Shuk On Annie Leung

Next-Generation Sequencing in the Diagnosis of Metastatic Lesions: Reclassification of a Glioblastoma as an Endometrial Cancer Metastasis to the Brain

Abstract Endometrial cancer is the most common gynecologic cancer in the U.S., but metastasis to the brain is rare, and diagnosis can be challenging. Traditional tools for determining if a tumor is a primary or metastatic lesion include pan-imaging, histopathologic studies, and immunohistochemistry. Molecular testing with next-generation sequencing has been increasingly used to augment these tests. We present a case of a patient who initially presented with a brain lesion diagnosed as glioblastoma on histology and immunohistochemistry, but whose diagnosis was later changed to metastasis from an endometrial primary based on molecular findings. The two tumors shared a common microsatellite instability signature and 51 DNA variants, including oncogenic driver mutations KRAS p.G13D, PIK3CA p.E545A, and PTEN p.I135V and p.K267Rfs*9. This highlights the power of molecular analysis in making the diagnosis in cases of rare metastases. Key Points Brain metastasis from endometrial primary is rare, and histopathological features may be augmented with molecular analysis to aid in diagnosis. Comparison of the molecular makeup of the primary endometrial lesion with the metastatic lesion may reveal high-risk molecular features that may be indicative of metastatic potential.

Small cell neuroendocrine carcinoma of the cervix: diagnostic challenges and emerging molecular insights †

Abstract Small cell neuroendocrine carcinoma of the cervix (SCNECC) is a rare and highly aggressive malignancy with poor prognosis that predominantly affects premenopausal women. Histopathological evaluation is central to diagnosis and clinical management; however, distinguishing SCNECC from other ‘small blue round cell’ malignancies often requires a multimodal approach that integrates morphology, immunohistochemistry, and advanced molecular testing. In the absence of specific and sensitive biomarkers, SCNECC largely remains a diagnosis of exclusion, underscoring the need for comprehensive diagnostic algorithms. A study by Pan, Yan, Yuan et al employed whole transcriptome profiling and identified three molecular subgroups within SCNECC. Importantly, one subgroup displayed an inflamed phenotype, characterized by high expression of MHC‐II complex and IFN‐α/β–related genes, suggesting potential susceptibility to immunotherapy, a finding that mirrors observations in small cell lung cancer. These findings highlight the biological heterogeneity of SCNECC and reinforce the importance of integrating molecular data to refine diagnostic accuracy and guide therapeutic decision‐making. This commentary emphasizes the pressing need for comprehensive diagnostics and further research to advance treatment strategies for this rare and challenging malignancy. © 2025 The Pathological Society of Great Britain and Ireland.

Dysregulation of Cholesterol Homeostasis in Ovarian Cancer

Cholesterol plays an essential role in maintaining the rigidity of cell membranes and signal transduction. Various investigations confirmed empirically that the dysregulation of cholesterol homeostasis positively correlates with tumor progression. More specifically, recent studies suggested the distinct role of cholesterol in ovarian cancer cell proliferation, metastasis and chemoresistance. In this review, we summarize the current findings that suggest the contribution of cholesterol homeostasis dysregulation to ovarian cancer progression and resistance to anti-cancer agents. We also discuss the therapeutic implications of cholesterol-lowering drugs in ovarian cancer.

Triaging abnormal cervical cancer screening tests using p16INK4a detection by ELISA on fresh cervical samples

AbstractProblemCervical cancer screening strategies in the United States include cotesting (human papillomavirus (HPV) with cytology), primary HPV with genotyping and reflex cytology, and cytology alone. An ongoing challenge is the appropriate triage of patients to colposcopy to those at highest risk. We investigated whether incorporation of p16INK4a immunodetection by enzyme‐linked immunosorbent assay (ELISA) on fresh cervical samples obtained at the time of screening could improve appropriate referral to colposcopy.Method of StudyA derivation group comprised of cervical swabs collected from subjects with high‐grade dysplasia or cancer (positive control) and from subjects with negative screening history (negative control). Samples collected from colposcopy were used to evaluate the existing screening strategies individually and with incorporation of p16INK4a ELISA. Histology was used as the gold standard.ResultsAmong 163 subjects recruited, 138 were included. In the derivation group, mean p16INK4a level was 2.86 ng/mL (n = 31) and 0.58 ng/mL (n = 20) among positive and negative controls respectively (p = 0.002) with an area under the receiver operator characteristic curve of 0.79 (p < 0.001). Among colposcopy subjects, sensitivity/specificity for cotesting, primary HPV, and cytology were 94%/42%, 88%/45%, and 88%/49%, respectively. Incorporation of p16INK4a resulted in similar sensitivity and improved specificity (cotesting+p16 88%/58%, primary HPV+p16 88%/57%, cytology+p16 81%/62%; p = 0.23/p = 0.008) with decrease in colposcopy referrals by 15% to 22% (p = 0.01).ConclusionsThese results demonstrate the feasibility of quantifying p16INK4a by ELISA in fresh cervical samples, and its potential as an adjunct to existing screening strategies in the identification of high grade‐dysplasia while reducing the number of colposcopic referrals.

An Interactive Educational Tool to Improve Human Papillomavirus Vaccine Knowledge and Recommendation Among Nurses

In United States, only 57% of  women and 53% of men in the recommended age groups have received all recommended doses of the human papillomavirus (HPV) vaccine. Healthcare provider education has been associated with strong vaccine recommendation and vaccination uptake. Our objective was to create a 7-min interactive online educational tool to improve knowledge and willingness to recommend the HPV vaccine among nurses. This is a prospective pre-test/post-test study to evaluate the effectiveness of the educational tool consisting of 10 flashcards in a question-answer format. Oncology nurses at our cancer center were invited to participate by email, which led them to the educational tool (i.e., intervention) along with pre- and post-test questions on HPV-associated cancers, vaccine-eligible age groups, dosing schedules, adverse events, and willingness to recommend. Of the 110 participants (mean age of 41.2 ± 11.4, 98% female, 64% >10 years of practice), there was improvement in knowledge after intervention in HPV-associated cancers (81% to 97%; p = 0.02), percentage of cervical caused by HPV (33% to 64%; p < 0.05), and dosing schedule (47% to 93%; p < 0.05). All participants correctly stated that continued screening is needed after vaccination both pre- and post-intervention. Eighty-five percent strongly agreed that the intervention improved their HPV knowledge, and 77% stated they were more likely to recommend the HPV vaccine after the intervention. While nurses are willing to recommend the vaccine, there remains persistent knowledge gaps. A brief 7-min self-administered online interactive flashcard educational intervention is effective in improving the HPV vaccine knowledge among nurses.