Loss of KLK4::KLKP1 pseudogene expression by RNA chromogenic in-situ hybridization is associated with PTEN loss and increased risk of biochemical recurrence in a cohort of middle eastern men with prostate cancer.

BACKGROUND: KLK4::KLKP1 fusion is a recently described pseudogene that is enriched in prostate cancer (PCa). This new biomarker has not been characterized in the Middle Eastern population. OBJECTIVE: To establish the incidence and prognostic value of KLK4::KLKP1 fusion in a cohort of Middle Eastern men with PCa and explore the relationship of this marker to other relevant biomarkers (PTEN, ERG, SPINK1). DESIGN, SETTING, AND PARTICIPANTS: We interrogated a cohort of 340 Middle Eastern men with localized PCa treated by radical prostatectomy between 2005 and 2015. KLK4::KLKP1 fusion status was assessed by RNA Chromogenic in situ hybridization (CISH) and correlated to pathological and clinical parameters. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: RNA-CISH expression of KLK4::KLKP1 was correlated with prognostic factors, ERG, PTEN, and SPINK1 expression, and biochemical recurrence (BCR) following prostatectomy. RESULTS AND LIMITATIONS: 51.7% of patient samples showed positive KLK4::KLKP1 expression; more commonly in cores of PCa (38%) versus non-cancer (20.6%) (p < 0.0001) and in lower Gleason Grade Group tumors (1-3) vs (4-5). KLK4::KLKP1 expression positively correlated with ERG positivity and inversely associated with PTEN loss. No significant association was found with SPINK1 expression, seminal vesicle invasion, positive surgical margin, pathological stage, or patient age (< 50 or ≥ 50). The association between PTEN loss and BCR increased when combined with KLK4::KLKP1 negativity (HR 2.31, CI 1.03-5.20, p = 0.042). CONCLUSIONS: KLK4::KLKP1 expression is more common in this cohort of Middle Eastern men than has been reported in North American men. It is associated with ERG positivity and inversely correlated with PTEN loss. In isolation, KLK4::KLKP1 expression was not significantly associated with clinical outcome or pathological parameters. However, its expression is associated with certain molecular subtypes (ERG-positive, PTEN-intact) and as we demonstrate may help further stratify the risk of recurrence within these groups.

Interpretive Errors in Fine-Needle Aspiration of Thyroid: A 13-Year Institutional Experience in Lebanon.

INTRODUCTION: Fine-needle aspiration (FNA) is a worldwide established diagnostic tool for the assessment of patients with thyroid nodules. All thyroid FNA interpretive errors (IEs) were reviewed at the American University of Beirut Medical Center over a 13-year period, in order to identify and analyze them. MATERIALS AND METHODS: All FNAs and their corresponding pathology results are correlated yearly for quality assurance. Discrepant cases are segregated into sampling errors and IEs. All thyroid FNAs with IEs were collected from 2005 to 2017. FNA and pathology slides were reviewed by trained, board-certified cytopathologists, adhering to the latest Bethesda criteria. Reasons for erroneous diagnoses were studied. RESULTS: There was a total of 11 IEs out of 340 thyroid FNAs followed by surgical resection. Five benign follicular nodules (BFNs) were misinterpreted as suspicious for carcinoma. Focal nuclear atypia in cyst-lining or follicular cells and a monotonous population of macrophages misinterpreted as Hurthle cells (HCs) were the causes of IEs in this category. Four Hashimoto's thyroiditis (HT) cases were misinterpreted as suspicious for malignancy. Innate atypia of HCs and sampling misinterpretation were the causes of IEs in HT. One medullary and 1 follicular carcinoma were misinterpreted as suspicious for follicular neoplasm and BFN, respectively. Nine cases were better classified after review. CONCLUSION: Thyroid FNA IEs can be mitigated by meticulous screening and identification of all elements on FNA smears. Awareness of focal nuclear atypia in reactive cyst-lining and follicular cells in BFN, as well as HCs in HT, is highlighted. Adherence to The Bethesda System for Reporting Thyroid Cytopathology and consulting experienced cytopathologists significantly decrease IEs.

Microsatellite Instability in Near East Sebaceous Neoplasms: Toward Improved Prediction.

Sebaceous neoplasms (SN) comprise a heterogeneous spectrum of tumors with different biological behaviors. In the Near-East Region (NER), microsatellite instability (MSI) in SN's development, and its correlation with the clinicopathologic features of tumors is not well elucidated. A cohort of 225 SN patients (40 benign SNs and 185 sebaceous carcinomas) from the NER was retrospectively reviewed. Clinical variables and available follow-up information were recorded. MSI proteins (MLH1, MSH2, MSH6, and PMS2) as well as P53, P16, EMA, CD8, and PDL-1 expressions were examined by immunohistochemistry. Detection of human papilloma virus was determined by polymerase chain reaction. Microscopic features such as mitotic count and tumor-infiltrating lymphocytes were documented. A minority of SNs from benign (n=2) or malignant (n=3) tumors in the NER exhibit MSI (2.2%). MSI is exclusively found in patients with extraocular lesions (back, n=5) and presented a poor outcome. Among these, PMS2 protein was mostly lost (average=80%, n=4). SN with MSI exhibited a significant increase in p53 expression, (average=62.10%, P=0.002). There was no significant correlation between MSI status and any of the following: PD-L1, CD8, p16, and human papilloma virus infection. Microscopically, SN with MSI show significantly higher mitotic count, cystic changes and increased tumor-infiltrating lymphocytes. MSI is rarely found in NER's SN. When detected, it is exclusively in extraocular SNs with minimal predicative microscopic features and worse outcome.

Prevalence of programmed death ligand-1 in patients diagnosed with non-small cell lung cancer in Lebanon.

INTRODUCTION: Programmed death ligand-1 expression has been shown to be a good predictor of response to cancer therapy with checkpoint inhibitors. Its expression varies among different tumor types and among non-small cell lung cancer patients with different clinical and demographic characteristics. The prevalence and determinants of programmed death ligand-1 expression have been previously reported from various regions of the world, but data from Lebanon are lacking. This study examines the prevalence and the clinical, demographic and pathological predictors of programmed death ligand-1 expression in patients diagnosed with non-small cell lung cancer in Lebanon. METHODS: Medical records of 180 patients diagnosed with primary non-small cell lung cancer at our institution and tested for programmed death ligand-1 expression were reviewed. Clinical, demographic and pathological information were collected and correlated with programmed death ligand-1 expression using the chi-square test and logistic regression. RESULTS: One hundred eleven of the 180 non-small cell lung cancer tumor samples tested positive for programmed death ligand-1 expression (61.7%). 27.2% of those tumor samples expressed programmed death ligand-1 in 1%-49% of tumor cells, while 34.4% of tumor samples expressed programmed death ligand-1 in 50% or more of their cells. Squamous histology and advanced stage were significant predictors of programmed death ligand-1 expression (odds ratio = 2.79, 95% confidence interval [1.13-6.90], p = 0.012 and odds ratio = 2.48, 95% confidence interval [1.23-4.99], p = 0.044, respectively). CONCLUSION: Similar to reports from other populations, our results suggest that programmed death ligand-1 expression in non-small cell lung cancer is highly prevalent in the Lebanese population, especially in patients with advanced stage at diagnosis or squamous cell carcinoma histology. Because of the small sample size, while more that 60% of the patients are Lebanese, the results of this article cannot be extrapolated to the Middle Eastern and the Levantine population.

Sebaceous neoplasms: prevalence of HPV infection and relation to immunohistochemical surrogate markers.

BACKGROUND: Sebaceous neoplasms (SNs) and carcinomas (SCs) represent rare skin adnexal tumours. OBJECTIVES: To establish the prevalence of HPV in SNs, assess the relationship between HPV, p16 and p53 expression, and further elucidate the carcinogenetic course of SCs. MATERIALS & METHODS: A total of 113 resected SNs (five sebaceous adenomas, 10 sebaceomas and 98 SCs) from the Near-East were reviewed. Clinical information (age, gender, size and anatomical location), microscopic variables, and expression of several immunohistochemical markers (EMA, CK5/6, p63, p40, AR, p16 and p53) were documented. Cases were evaluated by fluorescently labelled PCR for HPV detection, followed by DNA microarray hybridization for subtype detection. RESULTS: HPV infection was detected in 9.4% of SNs: 28.6% sebaceous adenomas (HPV-16 and HPV-66), 9.1% sebaceomas (HPV-18) and 8.1% SCs. High-risk HPV types (HPV-16, -18, -52 and -66) constituted 90.9% of HPV infections. Histologically, HPV-positive SCs showed significantly milder cytologic atypia and patchy cellular necrosis. p16 was expressed in SNs irrespective of HPV status (20.0%, 33.3% and 65.5% of HPV-negative sebaceous adenomas, sebaceomas, and SCs, respectively), and p53 was abnormally expressed in 95.5% of HPV-negative SCs and all HPV-positive SCs. CONCLUSION: HPV infection is significantly present in benign and malignant SNs. HPV-positive SCs exhibit less cytologic atypia and necrosis than HPV-negative cases. p16 is not a surrogate marker of HPV infection in the SN setting. Further elucidation of various carcinogenic mechanisms in SCs will allow clinicians to single out the various populations at risk, optimize possible preventive strategies and develop targeted therapies.

PD-L1 expression in sebaceous carcinomas.

BACKGROUND: Traditional systemic treatments for unresectable, recurrent, and/or advanced sebaceous carcinoma (SC) are ineffective. Tumoral immune microenvironment characterization is essential for considering immune checkpoint inhibitors as a treatment option. METHODS: A total of 173 resected SCs were reviewed. Clinical information, lesion size, and location were collected. Microscopic examination documented histopathologic features and expression of immunohistochemical markers PD-L1 and CD8. PD-L1 percentage was assessed amongst tumor (PD-L1 + Tu) and immune infiltrating cells (PD-L1 + Inf). Each case was attributed a combined positive score (CPS) following Head and Neck squamous cell carcinoma recommendations. PD-L1 expression was evaluated according to clinicopathologic parameters. Human Papilloma Virus presence (HPV) was analyzed using PCR microarray scanning. RESULTS: A therapeutically relevant CPS was seen in 51.4% of cases. Higher PD-L1 + Tu, PD-L1 + Inf, and CPSs were positively associated with greater lesion size and an extraocular location. No association was seen with patient age or gender. 9.2% of SCs showed PD-L1 + Tu ≥ 1, while 52.0% showed PD-L1 + Inf ≥ 1. A higher CD8 + T-lymphocyte density was significantly associated with a higher CPS, PD-L1 + Tu, and PD-L1 + Inf. Tumor-associated T-cell infiltrate's density was higher along tumor periphery. HPV-16, HPV-43, HPV-52, and HPV-66 were detected in 8.4% of SCs. There was no significant association between HPV status, PD-L1 expression, and CPS. A significant number of SCs express PD-L1 at therapeutic levels. Nevertheless, PD-L1 expression shows a higher intertumoral heterogeneity, in extraocular than in biologically distinct periocular cases. CONCLUSION: Our data support the need for large-scale prospective studies evaluating anti-PD-L1 immunotherapy mainly in extraocular SC treatment.

Efficacy and safety-in analysis of short-course radiation followed by mFOLFOX-6 plus avelumab for locally advanced rectal adenocarcinoma.

BACKGROUND: Neoadjuvant chemotherapy and short-course radiotherapy followed by resection has been gaining recognition in the treatment of rectal cancer. Avelumab is a fully human immunoglobulin that binds Programmed Death-Ligand 1 (PD-L1) and prevents the suppression of the cytotoxic T cell immune response. This phase II trial evaluates the safety and pathologic response rate of short-course radiation followed by 6 cycles of mFOLFOX6 with avelumab in patients with locally advanced rectal cancer (LARC). METHODS: This study is prospective single-arm, multicenter phase II trial adopting Simon's two-stage. Short-course radiation is given over 5 fractions to a total dose of 25 Gy. mFOLFOX6 plus avelumab (10 mg/kg) are given every 2 weeks for 6 cycles. Total mesorectal excision is performed 3-4 weeks after the last cycle of avelumab. Follow up after surgery is done every 3 months to a total of 36 months. Adverse event data collection is recorded at every visit. RESULTS: 13 out of 44 patients with LARC were enrolled in the first stage of the study (30% from total sample size). All patients met the inclusion criteria and received the full short-course radiation course followed by 6 cycles of mFOLFOX6 plus avelumab. 12 out of the 13 patients completed TME while one patient had progression of disease and was dropped out of the study. The sample consisted of 9 (69%) males and 4 (31%) females with median age of 62 (33-73) years. The first interim analysis revealed that 3 (25%) patients achieved pathologic complete response (pCR) (tumor regression grade, TRG 0) out of 12. While 3 (25%) patients had near pCR with TRG 1. In total, 6 out of 12 patients (50%) had a major pathologic response. All patients were found to be MMR proficient. The protocol regimen was well tolerated with no serious adverse events of grade 4 reported. CONCLUSION: In patients with LARC, neoadjuvant radiation followed by mFOLFOX6 with avelumab is safe with a promising pathologic response rate. Trial Registration Number and Date of Registration ClinicalTrials.gov NCT03503630, April 20, 2018. https://clinicaltrials.gov/ct2/show/NCT03503630?term=NCT03503630&draw=2&rank=1 .

Short-course radiation followed by mFOLFOX-6 plus avelumab for locally-advanced rectal adenocarcinoma.

BACKGROUND: Current standard practice for locally advanced rectal cancer (LARC) entails a multidisciplinary approach that includes preoperative chemoradiotherapy, followed by total mesorectal excision, and then adjuvant chemotherapy. The latter has been accompanied by low compliance rates and no survival benefit in phase III randomized trials, so the strategy of administering neoadjuvant, rather than adjuvant, chemotherapy has been adapted by many trials, with improvement in pathologic complete response. Induction chemotherapy with oxaliplatin has been shown to have increased efficacy in rectal cancer, while short-course radiation therapy with consolidation chemotherapy increased short-term overall survival rate and decreased toxicity levels, making it cheaper and more convenient than long-course radiation therapy. This led to recognition of total neoadjuvant therapy as a valid treatment approach in many guidelines despite limited available survival data. With the upregulation (PDL-1) expression in rectal tumors after radiotherapy and the increased use of in malignant melanoma, the novel approach of combining immunotherapy with chemotherapy after radiation may have a role in further increasing pCR and improving overall outcomes in rectal cancer. METHODS: The study is an open label single arm multi- center phase II trial. Forty-four recruited LARC patients will receive 5Gy x 5fractions of SCRT, followed by 6 cycles of mFOLFOX-6 plus avelumab, before TME is performed. The hypothesis is that the addition of avelumab to mFOLFOX-6, administered following SCRT, will improve pCR and overall outcomes. The primary outcome measure is the proportion of patients who achieve a pCR, defined as no viable tumor cells on the excised specimen. Secondary objectives are to evaluate 3-year progression-free survival, tumor response to treatment (tumor regression grades 0 & 1), density of tumor-infiltrating lymphocytes, correlation of baseline Immunoscore with pCR rates and changes in PD-L1 expression. DISCUSSION: Recent studies show an increase in PD-L1 expression and density of CD8+ TILs after CRT in rectal cancer patients, implying a potential role for combinatory strategies using PD-L1- and programmed-death- 1 inhibiting drugs. We aim through this study to evaluate pCR following SCRT, followed by mFOLFOX-6 with avelumab, and then TME procedure in patients with LARC. TRIAL REGISTRATION: Trial Registration Number and Date of Registration: ClinicalTrials.gov NCT03503630, April 20, 2018.

Neoadjuvant chemotherapy and Avelumab in early stage resectable nonsmall cell lung cancer.

Multiple randomized studies have shown that combination of chemotherapy and immune checkpoint inhibitors (ICIs) leads to better response rates and survival as compared to chemotherapy alone in the advanced stage of NSCLC. Data suggesting a benefit to using ICIs in the neoadjuvant therapy of patients with early stage NSCLC are emerging. Eligible subjects were treatment naïve patients with stage IB, II, and resectable IIIA NSCLC. Patients received three cycles of neoadjuvant chemotherapy with four doses of avelumab every 2 weeks. Patients with squamous cell cancer received cisplatin or carboplatin on day 1 and gemcitabine on days 1 and 8 of each cycle of chemotherapy. Patients with nonsquamous histology received cisplatin or carboplatin with pemetrexed on day 1 of each cycle. Patients then proceeded to their planned surgery. Out of 15 patients accrued as part of stage 1 of the study, four had a radiologic response (1 complete response), lower than the minimum of six responses needed to continue to phase 2 of the study. The study was therefore terminated. Majority had adenocarcinoma histology and stage IIIA disease. The treatment was well tolerated with no unexpected side effects. Four patients (26.7%) had grade III/IV CTCAE toxicity. This study confirms that the preoperative administration of chemotherapy and avelumab is safe. There was no indication of increased surgical complications. The benefit of adding immunotherapy to chemotherapy did not appear to enhance the overall response rate of patients in the neoadjuvant setting in patients with resectable NSCLC because this study failed to meet its primary endpoint.

Expanded genome-wide comparisons give novel insights into population structure and genetic heterogeneity of Leishmania tropica complex.

Leishmania tropica is one of the main causative agents of cutaneous leishmaniasis (CL). Population structures of L. tropica appear to be genetically highly diverse. However, the relationship between L. tropica strains genomic diversity, protein coding gene evolution and biogeography are still poorly understood. In this study, we sequenced the genomes of three new clinical L. tropica isolates, two derived from a recent outbreak of CL in camps hosting Syrian refugees in Lebanon and one historical isolate from Azerbaijan to further refine comparative genome analyses. In silico multilocus microsatellite typing (MLMT) was performed to integrate the current diversity of genome sequence data in the wider available MLMT genetic population framework. Single nucleotide polymorphism (SNPs), gene copy number variations (CNVs) and chromosome ploidy were investigated across the available 18 L. tropica genomes with a main focus on protein coding genes. MLMT divided the strains in three populations that broadly correlated with their geographical distribution but not populations defined by SNPs. Unique SNPs profiles divided the 18 strains into five populations based on principal component analysis. Gene ontology enrichment analysis of the protein coding genes with population specific SNPs profiles revealed various biological processes, including iron acquisition, sterols synthesis and drug resistance. This study further highlights the complex links between L. tropica important genomic heterogeneity and the parasite broad geographic distribution. Unique sequence features in protein coding genes identified in distinct populations reveal potential novel markers that could be exploited for the development of more accurate typing schemes to further improve our knowledge of the evolution and epidemiology of the parasite as well as highlighting protein variants of potential functional importance underlying L. tropica specific biology.

CYR61/CCN1 expression in resected pancreatic ductal adenocarcinoma: A retrospective pilot study of the interaction between the tumors and their surrounding microenvironment.

BACKGROUND: CCN1 is an extracellular matrix-associated protein thought to be implicated in tumor-stromal interaction in several solid tumors. The aim of our pilot study was to evaluate the correlation between CCN1 expression in stromal cells, pancreatic intraepithelial neoplasia (PanIN) and pancreatic ductal adenocarcinoma cells in resected pancreatic ductal adenocarcinoma (PDAC) specimens, and correlate that clinically. METHODS: A total of 42 paraffin-embedded PDAC tumor specimens were stained for CCN1 and evaluated via immunohistochemical (IHC) analysis. Statistical analysis was performed to correlate between CCN1 expression profiles in tumor tissues and clinicopathological parameters of patients. RESULTS: Our results showed CCN1 (CYR61) gene was highly expressed in PDAC tissues relative to other organ specific tumor tissues. Also, moderate and overexpression of CCN1 in PanIN was associated with PanIN grade 3 tissues. A statistically significant association was found between PanIN CCN1 scores on one hand and cancer stage, cancer grade, and CCN1 expression among ductal tumor cells and adjacent stromal cells on the other hand. DISCUSSION: The associations demonstrated suggest that CCN1 might be contributing to a substantial role in the interaction between the pancreatic tumors on one hand and their surrounding microenvironment and their precursors on the other hand; hence, it might serve as a potential therapeutic target for PDAC.

Clinical, microscopic and molecular presentation in pediatric versus adult old world cutaneous Leishmaniasis.

BACKGROUND: Cutaneous leishmaniasis (CL) is an emerging uncontrolled tropical parasitic disease in endemic and nonendemic areas with a high prevalence in the pediatric age group. METHOD: A total of 382 individuals from Lebanon, Saudi Arabia, Pakistan, and Syria diagnosed with CL by punch biopsy/scrapings were grouped into adults (>18 years) and pediatrics (≤18 years). Data recorded included clinical features [number, location, type, size, and extensiveness (size larger than 3 cm, more than 5 lesions per patient, lesion present for more than 12 months, special types, disfiguring lesion or closeness to vital sensory organs) of lesions] and microscopic findings [Ridley's Parasitic Index and Ridley's Pattern]. In addition, molecular confirmation and speciation were performed. RESULTS: In comparison with adults, patients in the pediatric group (n = 158, 41.4%) showed significantly higher number of lesions, more facial involvement, and more extensive disease (P < .05). Microscopically, a more advanced Ridley's pattern was observed. The other variables did not show statistical difference between the two groups. CONCLUSION: Historically, CL has been known to be a neglected tropical disease of poverty and pediatric predilection. In our pediatric group, CL manifests with more extensive disease clinically mirrored by more advanced lesions microscopically.

Molecular characterization of prostate cancer in Middle Eastern population highlights differences with Western populations with prognostic implication.

BACKGROUND: To investigate the incidence and prognostication of ERG, PTEN and SPINK1 protein expressions in prostate cancer cohort of Middle Eastern descent in comparison to published data from Western population. METHODS: Immunohistochemistry for ERG, PTEN and SPINK1 was performed in a cohort of localized PCA (n = 340). The data were correlated to pathological and clinical outcomes and compared to Western populations. RESULTS: ERG expression and PTEN loss were noted in 123/288 (42.7%) and 91/297 (30.6%) of patients, respectively. SPINK1 expression was assessed in a subset of cases, noted in 6/150 (4%) of patients. Only ERG expression was associated with grade groups, being more common in the lower grade groups (1-3 vs 4-5; p = 0.04). In contrast to the Western population, PTEN loss foci were more likely to be ERG negative, observed in 81% of tumor foci and patients with PTEN neg/ERG pos were more likely to exhibit biochemical recurrence (OR 2.831; 95% CI 1.10-726, p = 0.03). This association remained significant in multivariate analysis (OR 2.68; 95% CI 0.98-7.33, p = 0.05), after adjusting for GG, path stage and surgical margin. CONCLUSION: This study documents significant differences in key molecular events in PCA in Middle Eastern population compared to Western populations that could explain differences in PCA incidence, progression and prognostication. ERG, PTEN and SPINK1 genomic alteration occur less frequently and the enrichment of ERG for PTEN loss is not observed. Additionally, patients with combined PTEN loss/ERG positive are at highest risk for BCR vs North American Caucasian population where PTEN loss alone seems to be associated with the worst clinical outcome. The data presented here further support differences in clonal evolution between Middle Eastern and Western population in relation to PCA and add further insight to understanding PCA molecular pathways.

Resistance Mechanisms to Anti-angiogenic Therapies in Cancer.

Tumor growth and metastasis rely on tumor vascular network for the adequate supply of oxygen and nutrients. Tumor angiogenesis relies on a highly complex program of growth factor signaling, endothelial cell (EC) proliferation, extracellular matrix (ECM) remodeling, and stromal cell interactions. Numerous pro-angiogenic drivers have been identified, the most important of which is the vascular endothelial growth factor (VEGF). The importance of pro-angiogenic inducers in tumor growth, invasion and extravasation make them an excellent therapeutic target in several types of cancers. Hence, the number of anti-angiogenic agents developed for cancer treatment has risen over the past decade, with at least eighty drugs being investigated in preclinical studies and phase I-III clinical trials. To date, the most common approaches to the inhibition of the VEGF axis include the blockade of VEGF receptors (VEGFRs) or ligands by neutralizing antibodies, as well as the inhibition of receptor tyrosine kinase (RTK) enzymes. Despite promising preclinical results, anti-angiogenic monotherapies led only to mild clinical benefits. The minimal benefits could be secondary to primary or acquired resistance, through the activation of alternative mechanisms that sustain tumor vascularization and growth. Mechanisms of resistance are categorized into VEGF-dependent alterations, non-VEGF pathways and stromal cell interactions. Thus, complementary approaches such as the combination of these inhibitors with agents targeting alternative mechanisms of blood vessel formation are urgently needed. This review provides an updated overview on the pathophysiology of angiogenesis during tumor growth. It also sheds light on the different pro-angiogenic and anti-angiogenic agents that have been developed to date. Finally, it highlights the preclinical evidence for mechanisms of angiogenic resistance and suggests novel therapeutic approaches that might be exploited with the ultimate aim of overcoming resistance and improving clinical outcomes for patients with cancer.

HPV-related oropharyngeal cancer prevalence in a middle eastern population using E6/E7 PCR.

BACKGROUND: Given the paucity of data and widely variable rates that have been reported, the main objective of this study was to examine the prevalence of HPV-positivity in oropharyngeal squamous cell carcinoma (OPSCC) in Middle Eastern patients presenting to one of the region's largest tertiary care centers using polymerase chain reaction (PCR) amplification of the HPV E6/E7 oncogenes, a highly sensitive and specific method of detection. METHODS: Medical charts and archived pathological specimens were obtained for patients diagnosed with biopsy proven oropharyngeal cancer who presented to the American University of Beirut Medical Center between 1972 and 2017. DNA was extracted from paraffin-embedded specimens and tested for 30 high-risk and low-risk papilloma viruses using the PCR-based EUROarray HPV kit (EuroImmun). RESULTS: A total of 57 patients with oropharyngeal cancer were initially identified; only 34 met inclusion/exclusion criteria and were included in the present study. Most patients were males (73.5%) from Lebanon (79.4%). The most common primary tumor site was in the base of tongue (50%), followed by the tonsil (41.2%). The majority of patients (85.3%) tested positive for HPV DNA. CONCLUSION: The prevalence of HPV-positivity amongst Middle Eastern OPSCC patients, specifically those from Lebanon, may be far greater than previously thought. The Lebanese population and other neighboring Middle Eastern countries may require a more vigilant approach towards HPV detection and awareness. On an international level, further research is required to better elucidate non-classical mechanisms of HPV exposure and transmission.

Characteristics of Breast Cancer Metastasizing to Bone in a Mediterranean Population.

AIM: This study examines clinicopathological, molecular, and radiological characteristics of breast cancer metastasizing to the bone in a Mediterranean population. METHODS: Cases of breast cancer with metastasis to bone were retrieved from the pathology department archives. Descriptive statistics and bivariate inferential statistics of retrieved clinical (demographic, focality, laterality, axillary lymph node status, and metastasis-free interval), radiological (skeletal site of bone metastasis, type of bone lesion), and microscopic (grade, subtype of breast cancer, lymphovascular status, perineural status, lymph node involvement, nodal extracapsular extension, molecular subtype) data were conducted. RESULTS: Out of 123 cases analyzed, 93.5% were ductal, 90% had axillary lymph node metastasis, 60.5% were luminal A, 59.6% were osteolytic, and 54.4% had grade III. Discordance in the status of ER, PR, and HER2 between the primary breast tumor and the corresponding bone metastases was noted, with the highest rate of change reported for PR (35.7%). Significance was detected at the level of difference between the subtype of breast cancer with regards to the radiologic features where the ductal subtype was found to be mostly osteolytic while the lobular subtype was mostly either osteoblastic or mixed (p-value=0.05). The metastasis-free interval was significantly associated with the number of metastatic bone lesions (P=0.001). CONCLUSION: The significant association between metastasis-free interval and the number of metastatic bone lesions suggests that a higher interval allows more time for tumors to manifest multiple lesions. The high rate of discordance in the status of PR, ER, and HER2 was congruent with the literature highlighting the need to further investigate underlying mechanisms.

A Patient With a Protuberant Fibro-Osseous Lesion of the Temporal Bone.

Protuberant fibro-osseous lesion of the temporal bone, otherwise known as "Bullough's lesion", is a rare, benign exophytic fibro-osseous tumor. In this brief report, we present a case of a 61-year-old woman with a history of a right-sided skull mass that had been increasing in size for approximately 6 years before presentation. Clinical, radiological and histological features are examined and discussed. We achieved excellent results with surgical resection, with no evidence of recurrence.

Large esophageal schwannoma: En-bloc resection with primary closure by esophagoplasty.

BACKGROUND: Gastrointestinal schwannomas are submucosal tumors accounting for 2-7% of mesenchymal gastro-intestinal neoplasms; the stomach being the most common site. Esophageal schwannomas are more frequent in women, and are usually located in the upper to mid portion. Dysphagia is the main presenting symptom. A definitive diagnosis requires confirmation by histopathological and immunohistochemical studies. CASE PRESENTATION: A 50-year-old healthy lady, presented with gradual increasing onset of dyspnea, with minimal dysphagia to solid food, over a period of several years. Enhanced CT scan of the chest revealed a well-defined soft tissue mass arising from the proximal third of the esophagus, measuring 7.8 × 5.4 x 10.5 cm. Esophagogastric endoscopy with ultrasonography showed an elevated, smooth surface lesion, arising from the submucosal layer of the esophagus, with a hypervascular mucosa. Enucleation of this large tumor, with preservation of the overlying mucosa, was difficult to accomplish due to its large size. Making use of a dilated proximal esophageal segment, total en-bloc excision of the mass rendered a 15 cm esophagotomy gap, which was easily closed, in two layers, without affecting the overall caliber thus achieving a good esophagoplasty result. Histologically, abundance of spindle-shaped cells with positive S-100 proteins, confirmed the diagnosis of esophageal schwannoma. CONCLUSION: Variations in mesenchymal gastrointestinal tumors is vast, rendering diagnosis by radiology alone difficult. As such, characteristic histologic and immunostaining features are cornerstones in precise diagnosis of esophageal schwannomas. Despite being rare in incidence, symptomatic esophageal schwannoma lesions can be excised entirely, with low rate of recurrence and favorable overall outcomes.