Increased Prevalence of EBV Infection in Nasopharyngeal Carcinoma Patients: A Six-Year Cross-Sectional Study.

Epstein Barr Virus (EBV) is implicated in the carcinogenesis of nasopharyngeal carcinoma (NPC) and currently associated with at least 1% of global cancers. The differential prognosis analysis of NPC in EBV genotypes remains to be elucidated. Medical, radiological, pathological, and laboratory reports of 146 NPC patients were collected retrospectively over a 6-year period between 2015 and 2020. From the pathology archives, DNA was extracted from tumor blocks and used for EBV nuclear antigen 3C (EBNA-3C) genotyping by nested polymerase chain reaction (PCR). We found a high prevalence of 96% of EBV infection in NPC patients with a predominance of genotype I detected in 73% of NPC samples. Histopathological examination showed that most of the NPC patients were in the advanced stages of cancer: stage III (38.4%) or stage IV-B (37.7%). Only keratinized squamous cell carcinoma was significantly higher in EBV negative NPC patients compared with those who were EBV positive (OR = 0.01, 95%CI = (0.004-0.32; p = 0.009)), whereas the majority of patients (91.8%) had undifferentiated, non-keratinizing squamous cell carcinoma, followed by differentiated, non-keratinizing squamous cell carcinoma (7.5%). Although NPC had metastasized to 16% of other body sites, it was not associated with EBV infection, except for lung metastasis. A statistically significant reverse association was observed between EBV infection and lung metastasis (OR = 0.07, 95%CI = (0.01-0.51; p = 0.008)). Although 13% of NPC patients died, the overall survival (OS) mean time was 5.59 years. Given the high prevalence of EBV-associated NPC in our population, Saudi could be considered as an area with a high incidence of EBV-associated NPC with a predominance of EBV genotype I. A future multi-center study with a larger sample size is needed to assess the true burden of EBV-associated NPC in Saudi Arabia.

Temporal Bone Langerhans Cell Histiocytosis: An Uncommon Bilateral Presentation.

Langerhans cell histiocytosis (LCH) is a rare condition that presents clinically in various ways. The cause and subsequent development of LCH are idiopathic and not fully understood. This disease is mainly seen in childhood. It is rare to have bilateral temporal bone LCH as the initial presentation. LCH can affect many organs. However, the bilateral involvement of the temporal bone is very uncommon. Therefore, we believe documenting cases of this presentation can lead to a better understanding of the epidemiology and prevalence of the disease, which can contribute to its management planning. A one-year-old boy was referred to a tertiary otolaryngology clinic with bilateral postauricular swelling, hearing loss, but no tenderness or ear discharge. During the patient evaluation, a CT scan was requested to further investigate the bilateral swelling, which showed bilateral bony destructive lesions in the temporal bone area. Next, the patient was scheduled for a biopsy of this lesion under general anesthesia. A biopsy of the right mastoid confirmed the diagnosis of LCH. The patient was started on LCH IV protocol for multifocal bone lesions (MFB) with special site induction. A follow-up fluorodeoxyglucose positron emission tomography/CT (FDG PET/CT) was performed on the whole body with the impression of mild interval improvement of the temporal bones' masses bilaterally with stable bilateral cervical lymphadenopathy. LCH is a rare pathology that requires comprehensive effort from various medical and surgical teams to reach the right diagnoses and start the patient on the best available treatment plan.

Malignant Otitis Externa in a 20-Year-Old Male Patient With Erdheim-Chester Disease: A Case Report.

Malignant otitis externa (MOE) is an uncommon, potentially life-threatening, invasive infection of the external auditory canal and lateral skull base. It is mainly seen in older adults with diabetes or immunocompromised patients and rarely seen in children. Erdheim-Chester disease (ECD) is a rare, non-Langerhans histiocytosis disorder. It is a multisystem disease with a poorly understood etiology. It commonly affects the skeletal system, central nervous system (CNS), cardiovascular system, lungs, retroperitoneum, kidneys, and skin. CNS involvement confers poor prognosis and reduced response to treatment. Cardiovascular involvement is another indicator of poor prognosis. This report describes the case of a 20-year-old male with ECD who had bilateral malignant otitis externa/skull base osteomyelitis and hearing loss. The patient was not responding well to treatment. He was on intravenous antibiotics, underwent left mastoidectomy, received targeted immunotherapy, and had four rounds of chemotherapy. The patient died after six months from the diagnosis and targeted treatment, which indicates the aggressiveness of the disease. MOE should be suspected in any patient presenting with intractable otalgia with otorrhea that is not responsive to local treatment for uncomplicated otitis externa or otalgia with temporomandibular joint (TMJ) pain aggravated by chewing. This is the first report of malignant otitis externa in a young patient with ECD to the best of the author's knowledge. This case emphasizes the importance of suspecting MOE in young patients, especially if the risk factors of the disease are present because early diagnosis can prevent or minimize life-threatening complications.

Familial hypercholesterolemia with bilateral cholesterol granuloma: A case series.

INTRODUCTION: Cholesterol granuloma is a benign mass that commonly involves the petrous apex but rarely affects other structures, such as the mastoid cavity. It is diagnosed histologically by the presence of giant cells, and Its management is individualized based on some factors such as the size and location of the lesion. PRESENTATION OF CASE: The first case was a 33-year-old man who presented to the outpatient clinic with a two-year history of right-sided pulsatile tinnitus, hearing loss, and vertigo. Upon investigations, a large, destructive mass in the tympanomastoid region was found and managed surgically. The other case was for a 41-year-old man who presented to the emergency department with loss of consciousness. Urgent CT was done and revealed an aggressive hypodense posterior fossa mass destroying the right temporal bone that was managed surgically. DISCUSSION: In this report, we describe two patients with familial hypercholesterolemia who developed bilateral cholesterol granuloma that were managed surgically. CONCLUSION: These cases are reported because of their rare location and presentation since few cases of bilateral cholesterol granuloma have been reported in the literature.

Absence of human papillomavirus in oral cavity squamous cell carcinomas among Saudi patients.

This study aimed to examine the possible association of human papillomavirus (HPV) with oral cavity squamous cell carcinomas (OCSCCs) in Saudi Arabia. Forty-five paraffin-embedded tumor blocks that represent different subsets of OCSCCs between 2010 and 2014 were retrieved and histologically evaluated. The presence of high-risk HPV (16, 18, 31, and 33) was assessed by p16-immunohistochemistry followed by DNA detection using in situ hybridization technique. Twenty-four patients were male with the mean age of 59.3 years, and 21 patients were female with the mean age of 61.2 years. Forty-one cases were positive for p16 immunostaining, and the remaining four cases were negative. However, none of the 45 cases showed DNA-expression for any HPV subtypes (16, 18, 31, and 33). High-risk HPV appears not to be involved in the etiology of OCSCCs in older Saudi patients, but further studies with cross section of a younger age group are still required.

Tall Cell Variant Papillary Thyroid Carcinoma in Saudi Patients: A clinicopathological and Outcomes Analysis.

OBJECTIVES: To evaluate the clinicopathological features and treatment outcomes of papillary thyroid carcinoma tall cell variant (PTC-TCV) in Saudi population. Methods: This retrospective study were medical records of 776 treated PTC patients between December 2007 and 2015, at King Fahad Medical City and King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia was probed for PTC-TCV. Total 42 (5.4%) patients were found to have PTC-TCV, which were investigated for demographic, symptoms, histopathological features, and treatment outcomes locoregional control (LRC), distant metastasis control (DMC), disease free survival (DFS), and overall survival (OS) rates. Results: Mean age of cohort was 52.3 years (range: 46-80), with female predominance (73.8%). Mean tumor size was 3.62 cm (range: 0.4-10). Rates of LVSI (59.5%), positive pathological lymph nodes (66.7%), multifocality (42.9%) and extrathyroidal extension, (45.3%). Median follow-up was 37.4 months (range: 6-60). Local recurrence rate were seen in 6/42 (14.2%) patients and 8/42 (19%) developed distant metastasis. The 5 year rates of LRC (82.3%), DMC (77.8%), DFS (69.2%), and OS (86.7%) multivariate analysis showed PTC-TVC as an important independent prognosticator (odds ratio: 4.2; 95% confidence interval: 1.79-7.3; p=0.03)  Conclusion: Papillary thyroid carcinoma tall cell variant is associated with aggressive biological behavior.

Comparative clinicopathological and outcome analysis of differentiated thyroid cancer in Saudi patients aged below 60 years and above 60 years.

INTRODUCTION: The aim of this study was to evaluate the treatment outcomes of differentiated thyroid cancer in Saudi patients aged above 60 years. MATERIALS AND METHODS: Comparative analysis was performed in 252 patients aged 46-60 years (Group A) and 118 patients aged above 60 years (Group B), who had thyroidectomy, radioactive iodine-131, and thyroid-stimulating hormone suppression therapy between July 2000 and December 2012. Different clinicopathological features, treatment, complications, disease-free survival, and overall survival rates were compared. RESULTS: Mean age of patients in Group A was 51.9 years (range: 46-60), and mean age of those in Group B was 68.6 years (range: 62-97). Group B patients had higher positive lymph nodes (43.2%), P=0.011. The frequency of extrathyroidal extension, multifocality, and lymphovascular space invasion was seen more in Group B than in Group A. Postsurgical complications (permanent hypoparathyroidism, bleeding, and wound infections) were also seen more in Group B (P=0.043, P=0.011, and P=0.021, respectively). Group B patients experienced more locoregional recurrences (11.0%, P=0.025); similarly, more distant metastases were observed in Group B (15.3%, P=0.003). The 10-year disease-free survival rates were 87.6% in Group A and 70.8% in Group B (P<0.0001). CONCLUSION: Differentiated thyroid cancer in patients aged above 60 years are more aggressive biologically and associated with a worse prognosis, and the morbidity is significantly high as compared to patients aged below 60 years.

Adenoid cystic carcinoma of the upper airway mimicking a thyroid tumor: A case report.

Adenoid cystic carcinoma (ACC) is a rare malignant tumor, reportedly representing <1% of all head and neck cancers. There have been few reported cases of ACC of the upper airway presenting as a midline mass. This is the case report of a 47-year-old female patient who presented with such a midline neck mass. The mass was approached and investigated as a thyroid mass, but was ultimately found to be a tracheal tumor with thyroid invasion. We herein discuss in detail the patient history, investigation and treatment.

Clinicopathological features and treatment outcomes of the rare, salivary duct carcinoma of parotid gland.

BACKGROUND: Salivary ductal carcinoma (SDC) of parotid gland is a rare and aggressive entity; accounting for 1-3 % of all malignant salivary gland tumors, 0.2 % of epithelial salivary gland neoplasms, 0.5 % of salivary gland carcinomas, and 1.1 % of parotid gland carcinomas. Here in we aimed to evaluate the clinico-pathological features and treatment outcomes of parotid gland SDC in Saudi population. METHODS: Among 38 patients with parotid malignancies, who were treated in two major tertiary care referral cancer centers between December 2007 and December 2014, seven cases (18.4 %) were found to have SDC, which were investigated for clinicopathological features, locoregional recurrences (LRRs), distant metastasis (DM) and survival rates. RESULTS: Mean age of cohort was 62.3 years (range: 41-83) and female predominant (71.4 %). All patients underwent total parotidectomy and ipsilateral neck dissection. Mean tumor size was 3.4 cm (range: 2.1-5.3); perineural invasion (85.8 %); lymph node involvement (42.9 %); and HER-2 neu overexpression (28.6 %). Postoperative radiation therapy (PORT) was given to six patients (dose: 50-66 Gy). Median follow-up was 20.2 months (range: 11-48). LRRs were seen in five (71.4 %) patients (base of skull, 3 patients; cervical nodes, one patient; parotid bed, one patient). LRRs were salvaged with resection (two patients) and re-irradiation (one patient with base of skull). DM in lungs was seen in three patients (42.8 %); one treated with carboplatin/paclitaxel based chemotherapy. The 4-year disease free and overall survival rates were 16.7 % and 40 % respectively. CONCLUSION: SDC of parotid gland is a rare and aggressive entity, and most of LRRs were seen in the base of skull, which warrants inclusion of base of skull in clinical target volume in PORT planning. Role of anti HER-2 targeted therapy in SDC with HER-2 neu overexpression needs further investigations.

Myofibroblastoma of the mandible in a 3-year-old child.

UNLABELLED: Myofibroblastoma is a rare benign tumor of the head and neck region, which is characterized by a large, rapidly growing, and destructive mass. A 3-year-old boy presented with an 8-week history of a rapidly growing swelling of the right mandible. Examination revealed a firm 13-cm mass occupying the entire right body and ramus of the mandible. The clinical and radiological features were suggestive of a sarcoma. An initial biopsy taken in the referring hospital was inconclusive, and the second biopsy showed a myofibroblastic neoplasm consistent with a desmoplastic fibroma. Progressive tumor growth necessitated a tracheostomy. Right hemimandibulectomy was performed, and the defect was reconstructed with free microvascular fibula flap. Histopathology and immunocytochemistry revealed a myofibroblastoma. This entity differs from other myofibroblasts and fibroblast tumors such as inflammatory myofibroblastic tumor (IMT), myofibroma, and desmoplastic fibroma. The child has been followed up for 2 years. CONCLUSION: Differentiation between myofibroblasts and fibroblastic tumors as well as some malignancies can be challenging. Myofibroblastoma can behave as a malignant neoplasm, and the clinical distinction of this entity lies primarily in its recognition as a benign neoplasm.

Adjuvant Radioactive iodine 131 ablation in papillary microcarcinoma of thyroid: Saudi Arabian experience [corrected].

BACKGROUND: Papillary Microcarcinoma (PMC) of thyroid is a rare type of differentiated thyroid cancer (DTC), which according to the World Health Organization measures 1.0 cm or less. The gold standard of treatment of PMC is still controversy. Our aim was to contribute in resolving the debate on the therapeutic choices of the surgical and adjuvant I-131 (RAI) treatment in PMC. METHODS: From 2000 to 2012, 326 patients were found to have PMC and were retrospectively reviewed for clinicopathological characteristics, treatment outcomes and prognostic factors. RESULTS: Mean age of cohort was 42.6 years (range: 18-76) and the mean tumor size was 0.61 cm ± 0.24; lymph node involvement was seen in 12.9 % of cases. Median follow up period was 8.05 years (1.62-11.4). Total 23 all site recurrences (7.13 %) were observed; more observed in patients without I-131 ablation (p <0.0001). Ten year DFS rates were 89.6 %. Cox regression Model analysis revealed size, histopathologic variants, multifocality, extrathyroidal extension, lymphovascular space invasion, nodal status, and adjuvant RAI ablation the important prognostic factors affecting DFS. DISCUSSION: Despite excellent DFS rates, a small proportion of patients with PMC develop recurrences after treatment. Adjuvant RAI therapy improves DFS in PMC patients with aggressive histopathologic variants, multifocality, ETE, LVSI, tumor size (> 0.5 cm) and lymph node involvement. Failure of RAI ablation to decrease risk in N1a/b supports prophylactic central neck dissection during thyroidectomy, however more trials are warranted. CONCLUSION: Adjuvant I-131 ablation following thyroidectomy in PMC patients, particularly with poor prognostic factors improves DFS rates.

Calvarium and dura mater as delayed sites of distant metastasis from papillary thyroid carcinoma.

BACKGROUND: Skull calvarium and dura mater are rare sites of distant metastasis, and mostly have been reported in lung, breast, and prostate malignancies. However, the calvarial and dural metastases from papillary thyroid cancer (PTC) are rare entities and pose diagnostic and therapeutic challenges. To date, only seven cases of calvarial metastasis with intracranial extension from PTC have been reported in literature. However, true dural metastasis from PTC has not yet been reported. CASE PRESENTATION: A 65-year-old Saudi woman presented with 6 months history of painful posterior scalp lump, 7 years after initial diagnosis of PTC. Computed tomography and magnetic resonance imaging showed occipitoparietal calvarial lesion with massive intracranial extension. Another para-sagittal lesion was found at the top of corpus callosum mimicking a meningioma. Histopathology of para-sagittal lesion and the biopsy of calvarial mass confirmed the diagnosis of metastatic PTC. After surgical resection, residual tumors were treated with postoperative intensity-modulated radiation therapy. At 13 months of follow-up, patient was alive and without any signs of recurrence. CONCLUSION: Calvarial and dural metastases from PTC are extremely rare clinical entities. Surgical resection followed by postoperative radiotherapy is the treatment of choice. However, for such cases, multidisciplinary approach can prolong the treatment outcome and survival.

Co-existence of lip and epiglottis Kimura's disease.

Kimura's disease is a rare, chronic inflammatory condition of unknown etiology; with a predilection in the head and neck region. However, the involvement of the lip and epiglottis is extremely rare, and poses a diagnostic challenge. Here, we report a case of a 32-year-old Saudi male presenting with lip mass and epiglottic swelling without any history of hoarse voice or airway compromise. Serology showed elevated immunoglobulin E levels, and histopathological examination of biopsied lesions revealed well-developed lymphoid follicles with eosinophilic infiltration confirming Kimura's disease. At the time of last follow-up, his condition was satisfactory without any signs of recurrence.

Proliferative verrucous leukoplakia: recognition and differentiation from conventional leukoplakia and mimics.

The majority of conventional leukoplakia remains constant and only a subset progress to high-grade dysplasia or invasive carcinoma. A less recognized form known as proliferative verrucous leukoplakia (PVL) represents a unique progressive and elusive variant. Identifying patients with this form can only be achieved through the keen clinical observation of the temporal gross and histologic progression in individual patients with squamous cell carcinoma. The difficulty in the early diagnosis of PVL stems from the overlapping clinical and pathologic features with conventional multifocal leukoplakia with dysplasia. We present the current view on the clinicopathologic and biological characteristics of PVL and discuss their diagnosis, differential diagnosis, and management.

One patient--three head and neck primaries: nasopharyngeal, tongue and thyroid cancers.

BACKGROUND: We report a rare case of three head and neck malignancies in one patient. Squamous cell carcinoma of tongue and papillary thyroid carcinoma occurred as metachronous cancers in a patient with primary nasopharyngeal carcinoma. These three pathologically distinct malignancies of head and neck region in one patient is a rare phenomenon and is not reported so far. CASE PRESENTATION: A 60 year old Saudi female patient presented in March 2011 with locally advanced nasopharyngeal carcinoma. After completion of concurrent chemoradiation in June 2011, she developed two new primaries i-e thyroid cancer and tongue cancer in May 2012 along with recurrent nasopharyngeal carcinoma. We discuss histopathologic features, diagnostic tools and treatment modalities for this rarely existing case. CONCLUSION: High index of suspicion and thorough work up is essential in follow up of patients with head and neck primary cancers. The effect of field cancerization and environmental factors need to be explored in greater depths in such selected cases. However, which patients are at increased risk of triplet primaries, is still unknown.

Proliferative verrucous leukoplakia (PVL): a review of an elusive pathologic entity!

Proliferative verrucous leukoplakia (PVL) is a rare less recognized form of oral leukoplakia. Patients with this condition represent a unique clinically and pathologically progressive characteristic from conventional leukoplakia. Because of the lack of defined pathologic lesions, identifying patients with the early diagnosis of PVL is challenging. This is largely due to the overlapping clinical and pathologic early features with conventional multifocal leukoplakia with dysplasia. The diagnosis can only be achieved through the keen clinical observation of the temporal progression in individual patients to verrucous and/or conventional squamous carcinoma. We present a brief view of the clinicopathologic and biological characteristics of PVL and discuss diagnosis, differential diagnosis, and management.

MicroRNA profiling of salivary adenoid cystic carcinoma: association of miR-17-92 upregulation with poor outcome.

BACKGROUND: Salivary adenoid cystic carcinoma (ACC) is a rare relentlessly progressive malignant tumor. The molecular events associated with ACC tumorigenesis are poorly understood. Variable microRNAs (miRNA) have been correlated with tumorigenesis of several solid tumors but not in ACC. To investigate the association of miRNAs with the development and/or progression of ACC, we performed a comparative analysis of primary ACC specimens and matched normal samples and a pooled salivary gland standard and correlated the results with clinicopathologic factors and validated selected miRNAs in a separate set of 30 tumors. METHODS: MiRNA array platform was used for the identification of target miRNAs and the data was subjected to informatics and statistical interrelations. The results were also collected with the MYB-NFIB fusion status and the clinicopathologic features. RESULTS: Differentially dysregulated miRNAs in ACC were characterized in comparison to normal expression. No significant differences in miRNA expression were found between the MYB-NFIB fusion positive and -negative ACCs. Of the highly dysregulated miRNA in ACC, overexpression of the miR-17 and miR-20a were significantly associated with poor outcome in the screening and validation sets. CONCLUSION: Our study indicates that the upregulation of miR-17-92 may play a role in the biology of ACC and could be potentially targeted in future therapeutic studies.

Distal humerus as delayed site of metastasis from small cell carcinoma of gallbladder.

Background. Small cell carcinoma (SCC) of the gallbladder is a rare entity and is often seen in elderly women. SCC of gallbladder is typically a nonsecretory carcinoid tumor without overt clinical symptoms and is often discovered at advanced stages. SCC of gallbladder carries a dismal prognosis as compared to SCC of lung and adenocarcinoma of gallbladder. To date, only 73 case reports have been published in the world literature. Case Presentation. Herein, we report a case of a 73-year-old Saudi woman who presented with one week history of right upper quadrant abdominal pain and obstructive jaundice and was found to be a case of locally advanced, metastatic SCC of gallbladder cT4N1M1 (liver, para-aortic lymph nodes, and bone). The patient was treated with neoadjuvant etoposide and cisplatin (EP) chemotherapy three cycles after biliary stenting followed by radical cholecystectomy, lymphadenectomy, and adjuvant EP chemotherapy and then one year later developed distal humerus osseous metastasis. Conclusion. SCC of the gallbladder is very rare entity and is often seen at advanced stages. Osseous metastases of peripheral skeleton from SCC gallbladder are rarely reported. Surgery is curative option but only for early stage tumors. Incorporation of chemotherapy along with radical resection increases the survival.

Primary intestinal-like adenocarcinoma of major salivary glands: 2 instances of previously undocumented phenotype.

BACKGROUND: Primary intestinal-like adenocarcinoma of the major salivary glands has not previously been reported. METHODS: The clinical and radiological findings of 2 patients with primary submandibular and sublingual tumors are presented. Histopathologic and immunohistochemical examinations of tumor sections were performed. Metastatic workup for distant occult primary was carried out. RESULTS: The light-optic and the immunomarkers revealed intestinal-like adenocarcinoma consistent with upper respiratory tract origin. Metastatic workup of both patients was negative for primary gastro-intestinal primary. CONCLUSION: Primary intestinal-like adenocarcinoma can develop in major salivary glands and should be considered in the differential diagnosis.