ERK pathway alterations (BRAF-/NTRK-/FGFR-fusions, n=5/9; BRAFV600E mutation, n=4/12) and transformed to non-diffuse HGG (n=14), but also to diffuse grade 4 HGG. H3 K27M-/BRAFV600E co-mutation in two of these patients eventually resulted in MT to fatal diffuse midline glioma. Thirty-five sHGG patients received radio-chemotherapy. Overall survival at 5 and 10 years following MT was 49±8% and 31±8%. CONCLUSIONS Our findings underline the importance of careful long-term follow-up of patients with pLGG. Repeated resection/biopsy of recurrent/progressing or “atypical” tumors should be pursued and include molecular typing to identify patients at risk for MT and initiate appropriate treatment.

Mucosa color and size may indicate malignant transformation of chicken skin mucosa-positive colorectal neoplastic polyps.

Lipid metabolism reprogramming is suspected to exist in pre-cancerous lesions, including colorectal adenoma. Screening colonoscopy frequently reveals chicken skin mucosa (CSM; white or yellow-white speckled mucosa) surrounding colorectal polyps, caused by macrophages engulfing and accumulating the lipids decomposed by colon cells or adjacent tumors. CSM-positive colorectal polyps are associated with various diseases; however, their prognosis varies greatly. Cold snare polypectomy is commonly used to resect lesions up to 10 to 15 mm in diameter without signs of submucosal invasion but is controversial for CSM-positive colorectal polyps. Improved imaging is required to diagnose and treat CSM-positive colorectal polyps. To highlight the clinical significance of CSM surrounding colorectal polyps and clarify the associated treatment for endoscopists. This retrospective cohort study included 177 patients with CSM-positive colorectal polyps diagnosed using endoscopy. All patient-related information was extracted from the Goldisc soft-clinic DICOM system or electronic medical record system. Based on the pathological results, patients were classified as non-neoplastic polyps (five juvenile polyps), neoplastic polyps, non-invasive high-grade neoplasia (NHGN), or submucosal invasive carcinoma (SM stage cancer). We analyzed and compared the clinical features, suspected risk factors for malignant transformation of neoplastic polyps, and early infiltration of submucosal carcinoma. The diameters of NHGN and SM polyps were much smaller than those of neoplastic polyps. Most NHGN polyps had a deeper red mucosal color. On logistic regression analyses, diameter and deeper red mucosal color were independent risk factors for malignant transformation of neoplastic polyps. Type 1 CSM was more common in high-grade intraepithelial neoplasia and SM; type 2 CSM was more common in neoplastic polyps. Logistic regression analyses revealed no significant differences in the malignant transformation of neoplastic polyps or early submucosal invasion of CSM-positive colorectal cancer. Changes in the CSM mucosa surrounding neoplastic polyps and submucosal invasion of colorectal cancer disappeared within 12 months. No tumor recurrence was found during either partial or complete endoscopic resection of the CSM. CSM-positive colorectal polyps > 1 cm in diameter or with deeper red mucosa may be related to NHGN. Resection of CSM surrounding colorectal adenomas did not affect tumor recurrence.

Analysis of ultrasonic imaging changes and factors related to malignant transformation in postmenopausal patients with endometrial polyps.

To examine the ultrasonic changes in postmenopausal endometrial polyps and analyze factors related to their malignant transformation. This retrospective study analyzed clinical data from 200 postmenopausal patients with endometrial polyps treated at Jinan Maternity and Child Care Hospital and Pingyin Hospital of Traditional Chinese Medicine from December 2020 to December 2023. All patients underwent pathological biopsies to diagnose the nature of the endometrial polyps. This study compared the clinical and ultrasonic imaging features of these patients and analyzed factors influencing the malignant transformation of postmenopausal endometrial polyps. Pathological findings classified 160 patients (80.00%) into the benign group and 40 patients (20.00%) into the malignant group. Significant differences were noted in endometrial thickness, polyp diameter, heterogeneity of lesion echogenicity, and vascularization between the groups (all P<0.05). The malignant group exhibited notably higher blood flow (Grade II+III constituted 70.00% compared to 29.38% in the benign group, P<0.05). The time average velocity (TAV), pulse index (PI), and resistance index (RI) were significantly lower in the malignant group (all P<0.05). The area under curve (AUC) values for TAV, PI, and RI in diagnosing malignant endometrial polyps were 0.754, 0.713, and 0.771, respectively. Increased body mass index (BMI), irregular premenopausal menstruation, and ≥2 occurrences of postmenopausal bleeding were identified as risk factors for malignant transformation (all P<0.05). These six indicators were used to create a predictive model for malignant transformation, achieving an AUC of 0.942. Malignancy in postmenopausal endometrial polyps is uncommon, yet distinct differences exist in the transvaginal color Doppler ultrasound characteristics between benign and malignant cases. Factors such as increased BMI, irregular premenopausal menstruation, and ≥2 occurrences of postmenopausal bleeding significantly contribute to the risk of malignant transformation. These findings, combined with ultrasound features, provide a robust basis for screening and monitoring these patients.

Malignant transformation rate of erosive oral lichen planus: a retrospective study

Oral lichen planus (OLP) is a chronic inflammatory oral condition previously known to have a rate of malignant transformation of around 1%. Additionally, erosive lichen planus, a subtype of lichen planus, which is a known risk factor for malignant transformation, has previously been unquantified in a large cohort of patients. In a single unit observation between 2005 and 2021 we retrospectively assessed 1,920 patients who underwent histological analysis for suspected oral lichen planus, and followed the progression of their disease to assess the rate of malignant transformation. In total, 1.39% of OLP transformed to oral squamous cell carcinoma over an average of 5.8 years. However, we found that the transformation rate of erosive OLP into malignancy was 5.98% with an aggressive clinical pathway. To our knowledge the incidence of erosive OLP has not previously been quantified in a large cohort of patients. This retrospective study sheds light on, and raises warning signs about, the seriousness of this condition.

Abstract A054: Interleukin-16 is a novel target to prevent age-associated epigenetic changes leading to malignant transformation associated with ovarian high-grade serous carcinoma (HGSOC)

Abstract Low-grade chronic inflammation and persistent oxidative stress are hallmarks of malignant transformation. High-grade serous ovarian carcinoma (HGSOC) is a fatal malignancy of women, and the median age of its incidence is 60-65 years. Our earlier studies showed enhanced expression of interleukin 16 (IL-16, an inflammatory cytokine), its receptor CD9, and glucose-regulated protein (GRP78, a marker of cellular stress and inhibitor of DNA damage repair mechanism) in postmenopausal ovaries and patients with HGSOC as compared with premenopausal subjects. It is possible that these age-associated increases in IL-16, CD9, and GRP78 expression may contribute to HGSOC-related epigenetic modifications of gH2A histone family member X (gH2AX, a marker for double-stranded DNA breaks), and histone deacetylase 1 (HDAC1), involved in DNA repair. The goal of this study was to examine if age-associated such changes lead to HGSOC-associated malignant transformation and if so, to determine mechanisms involved in such transformation. Materials and Methods: Exploratory study: Archived tissue specimens were selected for immunohistochemical, immunoblotting, genomic studies, and immunoassays based on the review of their hematoxylin and eosin staining and final pathological reports. Specimens were grouped as normal premenopausal women (30-50 years old), normal postmenopausal women (55-85 years old), and ovarian high-grade serous carcinoma (HGSC). In vitro study: human ovarian surface epithelium (HOSE) cells were treated with or without recombinant human IL-16 (rhIL-16) and recombinant human GRP78 (rhGRP78), and small interfering RNA-GRP78 (siGRP78) for 24 hours or 48 hours. Nuclear fractionations from treated- or untreated HOSE cells or OVCAR3 (HGSOC cell line) cells were extracted. Results: Compared to premenopausal women, a subset of postmenopausal women exhibited significantly elevated expression (P&amp;lt;0.01) of inflammatory markers IL-16, and its receptor CD9, as well as a marker of oxidative stress (GRP78). Additionally, markers of epigenetic changes, including gH2AX and HDAC1, presented similar patterns of increase in their expression. These observations were also consistent in HGSOC patients. Enhanced expression of GRP78, gH2AX, HDAC1, and CD9 in rhIL-16 treated HOSE cells like OVCAR3 cells and their reduction in siGRP78 treated HOSE cells suggests that age-associated increase in IL-16 in postmenopausal women may be a risk factor for malignant transformation and GRP78 may be a mechanism for IL-16-induced HGSOC development. Thus, IL-16 and GRP78 represent novel targets that may be used to develop novel targeted therapies to prevent HGSOC. Expression of gH2AX and HDAC1 increased in rhGRP78-treated HOSE cells. Conclusion: The results of this study suggest that age-associated increases in IL-16 (a marker of chronic inflammation) and GRP78 (a marker of oxidative stress) may contribute to the predisposition for HGSOC-associated malignant transformation. IL-16 and GRP78 offer potential targets for the prevention of HGSOC in women. Support: The Portes Foundation Citation Format: Jessica Ramirez, Animesh Barua. Interleukin-16 is a novel target to prevent age-associated epigenetic changes leading to malignant transformation associated with ovarian high-grade serous carcinoma (HGSOC) [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A054.

Features of aminothiol metabolism and progression of breast cancer

Background. Imbalance of aminothiol metabolism is a potential risk factor for malignant transformation of cells and caner development, including breast cancer, which is the most commonly diagnosed cancer in the world. The purpose of the study was to summarize the available data on the characteristics of thiol metabolism as one of the factors contributing to the progression of breast cancer. Material and Methods. Data were searched from 1999 to 2022 using the Web of Science, Scopus, MedLine, The Cochrane Library, PubMed databases, which made it possible to assess the role of thiol-dependent metabolic disturbances in the regulation of tissue redox balance in breast cancer genesis. Results. The review considers the results of both our own data and international studies on breast cancer, which suggest that an imbalance of thiol compounds necessary to maintain a moderately reducing cellular environment that counteracts oxidative stress during cellular metabolism and detoxifcation under conditions of tumor progression can provoke reprogramming of the leading links of antiblastoma resistance, contributing to cancer progression. Conclusion. A more detailed study of the mechanisms of aminothiol metabolism in breast cancer emphasizes their particular importance for stabilizing the cellular genome and providing antitoxic protection of the cell, as well as understanding the important role of thiols as a coordination center in redox signaling. Disturbances at any stage of thiol metabolism can play an etiological role in oncogenetic pathologies, while the role of thiols as signaling molecules and the regulation of their metabolism should not be generalized for the entire group of diseases. Determination of serum markers of the redox state in patients with breast cancer, especially during antitumor therapy, can serve for an objective assessment of the effectiveness of treatment and the adaptive capabilities of the body, as well as predicting tumor growth and optimizing the program for screening and preventing cancer.

Adenomyosis and Its Possible Malignancy: A Review of the Literature.

Cancer arising from adenomyosis is very rare, with transformation occurring in only 1% of cases and in older individuals. Adenomyosis, endometriosis and cancers may share a common pathogenic mechanism that includes hormonal factors, genetic predisposition, growth factors, inflammation, immune system dysregulation, environmental factors and oxidative stress. Endometriosis and adenomyosis both exhibit malignant behaviour. The most common risk factor for malignant transformation is prolonged exposure to oestrogens. The golden standard for diagnosis is histopathology. Colman and Rosenthal emphasised the most important characteristics in adenomyosis-associated cancer. Kumar and Anderson emphasised the importance of demonstrating a transition between benign and malignant endometrial glands in cancer arising from adenomyosis. As it is very rare, it is difficult to standardize treatment. In this manuscript, we try to emphasize some aspects regarding the management strategy, as well as how heterogenous the studies from the literature are in terms of prognosis in both cancers that develop from adenomyosis or those that are only associated with adenomyosis. The pathogenic mechanisms of transformation remain unclear. As these types of cancer are so rare, there is no standardised treatment. A novel target in the diagnosis and treatment of gynaecological malignancies associated with adenomyosis is also being studied for the development of new therapeutic concepts.

Analysis of prognostic factors for vocal fold leukoplakia based on 344 cases at a two-year follow up.

To evaluate risk factors for poor prognosis in vocal fold leukoplakia. Clinical data were collected for 344 patients with vocal fold leukoplakia who received surgical treatment in our otolaryngology department from October 2010 to June 2019. Univariate and multivariate logistic regression analyses of the relevant factors were conducted. Among the 344 patients, 98 exhibited recurrence and 30 underwent a malignant change. Multivariate logistic regression analysis showed that size of the lesion (p = 0.03, odds ratio = 2.14), form of the lesion under white light (p < 0.001), surgical method (p < 0.001, odds ratio = 0.28) and pathological type (p < 0.001) were independent factors that affected the recurrence of vocal fold leukoplakia. In both univariate and multivariate analyses, the sole independent risk factor for malignant transformation of vocal fold leukoplakia was pathological type (p < 0.001). The outlook for vocal fold leukoplakia depends on several clinical factors, especially pathological type. The more severe the pathological type, the more likely it is to recur or become cancerous.

Rate of Malignant Transformation Differs Based on Diagnostic Criteria for Oral Lichenoid Conditions: A Systematic Review and Meta-Analysis of 24,277 Patients.

This systematic review and meta-analysis aims to evaluate the evidence on the malignant potential of oral lichenoid conditions (OLCs) including oral lichen planus (OLP), oral lichenoid lesions (OLL), and lichenoid mucositis dysplasia (LMD). In addition, it aims to compare the rate of malignant transformation (MT) in OLP patients diagnosed according to different diagnostic criteria, and to investigate the possible risk factors for OLP MT into OSCC. A standardized search strategy was applied across four databases (PubMed, Embase, Web of Science, and Scopus). Screening, identification and reporting followed the PRISMA framework. Data on MT were calculated as a pooled proportion (PP), subgroup analyses and possible risk factors for MT were pooled as odds ratios (ORs). Among 54 studies with 24,277 patients, the PP for OLCs MT was 1.07% (95% CI [0.82, 1.32]). The estimated MT rate for OLP, OLL and LMD was 0.94%, 1.95% and 6.31%, respectively. The PP OLP MT rate using the 2003 modified WHO criteria group was lower than that using the non-2003 criteria (0.86%; 95% CI [0.51, 1.22] versus 1.01%; 95% CI [0.67, 1.35]). A higher odds ratio of MT was observed for red OLP lesions (OR = 3.52; 95% CI [2.20, 5.64]), smokers (OR = 1.79; 95% CI [1.02, 3.03]), alcohol consumers (OR = 3.27, 95% CI [1.11, 9.64]) and those infected with HCV (OR = 2.55, 95% CI [1.58, 4.13]), compared to those without these risk factors. OLP and OLL carry a low risk of developing OSCC. MT rates differed based on diagnostic criteria. A higher odds ratio of MT was observed among red OLP lesions, smokers, alcohol consumers, and HCV-positive patients. These findings have implications for practice and policies.

Excision of a Superior Ramus Osteochondroma Through the Modified Stoppa Approach

Excision of a Superior Ramus Osteochondroma Through the Modified Stoppa Approach

Actinic keratosis as a predictor of primary multiple synchronous squamous cell skin cancer: a clinical case

We present a clinical case of a primary multiple synchronous highly differentiated keratinizing squamous cell skin cancer in an 84-year old patient with multiple actinic keratosis and actinic cheilitis. The clinical case is unique for the simultaneous development of primary multiple squamous cell carcinoma of the tip of the nose and the vermilion zone of the lower lip in a patient with a past occupational and solar burden, a light phenotype, and signs of chronic photo injury the skin. Clinical, dermatoscopic and sonographic signs of keratotic actinic keratosis were identified in the patient and confirmed by pathomorphological examination. The risk factors for malignant transformation of actinic keratosis were found, such as multiple efflorescences and a long disease history. The malignant transformation of the actinic areas manifested as rapidly progressive ulceration zones more than 1 cm in diameter, pronounced hyperkeratosis, inflammation and infiltration of the underlying tissues, increased bleeding and pain. It is to be underlined that definitive and differential diagnosis requires pathomorphological assessment of the skin biopsy sample. This clinical case indicates that patients with multiple foci of actinic keratosis should be under a lifelong follow-up by dermatovenereologists, with mandatory treatment and prevention measure.

Squamous Cell Carcinoma Arising in Lesions of Discoid Lupus Erythematosus in a Patient with Overlap Syndrome: A Chronic Rare Complication.

Squamous Cell Carcinoma Arising in Lesions of Discoid Lupus Erythematosus in a Patient with Overlap Syndrome: A Chronic Rare Complication.

Elucidating the Genetic Landscape of Oral Leukoplakia to Predict Malignant Transformation.

Oral leukoplakia is the most common oral potentially malignant disorder with an annual malignant transformation rate of 1% to 5%. Consequently, oral leukoplakia patients have a 30% to 50% lifetime risk to develop oral squamous cell carcinoma. Although risk factors for malignant transformation of oral leukoplakia have been investigated, no definitive risk stratification model has been proposed. Next-generation sequencing can elucidate the genetic landscape of oral leukoplakia, which may be used to predict the risk for malignant transformation. We investigated a retrospective cohort of 89 oral leukoplakia patients, and analyzed their oral leukoplakia lesions for the presence of genomic copy-number alterations and mutations in genes associated with oral squamous cell carcinoma. In 25 of 89 (28%) patients, oral squamous cell carcinoma developed during follow-up. Seventy-nine of 89 (89%) oral leukoplakias harbored at least one genetic event. Copy-number alterations were present in 61 of 89 (69%) oral leukoplakias, most commonly gains of chromosome regions 8q24 (46%) and 20p11 (20%) and loss of 13q12 (19%). Mutations were present in 59 of 89 (66%) oral leukoplakias, most commonly in TP53 (28%), FAT1 (20%), and NOTCH1 (13%). Genetic data were combined with the presence of dysplasia to generate a prediction model, identifying three groups with a distinct risk for malignant transformation. We provide an extensive description of genetic alterations in oral leukoplakia and its relation to malignant transformation. On the basis of our data we provide a model for the prediction of malignant transformation of oral leukoplakia using dysplasia and genetic markers.

Hereditary ovarian cancer

Background. Hereditary genetic mutations are a significant risk factor for malignant transformation of cells and cancer development. Hereditary genetic mutations account for 15 to 25 % of all ovarian carcinomas. Purpose of the study: to summarize data on hereditary ovarian malignancies, namely: genetic defects, features of the clinical course, treatment options, and disease prevention. Material and methods. A systemic search was undertaken using PubMed, Medline, Cochrane Library databases for publications from 1999 to 2021. Results. The review describes the main genetic defects and hereditary cancer syndromes predisposing to the development of hereditary malignant ovarian tumors. The features of the clinical course and response to drug therapy have been presented. This article summarizes clinical guidelines of the professional communities (National Comprehensive Cancer Network (NCCN), American Society Of Clinical Oncology (ASCO), The U.S. Preventive Services Task Force, and European Society For Medical Oncology (ESMO). These guidelines contain early detection strategies and approaches to prevent the development of cancers in mutation carriers. Conclusion. Detection of hereditary cancer syndromes is important for patients and their families. Recognizing hereditary predisposition to cancer is important to allow timely surveillance and preventative interventions for both patients and family members.

Stratification Based on Risk Factors at Diagnosis Could Predict Progression in Patients with Pancreatic Cysts.

Predicting the risk of malignant transformation in pancreatic cyst patients is challenging. We retrospectively investigated the risk factors for malignant transformation in pancreatic cyst patients. Patients with pancreatic cysts diagnosed using imaging tests were followed from November 2008 to December 2021. A significant change was defined as the additional development of high-risk stigmata (HRS), worrisome features (WFs), or pancreatic cancer during monitoring. In total, 479 patients were analyzed, with a median observation period of 50months. Forty-four patients (9.2%) showed significant changes, and eight (1.7%) developed pancreatic cancer. The univariate analysis showed that the cyst diameter at diagnosis (≥ 14mm), main pancreatic duct (MPD) diameter at diagnosis (≥ 3mm), presence of multilocular cysts, and an inconsistent MPD caliber were significant predictive factors for a significant change. One point was assigned for each significant factor. We grouped the patients into three groups: the low-risk group (total score 0), medium-risk group (score 1-2), and high-risk group (score 3-4). The high-risk group had a higher risk of a significant change than the medium- and low-risk groups (age-adjusted HRs for the medium-risk and high-risk groups were 3.0 and 5.2 compared with the low-risk group). Stratification based on risk factors may help predict the development of significant changes in pancreatic cyst patients.

Mitochondrial DNA mutations in ageing and cancer.

Advancing age is a major risk factor for malignant transformation and the development of cancer. As such, over 50% of neoplasms occur in individuals over the age of 70. The pathologies of both ageing and cancer have been characterized by respective groups of molecular hallmarks, and while some features are divergent between the two pathologies, several are shared. Perturbed mitochondrial function is one such common hallmark, and this observation therefore suggests that mitochondrial alterations may be of significance in age‐related cancer development. There is now considerable evidence documenting the accumulation of somatic mitochondrial DNA (mtDNA) mutations in ageing human postmitotic and replicative tissues. Similarly, mutations of the mitochondrial genome have been reported in human cancers for decades. The plethora of functions in which mitochondria partake, such as oxidative phosphorylation, redox balance, apoptosis and numerous biosynthetic pathways, manifests a variety of ways in which alterations in mtDNA may contribute to tumour growth. However, the specific mechanisms by which mtDNA mutations contribute to tumour progression remain elusive and often contradictory. This review aims to consolidate current knowledge and describe future direction within the field.

Comparative Longitudinal Analysis of Malignant Transformation in Pleomorphic Adenoma and Recurrent Pleomorphic Adenoma.

Background: Recurrence in pleomorphic adenoma (PA) has been debated as a risk factor for malignant transformation (MT). In this study, we investigated whether recurrence is a risk factor for MT, by longitudinally analyzing cases with recurrent PA (RPA), and carcinomas from PA (CXPA) or RPA (CXRPA). Methods: The study population included 24 CXPA, 24 RPA, 6 CXRPA, and 386 PA cases (study period 2010–2018). Time and event data were collected from the medical documents to identify the time–event sequences. Results: The time interval to MT in CXRPA was significant longer than that of benign recurrence (median 342.0 vs. 109.5 months). In CXRPA, the recurrence intervals were not shorter than those in RPA according to recurrence frequency. Crudely, the MT rate was 5.9% among primary cases and 20.0% among recurrent cases. However, the time-adjusted MT rates increased up to 11.4% (incubation time > 60 months) and 20.0% (>120 months) in primary cases, which were not different from recurrent cases. Conclusion: In these longitudinal analyses, we did not find any clinical evidence that recurrence facilitates MT in the background of PA. Instead, a long incubation time seems to be a key factor for MT of underlying RPA.

Dentists’ Perception of Oral Potentially Malignant Disorders

ObjectivesDentists play a major role in the diagnosis of oral potentially malignant disorders (OPMDs) that may lead to malignancy. Their knowledge on OPMDs and the risk factors associated with malignant disease needs to be sufficient. The aim of this study was to assess the level of knowledge, attitudes, and awareness of OPMDs amongst general dentists and dental specialists working in Saudi Arabia. Material and methodsQuestionnaires were distributed to dentists working in Saudi Arabia. A total of 303 dentists participated in the study. The questionnaire included 20 questions on knowledge, attitudes, and awareness of OPMDs. ResultsThe response rate was 55%. There was no significant difference between general dental practitioners and dental specialists regarding leukoplakia, which is the most common OPMD (P > .05) and in identifying tobacco and alcohol as the main risk factors for malignant transformation of OPMDs into cancer (P > .05). However, there was a significant difference (P < .05) between specialists (75.3%) and general practitioners (52.3%) in the diagnosis of OPMDs. There was a significant difference (P < .05) between specialists (63.5%) and general practitioners (28.0%) in recognising the likelihood of malignant transformation of proliferative verrucous leukoplakia. There was a significant difference between specialists (61.2%) and general practitioners (25.2%, P < .05) in recognising the erosive form or atrophic type of oral lichen planus, considering that it is more likely to undergo malignant transformation. ConclusionsDental specialists have better knowledge and awareness than general dentists regarding OPMDs. Improved continuous education programmes on the risk factors and diagnosis of OPMDs should be organised to train dentists.

Malignant Transformation of a Peripheral Nerve Sheath Tumour in Neurofibromatosis Type 2

NF2 is a hereditary disorder which presents with both central and peripheral nervous system tumours; caused by defects in the long arm of chromosome 22. The prevalence of NF2 is 1 in 50,000. NF2 is not a recognised risk factor for malignant transformation of schwannomas and this in this group is rarely seen, despite their high burden of schwannomas.