Identifying knowledge deficiencies in genetics education among medical students and interns in Saudi Arabia- A cross-sectional study.

BACKGROUND: Understanding genetics is crucial for medical students, particularly in Saudi Arabia, where genetic disorders are prevalent owing to high rates of consanguineous marriages. This knowledge is essential for the early detection, prevention, and management of genetic disorders, and for incorporating medical genetics and genomics into patient care. This study aimed to assess the current state of genetics knowledge among medical students and interns across Saudi Arabia and to identify knowledge gaps in genetics. METHOD: A cross-sectional study was conducted between August and September 2023 involving 732 medical students from all regions of Saudi Arabia. The participants completed a validated questionnaire assessing their knowledge of basic genetics, genetic inheritance, genetic testing, and clinical genetics. RESULT: Over 60% of medical students and interns reported that they considered themselves to have only slight knowledge in all areas of genetics. The results revealed a general lack of medical genetic understanding among students and interns, particularly regarding genetic inheritance and testing. For genetic inheritance, slight knowledge was found in 65.2% of pre-clinical, 60.1% of clinical, and 53.2% of interns, with significant differences between groups (p < 0.001). In genetic testing, 75.4% of pre-clinical, 83.9% of clinical, and 90.6% of interns showed slight knowledge, with significant differences across stages (p = 0.021). This study also found that lectures, genetics laboratories, and problem-solving sessions were the preferred resources for learning genetics. CONCLUSION: The current study revealed a notable deficiency in the understanding of medical genetics among medical students and interns in Saudi Arabia, particularly regarding genetic inheritance and testing. This is consistent with previous research highlighting the widespread lack of genetics knowledge among medical students. Integrating more comprehensive genetics education, especially during the clinical years, could improve students' preparedness and confidence in managing genetic disorders. These findings highlight the critical need for curriculum development to equip future physicians with the essential skills for managing genetic disorders.

Expression of p16 protein in breast cancer.

Breast cancer is the most common cancer and a leading cause of death in women in Saudi Arabia. P16 is a tumour suppressor gene that plays a crucial role in regulating cell cycle. Several studies have investigated the significance of p16 expression in various cancer types. However, the significance of p16 in breast cancer remains controversial and insufficiently studied. The present study aims to examine the association between p16 expression and clinicopathological factors in breast cancer using immunohistochemistry staining. The study utilised 475 prospectively collected tissue samples from 475 women with breast cancer in Saudi Arabia. Nuclear and cytoplasmic immunohistochemical staining of p16 was observed in 338 (71%) of the cases and showed significant direct associations with adverse tumour features, including high tumour grade (p < 0.0001), negative oestrogen receptor/progesterone receptor status (p < 0.001), and lymph node metastasis (p = 0.02). Our study revealed a significant association between p16 protein expression and the established negative prognostic parameters in breast carcinoma including tumour grade, lymph node metastasis, and oestrogen receptor and progesterone receptor status.

The Role of Epithelial Cell Adhesion Molecule Cancer Stem Cell Marker in Evaluation of Hepatocellular Carcinoma.

Background and Objectives: Hepatocellular carcinoma (HCC) is a prevalent form of malignancy that is characterized by high mortality rates and prognosis that remain suboptimal, largely due to treatment resistance mechanisms. Recent studies have implicated cancer stem cells (CSCs), particularly those expressing epithelial cell adhesion molecule (EpCAM), in HCC progression and resistance. In the present study, we sought to assess EpCAM expression in HCC patients and its correlation with various clinicopathological parameters. Materials and Methods: Tissue samples from 42 HCC patients were subjected to immunohistochemical staining to evaluate EpCAM expression. Clinicopathological data were obtained including the size, grade and stage of tumors, vascular invasion status, alpha-fetoprotein levels, and cirrhosis status. The Chi square and Fisher's exact tests were employed to assess the association between categorical groups. Independent Student-t test or Mann-Whitney U test was used to investigate the association between continuous patient characteristics and survival. Results: Immunohistochemical analysis revealed EpCAM expression in 52.5% of HCC cases. EpCAM-positive tumors exhibited characteristics indicative of aggressive disease, including larger tumor sizes (p = 0.006), greater tumor multiplicity (p = 0.004), higher grades (p = 0.002), more advanced stages (p = 0.003), vascular invasion (p = 0.023), elevated alpha-fetoprotein levels (p = 0.013), and cirrhosis (p = 0.052). Survival analysis demonstrated that EpCAM expression was significantly associated with lower overall rates of survival and higher rates of recurrence in HCC patients. Conclusions: Our findings suggest that EpCAM expression may serve as a prognostic biomarker for HCC with a potential role in patient management. Targeting EpCAM-positive CSCs may represent a promising approach to overcome treatment resistance and improve clinical outcomes in HCC. However, further investigation into the molecular mechanisms underlying EpCAM's role in HCC progression is warranted to facilitate the development of personalized therapeutic interventions.

The Expression of Stem Cell Marker LGR5 and Its Coexpression with Β-Catenin in Sporadic Colorectal Carcinoma and Adenoma: A Comparative Immunohistochemical Study.

Background: LGR5 is one of the most important stem cell markers for colorectal cancer (CRC), as it potentiates Wnt/Β-catenin signaling. The well-characterized deregulation of Wnt/Β-catenin signaling that occurs during adenoma/carcinoma sequence in CRC renders LGR5 a hopeful therapeutic target. We assessed the immunohistochemical expression of LGR5 and Β-catenin in normal colonic and tumorous lesions with a clinicopathological correlation. Methods: Tissue blocks and clinical data of 50 selected cases were included: 8 from normal mucosa, 12 cases of adenoma, and 30 cases of CRC, where sections were cut and re-examined and the immunohistochemical technique was conducted using anti-LGR5 and anti-Β-catenin to measure the staining density. Results: There was no expression of LGR5 in normal mucosa compared to samples of adenoma and CRC samples. The association analysis showed that CRC specimens were more likely to have strong LGR5 and Β-catenin expressions than the other two groups (p = 0.048 and p < 0.001, respectively). Specimens with high-grade dysplastic adenoma were more likely to express moderate-to-strong expression of LGR5 and Β-catenin (p = 0.013 and p = 0.036, respectively). In contrast, there were no statistically significant associations between LGR5 and Β-catenin expression with grade and stage. Conclusion: These results suggest and support the possible role of LGR5 as a potential marker of cancer stem cells in sporadic colorectal carcinogenesis in addition to a prognostic value for LGR5 and Β-catenin in adenomatous lesions according to immunohistochemical expression density. A potential therapeutic role of LGR5 in CRC is suggested for future studies based on its role in pathogenesis.

Orbital Involvement by Biphenotypic Sinonasal Sarcoma With a Literature Review.

PURPOSE: To document a case of a biphenotypic sinonasal sarcoma that impinged on the orbit via a tumor-induced mucocele and review the previous literature devoted to this condition. METHODS: A clinicopathologic case report with detailed histopathologic, immunohistochemical, and radiological studies with tabulations of previously reported cases and immunohistochemical stains for ruling out mimicking lesions. RESULTS: A biphenotypic sinonasal sarcoma arose from the ethmoid sinus in a middle-aged man. The tumor induced a mucocele that bowed the medial orbital lamina papyracea into the orbit and caused diplopia and mild proptosis. The biopsy's dual positivity for S100 and smooth muscle actin together with positive paired box 3 immunohistochemical staining established the diagnosis of biphenotypic sinonasal sarcoma. CONCLUSION: Biphenotypic sinonasal sarcoma, which can involve the orbit in 25% of cases, is a rare head and neck malignancy that has only recently been described. Biphenotypic sinonasal sarcoma is a low-grade, locally aggressive, nonmetastasizing sarcoma displaying both neural and muscle differentiation. It is further characterized by rearrangements of the PAX3 gene with multiple fusion partners, most commonly MAML3 (Mastermind like transcriptional coactivator 3). It occurs predominantly in middle-aged women and exclusively in the sinonasal tract. However, it can spread throughout the central facial structures to invade the brain if not detected early. Ophthalmologists should be aware of this new entity to avoid delays in diagnosis and treatment. The previous literature devoted to this condition was reviewed and analyzed for clinical, radiological, histopathological, and immunohistochemical features. In circumstances where molecular testing is not available, paired box 3 immunohistochemical staining can be used as an alternative diagnostic marker. The current case is most unusual because the orbital findings were induced by a mucocele caused by the tumor that obstructed the sinus ostium. This produced diplopia without direct tumor invasion into the orbital fat.

Conjunctival Implantation Cyst in the Orbicularis Oculi Muscle: Review of a Possible Origin From Displaced Stem Cells With a Differential Diagnosis.

PURPOSE: To document a unique case of a corneal/conjunctival epithelial inclusion cyst located in the orbicularis oculi muscle with a comprehensive review of variant conjunctival cysts and simulating conditions. METHODS: Clinicopathologic case report with detailed histopathologic and immunohistochemical evaluation for cytokeratins combined with a tabulation of mimicking lesions and relevant literature citations. RESULTS: A 59-year-old man experienced severe blunt left periorbital trauma that resulted in a limbal partial-thickness corneal wound with an associated epithelial abrasion and a full-thickness eyelid laceration extending from the superior fornix to the margin. Several months after surgical repair of the eyelid a cyst appeared in the superior pretarsal skin. Histopathologic and immunohistochemical investigations supplied data suggesting that the cyst had a high probability of a corneoscleral limbal stem cell origin. Distinctive features of the lesion are contrasted with those of allied or simulating cysts. CONCLUSIONS: Stem cells are now believed to be located at the corneoscleral limbus, in the inferior fornix, in the medial canthal region, and at the eyelid margin where transitions from conjunctival epithelium to epidermal epithelium occur. Due to their replicative, hardy and robust nature, stem cells displaced to alien environments are most likely to survive and produce cysts. The cyst's corneal-type cytologic characteristics, the absence of goblet cells, and the expression of a broad spectrum of cytokeratin biomarkers in the current case give support to the proposal that limbal stem cells in the region of the corneal laceration were displaced to the eyelid orbicularis muscle and were responsible for this most extraordinary cyst. Comparison with other epithelial cystic linings lends further evidence for this conclusion.

Adult Primary Capillary Hemangioma of the Sclera: A Previously Undescribed Entity With a Review of Epibulbar Vascular Lesions.

PURPOSE: The objective of this article is to document a unique case of a primary hemangioma and review epibulbar vascular tumors of the conjunctiva and episclera. METHODS: A case report with detailed histopathologic, histochemical, and immunohistochemical studies coupled with a comprehensive review of the relevant literature with a tabulation of previously reported epibulbar vascular lesions was performed. RESULTS: A vascular tumor developed in a 46-year-old woman over 2-3 months that histopathologically was located in the superficial third of the normally avascular sclera and was composed of capillary caliber vessels. CD31 and CD34 positivity established the vascular nature of the lesion. Despite its adult onset, the tumor was also glut-1 positive, a vascular characteristic of childhood capillary hemangiomas that will ultimately involute. Smooth muscle actin was positive in the endothelial cells and associated pericytes. An ectatic muscular vessel identified in the midst of the lesion was interpreted as an anomalous intrascleral branch of an epibulbar anterior ciliary artery, where it perforated the sclera in the vicinity of the insertion of an extraocular rectus muscle. It was deduced to be the source of the capillary proliferation. A literature review failed to identify any previously reported epibulbar vascular tumor that originated primarily in the sclera or secondarily infiltrated this ocular tunic. CONCLUSION: An adult primary capillary intrascleral neoplasm is described as the rarest of all epibulbar vascular tumors and in keeping with the exceptional status of the ocular endothelium was glut-1 positive. This lesion must be distinguished from an array of other common and esoteric epibulbar vascular conditions.

Prognostic value of Osteopontin (SPP1) in colorectal carcinoma requires a personalized molecular approach.

Stratification of colorectal cancer for better management and tangible clinical outcomes is lacking in clinical practice. To reach this goal, the identification of reliable biomarker(s) is a prerequisite to deliver personalized colorectal cancer theranostics. Osteopontin (SPP1) is a key extracellular matrix protein involved in several pathophysiological processes including cancer progression and metastasis. However, the exact molecular mechanisms regulating its expression, localization, and molecular functions in cancer are still poorly understood. This study was designed to investigate the SPP1 expression profiles in Saudi colorectal cancer patients, and to assess its prognostic value. Hundred thirty-four (134) archival paraffin blocks of colorectal cancer were collected from King Abdulaziz University Hospital, Saudi Arabia. Tissue microarrays were constructed, and automated immunohistochemistry was performed to evaluate SPP1 protein expression patterns in colorectal cancer. About 20% and 23% of our colorectal cancer samples showed high SPP1 cytoplasmic and nuclear expression patterns, respectively. Cytoplasmic SPP1 did not correlate with age, gender, tumor size, and location. However, significant correlations were observed with tumor grade (p = 0.008), tumor invasion (p = 0.01), and distant metastasis (p = 0.04). Kaplan-Meier survival analysis showed a significantly lower recurrence rate in patients with higher SPP1 cytoplasmic expression (p = 0.05). At multivariate analysis, high SPP1 cytoplasmic expression was an independent favorable prognostic marker (p = 0.02). However, nuclear SPP1 expression did not show any prognostic value (p = 0.712). Our results showed a particular SPP1 prognostic relevance that is not in line with most colorectal cancer previous studies that may be attributed to the molecular pathophysiology of our colorectal cancer cohort. Saudi Arabia has both specific genomic makeup and particular environment that could lead to distinctive molecular roots of cancer. SPP1 has several isoforms, tissue localizations and molecular functions, signaling pathways, and downstream molecular functions. Therefore, a more individualized approach for CRC studies and particularly SPP1 prognosis outcomes' assessment is highly recommended toward precision oncology.

Eye and adnexa hospitalization in Australia: An ecological study.

To investigate the trends of hospital admissions concerning diseases of the eye and adnexa in Australia in the past 2 decades. This is a descriptive ecological study on the population level that examined hospitalization data for the duration between 1998 and 2021 in Australia. Hospitalization data were extracted from the National Hospital Morbidity Database. The chi-squared test was utilized to assess the difference in admission rates between the years 1998 and 2021. Hospital admission rate for diseases of the eye and adnexa increased by 1.20-fold (from 852.32 [95% confidence interval [CI] 848.16-856.47] in 1998 to 1873.72 [95% CI 1868.48-1878.96] in 2021 per 100,000 persons, P < .01). The most common cause of hospitalization for diseases of the eye and adnexa was disorders of the lens (65.7%), followed by disorders of the choroid and retina (15.6%), followed by disorders of the eyelid, lacrimal system, and orbit (7.7%). Hospital admission rate among males increased by 1.25-fold (from 737.67 [95% CI 732.18-743.16] in 1998 to 1657.19 [95% CI 1650.19-1664.20] in 2021 per 100,000 persons). Hospital admission rate among females increased less sharply by 1.03-fold (from 965.37 [95% CI 959.14-971.59] in 1998 to 1964.35 [95% CI 1956.80-1971.90] in 2021 per 100,000 persons). There are clear gender and age roles in the epidemiology of hospital admissions related to eye and adnexa disorders. Lens disorders were the most common cause of hospital admission. The admission rate increase during the past decades could be due to increases in life expectancy, lifestyle changes, and improvements in screening protocols.

Medical Students' Perception of Pathology in Saudi Arabia.

Pathology is the bridge between basic science and clinical practice. An inadequate perception of pathology leads to an incomplete understanding of diseases, which consequently affects its management. This study aims to identify medical students' perceptions of pathology in medical colleges around Saudi Arabia and use their feedback to improve teaching strategies. A validated online self-structured questionnaire form was distributed to medical students in basic and clinical years, including private and governmental universities in all regions of Saudi Arabia. The study comprised a total of 476 medical students. It revealed that n = 226 (48%) of the participants were not aware of pathologists' roles, and n = 262 (55%) of students reported that the main reason was insufficient exposure to actual pathology practice. A total of n = 209 (44%) students believed the current teaching methods in the basic years were insufficient to provide clear perceptions of pathology. The majority of participants n = 366 (77%) chose practical sessions as the most effective strategy in teaching pathology. Our study demonstrated that medical students require more engagement in laboratories to improve their perception. We suggest that Saudi medical schools need to deliver more comprehensive and practical teaching methods that reflect the actual practice of pathology.

Prognostic value of glucose transporter proteins-1 (GLUT1) in breast carcinoma.

Several studies have reported increased glucose transporters (GLUT) expression in different cancer types, including breast cancer. The primary purpose of this study is to examine GLUT1 immunoexpression in breast cancer patients in Saudi Arabia and to determine its significance. The study examined the association between GLUT1 immunophenotype and the clinicopathological characteristics in breast cancer. GLUT1 expression was analyzed in retrospectively collected tissue samples (n = 578) from breast cancer patients using immunohistochemistry. A total of 311 (54%) of the cases expressed GLUT1 cytoplasmic immunohistochemical staining. In univariate analysis, we found a significant association between GLUT1 expression and high-grade tumors (p < 0.0001). Positive estrogen and progesterone receptor results predicted lower GLUT1 immunoexpression (p < 0.0001 for both). Vascular invasion showed a significant association with GLUT1 immunoexpression (p = 0.045). Our findings support that GLUT1 immunohistochemistry can be used as a marker to determine the grade and hormonal receptor status in breast cancer.

Recurrent keratoconus: an analysis of breaks in Bowman's layer in corneal grafts.

OBJECTIVE: To study in a masked fashion whether an objective histological feature associated with keratoconus (KCN) occurs in donor corneas in eyes originally receiving a corneal graft for KCN. METHODS: Two ocular pathologists performed a retrospective masked histological analysis of slides from donor buttons recovered from 21 eyes with a history of KCN undergoing repeat penetrating keratoplasty (failed-PK-KCN), 11 eyes that underwent their first PK due to KCN (primary KCN), and 11 eyes without history of KCN which underwent PK for other conditions (failed-PK-non-KCN). Breaks/gaps in Bowman's layer served as the pathological feature indicative of recurrent KCN. RESULTS: Breaks in Bowman's layer were present in 18/21 (86%) of the failed-PK-KCN group, 10/11 (91%) of the primary KCN group, and in 3/11 (27%) of the failed-PK-non-KCN group. Pathological evidence suggests that the prevalence of breaks is significantly higher in grafted patients with a history of KCN than non-KCN controls (OR: 16.0, 95% CI 2.63 to 97.2, Fisher's exact test p=0.0018) with a conservative Bonferroni criterion of p <0.017 to account for multiple group comparisons. There was no statistically significant difference found between the failed-PK-KCN and primary KCN groups. CONCLUSIONS: This study provides histological evidence that breaks and gaps in Bowman's layer, consistent with those found in primary KCN, may develop within the donor tissue in eyes with a history of KCN.

Pathologic, immunologic, and clinical analysis of the microsatellite instability phenotype in endometrial carcinoma.

The objective of this study was to determine if quantifying the microsatellite instability (MSI) phenotype could serve as a biomarker for clinical and immunologic features of deficient mismatch repair (dMMR) endometrial cancer (EC). Patients with EC undergoing hysterectomy whose tumors demonstrated dMMR were included. Immunohistochemistry (IHC) of mismatch repair proteins and polymerase chain reaction analysis of NR27, BAT25, BAT26, NR24, and NR21 microsatellite loci were performed on each case. The MSI phenotype was quantified by subtracting the number of nucleotides of each microsatellite in tumor tissue from the corresponding microsatellite in paired normal tissue and summing the absolute differences. This was termed marker sum (MS) and is a novel quantification. Tumor-infiltrating lymphocytes (TILs) were identified by IHC for CD3, CD4, and CD8 and quantified with digital image analysis. Tumor infiltration of lymphocytes and clinical characteristics were stratified by MS. Four hundred fifty-nine consecutive patients with dMMR EC were analyzed. MS ranged from 1 to 32. Post hoc, 2 cohorts were defined using receiver operating characteristic curves (MS less than 13 and MS greater than 12). With the exception of tumor grade, all clinical and pathologic features, all tumor characteristics, and the numbers of TILs were similar between cohorts. The MSI phenotype is highly variable in dMMR EC, and no correlation between the immune profile and the severity of the MSI phenotype was observed.

Identification of cystic fibrosis transmembrane conductance regulator gene (CFTR) variants: A retrospective study on the western and southern regions of Saudi Arabia.

OBJECTIVES: To investigate the geographic distribution of common cystic fibrosis (CF) variants in the western and southern regions of Saudi Arabia. METHODS: A retrospective study was conducted on 69 patients diagnosed with CF at King Faisal Specialist Hospital & Research Center, Jeddah. Patient data were collected retrospectively between June 2000 and November 2021. Various parameters were considered, including patient demographic information, CFTR variants, and respiratory cultures. RESULTS: We identified 26 CFTR variants in 69 patients with CF, including one novel variant that had not been reported or published before (1549del G) in 2 patients with CF. The 6 most prevalentvariants were as follows: c.1521_1523delCTT (19%), c.1418delG (10.2%), c.579+1G>T (8.8%), c.2988+1G>A (8.8%), c.3419 T>A (7.2%), and c.4124A>C (5.8%). In addition, respiratory cultures revealed that Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae, and Streptococcus pneumoniae were highly common among patients with CF. CONCLUSION: This study highlighted features of patients with CF residing in the Western and Southern regions of Saudi Arabia. Six of the 26 CFTR variants were common in these patients. We also report, for the first time, a novel variant and other CFTR variants that are yet to be reported in Saudi Arabia. These findings could help establish a foundation for cystic fibrosis screening in Saudi Arabia and may assist in clinical diagnosis and prognosis.

Clinico-Pathological Features and Immunohistochemical Comparison of p16, p53, and Ki-67 Expression in Muscle-Invasive and Non-Muscle-Invasive Conventional Urothelial Bladder Carcinoma.

INTRODUCTION: The identification of bladder detrusor muscle invasion in urothelial cancer is essential for prognosis and management. We studied the clinical, histological, and immunohistochemical expression of p16, p53, and Ki-67 in urothelial detrusor muscle-invasive bladder cancer (MIBC) and urothelial non-detrusor muscle-invasive bladder cancer (NMIBC) in Egyptian patients. METHODS: Sixty-two bladder urothelial cancer cases obtained through TURBT were included and divided into two groups: (MIBC, stage T2) and NMIBC (T1). Tissue blocks were recut and re-examined microscopically; then, the immunostaining of p16, p53, and Ki-67 was performed to compare both groups and evaluate the 13% cut-off for Ki-67, 20% for p53, and p16 intensity in various conditions aided by telepathology technology. RESULTS AND CONCLUSION: Hematuria was the main clinical first presentation, with no significant difference between either group. The mean age was 61.6 years, with male predominance (52 males and 10 females). The absence of papillary histological pattern was associated with a higher stage, including detrusor muscle invasion (p = 0.000). The overall average percent of p53 immunostaining was 12.9%, revealing no significant difference between MIBC and NMIBC when a cut-off of 20% was implicated. The Ki-67 expression was correlated with higher grade and muscle invasion; however, no association was found with the other two markers' expression. The negative immunostaining of p16 was associated with low grade and NMIBC in the case of the preservation of the papillary pattern. We recommend further studies on the cut-off of widely used markers and more immunohistochemical and genetic studies on the p16(INK4A), taking into consideration the histological pattern of conventional carcinomas.

Utility of Single-Gene Testing in Cancer Specimens.

Molecular testing is now considered the standard of care to screen for disease, confirm the diagnosis, guide management, and use target therapy. Currently, several testing strategies are being used. One of the most common strategies is single-gene testing, which is often conducted for known mutations, such as BRAF in melanoma and EGFR in lung cancer. Subsequently, next-generation sequencing (NGS), which tests many genes simultaneously, was developed using targeted gene panels, whole-exome, or whole-genome sequencing. Ordering the best diagnostic tool and choosing between single-gene testing and NGS depends on several factors. In this review, we discuss different single-gene testing methodologies and the impact of using them in comparison to NGS/multigene panel.

The Interpretation of Sequence Variants in Myeloid Neoplasms.

OBJECTIVES: To provide an overview of the challenges encountered during the interpretation of sequence variants detected by next-generation sequencing (NGS) in myeloid neoplasms, as well as the limitations of the technology with the goal of preventing the over- or undercalling of alterations that may have a significant effect on patient management. METHODS: Review of the peer-reviewed literature on the interpretation, reporting, and technical challenges of NGS assays for myeloid neoplasms. RESULTS: NGS has been integrated widely and rapidly into the standard evaluating of myeloid neoplasms. Review of the literature reveals that myeloid sequence variants are challenging to detect and interpret. Large insertions and guanine-cytosine-heavy areas prove technically challenging while frameshift and truncating alterations may be classified as variants of uncertain significance by tertiary analysis informatics pipelines due to their absence in the literature and databases. CONCLUSIONS: The analysis and interpretation of NGS results in myeloid neoplasia are challenging due to the varied number of detectable gene alterations. Familiarity with the genomic landscape of myeloid malignancies and knowledge of the tools available for the interpretation of sequence variants are essential to facilitate translation into clinical and therapy decisions.

Overlapping Immunohistochemical Features of Adenocarcinoma of the Nonpigmented Ciliary Body Epithelium and Renal Cell Carcinoma.

PURPOSE: To find immunohistochemical markers that distinguish adenocarcinoma of the nonpigmented ciliary epithelium (NPCE) from metastatic carcinoma, especially metastatic renal cell carcinoma. DESIGN: Retrospective case series. METHODS: Three cases of adenocarcinoma of the NPCE were examined histologically with hematoxylin-eosin stain and immunohistochemical stains including vimentin, AE1/AE3, Cam 5.2, CK7, PAX2, PAX8, AMACR, and CAIX. We also reviewed previously reported cases of this tumor. RESULTS: We found that the immunohistochemical profile of adenocarcinoma of the NPCE can overlap with renal cell carcinoma. Both tumors can express vimentin, cytokeratin AE1/AE3, Cam 5.2, PAX2, PAX8, and AMACR. One of the adenocarcinomas of the NPCE in our series also expressed CD10 and the renal cell carcinoma marker (RCC Ma). Carbonic anhydrase IX (CAIX) was not detected in any of the 3 tumors. CONCLUSIONS: Adenocarcinomas arising in phthisic eyes can be diagnostically challenging. We have found it particularly difficult to distinguish adenocarcinoma of the NPCE from metastatic carcinoma, especially metastatic clear cell renal cell carcinoma and papillary renal cell carcinoma. Because of the immunophenotypic overlap, most patients will require systemic workup including imaging of the kidneys to be certain of the diagnosis.

Molecular Genetics of Intraocular Tumors.

PURPOSE: To explore the value of molecular technologies in the pathologic evaluation, diagnosis, and treatment of retinoblastoma and uveal melanoma. METHODS: Review of the peer-reviewed literature on the molecular pathology of primary intraocular tumors. CONCLUSION: Molecular tests are playing an increasingly important role in the diagnosis of intraocular tumors. They provide information valuable for diagnosis, prognosis, screening regimens, genetic counselling, and treatment. These technologies are becoming easier, faster, and with higher sensitivity and accuracy.

Ocular Human Papillomavirus Infections.

CONTEXT: - Human papillomavirus (HPV) has a well-known role in the pathogenesis of squamous cell carcinoma and precursor lesions of the cervix, anogenital region, and head and neck, but its role in the development of squamous neoplasms of the eye, particularly the conjunctiva, remains unclear. OBJECTIVE: - To review recent evidence implicating HPV in the pathophysiology of ocular lesions. DATA SOURCES: - Published articles obtained from a PubMed search of the English literature were the primary sources for this review. CONCLUSIONS: - The low-risk HPV types 6 and 11 appear to play a role in the development of at least a subset of conjunctival squamous papillomas. The role of HPV in the pathogenesis of pterygium and ocular surface squamous neoplasia is less well defined. There is evidence to suggest that HPV may be a cofactor in the development of these lesions, acting in concert with ultraviolet radiation and/or human immunodeficiency virus infection in a subgroup of cases.