Intermittent PI3Kδ inhibition sustains anti-tumour immunity and curbs irAEs.

Phosphoinositide 3-kinase δ (PI3Kδ) has a key role in lymphocytes, and inhibitors that target this PI3K have been approved for treatment of B cell malignancies1-3. Although studies in mouse models of solid tumours have demonstrated that PI3Kδ inhibitors (PI3Kδi) can induce anti-tumour immunity4,5, its effect on solid tumours in humans remains unclear. Here we assessed the effects of the PI3Kδi AMG319 in human patients with head and neck cancer in a neoadjuvant, double-blind, placebo-controlled randomized phase II trial (EudraCT no. 2014-004388-20). PI3Kδ inhibition decreased the number of tumour-infiltrating regulatory T (Treg) cells and enhanced the cytotoxic potential of tumour-infiltrating T cells. At the tested doses of AMG319, immune-related adverse events (irAEs) required treatment to be discontinued in 12 out of 21 of patients treated with AMG319, suggestive of systemic effects on Treg cells. Accordingly, in mouse models, PI3Kδi decreased the number of Treg cells systemically and caused colitis. Single-cell RNA-sequencing analysis revealed a PI3Kδi-driven loss of tissue-resident colonic ST2 Treg cells, accompanied by expansion of pathogenic T helper 17 (TH17) and type 17 CD8+ T (TC17) cells, which probably contributed to toxicity; this points towards a specific mode of action for the emergence of irAEs. A modified treatment regimen with intermittent dosing of PI3Kδi in mouse models led to a significant decrease in tumour growth without inducing pathogenic T cells in colonic tissue, indicating that alternative dosing regimens might limit toxicity.

Evaluation of possible role of fluoride in pathogenesis of oral submucous fibrosis: A pilot study.

BACKGROUND: Oral submucous fibrosis (OSMF) is a potentially malignant disorder. Although areca nut chewing is an established risk factor, its low prevalence among nut chewers indicates additional factors likely facilitates pathogenesis. We recently demonstrated high fluoride levels in smokeless tobacco products and hypothesized a potential pathological role of fluoride in OSMF. Further exploring this novel role, this study compared fluoride levels in tissue, serum, and saliva samples from OSMF patients and healthy controls. METHODS: The ethically approved study included 25 clinically confirmed OSMF patients and 25 healthy matched controls. OSMF cases underwent buccal mucosal incisional biopsy, while controls had buccal mucosa tissue sampling during third molar removal. Fasting venous blood and unstimulated saliva were collected. Fluoride levels were analysed using ion chromatography and expressed as median (IQR). RESULTS: OSMF cases showed significantly higher fluoride concentrations compared with controls in tissue biopsies (30.1 vs. 0 mg/kg, p < 0.0001), serum (0.4 vs. 0 mg/L, p = 0.005) and saliva (1.3 vs. 0 mg/L, p < 0.0001). Majority (68%) of controls had undetectable fluoride levels across all samples. Tissue fluoride weakly correlated with OSMF severity (r = -0.158, p = 0.334). CONCLUSION: The preliminary findings demonstrated increased tissue fluoride levels in OSMF patients compared with healthy controls. Along with a previous study showing high fluoride content in smokeless tobacco products, these findings provided early evidence suggesting fluoride could play a contributory role in OSMF pathogenesis. Further large-scale investigation is warranted to definitively establish whether the association between fluoride exposure and OSMF is indicative of causation.

The hidden costs of the intercollegiate membership of the Royal College of surgeons examinations: Can trainees afford it?

BACKGROUND: The Intercollegiate Membership of the Royal College of Surgeons (MRCS) examination is a mandatory requirement for higher specialty surgical training in the UK. However, there is a significant economic impact on trainees which raises the question of whether the costs of this exam hinder surgical career progression. This study explores the burden of these exams on trainees. METHODS: A 37-point questionnaire was distributed to all trainees who were preparing for or have sat MRCS examinations. Univariate analyses included the cost of the preparatory resources, extra hours worked to pay for these and the examinations, and the number of annual leave (AL) days taken to prepare. Pearson correlation coefficients were used to identify possible correlation between monetary expenditure and success rate. RESULTS: On average, trainees (n â€‹= â€‹145) spent £332.54, worked 31.2 â€‹h in addition to their rostered hours, and used 5.8 AL days to prepare for MRCS Part A. For MRCS Part B/ENT, trainees spent on average £682.92, worked 41.7 extra hours, and used 5 AL days. Overall, the average trainee spent 5-9% of their salary and one-fifth of their AL allowance to prepare for the exams. There was a positive correlation between number of attempts and monetary expenditure on Part A preparation (r(109)=0.536, p â€‹< â€‹0.001). CONCLUSIONS: There is a considerable financial and social toll of the MRCS examination on trainees. Reducing this is crucial to tackle workforce challenges that include trainee retention and burnout. Further studies exploring study habits can help reform study budget policies to ease this pressure on trainees.

Applying human factors to improve patient safety, morale and team working for oral pathology and medicine specialists.

BACKGROUND: Human error is inevitable, and therefore can be considered as a 'normal' part of everyday life. Unfortunately, error can never be eliminated completely. However, learning from our mistakes can help reduce problems in future. Fifty years ago, most clinicians paid little or no attention to the human factors (HF) that can affect individual and team performance. It has only been in the last 20-25 years that colleagues in healthcare have truly begun recognizing the importance of HF and non-technical skills in medicine and dentistry and how their application can significantly improve patient safety and aid better team working and staff morale in the clinical setting and laboratory. DISCUSSION: Personal factors such as stress, tiredness, hunger and dehydration all reduce human performance and can raise the risk of mistakes. In addition, how we work and interact with the wider team is important since many errors can occur because of ineffective communication, steep hierarchal (authority) gradients and loss of situational awareness.  This short HF overview in the 50th commemorative special of JOPM issue is timely. It provides a contemporary overview of human factors and performance that the authors consider important for oral medicine and pathology colleagues and which can affect individuals and teams This article also discuss ways to reduce the chances of medical and dental error and improve patient safety.

Human papilomaviru-related oropharyngeal squamous cell carcinoma and radiomics: A new era?

BACKGROUND: The increase of the incidence of human papillomavirus dependent oropharyngeal squamous cell carcinoma is alarming, although we have greatly progressed in the classification and staging of this disease. We now know that human papillomavirus related oropharyngeal squamous cell carcinoma is a sub-type of head and neck squamous cell carcinoma with favourable prognosis and good response to therapy that needs a proper system of classification and staging. Thus, in routine practice it is essential to test patients for the presence of human papillomavirus. The most popular technique to assess human papillomavirus status is immunohistochemistry on biopsy samples with p16, which is an excellent surrogate for high-risk human papillomavirus infection. Another highly sensitive and specific tissue-based technique for the detection of human papillomavirus is RNAscope In situ hybridization that has a prohibitive cost, limiting its use in routine practice. Radiomics is an artificial intelligence based non-invasive method of computational analysis of computed tomography, magnetic resonance imaging, positron emission tomography, and ultrasound images. METHODS: In this review, we summarise the last findings of radiomics applied to human papillomavirus associated oropharyngeal squamous cell carcinoma. RESULTS: A growing body of evidence suggest that radiomics is able to characterise and detect early relapse after treatment, and enable development of tailored therapy of human papillomavirus positive oropharyngeal squamous cell carcinoma.

Beyond the hype: A critical appraisal of the limitations and misconceptions of systematic reviews in the Oral pathology and medicine field.

BACKGROUND: Systematic reviews (SRs) have become a popular approach for evidence-based practice, being considered a lens through which evidence is viewed and applied. However, several published studies have been identified as scoping reviews rather than SRs. This methodological error can negatively impact clinical decision-making or new research conceptualization. AIM: This letter focuses on the increasing number of SRs in oral pathology and medicine, highlighting the most frequent methodological mistakes. RESULTS: We providing general guidance to help researchers conceptualize better their SRs and for the critical evaluation of SRs by scientific journal reviewers. CONCLUSION: Clinicians, pathologists, and reviewers, must ensure the quality of the published information.

A conservative approach for unicystic ameloblastoma: Retrospective clinic-pathologic analysis of 12 cases.

BACKGROUND: Unicystic ameloblastoma is an encapsulated odontogenic neoplasm with a single cyst cavity. The conservative or aggressive surgical approaches used to treat the tumor directly affect recurrence rates. However, there is a lack of a standard protocol that can guide its management. STUDY DESIGN: We retrospectively reviewed the clinicopathological findings and therapeutical procedures of 12 unicystic ameloblastoma cases treated by the same surgeon during the past 20 years. METHODS: All cases of unicystic ameloblastoma diagnosed by biopsy and treated by the same surgeon between 2002 and 2022 were reviewed. Eligibility criteria were patients with completely filled-out charts containing the follow-up period and confirmation of the diagnoses based on the microscopic findings of the whole excised specimens. Data collected were categorized into clinical, radiographic, histological, surgical, and recurrence aspects. RESULTS: There was a female predilection (2:1), and ages ranged between 18 and 61 years (mean: 27.25, ±12.45). Almost all (92%) affected the posterior mandible. Radiographically, the mean length of the lesions was 46.14 mm ± 14.28 mm which 92% were unilocular and 8.3% multilocular. Root resorption (n = 7, 58%), tooth displacement (n = 9, 75%), and cortical perforation (n = 5, 42%) were also observed. The mural histological subtype corresponded to 9 (75%) of the cases. The same conservative protocol was performed in all cases. The follow-up period ranged between 12 and 240 months (~62 ± 65) and recurrence occurred in only one patient (8%). CONCLUSION: Our findings suggest a conservative approach should be the first option for unicystic ameloblastoma treatment, even for those with mural proliferation.

Prognostic significance of the neural invasion in oral squamous cell carcinoma.

BACKGROUND: Although nerve involvement can predict recurrence and prognosis in oral squamous cell carcinomas, there still have controversies and limitations regarding the standardization for its detection. In this study, we explore the impact of neural invasion in oral squamous cell carcinomas prognosis, comparing intraneural invasion (tumor cells inside nerve structure) and perineural invasion (cells involving the nerve, but not invading its sheath). METHODS: Surgical slides stained with hematoxylin and eosin from 235 patients with oral squamous cell carcinomas were carefully verified for the presence of intraneural invasion and perineural invasion. The location in the tumor (intratumoral vs. peritumoral) and number of foci (unifocal or multifocal) were also explored. Survival analyses for cancer-specific survival and disease-free survival were performed with Cox proportional model. RESULTS: Neural invasion was identified in 74 cases, 64.9% displayed intraneural invasion and 35.1% displayed perineural invasion. Univariate analysis revealed a significantly poorer cancer-specific survival, but not disease-free survival, in patients with intraneural invasion, in contrast to cases with perineural invasion that did not achieve significant association with both cancer-specific survival and disease-free survival. Further analyses revealed that the location in the tumor and number of foci had little impact on discriminatory ability of intraneural invasion. Multivariate analysis confirmed that intraneural invasion is significantly and independently associated with poor cancer-specific survival (hazard ratio: 2.50, 95% CI: 1.31-3.79, p = 0.003). CONCLUSION: This study provides evidence that intraneural invasion, but not perineural invasion, is a relevant predictor of survival in patients with oral squamous cell carcinomas, suggesting that its association with other clinical and pathological prognostic factors should be consider in determining the optimal treatment protocol and prognosis of these patients.

Exploring the combination of tumor-stroma ratio, tumor-infiltrating lymphocytes, and tumor budding with WHO histopathological grading on early-stage oral squamous cell carcinoma prognosis.

BACKGROUND: While the relevance of the World Health Organization histopathological grading system as a prognostic tool for oral squamous cell carcinoma has received many critics, other histopathological features such as tumor-stroma ratio, tumor-infiltrating lymphocytes, and tumor budding are displaying promising results. Here, we evaluated the prognostic impact of the incorporation of tumor-stroma ratio, tumor-infiltrating lymphocytes, and tumor budding into World Health Organization histopathological grading for patients with oral squamous cell carcinoma. METHODS: A total of 95 patients with early-stage oral squamous cell carcinoma were enrolled in the study, and World Health Organization tumor grading, tumor-stroma ratio, tumor-infiltrating lymphocytes, and tumor budding were evaluated in surgical slides stained with hematoxylin and eosin. Survival analyses for cancer-specific survival and disease-free survival were performed using Cox regression models, and receiver operating characteristic curves were applied for assessment of the performance of the combinations. RESULTS: Tumor-stroma ratio (stroma-rich) was significantly and independently associated with both shortened cancer-specific survival and poor disease-free survival, individually and in combination with World Health Organization histopathological grading. The combination of tumor-stroma ratio with World Health Organization grading did not improve the discriminatory ability compared to tumor-stroma ratio alone. Although low tumor-infiltrating lymphocytes were associated with shortened cancer-specific survival, the association did not withstand multivariate analysis. However, in combination with World Health Organization grading, low tumor-infiltrating lymphocytes were independently associated with poor cancer-specific survival. The combination of tumor-infiltrating lymphocytes and World Health Organization histopathological grading displayed a better discrimination of poor cancer-specific survival than tumor-infiltrating lymphocytes alone, but not at a significant level. CONCLUSION: Our findings support tumor-stroma ratio as a potential prognostic marker for patients with oral squamous cell carcinoma, and the incorporation of tumor-infiltrating lymphocytes into the World Health Organization grading system improves the prognostic ability of the tumor grading alone.

Radiological aspects of lymphomas and leukaemias affecting the jaws: A systematic review.

BACKGROUND: This systematic review aimed to investigate the radiological features of lymphomas and leukaemias affecting the jaws. METHODS: A systematic literature review was conducted using the electronic databases of PubMed, Web of Science and Scopus. Articles that contained sufficient radiographic examinations (periapical, panoramic or computed tomography images) for individual cases were included. Additionally, either immunohistochemical or molecular confirmation was required prior to inclusion. Three authors evaluated and described the image quality and radiological features. RESULTS: From an initial 1079 articles screened, 129 cases were included, containing 88 tomographic, 76 panoramic and 26 periapical examinations. The quality of the majority of images was sufficient for evaluation. Diffuse large B-cell lymphoma, Burkitt lymphoma, leukemic infiltration, plasmablastic lymphoma and extranodal Natural killer (NK)/T-cell lymphoma, nasal type were the most common subtypes. Involved teeth presented with mobility in 37.2% of the cases and a provisional diagnosis of inflammatory/infectious dental disease was considered in 49.2% of cases. Computed tomography exams were available for 76% of the cases, with most presented with an osteolytic lesion with ill-defined borders. Periosteal reactions were uncommon. CONCLUSION: Lymphoma/leukaemia infiltrates of the jaw bones are usually of high-grade subtypes and rarely present with periosteal reactions.

Are foundation doctors equipped with the skills necessary for the assessment and referral of a patient presenting with a suspected facial skin malignancy?

BACKGROUND: The incidence of skin cancer (SC) has increased in recent years with it being the most common cancer within the UK. The management of SC requires a multidisciplinary approach involving dermatologists and surgical specialities. OBJECTIVES: To assess the confidence of current foundation trainees (FTs) in the assessment of facial SC and referral for surgical management and reconstruction. METHODS: An online survey was distributed via social media and completed by 142 FTs across 13 deaneries. Two higher training respondents were excluded. RESULTS: We found that 50% (71/142) of trainees had only examined one or two patients with SC and 25.3% (36/142) had no experience in SC assessment. Most FTs were not confident in performing a full skin examination (90.2%, 119/132), formulating differential diagnoses for a pigmented facial lesion (45.3%, 64/141) or investigating a facial SC (87.9%, 124/141). Facial defects requiring reconstruction (87.3%, 124/142) were more likely to be referred to plastic surgery. CONCLUSIONS: FTs were not confident in performing full skin examinations nor formulating diagnoses for pigmented lesions. This is concerning given that the majority of FTs will enter general practice and therefore exposure to SC will be common. This may in turn place greater burden on secondary care services such as dermatology and allied surgical specialities resulting in a greater caseload in an already stretched service in the UK. The integration of the British Association of Dermatology undergraduate syllabus into the medical school curriculum should improve confidence in the detection and management of SC at both undergraduate and postgraduate levels.

Examining the diversity of MRCS examiners.

BACKGROUND: MRCS examiners are the face of the Royal College of Surgeons for early-career surgeons and should therefore represent the workforce they are examining as not to marginalise or negatively impact on the assessment experience of candidates from minoritised groups. This study aimed to explore the diversity of MRCS examiners and whether they represent the demographics of the MRCS candidates. METHODS: A retrospective observational study including all active examiners and examination candidates who attempted MRCS Part A or Part B between January 2020 and July 2021. Self-declared demographic data collected by the Intercollegiate Committee for Basic Surgical Examinations (ICBSE) included gender, sexual orientation, disability status and ethnicity. Following data anonymisation, total group response frequencies were made available to the research team for statistical analysis. RESULTS: Chi-squared analyses showed statistically significant differences in the representation of gender, disability and ethnicity between candidates and examiners (all p < 0.001). Men (83.9% (n = 1121) vs 70.9% (n = 6017) respectively), individuals without disability (98.7% (n = 917) vs 96.1% (n = 6847)) and individuals of White ethnicity (36.6% (n = 346) vs 20.4% (n = 1223)) were significantly overrepresented in the examiners compared to the examination candidates. There was no statistically significant difference in sexual orientation between examiners and candidates (p = 0.712). CONCLUSIONS: Broadly speaking, the socio-demographic profile of MRCS examiners reflects that seen in senior and leadership positions in surgery in the UK - that is, predominantly male and White - but not that seen in early-career surgeons. Positive action is now required in examiner recruitment by the Royal Colleges to ensure that the cohort of MRCS examiners reflects the modern surgical workforce.

Establishing the predictive validity of the intercollegiate membership of the Royal Colleges of surgeons written examination: MRCS Part A.

Successful completion of the Intercollegiate Membership of the Royal Colleges of Surgeons (MRCS) examination is mandatory for surgical trainees entering higher specialist training in the United Kingdom. Despite its international reputation, and the value placed on the examination in surgical training, there has been little evidence of its predictive validity until recently. In this review, we present a summary of findings of four recent Intercollegiate studies assessing the predictive validity of the MRCS Part A (written) examination. Data from all four studies showed statistically significant positive correlations between the MRCS Part A and other written examinations taken by surgical trainees over the course of their education. The studies summarised in this review provide compelling evidence for the predictive validity of this gatekeeping examination. This review will be of interest to trainees, training institutions and the Royal Colleges given the value placed on the examination by surgical training programmes.

Establishing the predictive validity of the intercollegiate membership of the Royal Colleges of surgeons written examination: MRCS part B.

The Intercollegiate Membership of the Royal Colleges of Surgeons (MRCS) is a high-stakes postgraduate examination taken by thousands of surgical trainees worldwide every year. The MRCS is a challenging assessment, highly regarded by surgical training programmes and valued as a gatekeeper to the surgical profession. The examination is taken at considerable personal, social and financial cost to surgical trainees, and failure has significant implications for career progression. Given the value placed on MRCS, it must be a reliable and valid assessment of the knowledge and skills of early-career surgeons. Our first article 'Establishing the Predictive Validity of the Intercollegiate Membership of the Royal Colleges of Surgeons Written Examination: MRCS Part A' discussed the principles of assessment reliability and validity and outlined the mounting evidence supporting the predictive validity of the MRCS Part A (the multiple-choice questionnaire component of the examination). This, the second article in the series discusses six recently published studies investigating the predictive validity of the MRCS Part B (the clinical component of the examination). All national longitudinal cohort studies reviewed have demonstrated significant correlations between MRCS Part B and other assessments taken during the UK surgical training pathway, supporting the predictive validity of MRCS Part B. This review will be of interest to trainees, trainers and Royal Colleges given the value placed on the examination by surgical training programmes.

An update on extracapsular dissection for the management of parotid gland pleomorphic adenoma.

Superficial parotidectomy has been the gold standard for surgical removal of benign mobile parotid gland tumours. The comparatively newer technique of extracapsular dissection, which involves careful dissection of the tumour itself without the need for formal gland excision, has gained popularity in recent years. Tumours can be removed via smaller incision, and the technique reduces the risk of Frey's syndrome (gustatory sweating) and hollowing at the site of surgery. The risk of facial nerve damage can also be lower with extracapsular dissection. If done carefully, the incidence of tumour recurrence, particularly for pleomorphic adenomas, is comparable with formal parotidectomy. We provide a brief update overview of the current evidence for extracapsular dissection in the treatment of benign parotid tumours and include several meta-analyses which provide evidence for the safety of the technique. We have also included our audited results of over 100 recent extracapsular dissections, with 0% incidence of permanent facial nerve weakness, reported Frey's syndrome and recurrence rates over the last 5 years.

European Association of Oral Medicine 2021 Conference - Crispian Scully Lecture: Applying Human Factors to Improve Patient Safety and Performance.

BACKGROUND: This paper is a synopsis of the Crispian Scully Lecture, presented by one of the authors (PAB), at the 2021 European Association of Oral Medicine (EAOM) Conference in Lisbon, Portugal. It provides an overview of human factors that affect individuals and teams, highlighting ways to reduce the chances of error and improve patient safety. DISCUSSION AND CONCLUSION: Error is an inevitable and 'normal' part of being human, and it can never be completely eliminated, though learning from mistakes is essential. Human factor application in health care can greatly improve patient safety and lead to better team working and staff morale. Personal factors including tiredness, hunger, dehydration and stress can all reduce performance and raise the risk of clinical error. It is also important to understand and optimise interaction within the clinical team. Poor communication, steep hierarchy and loss of situational awareness can all potentially compromise patient safety.

Surgical tumour margins and their significance in oral squamous cell carcinoma.

There are many prognostic indicators used to predict tumour recurrence and overall prognosis in oral squamous cell carcinoma (OSCC). Most of these biological factors cannot be directly influenced by clinicians managing these heterogeneous group of tumours. Excision margins can potentially be increased at the time of surgery by including more normal tissue than the commonly accepted 1 cm resection distance from the macroscopic tumour edge. However, this can lead to poorer quality of life for patients and does not necessarily address microscopic extensions or dicohesive patterns of tumour growth. Surgical margins can be affected by tissue shrinkage immediately following resection and the choice of instrument used for surgery. Currently, most regard a clear resection margin as being >5 mm, a close margin as more than 1 mm but <5 mm and an involved margin <1 mm. In this article, we provide a brief overview of tumour margins in OSCC, including several recently published large meta-analyses. Based upon these and other studies, there is still conflicting data in the literature about the ideal margin for OSCC. There is a growing body of evidence that suggests a clearance of 1 mm might be adequate for some cancers. However, adequacy of resection should be considered along with the many other prognostic indicators of OSCC when the multi-disciplinary team considers further treatment for these patients.

Angiosarcomas of the head and neck: Impact of large data analysis on clinical management.

Angiosarcoma is a rare but often fatal malignancy from blood and lymphatic vessels that can arise anywhere in the body and often affects the head and neck region. Although its dismal prognosis is predominantly explained by its aggressive biology, several secondary factors contribute to poor outcomes. These include a phenotypic resemblance to innocuous blood vessel lesions, which contributes to a significant degree of late diagnosis. Another important factor is the rarity of angiosarcoma, which has impaired scientific determination of its optimal treatment significantly. As a result, treatment of angiosarcomas has largely been guided by information derived from the study of sarcomas at large, themselves a highly heterogeneous group of mesenchymal cancers both from a diagnostic as well as therapeutical perspective. The Digital Revolution and resultant Information Age promise to transform the clinical management of rare cancers from a generic to a more customized approach. In this paper, we review the current understanding of head and neck angiosarcomas within the context of this process.

Diagnostic accuracy of ultrasonography-guided core needle biopsy of parotid gland neoplasms: A large, single-institution experience in United Kingdom.

Salivary gland tumours present a pleomorphic and complex morphology and, apart from the most common neoplasms with well-established histopathological criteria, may create diagnostic difficulty for histopathologists. The majority of salivary gland tumours occur in the parotid gland and the use of ultrasound guided parotid biopsy (US-PB) has increased. US-PB in contrast with fine needle aspiration (FNA), which is an easy and relatively painless technique, is performed under local anaesthesia, usually by radiologists. US-PB offers some advantages over the FNA such as tumour grading and the possibility of performing immunohistochemistry. We report our experience of the diagnostic value of US-PB in a large, referral centre in the United Kingdom.

Hybrid odontogenic lesions: A systematic review of 203 cases reported in the literature.

BACKGROUND: Hybrid odontogenic lesions combine histopathological characteristics of two or more odontogenic cysts and/or tumours. The aim of this study was to evaluate the available data on hybrid odontogenic lesions (HOL) and to analyse their epidemiological/clinical features and biological behaviour. METHODS: An electronic search was done in January 2021 using multiple databases. Eligibility criteria encompassed publications with sufficient clinical and histological information to confirm the tumours' diagnoses. RESULTS: A total of 147 articles were included in this study, comprising 203 cases. Calcifying odontogenic cyst associated with odontoma (COC/OD) (37/18.2%) was the most common HOL. Females were more affected with a mean age of 24.9 years. Lesions presented as asymptomatic swellings, with a mean evolution time of 8.2 months (0.3-96), and mean tumour size of 4.8 cm (0.3-7). Radiographic aspects frequently showed radiolucent (139/68.4%) and unilocular (52/25.6%) images with well-defined limits (48/23.6%). The lesions mostly affected mandibular pre-molars (69/34%) and mandibular molars (69/34%) regions. Enucleation (89/43.8%) and surgical excision (59/29%) were the most common treatment modalities. The mean follow-up time was 33.8 months (0.5-216 months) and recurrences were observed in four cases (1.9%), all of which were central odontogenic fibroma associated with central giant cell granuloma (COF/CGCG). CONCLUSION: COC/OD is the most common HOL and recurrence is a rare event, being usually associated with the diagnosis of COF/CGCG.