Malignant Transformation Research Articles

Malignant Transformation of Recurrent Benign Phyllodes Tumor: A Case Report and comprehensive review of literature

Introduction: Phyllodes tumors (PTs) of the breast are rare fibroepithelial neoplasms, accounting for less than 1% of all breast tumors. The World Health Organization (WHO) classifies PTs into benign, borderline, or malignant categories based on histological features. While benign PTs generally have a favorable prognosis, they carry a risk of transformation into malignant variants, particularly in cases of recurrence. Case Presentation: A 33-year-old female presented with a recurrent benign PT, previously treated with lumpectomy on two occasions. Recent imaging suggested possible malignant transformation, and histopathological examination confirmed a malignant PT. Discussion: This case highlights the crucial role of imaging in the early detection of malignant transformation in PTs. Surgical management strategies are discussed, with an emphasis on the potential for recurrent benign tumors to progress to malignancy. Conclusion: Regular imaging and close follow-up are essential for early detection of malignant transformation in recurrent PTs, guiding timely and appropriate surgical intervention.

Recommendations for Research to Develop a Patient‐Centered Clinical Follow‐Up Protocol for Oral Epithelial Dysplasia

ABSTRACTOral epithelial dysplasia (OED) is the primary histological marker for assessing the progression of oral potentially malignant disorders (OPMDs) to cancer. Despite challenges in grading and low inter‐pathologist reproducibility, OED severity remains the key predictor of malignant transformation. However, globally accepted guidelines for OED monitoring are lacking, despite calls for individualized management based on host and lesion characteristics. The proposed research protocol involves acquiring high‐quality intraoral images, assessing oral hygiene and periodontal status, eliminating chronic mechanical irritation and Candida infections, and applying adjunctive diagnostic methods like toluidine blue staining, optical evaluation, and brush cytology. Tailored follow‐up regimens based on individual risk assessments are emphasized, with frequent monitoring for high‐grade dysplasia or patients at higher risk of progression. Therefore, effective OED management should consider the patient's immune status, dietary habits, and oral microbiota, aiming to develop personalized treatment strategies that optimize patient‐centered care.

Performance of the MOLES and TFSOM-DIM scores in classifying choroidal nevi and melanoma

AbstractChoroidal nevi are common benign melanocytic lesions often incidentally found during routine ophthalmic examinations. Patients with choroidal nevi are frequently referred to ocular oncology centers to differentiate these from choroidal melanoma and to exclude a malignant transformation which rarely occurs. However, this causes a high workload for referral centers and may delay diagnosis and treatment of patients with potentially severe conditions. To overcome this, the MOLES score was previously developed which may empower non-specialists to differentiate choroidal nevi from melanoma. In this retrospective study, the performance of the MOLES score was assessed in 695 patients with choroidal nevi and 53 with choroidal melanoma. With a specificity of 96% (choroidal nevi) and a sensitivity of 100% (melanoma) the MOLES score was highly successful in differentiating choroidal nevi from melanoma and may offer great potential to optimize monitoring and referral decisions, and for teleophthalmology applications. Furthermore, the TFSOM-DIM score using risk factors for determining tumor progression was applied and showed a good correlation with MOLES. A complementary use of MOLES and TFSOM-DIM may be beneficial for clinical routine: MOLES for screening by non-experts with limited diagnostic tools and TFSOM-DIM in a referral setting to counsel also regarding potential transformation.

Abstract B030: Productive T-cell-mediated immunoediting of developing sarcomas by distinct mechanisms

Abstract Immunoediting is the process where developing tumors are shaped by cells of the immune system. Tumors with low immunogenicity are likely to emerge after neoantigen-specific T cells eliminate the most immunogenic cell populations. However, direct interrogation of mechanisms by which this occurs has not possible due to the pre-emergent nature before the disease is verifiably established. By modifying a mouse model of soft-tissue sarcoma where emergent tumors are consistently edited, we developed a system to examine mechanisms underlying how T cells interact with pre-emergent tumor cell populations to suppress tumor emergence. This system involves production of neoantigen-expressing autochthonous tumors with a fluorescent reporter to define neoantigen-expression status of individual cells. Tumors emerge with lower penetrance and delayed onset in T cell-sufficient mice, while every tumor from T cell-deficient mice contain a significant fraction of neoantigen-negative tumor cells. Yet, ∼53% of T cell-sufficient mice never developed, which suggests that neoantigen silencing was necessary, but not sufficient for tumor emergence. Consistent with this, genetic removal of the neoantigen after malignant transformation shows that tumor development is only rescued when neoantigen loss occurs prior to the peak T cell response, occurring around 8 days post transformation. Moreover, clonality studies reveal the presence of T cells reduces the number clones that contribute to tumor emergence down to 1-2 clones per emerged tumor. Mechanistically, blockade of the T cell effector cytokine, IFNgamma, rescues the neoantigen-negative, but not neoantigen-expressing tumor cells, demonstrating that T cells control early tumors via at least two distinct mechanisms: IFNgamma-dependent suppression of neoantigen-negative tumors cells and IFNgamma-independent suppression of neoantigen-expressing cells. Thus, our findings support that neoantigen-negative cells are subjected to cytokine-mediated suppression from T cells responding to the neoantigen-positive population in the pre-emergent tumor microenvironment. This bystander suppression can prevent tumor emergence despite non-homogeneity in neoantigen expression. Citation Format: Brian G Hunt, Julie F. Cheung, Srividhya Venkatesan, Jennifer L. Loza, Kelli A. Connolly, Shudipto Wahed, Elaine Cheng, Ishan Bansal, Emily Borr, Wei Wei, Ivana William, Brittany Fitzgerald, Nikhil Joshi. Productive T-cell-mediated immunoediting of developing sarcomas by distinct mechanisms [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr B030.

Abstract C023: P21-positive senescent stromal cells promote prostate cancer immune suppression and progression that can be reversed by senolytic therapy

Abstract Cellular senescence is historically viewed as a tumor-suppressive cell cycle arrest program to limit outgrowth of pre-malignant cells. However, emerging evidence suggests senescent cell persistence contributes to immune suppression and cancer progression. Using prostate cancer patient samples and murine models, we find that p16+ senescent cells accumulate throughout malignant progression and are associated with immune suppression and poor survival. p16 ablation in mice eliminated senescent epithelial cells and reversed immune suppression mediated by immature myeloid cells but not prostate tumorigenesis. Single cell sequencing revealed an additional population of senescent p21+ fibroblasts and myeloid cells. Targeting BCL-xL or PD-L1 induced during senescence could remove both p16+ epithelial and p21+ stromal senescent cells, reactivate T cell immunity, and block tumor initiation as well as progression in advanced prostate cancer models. Our findings demonstrate that targeting heterogenous senescent populations can not only prevent malignant transformation but also yield therapeutic benefits in advanced prostate cancers through activating anti-tumor immunity. Citation Format: Lin Zhou, Kelly D. DeMarco, Katherine C. Murphy, Zhenpeng Wu, Jinping Li, Junhui Li, Calvin Johnson, Zhong Jiang, Shi Bai, Tianyi Ye, Karl Simin, Lihua Julie Zhu, Jason R Pitarresi, Hong Wu, Marcus Ruscetti. P21-positive senescent stromal cells promote prostate cancer immune suppression and progression that can be reversed by senolytic therapy [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr C023.

Evaluating the efficacy of curcumin in the management of oral potentially malignant disorders: a systematic review and meta-analysis

Background Oral potentially malignant disorders (OPMDs) not only harbour the risk of malignant transformation but can also affect patients’ quality of life owing to severe symptoms. Therefore, there is an urgent need for therapeutic strategies to improve patients’ quality of life. The objective of this meta-analysis was to comprehensively assess the efficacy of curcumin in the management of OPMDs. Methods PubMed, Embase, the Cochrane Library, and Web of Science were searched for clinical trials evaluating the efficacy of curcumin in the treatment of OPMDs from inception until March 2024. RevMan 5.4 software was used to perform statistical and subgroup analyses. Results Sixteen randomised controlled trials (1,089 patients) were selected. Curcumin exhibited comparable efficacy to conventional controls in alleviating pain (I2 = 98%, P = 0.49) and improving tongue protrusion (I2 = 94%, P = 0.51) in oral submucous fibrosis (OSF). Additionally, topical use of curcumin had an efficacy equivalent to that of conventional therapy in reducing pain (I2 = 83%, P = 0.31) and facilitating clinical remission (I2 = 67%, P = 0.38) of oral lichen planus (OLP). Conclusion The topical use of curcumin may palliate pain and promote clinical healing in OLP patients. Systemic curcumin can ameliorate the degree of pain and tongue protrusion in OSF. Therefore, our study suggests that curcumin could serve as an alternative treatment for managing OPMDs with lower medical toxicity than steroids, especially when steroids are not suitable. Further studies with larger sample sizes and adequate follow-up periods are required to validate our results.

Eradication of proliferative verrucous leukoplakia with toll-like receptor 7 agonist (topical imiquimod): a case report

Proliferative verrucous leukoplakia (PVL) is an aggressive and distinct type of oral precancerous lesion characterized by warty surfaced white plaque diffusely involving oral mucosa. Surgical excision is the treatment of choice. However, PVL has persistent and recurrent growth patterns, requiring multiple surgical procedures. Surgical intervention is especially challenging if PVL extends between teeth limiting access. These interproximally located lesions have a high propensity to undergo malignant transformation. We report a case of a 53-year-old man with recurrent PVL diffusely covering the maxillary and mandibular gingiva. Despite complete surgical excisions, PVL recurred, and a focal area in the interproximal mandibular gingiva progressed to invasive squamous cell carcinoma requiring marginal resection. The remaining PVL areas were treated with topical imiquimod (toll-like receptor 7 agonist) for six months, resulting in complete clinical and histological resolution. Topical agents can cover a larger surface area and penetrate in between interproximal areas. Importantly, it allows for maximal local exposure with minimal systemic toxicity, essential for long-term treatment and prophylactic use of the agent to prevent relapse.

Haematogenous seeding in mycosis fungoides and Sézary syndrome: Current evidence and clinical implications.

Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of diseases characterised by abnormal neoplastic T-cell growth in the skin. Mycosis fungoides (MF), the most common CTCL, manifests as erythematous skin patches and/or plaques, tumours or erythroderma. The disease may involve blood, lymph nodes and rarely viscera. Sézary syndrome (SS) is a unique leukaemia/lymphoma syndrome related to MF, which presents with blood and skin involvement at diagnosis. The pathogenesis of MF/SS is not fully elucidated. The presence of skin lesions at distant sites underpins a hypothesis that MF/SS lesions may develop through haematogenous seeding. Phenotypic similarities between malignant and normal T-cells led to the notion that disease-initiating mutations occur in specific subtypes of mature T-cells, which are responsible for most CTCLs. However, this mature T-cell precursor model is not always consistent with clinical observations and research on MF/SS pathogenesis. Here, we review evidence supporting an alternative model of pathogenesis for MF/SS involving haematogenous seeding as a key process responsible for the initiation and progression of the disease. According to this hypothesis, malignant transformation occurs at an early stage of T-cell development (probably in bone marrow or thymus), yielding circulating neoplastic T-cells which colonise the skin where the microenvironment is most permissive for proliferation and evolution. These mutated precursor cells seed the skin where they find a suitable niche to develop into clinically perceptible disease. Subsequently, malignant T-cells can re-enter the bloodstream, re-seed pre-existing lesions and seed new areas of the skin, causing synchronous and convergent changes in the transcriptomic profile of lesions and tumours, and clinical disease progression - 'consecutive haematogenous seeding' captures this temporal phenomenon. This model radically changes the current understanding of CTCL pathogenesis, transforming it from a primarily cutaneous disease with secondary involvement of blood, to a systemic disease, where the spread of malignant cells through the blood to the skin is not a phenomenon of advanced disease but is an essential component of pathogenesis. This understanding of MF/SS could have several clinical implications, including standardising our approach to assessing blood tumour burden, potential advances in prognosis and monitoring, and investigating combination treatments to improve patient outcomes.

Abstract A016: YBX1 is a negative regulator of post-transcriptional program associated with invasion and metastasis in cSCC

Abstract Y-box binding protein 1 (YB-1), which is encoded by YBX1 gene, is a multifunctional cold-shock protein that binds both DNA and RNA to orchestrate transcription as well as RNA processing and translation. Recently, we demonstrated that YBX1 is a post-transcriptional effector required for the maintenance of epidermal homeostasis. Although it was well known that YBX1 plays prominent pro-oncogenic roles in malignant transformation and cell invasion in a wide variety of cancers, the role of YBX1 in cutaneous squamous cell carcinoma (SCC) is poorly understood. Here, we report that YBX1 protein level is higher in SCC tumor compared with non-neoplastic skin, but it goes down during tumor progression, in invasive and metastatic states. Indeed, both in vitro and in vivo experiments show that YBX1 acts as an antagonist of SCC progression, inhibiting its migration, invasiveness and metastasis. YBX1 is predominantly found in the cytoplasm of SCC cells. Therefore, we focused on the role of YBX1 as a posttranscriptional regulator and performed an eCLIP-seq (crosslinking immunoprecipitation sequencing) to identify its direct RNA targets. We found that YBX1 binds pro-invasive RNA associated with cell-cell and cell-matrix adhesions. From the integration of eCLIP-seq data with RNA-Bisulfite Seq data, an increased number of m5C modifications was observed to be located within the 3'UTR and CDS of tumor-enriched YBX1 target regions. Upon silencing of YBX1, polysome fractionation analysis revealed that YBX1 KD regulates targets involved in cancer motility, revealing that the loss of function of YBX1 promotes migration and invasion at the post-transcriptional Citation Format: Stefano Sol, Anna Mandinova, Fabiana Boncimino, Kristina Todorova, Emery Di Cicco, Toma Tebaldi, Giorgia Bucciarelli. YBX1 is a negative regulator of post-transcriptional program associated with invasion and metastasis in cSCC [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr A016.

HPB SO06 - An advanced clinical practitioner (ACP) led pancreatic cyst surveillance programme

Abstract Background The prevalence of pancreatic cysts (PCs), including intraductal papillary mucous neoplasms (IPMNs), has increased substantially over recent decades. This rising prevalence is due largely to the increasing volume and quality of medical imaging technology. Although PC's are often an incidental finding in asymptomatic individuals, a small number do harbour a certain malignant potential and thus raise warranted concern. The challenge therefore is identifying the high-risk lesions for early resection through robust, guideline-driven surveillance. To ensure a consistent and evidence-based approach to PC surveillance, our trust has adopted a dedicated surveillance programme led by an Advanced Clinical Practitioner (ACP) in gastroenterology. Method A PC surveillance clinic was designed and delivered from April 2023. The service underwent a formal inauguration and was promoted at the regional HPB MDT. All patients receive a standardised approach to surveillance in-line with the current international guidelines or regional MDT recommendation. Surveillance diagnostics are arranged by the ACP and patients are updated with regard to their results and next steps during a telephone or face-to-face consultation. A robust database was designed to capture relevant patient details and serve as a future research aid. Results 144 referrals have been received (04/23-04/24). 134 are undergoing surveillance, with discontinuation due to frailty, patient choice, diagnosis of an inflammatory cyst or relocation in 10 cases. Most PCs under surveillance are side-branch IPMNs (70.9%). Malignant transformation has not yet been observed, however 18 cases display worrisome features and 3 have high-risk stigmata. These are undergoing intensive surveillance or awaiting MDT discussion. 93% of surveyed patients (16) report a greater sense of involvement in their PC surveillance and a greater awareness of their surveillance protocol (93%). Referrer feedback (7) has been positive and staff are satisfied with this service (100%). Conclusion Robust surveillance of patients with PC will likely improve early detection and prognosis of pancreatic cancer by enabling early identification of resectable cases. A centralised service that adopts a single agreed guideline will reduce variation in the management of these cysts, ensure these complex lesions are under specialist observation and offer a single point of contact which will improve retainment and follow-up of these patients. It is intended that synchronous data collection will serve to generate a comprehensive repository of information relating to PC. This databases will aid future research into this evolving field and steer future guideline development.

Case report: Metastatic melanoma derived from a somatic-type malignant transformation of a mediastinal teratoma treated with immune checkpoint inhibitors

The treatment of patients affected by a teratoma with somatic-type malignancy (STM) is challenging, since they are characterized by a poor prognosis, due to chemoresistance to standard cisplatin-based regimens. Only five more case reports were described for melanomatous STM and for which there are no data available for efficacy evidences of immune checkpoint inhibitors in this setting. Here we report the case of a patient with an initial diagnosis of mediastinal pure seminoma at the first biopsy. After four cycles of a standard cisplatin-based regimen and a partial response, a radical surgery was performed, revealing a mediastinal teratoma with triple STM component (melanoma, leiomyoarcoma and primitive neuroectodermal tumor). However, during post-surgical follow-up, he developed distant metastases from the melanomatous component and a first-line treatment with immune checkpoint inhibitors (ICI) was started.

OGC SO26 - Double tract reconstruction post total gastrectomy enables duodenal surveillance in familial polyposis: Case report

Abstract Background Familial polyposis syndromes such as Juvenille polyposis syndrome (JPS) and Familial adenomatous polyposis (FAP) are associated with ∼21% and ∼11% lifetime risk of foregut carcinoma respectively. In patients effected, routine oesophago-gastro-duodenoscopy (OGD) is recommended every 1-3 years, in JPS from 15 years old and in FAP from 25 years old. In patients with malignant transformation traditional resection with Roux-en-Y reconstruction inhibits future duodenoscopy. Method Between April and July 2024 two patients presented requiring total gastrostomy with familial polyposis syndromes. In both cases laparoscopic total gastrectomy with double tract reconstruction was decided upon to enable future duodenal surveillance. Results Case 1: 45 year old female with JPS (germline SMAD 4 mutation). Surveillance detected a massive circumferential proximal gastric polyp comprising ∼30% of total gastric mucosa, too large for endoscopic therapy. Biopsies showed JPS polyps. Patient had no early complications following laparoscopic total gastrectomy and a post operative barium swallow showed clear passage of contrast down the double tract. Case 2: 61 year old male with FAP (germline APC mutation). Surveillance detected innumerable fundic gland polyps with histology demonstrating multifocal high grade dysplasia. Previous subtotal colectomy Planned for laparoscopic total gastrectomy with double tract reconstruction in July 2024 Conclusion Roux-en-Y reconstruction is the most common reconstruction following total gastrectomy. However, in patients with familial polyposis syndromes ongoing lifelong duodenal surveillance is critical. In such patients double-tract reconstruction instead of Roux-en-Y may be preferable allowing future duodenoscopy and acceptable remnant foregut function.

Abstract A065: Estimation of HPV16-induced cervical cancer cells in routine Thin-prep cytology samples of cancer patients

Abstract Persistent infection with human papillomavirus has been implicated in the etiology of cervical cancer and sustained expression of its E7 oncoprotein has been rendered suggestive of malignant transformation. However, there are limited E7 protein-based detection assays. This might be due to paucity of data on steady-state expression level of E7 protein and the number of HPV-induced cervical cancer cells in routine Thin-prep cytology samples. So, the objective of the present study was to identify and estimate HPV16-induced cervical cancer cells in cytology samples of cancer patients, with the goal to generate a quantitative immunological method in the cytological diagnosis of cervical lesions. We collected 25 Thin-prep cytology samples of cervical cancer patients (PAP test confirmed) from Obstetrics and Gynecology department, AIIMS, New Delhi. Samples were conditioned to enrich cellular components and were then quantified using hemocytometer for total cell count, PAP staining for cancerous cell count and immunofluorescence using HPV16 E7 antibody for HPV16-induced cancerous cell count. The method devised efficiently found an average number of 7 × 103 cells/ ml to be E7 positive, out of total 27 x 104 cells/ ml. Although PAP test detected 71 x 103 cells/ ml to be abnormal or cancerous, only 10% of them were found to be HPV16 transformed, suggesting HPV E7 as the primary marker for detecting transformed cells and thereby, identifying patients at-risk and prompting a better prognosis. This simple and efficient method deduced allows optimizing the number of HPV16-induced cervical cancer cells from cytology samples which directly correlates to the amount of HPV-16 major oncoprotein- E7 expression, and the disease severity. Citation Format: Srishty Raman, Pranay Tanwar, Neerja Bhatla, Subhash Chandra Yadav. Estimation of HPV16-induced cervical cancer cells in routine Thin-prep cytology samples of cancer patients [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A065.

Abstract B037: Disks large-associated protein 5 (DLGAP5) is a putative prognostic biomarker for intraductal papillary mucinous neoplasm (IPMN) of pancreas

Abstract Pancreatic cancer is one of the deadliest malignant diseases, accounting for nearly 500,000 deaths worldwide each year. One of the pancreatic cancer precursors are mucinous pancreatic cystic lesions (PCL). Although only a minority of these PCLs undergo malignant transformation, the clinical significance is considerable, particularly given the prevalence of up to 45% in individuals over the age of 65. The most prevalent type of neoplastic PCL is intraductal papillary mucinous neoplasm (IPMN) and the management of different IPMN grades varies, with high- grade dysplasia and invasive carcinoma being indicated for surgery. However, the current guidelines for patient stratification are limited and often lead to either overtreatment or undertreatment, both of which are associated with high mortality and morbidity. Therefore, there is a pressing need to identify biomarkers associated with progression of IPMN from low to high grade that can be used for more accurate lesion assessment. Here we identified a novel biomarker highly correlated with IPMN progression – DLGAP5. Both mRNA as well as protein expression of DLGAP5 is positively associated with increased grade of IPMNs as determined by analysis of patient derived tumor samples. Additionally, in vitro experiments confirmed that knock down of DLGAP5 in pancreatic cancer cells leads to reduction of cell proliferation, and conversely, overexpression of DLGAP5 in IPMN precursor cells resulted in increased proliferation. Since one of the functions of DLGAP5 is microtubule stabilization, we hypothesized that the secretome of IPMN precursor cells will be altered by the expression of DLGAP5. Indeed, our mass spectrometry-based analysis of secreted proteins identified several hits (e.g. DKK1) that were correlated with DLGAP5 expression and were previously confirmed to be present in IPMN cyst fluid in patients. Subsequently, we aim to validate the correlation of the putative biomarkers in IPMN cyst fluid and serum with IPMN grade and patients’ clinical outcome in a prospective manner. To sum up, we validated DLGAP5 as an IPMN-progression biomarker and identified several secreted proteins that could serve as DLGAP5-surrogate biomarkers for stratification of the patients with IPMN and subsequent treatment optimalization. Citation Format: Radoslav Janostiak, Peter Mačinga, Lucia Csergeová, Ondřej Fabián, Eva Sticová, Jiří Zahradník, Martin Květoň, Tomáš Hucl. Disks large-associated protein 5 (DLGAP5) is a putative prognostic biomarker for intraductal papillary mucinous neoplasm (IPMN) of pancreas [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B037.

Mature cystic teratoma with malignant transformation: A rare case report

Mature cystic teratoma with malignant transformation: A rare case report

The Correlation Patterns of miRNA Expression with Targeted mRNA Transcripts in Glioma Patients with Wild-Type and Mutated Isocitrate Dehydrogenase (IDH) Genotypes.

Low-grade gliomas are divided into two main genetic phenotypes based on the presence or absence of mutations in the isocitrate dehydrogenase (IDH) genes. The mutated IDH phenotype (IDHmut), in contrast to the wild-type phenotype (IDHwt), is characterized by a more positive response to pharmacological intervention and a significantly longer survival time. In this study, we analyzed the differential co-expression of 225,000 microRNA-mRNA pairs at the level of correlations between microRNA levels and their potential mRNA targets. Analysis of the associative relationships of individual representatives of the selected pairs revealed that the level of mRNAs encoded by the ELN, ARL4C, C9orf64, PLAT, and FKBP9 genes associated with aggressive progression of glioma was increased in the IDHwt group. Meanwhile, the levels of miRNA-182, miRNA-455, and miRNA-891a associated with the negative prognosis in glioma were generally increased in the IDHmut group. Most (16/21) of the detected 21 microRNA-mRNA pairs with significant difference in regulation between IDHwt and IDHmut glioma samples had a weak or moderate positive correlation in IDHmut samples and a negative correlation in IDHwt samples. Therefore, our findings indicate that glioma samples from the IDHmut group with a positive prognosis potentially have a significantly less pronounced ability to microRNA-mediated regulation. We further suggest that such physiological disorders can lead to reduced tumor viability, resulting in an increased ability of the host to resist the spread of a malignant transformation of this genetic phenotype.

Lichen planus-the role of age and gender in clinical appearance and treatment : Anarrative review.

Lichen planus is acommon pruritic inflammatory disorder of the skin with an autoimmune background. It affects < 1% of the general population. The disease has significant comorbidities that must be considered in aholistic approach. Skin and skin adnexa, mucosa, eyes, and the esophagus may be affected. There are various clinical subtypes in addition to classical cutaneous lichen planus. These subtypes depend on age and gender. Nail involvement can result in functional and psychological impairment. Lichen planopilaris in adults leads to irreversible cicatrical alopecia. Erosive and ulcerated lichen planus of the mucosa carries an increased risk of malignant transformation, at least in adults. Treatment must consider the affected area, the severity of disease, age, gender, and comorbidities.

Refining MRI Protocols for Endometriosis: A Comparative Study of Abbreviated and Full MRI Sequences.

Endometriosis is a significant cause of chronic abdominal pain and infertility in females, often overlooked due to its resemblance to other abdominopelvic pathologies. This study aims to compare the diagnostic performance and agreement rate between an abbreviated MRI protocol (aMRI) and a full MRI protocol (fMRI) for detecting pelvic endometriosis. We retrospectively analyzed 446 consecutive MRI exams, including both full (fMRI) and abbreviated (aMRI) protocols, performed for suspected pelvic endometriosis. An expert radiologist assessed the presence of endometriosis at 14 distinct anatomical sites. Each MRI protocol was interpreted in random order, with a minimum two-week interval between sessions to minimize recall bias. Agreement between the protocols was evaluated using kappa statistics. The average age of the patients was 34.13 years. The highest incidences of endometriosis were found in the ovaries (88.8%) and the rectouterine pouch (65%). The MRI protocols demonstrated perfect agreement (kappa coefficient = 1) for the ovaries, bladder, uterus, and cesarean section scar. High agreement was also observed in the rectum and uterine ligaments (kappa coefficients of 0.98 and 0.97). Detection of malignant transformation in existing ovarian endometriomas showed substantial concordance with a kappa coefficient of 0.66. An abbreviated non-contrast MRI protocol exhibits diagnostic accuracy comparable to that of a comprehensive protocol in detecting pelvic endometriosis, with similar confidence and reproducibility. This study demonstrates that an abbreviated MRI protocol is as effective as a full protocol in diagnosing pelvic endometriosis, potentially allowing for quicker, cost-effective imaging without compromising diagnostic accuracy.

NIMG-36. PERFUSION, DIFFUSION, AND ANATOMICAL MRI BIOMARKERS FOR ASSESSING HISTOLOGICALLY-CONFIRMED MALIGNANT TRANSFORMATION IN MOLECULAR SUBTYPES OF IDH-MUTANT GLIOMAS

Abstract BACKGROUND Isocitrate dehydrogenase-mutant (IDHm) gliomas often initially present as low-grade (grade 2) gliomas but are expected to later progress into more aggressive higher-grade (grade 3-4) gliomas through malignant transformation (MT). MT is often determined non-invasively by emergence of contrast-enhancement on post-contrast T1-weighted magnetic resonance imaging (MRI), but contrast-enhancement is an imperfect surrogate for histologically-confirmed MT. This study explored perfusion, diffusion, and anatomical MRI biomarkers besides contrast-enhancement to study histologically-confirmed MT in IDHm 1p/19q-intact astrocytomas (IDHm-A) and IDHm 1p/19q-co-deleted oligodendrogliomas (IDHm-O). METHODS N=64 patients with initial histopathological grade 2 IDH-mutant glioma diagnosis who underwent repeated tissue sampling and were classified as histologically-confirmed MT (n=35) or non-MT (n=29) were retrospectively studied. Pre-surgical anatomical MRI (n=64) and, if available, diffusion-weighted imaging (n=61) and dynamic susceptibility contrast perfusion MRI (n=53) were analyzed. Tumor volumes of interest were segmented on the whole T2/FLAIR-hyperintense tumor. Measurable contrast enhancement (&amp;gt;1000mm3), tumor volume, sphericity, median apparent diffusion coefficient (ADC), and normalized relative cerebral blood volume (nrCBV) were compared between MT vs. non-MT IDHm-A and IDHm-O. RESULTS 81% of contrast-enhancing IDHm-A and 100% of contrast-enhancing IDHm-O underwent MT, while 41% of MT IDHm-A and 62% of MT IDHm-O were non-enhancing. Tumor volumes were significantly larger in the MT vs. non-MT groups for both IDHm-A (P=0.02) and IDHm-O (P=0.04). Whole tumor nrCBV was significantly higher (P=0.002), whole tumor ADC trended lower (P=0.06), and non-enhancing tumor sphericity was significantly lower (P=0.03) in MT vs. non-MT IDHm-A. There were no significant differences in ADC, nrCBV, nor sphericity when comparing MT vs. non-MT IDHm-O (P&amp;gt;0.05). CONCLUSIONS Many MT IDHm-gliomas remain non-enhancing. Tumor volumes can determine MT for both IDHm-A and IDHm-O. Diffusion and perfusion MRI show differences for MT in IDHm-A but not IDHm-O, which may reflect the different tumor biology of these IDHm molecular subtypes and their need for separate imaging biomarkers.

Malignant transformation of vestibular schwannoma 29 years after Gamma Knife radiosurgery: illustrative case.

Vestibular schwannomas are common posterior fossa tumors, often managed with stereotactic radiosurgery (SRS) due to its low invasiveness and high tumor control rates. However, malignant transformation of vestibular schwannoma (MTVS) is a rare but serious complication with a poor prognosis. The authors present a case of MTVS occurring 29 years after initial SRS, the longest latency reported. A 68-year-old woman developed sudden facial nerve paralysis, with magnetic resonance imaging revealing tumor regrowth. Surgical removal and histopathological analysis confirmed malignant transformation, characterized by spindle-shaped atypical cells and significant p53 positivity. Despite multiple surgeries and radiation therapy, the tumor exhibited rapid regrowth and cerebrospinal dissemination, leading to a poor prognosis. This case underscores the critical importance of long-term monitoring after SRS, as malignant transformation can occur decades later. Additionally, it highlights the potential necessity for early intervention during malignant transformation to improve patient outcomes, despite the challenges in identifying effective treatments for MTVS. https://thejns.org/doi/10.3171/CASE24526.