Preclinical models are relatively underutilized and underfunded resources for modeling the pathogenesis and prevention of ovarian cancers. Several reviews have detailed the numerous published models of ovarian cancer. In this review, we will provide an overview of experimental model systems, their strengths and limitations, and use selected models to illustrate how they can be used to address specific issues about ovarian cancer pathogenesis. We will then highlight some of the preclinical prevention studies performed to date and discuss experiments needed to address important unanswered questions about ovarian cancer prevention strategies.

Clear cell carcinoma (CCC) of the vulva is extremely rare. We report a case of a 54-year-old woman who presented with a 5 cm mass of the mons pubis. She underwent needle biopsy demonstrating CCC. She then underwent radical vulvectomy with bilateral inguinofemoral lymph node dissection. Surgical pathology revealed CCC of the vulva with lymphovascular space invasion (LVSI) and metastatic carcinoma in 1/7 inguinal lymph nodes. The patient has a history of endometriosis, raising suspicion that her CCC could have arisen from endometriosis in the mons. She completed adjuvant treatment with cisplatin and concurrent external beam radiation therapy with radiographic evidence of complete response. However, short-interval imaging demonstrated multi-focal recurrence, which was confirmed with supraclavicular lymph node biopsy. She then completed 8 cycles carboplatin, paclitaxel, and biosimilar bevacizumab-bvzr with favorable response on imaging. She was continued on bevacizumab maintenance. She was later started on pembroluzimab for disease progression based on new mediastinal adenopathy and worsening retroperitoneal lymphadenopathy. She received eight cycles of pembrolizumab with ongoing disease progression before enrolling in hospice and discontinuing cancer-directed treatment. As described in the related literature which we summarize here, the majority of reported cases of vulvar CCC arise from endometriosis implants at the site of prior episiotomy or from the Bartholins gland. This patient had clinical history of endometriosis; prior tissue sampling was not performed to support the diagnosis. Given the absence of data regarding this rare type of primary vulvar cancer, treatment of this patients disease was based on existing data specific to squamous cell carcinoma of the vulva and extrapolated from treatment guidelines for CCC of the ovary and endometrium. Continued research is needed on this rare form of vulvar carcinoma to determine the risk factors, prognostic factors, and treatment recommendations specific to this disease.

Eagle syndrome refers to a clinical syndrome caused by the abnormal elongation of the styloid process with calcification/ossification of the stylohyoid ligament. We present the first reported case of Eagle syndrome resulting in an external carotid artery (ECA) pseudoaneurysm. A patient presented to emergency room with an expanding, painful right-neck mass. CT angiography with three-dimensional volume rendering showed a bilobed 4.0-cm right ECA pseudoaneurysm and bilateral ossification of the stylohyoid ligaments with a sharpened edge of the right styloid process at the level of the carotid artery. Aneurysmectomy was performed, and a common carotid to internal carotid bypass with reversed saphenous vein restored arterial continuity. Local resection of the styloid process with a rotational sternocleidomastoid flap was performed. The pathology report was consistent with a diagnosis of a pseudoaneurysm. A six-month clinical follow-up confirmed the complete resolution of symptoms with no neurological deficits.

In February of 2024, the Society of Gynecologic Oncology (SGO) hosted a journal club focused on new treatment options for the management of advanced and metastatic endometrial cancer. This clinical commentary is intended to provide a summary report of that presentation. The session described the importance of molecular characterization shown in the work of The Cancer Genome Atlas (TCGA). The updated 2023 FIGO staging of endometrial cancer was reviewed. The panel then described the role of upfront immunotherapy for the treatment of advanced or recurrent endometrial cancer as demonstrated in four recent trials (RUBY, NRG-GY018, AtTEnd, and DUO-E studies). The DUO-E study uniquely examined the combination immunotherapy with a PARP inhibitor. The trials had unique differences in inclusion criteria, primary outcomes, and length of maintenance therapy, but all boasted similarly promising results particularly in mismatch repair deficient (dMMR) endometrial cancer. This era of rapid innovation in advanced and recurrent endometrial cancer will hopefully enhance individualized treatment approaches and improved outcomes for patients with endometrial cancer.

Introduction

Cytology is commonly used to diagnose non-small cell lung cancer (NSCLC) but is an inaccurate means of diagnosis of bronchioloalveolar carcinoma (BAC). The aims of this study were to calculate the sensitivity and specificity of cytologic diagnosis of BAC and to estimate the misclassification of BAC as other subtypes of NSCLC.

Methods

Preoperative fine-needle aspiration cytology diagnoses were compared to histology diagnoses in 222 patients, including 51 patients with pure or mixed BAC, who underwent lung resection for NSCLC at our institution since 1999.

Results

The sensitivity and specificity of a cytologic diagnosis of BAC were 12% and 99%, respectively. Based on cytologic diagnosis, 63% of BAC was misclassified as adenocarcinoma, and 18% was misclassified as undifferentiated NSCLC. In this cohort, 35% of adenocarcinomas and 12% of undifferentiated NSCLC diagnosed by cytology had BAC histology.

Conclusions

Diagnosis of NSCLC by cytology alone results in significant misclassification of BAC, most commonly as adenocarcinoma or undifferentiated NSCLC. Because patients with BAC respond differently to certain treatments such as endothelial growth factor receptor inhibitors and surgical resection of multifocal lung cancer, misclassification of BAC may have important therapeutic implications.

Although re-sequencing of gene panels and mRNA expression profiling are now firmly established in clinical laboratories, in-depth proteome analysis has remained a niche technology, better suited for studying model systems rather than challenging materials such as clinical trial samples. To address this limitation, we have developed a novel and optimized platform called SP3-Clinical Tissue Proteomics (SP3-CTP) for in-depth proteome profiling of practical quantities of tumour tissues, including formalin fixed and paraffin embedded (FFPE). Using single 10 μm scrolls of clinical tumour blocks, we performed in-depth quantitative analyses of individual sections from ovarian tumours covering the high-grade serous, clear cell, and endometrioid histotypes. This examination enabled the generation of a novel high-resolution proteome map of ovarian cancer histotypes from clinical tissues. Comparison of the obtained proteome data with large-scale genome and transcriptome analyses validated the observed proteome biology for previously validated hallmarks of this disease, and also identified novel protein features. A tissue microarray analysis validated cystathionine gamma-lyase (CTH) as a novel clear cell carcinoma feature with potential clinical relevance. In addition to providing a milestone in the understanding of ovarian cancer biology, these results show that in-depth proteomic analysis of clinically annotated FFPE materials can be effectively used as a biomarker discovery tool and perhaps ultimately as a diagnostic approach.

Amyloid-β-related angiitis (ABRA) is a rare complication of cerebral amyloid angiopathy in which amyloid-β deposition in the leptomeningeal and cortical vessels is associated with vasculitis characterized by transmural lymphohistiocytic, often granulomatous, inflammation. Patients usually present with acute to subacute cognitive dysfunction, headaches, and focal neurologic deficits. We report 2 cases of ABRA with unusual clinical presentations, including one case with fatal cerebral edema leading to herniation and Duret hemorrhages, and another associated with both lobar and deep parenchymal hemorrhages with intraventricular extension as well as hypercoagulability. Both showed extensive vascular amyloid-β deposition associated with granulomatous angiitis and foreign body-type multinucleated giant cells. One of our cases demonstrates the likely effects of ABRA on impairment of fluid regulation leading to severe cerebral edema, which is an uncommon manifestation of ABRA, and may be a result of impaired blood-brain barrier function or malfunction of the neurovascular unit.

A wealth of evidence has now demonstrated that the microenvironment in which a tumorigenic cell evolves is as critical to its evolution as the genetic mutations it accrues. However, there is still relatively little known about how signals from the microenvironment contribute to the early events in the progression to malignancy. To address this question, we used a premalignant mammary model to examine how fibroblasts, and the extracellular matrix (ECM) proteins they secrete, influence progression to malignancy. Their effect on metastatic malignant cells was also assessed for comparison. We found that carcinoma-associated fibroblasts, and the distinct aligned ECM they deposit, can cause both premalignant and malignant mammary epithelial cells to assume a mesenchymal morphology that is associated with increased dissemination and metastasis, while benign reduction mammoplasty fibroblasts favor the maintenance of an epithelial morphology and constrain early dissemination, tumor growth, and metastasis. Our results suggest that normalizing the organization of the ECM could be effective in limiting systemic dissemination and tumor growth.