Tumors Of Origin Research Articles

O-10 AN OVARIAN THECOMA PRESENTING WITH POST-MENOPAUSAL VIRILIZATION

Abstract Introduction Virilizing ovarian tumors are a rare cause of hyperandrogenism in women, account for less than 5% of all ovarian neoplasms. In most cases presents with increased serum testosterone levels and normal dehydroepiandrosterone-sulfate levels. Ovarian thecoma is a rare, benign tumor of stromal cell origin which represents less than 1% of ovarian tumor. It occurs most often in perimenopausal and postmenopausal women. Here we present a postmenopausal women presenting with hirsutism. Clinical Case A 53 year old female patient was referred to the endocrine outpatient clinic with the complaint of progressive hirsutism started after menopause in the last year. She had no special past medical history and medical history. She was in post-menopausal period for one year. She had androgenic alopecia and deepening voice. Her hemogram analysis, renal and liver function tests were in normal range. Hormonal analysis revealed a markedly increased serum testosterone level, 654 ng/dl, normal dehydroepiandrosterone-sulfate levels. High testosterone levels were confirmed in repeated examinations. Transvaginal ultrasonography and examination were found to be normal. Magnetic Resonance Imaging was performed due to significantly high testosterone levels and 30x18 mm right ovarian mass was found compatible with thecoma. Patient was referred to gynecology for surgery. Conclusion Ovarian thecoma is a very rare tumor accounting about 1 % of solid ovarian tumors. The İncidence of this tumor is highest in pre and postmenopausal period. Thecomas are mostly benign and solid. During reproductive age, patient presents with hirsutism, acne, virilization findings. In postmenopausal period patient may present with mild virilization, post-menopausal bleeding and endometrial hyperplasia/cancer. Surgery is the primary treatment modality for virilizing thecoma.

O-02 A RARE COLLISION TUMOR OF THE PITUITARY: CO-EXISTENCE OF CRANIOPHARYNGIOMA AND PROLACTINOMA

Abstract Introduction Pituitary adenomas are the most common lesions of the sellar region. The most common (40%) functional pituitary adenomas are prolactinomas. Craniopharyngiomas are epithelial tumors of embryonal origin originating from Rathke's sac. Very few cases of collision tumors co-existing with pituitary adenoma and craniopharyngioma have been described in the literature. Clinical Case We present a case of histopathologically proven craniopharyngioma accompanying prolactinoma in a 63-year-old female patient diagnosed with prolactinoma 40 years ago. She was treated with bromocriptine after the diagnosis, and the treatment was switched to cabergoline four years later. Although the biochemical remission was achieved, there was no significant decrease in tumor size. She had not received any treatment during last 4 years before the administration. She was admitted to our clinic with a complaint of headache. Her serum prolactin level was 1550 ng/ml ((Reference:4,79-23 ng/ml). According to the pituitary Magnetic Resonans Imaging(MRI); reports were as follows in 2007; an isolated 8x6x13 mm adenoma was observed, and then in 2015; another cystic lesion (craniopharyngioma?) was detected adjacent to the infindibular stalk in addition to the defined pituitary adenoma (Figure 1a). In the last pituitary MRI (2022); a cystic lesion extending from the sellar cavity to the suprasellar cistern and a solid mass lesion located left to the cavernous sinus, was observed (Figure 1b). Upon a dramatic increase of the tumor volume on pituitary MRI, she underwent pituitary surgery. The histopathological diagnosis was adamantinomatous craniopharyngioma. Postoperative prolactin level decreased to 10 ng/ml. Since prolactin levels decreased after the diagnosis of craniopharyngioma, the surgical material was re-evaluated by the pathologist. No evidence of prolactinoma was found. Significant regression was observed in the patient's 1st month follow-up pituitary MRI compared to the preoperative MRI. Postoperatively, prolactin levels remained within the normal range for the first 6 months. After the 6th month, cabergoline treatment was started when prolactin levels increased to 497 ng/ml. Conclusion Pituitary adenoma and craniopharyngioma collision tumors are extremely rare. Only 6 patients with the coexistence of craniopharyngioma and prolactinoma have been reported in the literature, including our case. Histopathological diagnosis may be necessary to differentiate craniopharyngioma from cystic macroprolactinoma.Figure 1:Magnetic Resonans ImagingFigure 1: a. Post-contrast coronal pituitary MRI examination revealed a pituitary adenoma (thick arrow) located in the left cavernous sinus. aAnother cystic mass lesion (thin arrow) was detected adjacent to the infindibular stalk.; b. Coronal contrast-enhanced pituitary MRI image showed cystic (arrow) and

Identifying Primary Sites of Spinal Metastases: Expert-Derived Features vs. ResNet50 Model Using Nonenhanced MRI.

The spinal column is a frequent site for metastases, affecting over 30% of solid tumor patients. Identifying the primary tumor is essential for guiding clinical decisions but often requires resource-intensive diagnostics. To develop and validate artificial intelligence (AI) models using noncontrast MRI to identify primary sites of spinal metastases, aiming to enhance diagnostic efficiency. Retrospective. A total of 514 patients with pathologically confirmed spinal metastases (mean age, 59.3 ± 11.2 years; 294 males) were included, split into a development set (360) and a test set (154). Noncontrast sagittal MRI sequences (T1-weighted, T2-weighted, and fat-suppressed T2) were acquired using 1.5 T and 3 T scanners. Two models were evaluated for identifying primary sites of spinal metastases: the expert-derived features (EDF) model using radiologist-identified imaging features and a ResNet50-based deep learning (DL) model trained on noncontrast MRI. Performance was assessed using accuracy, precision, recall, F1 score, and the area under the receiver operating characteristic curve (ROC-AUC) for top-1, top-2, and top-3 indicators. Statistical analyses included Shapiro-Wilk, t tests, Mann-Whitney U test, and chi-squared tests. ROC-AUCs were compared via DeLong tests, with 95% confidence intervals from 1000 bootstrap replications and significance at P < 0.05. The EDF model outperformed the DL model in top-3 accuracy (0.88 vs. 0.69) and AUC (0.80 vs. 0.71). Subgroup analysis showed superior EDF performance for common sites like lung and kidney (e.g., kidney F1: 0.94 vs. 0.76), while the DL model had higher recall for rare sites like thyroid (0.80 vs. 0.20). SHapley Additive exPlanations (SHAP) analysis identified sex (SHAP: -0.57 to 0.68), age (-0.48 to 0.98), T1WI signal intensity (-0.29 to 0.72), and pathological fractures (-0.76 to 0.25) as key features. AI techniques using noncontrast MRI improve diagnostic efficiency for spinal metastases. The EDF model outperformed the DL model, showing greater clinical potential. Spinal metastases, or cancer spreading to the spine, are common in patients with advanced cancer, often requiring extensive tests to determine the original tumor site. Our study explored whether artificial intelligence could make this process faster and more accurate using noncontrast MRI scans. We tested two methods: one based on radiologists' expertise in identifying imaging features and another using a deep learning model trained to analyze MRI images. The expert-based method was more reliable, correctly identifying the tumor site in 88% of cases when considering the top three likely diagnoses. This approach may help doctors reduce diagnostic time and improve patient care. 3 TECHNICAL EFFICACY: Stage 2.

Principles of Surgical Treatment of Soft Tissue Sarcomas

Soft tissue sarcoma (STS) is a group of highly heterogeneous tumors of mesenchymal origin that have variable primary site locations and clinical behavior. Despite the broad diversity of STS, the standard of care involves surgical resection with or without radiation therapy (RT) to control local recurrence and systemic treatment in select cases. The complexities of STS require a critical understanding of the preoperative work-up process, surgical treatment, and postoperative management. Advanced imaging plays a vital role in the characterization of the soft tissue mass, preoperative biopsy planning, and disease staging. Surgical treatment prioritizes wide resection with negative margins, supported by newer margin classification systems for better prognosis. Further, advancements in surgical technique have enabled limb-salvage surgery to largely replace amputation in the management of these tumors. Additional surgical considerations, such as nerve preservation, vascular reconstruction, and complex tissue closure, further highlight the complexity of STS management. Lastly, postoperative follow-up is critical for the early detection of local or distant recurrences. For complex cases, such as unplanned excisions or invasive tumors, strategies like re-resection may be beneficial. Ongoing research into imaging, chemotherapy, and targeted therapies will further refine management strategies, especially in complex and recurrent cases. This review highlights the essential aspects of STS surgical management and underscores the need for coordinated, multidisciplinary care to enhance both survival and quality of life for affected patients.

Patient-derived xenograft models of gastrointestinal stromal tumors: a ready-to-use platform for translational research.

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal malignancy of the gastrointestinal tract. Most GIST harbor mutations in oncogenes, such as KIT, and are treated with tyrosine kinase inhibitors (TKI), such as imatinib. Most tumors develop secondary mutations inducing drug resistance against the available TKI, which requires novel therapies. We established a GIST patient-derived xenograft (PDX) platform of GIST that can be used for preclinical drug testing. Tumor tissue from consenting GIST patients was transplanted subcutaneously to NMRI nu/nu mice. Once tumor growth was observed, the tumor was re-transplanted to a next generation of mice. Tumors were characterized histopathologically and molecularly at every re-transplantation and compared with the original patient tumor. We transplanted 112 tumor samples from 99 GIST patients, resulting in 12 established and well-characterized GIST models with different mutations and TKI sensitivity. Three models harbor secondary KIT mutations. One model is characterized by a primary, imatinib-resistant PDGFRA exon 18 p.D842V mutation. Our established platform of well-characterized GIST PDX models, covering the most relevant driver mutations, serves as an excellent tool for preclinical drug testing and tumor biology studies.

Inferred Developmental Origins of Brain Tumors from Single Cell RNA-Sequencing Data

Abstract Background The reactivation of neurodevelopmental programs in cancer highlights parallel biological processes that occur in both normal development and brain tumors. Achieving a deeper understanding of how dysregulated developmental factors play a role in the progression of brain tumors is therefore crucial for identifying potential targets for therapeutic interventions. Single-cell RNA sequencing (scRNA-Seq) provides an opportunity to understand how developmental programs are dysregulated and reinitiated in brain tumors at single-cell resolution. The aim of this study is to identify developmental origins of brain tumors using scRNA-Seq data. Methods Here, we introduce COORS (Cell Of ORigin like CellS), a computational tool trained on developmental human brain single-cell datasets that annotates “developmental-like” cell states in brain tumors. COORS leverages cell type-specific multilayer perceptron models and incorporates a developmental cell type tree that reflects hierarchical relationships and models cell type probabilities. Results Applying COORS to various brain cancer datasets, including medulloblastoma (MB), glioma, and diffuse midline glioma (DMG), we identified developmental-like cells that represent putative cells of origin in these tumors. Our method provides both cell of origin classification and cell age regression, offering insights into the developmental cell types of tumor subgroups. COORS identified outer radial glia (oRG) developmental cells within IDHWT glioma cells whereas oligodendrocyte precursor cells (OPCs) and neuronal-like cells in IDHMut. Interestingly, IDHMut subgroup cells that map to OPC show bimodal distributions, that are both early and late weeks in development. Furthermore, COORS offers a valuable resource by providing novel markers linked to developmental states within of MB, glioma and DMG tumor subgroups. Conclusion Our work adds to our cumulative understanding of brain tumor heterogeneity and helps pave the way for tailored treatment strategies.

"Update on pediatric primary liver tumors".

Liver masses are common in children, however primary malignant neoplasms are rare, representing only 1% of all pediatric cancers. Hepatocellular neoplasms are the most common primary liver malignancies and hepatoblastoma (HB) is the most frequently diagnosed. The incidence of HB, which is increasing, is approximately of 2 cases per million in the United States, followed by hepatocellular carcinoma (HCC). Pediatric primary liver tumors of mesenchymal origin are less common, except for benign vascular tumors (hemangiomas). Malignant mesenchymal neoplasms represent approximately 10-15% of all, the most common being embryonal sarcoma and malignant rhabdoid tumor. Malignant vascular tumors are rare, but epithelioid hemangioendothelioma (EHE) and angiosarcoma can be seen in children. The development and adoption of consensus diagnostic, therapeutic and risk-stratifying approaches for pediatric patients with malignant liver tumors has been historically challenged by their rarity and by their diverse clinical and histological appearance. On-going collaborative efforts of international consortia including the Children's Oncology Group (COG) in North America, the German Society of Paediatric Oncology and Haematology (GPOH), the Societe Internationale d' Oncologie Pediatrique Liver Tumor Study Group (SIOPEL) in Europe and the Japanese Liver Tumor group (JPLT), have made significant contributions to understanding the clinical and histopathological features, as well as the underlying biology of pediatric liver tumors, in particular HB. A new classification of pediatric liver tumors drafted at the international consensus meeting held in Los Angeles, has been incorporated in the recent WHO classification and is currently used by the PHITT (Paediatric Hepatic Malignancy International Tumour Trial) and other therapeutic protocols.This manuscript provides an overview of salient diagnostic features and updates in classification and molecular characterization for the most common pediatric primary liver neoplasms. It also includes a brief overview of other less common but relevant tumors, which should be considered in the differential diagnosis.

Whole-genome sequencing of cell-free DNA reveals DNA of tumor origin in plasma from patients with colorectal adenomas.

The presence of circulating tumor DNA (ctDNA) in patients with colorectal adenomas remains uncertain. Studies using tumor-agnostic approaches report ctDNA in 10-15% of patients, though with uncertainty as to whether the signal originates from the adenoma. To obtain an accurate estimate of the proportion of patients with ctDNA, a sensitive tumor-informed strategy is preferred, as it ensures the detected signal originates from the adenoma. Here, tumor-informed whole-genome sequencing-based ctDNA analysis (MRD-EDGESNV) was applied to two independent cohorts. Cohort 1, comprising 93 patients with stage III colorectal cancer (CRC) and 40 healthy individuals, was used to establish the signal threshold at 95% specificity. This threshold was then applied to Cohort 2, consisting of 22 patients with symptomatic and 20 with asymptomatic adenomas. In stage III, MRD-EDGESNV had an area under the curve of 0.98. ctDNA was detected in 50% and 25% of patients with symptomatic and asymptomatic adenomas, respectively. The median adenoma plasma tumor fraction was 5.9 × 10-5. These finding not only demonstrate the feasibility of ctDNA detection in patients with colorectal adenomas, but also provides an estimate of the necessary sensitivity required to detect these lesions, paving the way for future ctDNA-based screening strategies.

Depression and Psychological Distress in Patients with Lower Extremity Lymphedema: A Mixed-Method Study.

Background: Lower extremity lymphedema is a chronic and incurable condition. Treatment options for lymphedema have continued to advance and prognosis has improved; however, the condition still poses a substantial negative impact on patients' mental health. Therefore, the key questions raised in this study are "How many patients with lower limb lymph have depression symptoms?" and "Are there any differences in the symptoms and distress factors of patients with lower extremity lymphedema, and how do they experience distress?" Methods and Results: A total of 112 lower extremity lymphedema patients from June 2021 to December 2023 were enrolled in the study. Quantitative and qualitative data of patients were collected and analyzed. Participants completed the Patient Health Questionnaire (PHQ-9), and we interviewed participants with moderate/severe depressive symptoms with score ≥10. A total of 83 participants completed this study. Overall, 39.76% of the participants had a PHQ-9 score ≥5, indicating that they had mild depressive symptoms; 13.25% of the participants had a PHQ-9 score ≥10, indicating that they had moderate or severe depressive symptoms. Compared with participants who had received treatment before the study, participants who did not receive any treatment before the study had a higher risk of depression (χ2 = 6.705, p = 0.031). There was no significant difference in the degree of depression in patients with different stages of lymphedema (χ2 = 8.430, p = 0.077). From the qualitative interview data, we extracted five common themes: "loss of self," "isolation from surroundings," "discomfort caused by symptoms and complications," "concern about the progression or deterioration of the original malignant tumor," and "fear that surgical treatment may be ineffective." Conclusions: This study found that patients with lower extremity lymphedema are prone to psychological symptoms of depression. To clarify the reason that affect psychological distress is important information to improve the psychological health support for patients with lower extremity lymphedema.

Optimization of pre-analytical handling to maintain DNA integrity in diagnostic Papanicolaou tests.

Cell-free DNA of ovarian tumor origin can be detected in samples from the gynecologic tract. This study aims to evaluate how pre-analytical handling, and storage conditions affect DNA profile and integrity in Pap tests, to optimize its potential for detection of ovarian cancers (OC). Analysis of archived Pap tests from OC patients, kept at RT for 48h and stored at -80°C was complemented by in vitro experiments. Temperature-associated effects on DNA fragmentation were evaluated in samples stored at 4°C, -20°C or -80°C. Time-dependent DNA degradation at RT was evaluated in comparison to storage at 4°C (0-96h). Results were validated in prospectively collected Pap tests. The DNA integrity was assessed by fragment analysis. Accumulation of short DNA fragments was observed in archived Pap tests from OC patients. In vitro, fragments of 100-350bp increased 11.5-fold within 48h at RT compared to 1.7-fold when stored at 4°C. Consistent with the in vitro findings, prospectively collected samples showed reduced fragmentation when stored at 4°C compared to RT (p=0.007). Long-term storage at 4°C had a significant negative effect on DNA stability (p=0.013), while freezing slowed down fragmentation. This study highlights the need for optimization of pre-analytical handling for cfDNA analysis. Immediate storage at 4°C after sampling markedly reduces DNA degradation suggesting a simple way to decrease unwanted fragmentation for cfDNA analysis in Pap tests.

Advancing pancreatic cancer research and therapeutics: the transformative role of organoid technology.

Research on pancreatic cancer has transformed with the advent of organoid technology, providing a better platform that closely mimics cancer biology in vivo. This review highlights the critical advancements facilitated by pancreatic organoid models in understanding disease progression, evaluating therapeutic responses, and identifying biomarkers. These three-dimensional cultures enable the proper recapitulation of the cellular architecture and genetic makeup of the original tumors, providing insights into the complex molecular and cellular dynamics at various stages of pancreatic ductal adenocarcinoma (PDAC). We explore the applications of pancreatic organoids in dissecting the tumor microenvironment (TME); elucidating cancer progression, metastasis, and drug resistance mechanisms; and personalizing therapeutic strategies. By overcoming the limitations of traditional 2D cultures and animal models, the use of pancreatic organoids has significantly accelerated translational research, which is promising for improving diagnostic and therapeutic approaches in clinical settings, ultimately aiming to improve the outcomes of patients with pancreatic cancer.

Cholangioblastic Cholangiocarcinoma (NIPBL::NACC1 cholangiocarcinoma): Expanded Morphologic Spectrum and Further Genetic Characterization.

The cholangioblastic variant of intrahepatic cholangiocarcinoma is a distinctive neoplasm that typically affects young women without underlying liver disease. Morphologically, it demonstrates solid, trabecular, and tubulocystic architecture, biphasic small cell-large cell cytology, and immunoreactivity for inhibin, neuroendocrine markers, and biliary but not hepatocellular markers. In 2021, our group identified a characteristic NIPBL::NACC1 gene fusion in cholangioblastic cholangiocarcinoma, and since then ~20 genetically confirmed cases have been reported in the literature. We report 2 additional cases, both of which caused diagnostic challenges. The first was previously published as a "biliary adenofibroma with malignant features" which we now show recurred as a high-grade adenocarcinoma. Re-review of the original lesion demonstrated the morphologic and immunohistochemical features of highly cystic cholangioblastic cholangiocarcinoma, whereas the high-grade recurrence lacked many of these features. In addition to the characteristic NIPBL::NACC1 gene fusion, the recurrence demonstrated loss of the RB1 and PTEN genes which were found in the highly cystic, bland areas of the original tumor, suggesting that the recurrence was derived from this bland component. The second case was originally misclassified as metastatic well-differentiated neuroendocrine neoplasm and only focally demonstrated the characteristic biphasic small cell-large cell cytology. In addition, a review of 7 cholangioblastic cholangiocarcinomas in our files demonstrates that loss of chromosome 13q14.2 (where the RB1 gene resides) and loss of chromosome 6q15-q16.3 are recurrent secondary changes in these neoplasms. Expression profiling demonstrated alterations in the transforming growth factor receptor beta superfamily, and overexpression of MYC which was validated by immunohistochemistry. Our findings expand the morphologic and genetic spectrum of this neoplasm and provide insight into secondary genetic changes associated with progression.

Modern approaches for management patients with craniofacial tumors (literature review)

Despite a significant amount of information on approaches to managing patients with craniofacial tumors, the increasing number of modern high-tech technologies, there remain a number of controversial issues regarding the choice of treatment strategy that fully satisfies the requirements of objective assessment of effectiveness and the improvement of quality of life for patients suffering from oncological disease. Craniofacial approaches sufficiently adhere to oncological principles and allow for the removal of even extensive tumors which greatly improve immediate and long-term outcomes, reliably enhancing quality of life, which is the most important task in the surgery of malignant skull base tumors. As evident from the aforementioned modifications and classical approaches to reconstruction of defects following craniofacial resections, in order to summarize the vast amount of information on the advantages and disadvantages of corresponding methods, a multicenter independent prospective study is needed, during which data from different clinics would undergo critical analysis using modern evidence-based medicine methods. On the path to methodological comprehension of existing concepts and actions towards creating one’s own algorithms lies a multifactorial analysis of personal experience in management and undoubtedly the care of patients from a group with such an unfavorable prognosis for survival. An immediate observation that follows the realization of the practical significance of a surgical treatment algorithm common to all physicians and mid-level medical staff is that the most effective achievement of the above task lies in learning from one’s own mistakes during patient care. Very encouraging research results, in which attempts are made at mastering new materials, herald a future scientific breakthrough in craniofacial reconstruction. The use of bioprosthetics and synthetic analogs is particularly relevant for those patients for whom reconstruction using their own tissues is contraindicated for various reasons. This article demonstrates the most outstanding achievements in the treatment of patients with sinonasal tumors.Malignant tumors of the sinonasal region are rare and highly diverse in their histological origin neoplasms, accounting for an average of 0.2–1.1 % of all newly diagnosed tumors. Risk factors, to varying degrees pathogenetically linked to disease progression, include a mutation of the TP53 gene in 80 % of cases, prolonged exposure to industrial air pollutants, smoking, male gender, and age over 55 years in 85 % of cases, infection with human papillomavirus and Epstein–Barr virus. Despite a substantial amount of information on approaches to managing this patient population, the increasing number of modern technology-intensive methods has led to ongoing debates regarding the selection of a treatment strategy that fully meets the requirements for objectively assessing efficacy and improving the quality of life of patients suffering from oncological disease.Aim. To investigate modern approaches to treatment of patients with tumors of the craniocephalic location, identify factors of surgical treatment success and favorable long-term prognosis, develop a management algorithm for patients with sinonasal neoplasms, provide rationale for using various reconstruction techniques for postresection defects. Systemic approach to the analysis of effectiveness and expediency of modern approaches to treatment of patients with tumors of the craniocephalic region requires integration of several key concepts. Taking into account individual characteristics of the patient by an experienced surgical team can lead to good treatment results including increased survival rates.Development of algorithms for management of patients of this category and individualization of selection of reconstructive techniques are important problems in practical healthcare. Minimization of complications is one of the main goals of postoperative patient observation. The optimal approach to treatment even in this prospectless in the context of survival and social rehabilitation group of patients assumes greatest possible preservation of facial esthetic features and increased quality of life which can be achieved only with well-coordinated work of highly professional interdisciplinary team.

3D Bioprinted Head and Neck Squamous Cell Carcinoma (HNSCC) Model Using Tunicate Derived Nanocellulose (NC) Bioink.

Head and neck squamous cell carcinoma (HNSCC) are invasive solid tumors accounting for high mortality. To improve the clinical outcome, a better understanding of the tumor and its microenvironment (TME) is crucial. Three -dimensional (3D) bioprinting is emerging as a powerful tool for recreating the TME in vitro. To establish long-term HNSCC bioprinted constructs for personalized drug-testing, this proof-of-principle study aims to compare two different innovative tunicate-derived nanocellulose (NC) hydrogels against the widely used semi-synthetic gelatin methacryloyl (GelMA). Cell lines of different tumor origin sites are printed in TEMPO and Carboxy-NC, and GelMA in alginate (GelMAA). Both NC hydrogels show higher bioprintability than GelMAA. Carboxy-NC supported long-term HNSCC survival, proliferation, and maintenance of epithelial phenotype in 3D bioprinted constructs similar to GelMAA. The hydrogel microstructure revealed differences in pore size. Importantly, the established HNSCC bioprinted model allowed the testing of radiochemotherapy (RCT) both in cell lines and patient-derived cultures. Compared to a spheroid model, the cytotoxic effects are less, better reflecting the response in patients. The proof-of-principle findings indicate that Carboxy-NC is a viable alternative to gelatin-based bioink with improved bioprintability allowing personalized drug-testing. By adding other cell-types of the TME, this model can be advanced to a heterotypic one.

Accurate identification of primary site in tumors of unknown origin (TUO) using DNA methylation

Tumors of unknown origin (TUO) generally result in poor patient survival and are clinically difficult to address. Identification of the site of origin in TUO patients is paramount to their improved treatment and survival but is difficult to obtain with current methods. Here, we develop a random forest machine learning TUO methylation classifier using a large number of primary and metastatic tumor samples. Our classifier achieves high accuracy in primary site identification when applied to both publicly available and internal validation samples, with 97% of samples classified correctly and 85% receiving high probability scores (≥0.9). Moreover, by employing pathologist expertise and t-SNE visualization, the TUO classifier can assign samples to 46 different sites of origin/disease classes. This strategy also revealed multiple classes of yet unknown significance for future exploration. Overall, the presented TUO classifier represents a significant step forward in the diagnosis of TUO tumors.

CtDNA: A Gateway for Personalized Risk Stratification in Surgically Resectable Hepatocellular Cancer.

While deemed potentially curative, surgical resection of hepatocellular carcinoma (HCC) is associated with >70% risk of post-operative relapse. Recurrence is uniquely multifactorial in HCC, potentially stemming from metachronous re-occurrence of the original tumor or de novo cancerization. Circulating tumor DNA may improve personalized risk stratification post-resection, a setting where adjuvant immunotherapy has failed to provide survival benefits.

Mesenchymal stromal cells promote the formation of lung cancer organoids via Kindlin-2

BackgroundPatient-derived lung cancer organoids (PD-LCOs) demonstrate exceptional potential in preclinical testing and serve as a promising model for the multimodal management of lung cancer. However, certain lung cancer cells derived from patients exhibit limited capacity to generate organoids due to inter-tumor or intra-tumor variability. To overcome this limitation, we have created an in vitro system that employs mesenchymal stromal cells (MSCs) or fibroblasts to serve as a supportive scaffold for lung cancer cells that do not form organoids.MethodsWe successfully established an MSCs/fibroblast co-culture system to form LCOs. We analyzed the morphological and histological similarities between LCOs co-cultured with fibroblast and primary lung cancer lesions through HE and IF staining. We evaluated whether LCOs co-cultured with fibroblast retained the original genetic mutations of their source tumors based on WES. RNA sequencing was used to analyze the differences in gene expression profiles between LCOs co-cultured with fibroblast and paracancerous organoids (POs). Importantly, we have successfully validated the impact of Kindlin-2 on the regulation of MSCs in organoid formation through lentiviral vector-mediated interference or overexpression of kindlin-2.ResultsOur findings demonstrate that the addition of MSCs/fibroblasts to three tumor samples, initially incapable of forming organoids by traditional methods, successfully facilitated the cultivation of tumor organoids. Importantly, these organoids co-cultured with fibroblast faithfully recapitulate the tissue morphology of original lung tumors and replicate the genetic profile observed in the parental tumors even after prolonged in vitro culture. Moreover, drug responses exhibited by these organoids co-cultured with MSCs/fibroblasts are consistent with those observed in the original tumors. Mechanistically, we have also identified kindlin-2 as a crucial regulator linking extracellular matrix (ECM) and mitochondria that influence MSC/fibroblast-mediated support for tumor organoid formation.ConclusionThe results obtained from our research enhance the understanding of the mechanisms implicated in the formation of tumor organoids and aid in creating stronger patient-specific tumor organoid models. This advancement supports the refinement of personalized drug response assessments for use in clinical settings.Graphical

Establishment and characterization of a sigmoid colon cancer organoid with spinal metastasis.

Sigmoid colon cancer with spinal metastases is rare in distant metastasis. In addition, the prognosis of colon cancer patients with spinal metastases is extremely poor. In order to find effective therapeutic agents, we need to know the biological characteristics of such patients from related models. We collected sigmoid colon cancer tissue from a young female subject who was diagnosed with sigmoid colon cancer with multiple spinal metastases. We successfully established a sigmoid colon cancer organoid using this tissue and investigated drug screening in the patient. HE staining, immunohistochemistry, and DNA sequencing were utilized to compare the biological characteristics between the original tumor and the organoid. Furthermore, we investigated the drug screening of the sigmoid colon cancer organoid in vitro. A colon cancer organoid from sigmoid colon cancer with spinal metastases was successfully established. The organoid culture maintained the morphological features, histological features, and genomic landscape of the corresponding sigmoid colon cancer cells. Moreover, we performed drug screening tests to evaluate the effects of chemotherapeutic drugs and targeted drugs. The sigmoid colon cancer organoid with spinal metastases was a favorable preclinical model to explore the clinicopathologic characteristics of colon cancer patients with spinal metastases.

Female adnexal tumor of probable Wolffian origin (FATWO): a case report and literature review

Female adnexal tumor of probable Wolffian origin (FATWO): a case report and literature review

Immunohistochemical Study Protocol in Thyroid Pathology.

Immunohistochemical study proves valuable in the diagnosis of neoplastic pathology. Its application allows us to differentiate the origin of tumors, as seen with thyroglobulin and TTF1 in well-differentiated tumors of follicular origin and calcitonin or other neuroendocrine markers for tumors arising from C cells. At times, immunohistochemical study becomes necessary for the classification of thyroid carcinomas arising from follicular cells, although specific antibodies that would enable the exclusion of malignancy or differentiation between follicular carcinomas and papillary carcinomas have generally not been found; hence, various antibody panels are utilized. HMBE1 and galectin 3 can be beneficial in distinguishing malignancy from benignity, while CK19, galectin 3, and HMBE1 aid in identifying papillary carcinomas of follicular variant. In the differential diagnosis depending on histological morphology, various panels with automated protocols prove greatly useful.