Intracranial Cysts: A Single-Institution Experience With 27 Surgically Managed Cases.

Introduction Intracranial cysts (ICs) are rare pathologies that are often found incidentally during radiological examinations. They may appear in various brain regions and are categorized as normal, congenital, traumatic, or tumor-associated variants. ICs can be asymptomatic or cause symptoms, such as headaches, visual impairments, or seizures, depending on their size and location. Severe complications include obstructive hydrocephalus, loss of consciousness, and intracranial bleeding. Surgical excision is the most accepted type of management in most ICs. Objectives This study aimed to evaluate 27 surgically managed ICs in a tertiary hospital focusing on their clinical, radiological, histopathological, surgical outcomes, and prognosis to enhance understanding and management of these rare, benign cysts. Methodology This retrospective cohort study included 27 surgically managed ICs with pathological confirmation in King Abdulaziz Medical City, National Guard Health Affairs, Jeddah, Saudi Arabia, from May 2016 to May 2023. All extracranial and nonsurgically managed cysts have been excluded from this study. Data on demographics, clinical presentations, radiological features, surgical outcomes, and follow-up were retrospectively extracted and analyzed. MRI and CT scans were reviewed to determine cyst characteristics. Surgical outcomes and postoperative complications were recorded. Data were collected via Google Forms and analyzed using the JMP Pro software. Ethical approval was obtained from King Abdullah International Medical Research Center, Jeddah, Saudi Arabia. Results The study included 27 ICs: 11 (40.74%) colloid cysts, six (22.22%) epidermoid cysts, five (18.51%) adamantinomatous craniopharyngiomas, two (7.40%) neuroepithelial cysts, and one each of Rathke's cleft cyst (3.70%), xanthogranuloma (3.70%), and dermoid cyst (3.70%). All 27 cases were surgically managed (100.00%), with gross total resection achieved in 14 (51.85%) cases. Only 12 cases (44.44%) did not develop any surgical complications. Twenty-two cases (81.48%) experienced an improvement in the preoperative presenting symptoms. During the follow-up, only three cases (11.11%) had evidence of recurrence. Conclusion This study analyzed 27 ICs of various histopathological types. Each type showed distinct clinical and radiological features. Surgical management generally improved preoperative symptoms with low mortality and recurrence rates, although complications were common. Identifying specific radiological features is crucial for an accurate preoperative diagnosis and optimal surgical outcomes.

Influence of Breast Cancer Awareness Month on Public Interest of Breast Cancer in High-Income Countries Between 2012 and 2022: Google Trends Analysis.

BACKGROUND: Breast cancer is the most common cancer among women worldwide. High-income countries have a greater incidence and mortality rate of breast cancer than low-income countries. As a result, raising awareness about breast cancer is crucial in increasing the chances of early detection and treatment. Social media has evolved into an essential tool for Breast Cancer Awareness Month campaigns, allowing people to share their breast cancer stories and experiences while also providing a venue for education and support. OBJECTIVE: The aim of this study was to assess the level of public interest in searches linked to breast cancer among a sample of high-income nations with a sizable internet user base from 2012 to 2022. We also sought to compare the proportional search volume for breast cancer during Breast Cancer Awareness Month with that during other months of the year. METHODS: Google Trends was used to retrieve data on internet user search behaviors in the context of breast cancer from 2012 to 2022. Seven countries were evaluated in this study: Australia, Canada, Ireland, New Zealand, the United Kingdom, Saudi Arabia, and the United States, in addition to global data. Breast cancer relative search volume trends were analyzed annually, monthly, and weekly from 2012 to 2022. The annual percent change (APC) was calculated for each country and worldwide. Monthly and weekly data were used to identify potential trends. RESULTS: A fluctuating pattern in APC rates was observed, with a notable increase in 2018 and a significant decrease in 2020, particularly in Saudi Arabia. Monthly analysis revealed a consistent peak in search volume during October (Breast Cancer Awareness Month) each year. Weekly trends over a 20-year period indicated significant decreases in Australia, Canada, New Zealand, and the United States, while increases were noted in Ireland. Heatmap analysis further highlighted a consistent elevation in median search volume during October across all countries. CONCLUSIONS: These findings underscore the impact of Breast Cancer Awareness Month and suggest potential influences of governmental COVID-19 pandemic control measures in 2020 on internet search behavior.

Combined Preoperative Endovascular Embolization and Surgical Excision for Scalp Arteriovenous Malformations: A Systematic Review and Case Illustration.

OBJECTIVE: To evaluate the efficacy of the combined approach of preoperative endovascular embolization (EE) and surgical excision (SE) for scalp arteriovenous malformation (AVM) and present an illustrative case report. METHODS: A systematic review was conducted using online databases (PubMed/Medline, Cochrane, and Embase) on February 15, 2023. The inclusion criteria were any type of study of patients with scalp AVMs who were diagnosed and confirmed through angiography and treated with combined preoperative EE and SE. All the articles that met the inclusion criteria were included in this study. RESULTS: A total of 49 articles (91 patients) were included. The patients' age ranged from 10 days to 70 years at the time of presentation. The most common symptoms were a pulsatile mass in 51 patients (56.04%), progressively growing mass in 31 patients (34.06%), and bruits and/or thrills in 22 patients (24.17%). Complications of preoperative EE and SE were observed in only 5 patients; 3 patients (3.29%) had harvested skin graft marginal necrosis, 1 patient (1.09%) had skin necrosis, and 1 patient (1.09%) had a wound infection. Only 2 patients (2.19%) reported a recurrent or residual mass during a median follow-up period of 12 months. CONCLUSIONS: The management of scalp AVMs can be challenging; therefore, focused, and accurate identification of the complexity of the vascular anatomy is required. The combined method of preoperative EE and SE showed satisfactory outcomes with low rates of complications and recurrence; thus, we recommend this approach for the management of scalp AVMs.

Disease burden and projection of total and early-onset colorectal cancer in Gulf cooperation council countries from 1990 to 2019.

BACKGROUND: Early-onset colorectal cancer (EO-CRC) incidence and prevalence trends in the rise in high income countries, such as the Gulf Cooperation Council (GCC) countries. The study aimed to offer an up-to-date assessment of the overall burden of CRC, and EO-CRC in GCC countries and project its incidence and mortality in 2030. METHOD: The prevalence, incidence, mortality, years of life lived with disability (YLDs), and disability-adjusted life years (DALYs) of CRC were obtained from the Global Burden of Disease (GBD) Study 2019. The incidence and mortality of CRC, and EO-CRC up to 2030 were predicted. RESULTS: All GCC countries showed a higher annual average percentage changes (AAPC) AAPC incidence rate for EO-CRC compared to CRC. In Saudi Arabia the number of CRC cases has increased from 1990 1484.57; (95 % UI 1987.98,1083.86) 11.4-fold-increase to 16991.83; (95 % UI 21754.79,12892.12) in 2019. In 2030, the total incidence cases of CRC for the six Gulf countries are expected to reach 13,339 thousand, primarily driven by Saudi Arabia with 7,910.19 cases. In 2030, the CRC mortality rate is projected to be 7,647 cases, with nearly 57 % of CRC mortality cases anticipated in Saudi Arabia. CONCLUSION: This study sheds light on the alarming rise in CRC and EO-CRC across Gulf countries from 1990 to 2019, emphasizing Saudi Arabia's significant burden. It projects a concerning increase in CRC incidence and mortality by 2030, primarily in Saudi Arabia, and highlights the need for immediate public health interventions.

Solitary plasmacytoma of the calvarium: A successful management of a long-standing large lesion with a long-term follow-up.

Background: Solitary plasmacytoma of the calvarium (SPC), without evidence of multiple myeloma (MM), is extremely rare. We report a case of a long-standing large SPC that was treated successfully by surgical excision and adjuvant radiotherapy with a long follow-up period. Case Description: A 58-year-old male patient presented with a 5-year history of painless skull swelling. On the physical examination, the mass was 6 × 6 cm in size, oval, not tender, and firm in consistency with normal skin color. A brain computed tomography scan showed a destructive skull lesion. A brain magnetic reasoning imaging (MRI) showed a large expansile lytic mass lesion arising from the skull vault in the frontal-parietal region with multiple internal septa. The patient underwent a craniectomy and excision of the lesion, followed by cranioplasty using methyl methacrylate. The final diagnosis was consistent with plasmacytoma based on the histopathological features. One month follow-up brain MRI showed no evidence of residual tumor. The skeletal survey and bone marrow biopsy did not reveal any evidence of MM. The patient was referred to medical oncology for further treatment and received radiation therapy. During nine years of clinical and radiological follow-up, there was no evidence of any metastasis or recurrence. Conclusion: SPC is a rare disease with high rates of misdiagnosis. Careful evaluations are crucial to exclude systemic involvement. Surgical resection followed by radiotherapy may be adequate for the disease control. Close follow-up with regular lifelong examinations is important to avoid a generalized incurable disease.

Xanthogranuloma of the suprasellar region mimicking cystic craniopharyngioma: A case report.

Background: Xanthogranuloma of the sellar region is an extremely rare benign entity with only case reports and series documented in the literature. We aim to describe in this report a case of a suprasellar xanthogranuloma that was diagnosed initially as a cystic craniopharyngioma. Case Description: A 28-year-old woman presented to the clinic with a 2-week history of headaches, blurred vision, nausea, and vomiting. She had no medical or surgical history, no signs of hormonal disturbances, and no family history of brain tumors or endocrine diseases. Her neurological examination was unremarkable except for bitemporal hemianopia on visual field testing. A magnetic resonance imaging of the brain showed a cystic mass in the sellar region that was compressing the optic chiasm with radiological features representing cystic craniopharyngioma. She underwent endoscopic transnasal transsphenoidal surgery to excise the mass, and only subtotal excision was achieved to preserve the pituitary function. The histopathology confirmed the diagnosis of a xanthogranuloma of the sellar region. The postoperative course was unremarkable, and she did not receive any adjuvant therapy. There was no recurrence of the clinical symptoms or the mass during the 18-month follow-up period. Conclusion: Although xanthogranuloma is uncommon, it should be included in the differential diagnosis of sellar/suprasellar lesions. Due to its wide range of radiological features that sometimes can mimic other lesions, a definitive diagnosis can only be made postoperatively. Surgical excision is the most accepted treatment with a favorable prognosis and low rates of recurrence.

Awake craniotomy for fenestration of motor cortex neuroglial cyst: A case report.

Background: Neuroglial cysts (NCs) are uncommon benign cysts covered by an epithelial layer, accounting for <1% of all intracranial cysts. The optimal management approach for these cysts remains a subject of debate. Given their rarity, management principles used for arachnoid cysts can be applied to NCs. Case Description: We present a case of a 35-year-old male without prior medical history, who presented to the neurosurgery clinic with complaints of absence seizures. A neurological examination revealed subtle weakness in the left upper limb. Brain magnetic resonance imaging demonstrated a large cystic lesion in the posterior frontal and anterior parietal lobes of the right hemisphere. The patient underwent an awake craniotomy, during which a cystoventricular fenestration was performed on the motor cortex cyst. Histopathological examination confirmed the diagnosis of NC. At the 4-month follow-up, the patient experienced complete recovery, with normal strength (5/5) in all limbs and absence of seizure remission. Conclusion: This case highlights the successful use of awake craniotomy for the fenestration of an NC in the motor cortex. Given the rarity of NCs, there is no consensus on the optimal treatment strategy. However, in this particular case, the patient achieved complete recovery without any new neurological deficits following the procedure.

An Unusual Presentation of Hearing Impairment in an Adult with Pineal Region Germinoma: A Case Report.

Tumors of the pineal region typically present with symptoms and signs of mass effect and increased intracranial pressure. However, although rare and can be overlooked, hearing impairment is a potential clinical finding in these cases. The authors describe a 24-year-old male who presented to the emergency room complaining of bilateral hearing impairment. Brain computed tomography showed a pineal region tumor. Histopathological examination demonstrated features consistent with germinoma. This case reports a rare presentation rarely seen in the literature and in practice as evident by the conducted literature review. Therefore, we highlight the importance of considering hearing impairment as a presenting symptom of pineal region tumors since prompt recognition and intervention, as demonstrated in this case, can lead to successful outcomes.

Gliosarcoma Invading the Temporal Bone, Temporalis Muscle, and Skull Base.

Gliosarcoma (GS) is a primary central nervous system tumor. It is an unusual type of glioblastoma multiforme (GBM) and rarely invades the skull base. It has a biomorphic tissue pattern with rapid alternation zones of glial and mesenchymal differentiation. We report the case of a 62-year-old male who presented with a one-month history of unsteady gait associated with dizziness. Brain MRI showed a right temporal mass that invaded the skull base with perilesional edema and a significant mass effect on the right lateral ventricle. The patient underwent a right-sided frontotemporal craniotomy with gross total resection. The pathology confirmed the diagnosis of GS. Postoperatively, the patient had an uneventful recovery with no complications and was discharged two days post-surgery.

Central nervous system metastasis in a young female patient with primary mediastinal large B-cell lymphoma: A case report and literature review.

Background: Primary mediastinal B-cell lymphoma (PMBCL) is a subtype of diffuse large B-cell lymphoma that originates from a B cell in the thymus. It usually affects young female. Case description: A 30-year-old woman presented with mediastinal mass with history of shortness of breath and chest pain. blood analysis showed low levels of hemoglobin, hematocrit, and mean corpuscular volume and high red cell distribution width. A computed tomography (CT)-guided mediastinal core biopsy disclosed primary mediastinal large B-cell lymphoma (PMLBL) with a nongerminal center phenotype and lung tissue infiltrate. Moreover, after undergoing six cycles of rituximab, cyclophosphamide, hydroxydaunomycin, Oncovin, and prednisone (R-CHOP) chemotherapy and mediastinal radiotherapy, the patient presented with headache and visual disturbance due to multiple supratentorial lesions. Conclusion: Till date, only a few cases of central nervous system (CNS) metastasis have been reported in the literature. Moreover, CNS metastasis of refractory PMBCL is an uncommon event with a poor prognosis. Brain metastases are often the ultimate fatal consequence of many aggressive cancers, so early detection and treatment are important.

Hydroxychloroquine-Induced Myopathy Responding to Intravenous Immunoglobulin (IVIG).

Hydroxychloroquine (HCQ), a drug used to treat many diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), has limited reports documenting drug-induced myopathies as a side effect. This entity is underdiagnosed with unclear treatment interventions apart from discontinuing the offending drug. We report a case of a biopsy-proven hydroxychloroquine-induced myopathy in a 35-year-old female patient with SLE. The offending drug was stopped, but the patient did not improve. However, she showed marked improvement after the use of intravenous immunoglobulin (IVIG).

Intraparenchymal meningioma in the parieto-occipital region: A case report of a diagnostically challenging tumor.

Background: Intraparenchymal meningioma is a rare entity of one of the most common brain tumors. It is challenging to diagnose preoperatively due to the vague clinical presentation and absence of stereotypical radiological features. These atypical features might mislead the differential to favor high-grade gliomas or brain metastasis. Case Description: We describe a case of a 46-year-old male who presented with vertigo, right-sided sensorineural hearing loss, and bilateral blurred vision. Contrast-enhanced magnetic resonance imaging of the brain revealed a large parieto-occipital contrast-enhanced mass with a multi-loculated cystic component and diffusion restriction but without dural attachment. A gross total reaction was achieved, and the histopathological results yielded a World Health Organization Grade I meningioma diagnosis. The patient exhibited no signs of recurrence after 2 years of follow-up. Conclusion: Intraparenchymal meningiomas are difficult to identify without histopathological assessment. We emphasize the importance of considering this diagnosis when outlining an initial differential as it may direct management planning. Total surgical resection is the best treatment modality for such cases; however, radiotherapy is a valuable option. The prognosis of intraparenchymal meningiomas is generally favorable.

Pineal Parenchymal Tumors of Intermediate Differentiation: A Case Report and Literature Review.

Pineal parenchymal tumors of intermediate differentiation (PPTIDs) account for a significant proportion of pineal tumors and are classified as grade II/III according to the WHO classification. The management of PPTIDs remains controversial because of limited reported cases and the absence of standardized treatment guidelines. We present a case of an eight-year-old male child who presented with vomiting and a sudden squint of the eyes. Imaging revealed a well-defined heterogeneous enhancing lesion in the pineal region with acute hydrocephalus. The patient underwent surgical resection, and the tumor was diagnosed as PPTID. Local recurrence occurred 10 months later, requiring a second surgical intervention and adjuvant radiation therapy. A follow-up showed a regression of the tumor and improvement in symptoms. A literature review of reported PPTID cases revealed variability in clinical presentation, treatment approaches, and outcomes. Headaches were the most common symptom, and surgical resection was the primary treatment modality. Adjuvant therapies such as radiation therapy and chemotherapy were utilized in some cases. Tumor recurrence was observed in several instances, underscoring the need for long-term follow-up. In conclusion, PPTIDs are rare brain tumors with challenging diagnosis and management. Surgical resection remains the mainstay of treatment; however, the optimal approach is uncertain. Standardized reporting and larger studies are necessary to establish guidelines for the management of PPTIDs and improve long-term outcomes.

Diagnostic Discrepancies Between Intraoperative Frozen Section and Permanent Histopathological Diagnosis of Brain Tumors.

OBJECTIVE: Intraoperative frozen section (IOFS) diagnosis of brain tumors plays an important role in assessing the adequacy of the sample and determining the treatment plan. The aim of this study was to investigate the diagnostic accuracy between IOFS and permanent sections. MATERIAL AND METHOD: The authors reviewed the histopathological results of 383 brain tumors, including IOFS and permanent histological diagnosis. The cases were classified into three diagnostic compatibilities (i) Perfect fit; the diagnosis of IOFS was identical to the permanent diagnosis, (ii) Partial compatibility; IOFS diagnosis was not incorrect but was too broad to be considered full compatibility, (iii) Conflict; IOFS diagnosis is completely different from the permanent diagnosis. The permanent diagnosis was used as a primary criterion and was compared to IOFS diagnosis and recurrence rate using different statistical methods. RESULTS: 84% of the patients underwent craniotomy and tumor resection, while 15% only underwent tumor biopsy. Approximately, 53.8 % of the cases revealed perfect matching in the diagnosis between IOFSs and permanent sections, while 16.2% of the cases revealed complete mismatching in the diagnosis between the sections. The remaining 30% of the cases showed partial compatibility in the diagnosis between the two diagnostic methods. There was no significant difference in recurrence rate among all cases of different diagnostic compatibility (p=0.54). CONCLUSION: There is a diagnostic discrepancy between IOFSs and permanent sections. However, cases that revealed no consensus in the diagnoses showed no negative effect on the patient outcome. Further studies should be conducted to explore the reasons of this conflict in the two diagnostic methods.

The Impact of IDH1 Mutation and MGMT Promoter Methylation on Recurrence-Free Interval in Glioblastoma Patients Treated With Radiotherapy and Chemotherapeutic Agents.

The aim of this study is to investigate the relationship between isocitrate dehydrogenase-1 (IDH1) mutation and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation with recurrence-free interval in glioblastoma patients treated with chemoradiotherapies. Clinical data were collected from 82 patients with totally resected glioblastoma and treated with adjuvant therapies from 2014 to 2019. IDH1 mutation was assessed by immunohistochemistry and MGMT promoter methylation was assessed by different sequencing methods. IDH1 mutation was present in 32 cases and 50 cases were IDH1 wildtype; 54 and 28 patients had unmethylated and methylated MGMT promoter, respectively, Of the 82 patients, 62 patients received chemoradiotherapy while 20 patients only received radiation. Approximately, 61% of patients had a tumor recurrence after 1 year, and 39% showed a recurrence before 1 year of treatment. There was no significant relationship between IDH1 mutation and MGMT promoter methylation (p-value = 0.972). Patients with IDH1 mutation and their age <50 years showed a significant difference in recurrence-free interval (p-value = 0.014). Difference in recurrence-free interval was also statistically observed in patients with unmethylated MGMT promoter and treated with chemoradiotherapies (p-value = 0.031), by which they showed a late tumor recurrence (p-value = 0.016). This revealed that IDH1 mutation and MGMT methylation are independent prognostic factors in glioblastoma. Although IDH1-mutant glioblastomas showed late tumor recurrence in patients less than 50 years old, the type of treatment modalities may not show additional beneficial outcome. Patients with unmethylated MGMT and IDH1 mutation, treated with different chemoradiotherapies, showed a late tumor recurrence.

Prognostic value of TP53 expression and MGMT methylation in glioblastoma patients treated with temozolomide combined with other chemotherapies.

OBJECTIVE: To assess the recurrence interval and predictive significance of TP53 expression and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in glioblastomas treated with radiotherapy and combined chemotherapies, including temozolomide, lomustine, procarbazine and bevacizumab. METHOD: We reviewed the clinical outcomes of 52 totally resected glioblastoma patients, who received conventional radiotherapy and temozolomide with other chemotherapeutic agents. Correlation of TP53 expression and MGMT promotor methylation with recurrence interval was analyzed using Kaplan Meier estimates. RESULTS: No significant association was found between MGMT promotor methylation and TP53 expression in glioblastomas (P-value = 0.158). Patients with non-methylated MGMT who received temozolomide chemotherapy with other chemotherapeutic agents showed significantly later recurrence (P-value = 0.007) compared with patients with non-methylated MGMT who received temozolomide alone. No significant difference was found in recurrence interval among glioblastoma patients with methylated MGMT who received temozolomide alone or with other chemotherapies (P-value = 0.667). Moreover, patients with non-TP53-expressing tumors who received temozolomide with other chemotherapies had significantly later recurrence (P-value = 0.04) compared with patients who received temozolomide alone. CONCLUSION: Totally resected glioblastoma patients, with non-methylated MGMT or non-TP53-expressing tumors treated with radiotherapy and combined chemotherapies had a reduced chance of tumor recurrence and a more favorable outcome. Furthermore, both MGMT and TP53 are independent prognostic factors for glioblastoma.

Contribution of Pathologists in Leading Clinical Cancer Research Through Interdisciplinary Collaboration in Saudi Arabia.

Background Interdisciplinary collaboration is often the key to advance cancer research. This research collaboration is frequently observed between oncologists and pathologists. While clinical cancer research is often led by oncologists, the leading role of pathologists is likely limited to laboratory-based and preclinical research. Therefore, the magnitude and characteristics of clinical studies led by pathologists is largely unknown. Objectives The objective of our study was to assess the quantity and quality of clinical cancer-related publications led by Saudi pathologists over a 10-year period. Methods A PubMed search was conducted between January 2008 and December 2017 to extract all published clinical articles regarding cancer by at least one Saudi pathologist with the collaboration of other cancer specialists. Information about articles and authors were collected. The level of evidence (LOE) was independently assessed by two authors. Two five-year periods (2008 - 2012 and 2013 - 2017) were compared using the relevant parameters. Results A total of 127 publications met our inclusion criteria and were included. Review articles (27%) were the most common type of publication. There were no experimental studies. The LOE was III and IV in 59.1% and 40.9% of the included publications, respectively. Comparing the two five-year periods, the number of publications (p < 0.001), publications in international journals (p = 0.004), and international collaborations (p < 0.001) increased in the second period. The LOE and journal impact factor were the same in the two periods. Conclusions The pathologist-led clinical cancer research in Saudi Arabia increased over time. Despite the observed increase in international collaboration and publications in international journals, the LOE was low (III/IV) and did not change over time.

Synovial sarcoma of the spine: A case report and review of the literature.

BACKGROUND: Synovial sarcoma (SS) of the spine is a rare malignant soft-tissue tumor, and there are few reported cases. The aim of this paper is to report a rare case of spinal SS involving the paraspinal muscles, and to review all such cases reported in the literature. CASE DESCRIPTION: In this paper, we report a rare case of spinal SS involving the paraspinal muscles in a 12-year-old girl. The patient underwent surgical excision of the mass with adjuvant radiation and chemotherapy. At the 1-year follow-up, there was no evidence of local tumor recurrence, and the patient's symptoms had improved. In addition, we identified and reviewed 33 reported cases of SS involving the spine. CONCLUSION: Due to the limited number of reported cases in the literature, it is difficult to predict the outcomes of spinal SS. Further, different treatment modalities have been used to treat spinal SS. However, most of the reported cases had poor outcomes. Therefore, prospective multi-center studies are needed to further investigate the treatment strategies and outcomes for patients with spinal SS.

Molecular characterisation in tongue squamous cell carcinoma reveals key variants potentially linked to clinical outcomes.

BACKGROUND: Oral tongue squamous cell carcinoma (OTSCC) is a highly aggressive malignancy characterized by frequent recurrence, poor survival with relatively few therapeutic options due to the late diagnosis in many cases. OBJECTIVES: Understanding the molecular pathways underlying OTSCC tumourigenesis and the discovery of diagnostic and/or prognostic biomarkers. METHODS: We performed high-throughput mutational analysis of 44 OTSCC formalin-fixed paraffin-embedded (FFPE) cases using the Cancer Hotspots Panel (CHP) v2 on the Ion Torrent™platform. We determined the frequency of human papilloma virus (HPV) using PCR and Epstein bar virus (EBV) positivity using immunohistochemistry. As a control for EBV infection we screened matched non-tumourous tissues. RESULTS: Sequencing analysis identified missense, nonsense and frameshift mutations in TP53 (66%), PIK3CA (27%), CDKN2A (25%), EGFR (18%), and PTEN (14%). Interestingly, no significant associations were found between damaging mutations and clinicopathological data. A total of 10/44 of the OTSCC samples (23%) tested was positive for HPV18 DNA. OTSCC patients with positive HPV infection had worse overall survival compared to HPV-negative cases as determined by Kaplan-Meier survival (p= 0.023). Furthermore, EBNA1 expression showed a strong tumour-enriched expression pattern in 20 out of 21 samples (95%) in the epithelial compartments of the tissues analysed. CONCLUSIONS: Taken together, this study highlights that the two most common events in OTSCC are TP53 mutations and EBV positivity. Helping to understand the contribution of TP53 mutations and EBV infection events could serve as useful biomarkers for OTSCC.