Adult Tumors Research Articles

Salivary Gland Tumours in Children and Adolescents-A Study in Shaheed Monsur Ali Medical College & Hospital, Uttara, Dhaka, Bangladesh

Introduction: Salivary gland carcinomas (SGCs) are rare neoplasms in adults, but are exceedingly infrequent in children, with a reported annual incidence of 0.8–1.4 per million populations under 20 years old. Like other pediatric very rare tumors, SGCs in children and adolescents often present diagnostic and therapeutic challenges for pathologists, surgeons, and pediatric oncologists. Objective: To assess the salivary gland tumours in children and adolescents. Methods: A cross-sectional observational study was carried out at Dept. of ENT, Shaheed Monsur Ali Medical College & Hospital, Uttara, Dhaka, Bangladesh from January to June 2023. Total 60 patients included in our study. Our pre-operative clinical diagnoses were based on size, shape, mobility, fixity of the tumour to the underlying structures, ulceration of overlying skin, involvement of facial nerve by its malignant transformation and fine needle aspiration cytology. All patients, or their guardians, gave their informed consent for data collection within the national rare tumour group and analysis. Results: Total sixty (60) cases of salivary gland tumours were available for our study. Out of 55% were male and 45% were female patients. Incidence of tumours is highest in the age group of 41-50 with 13 cases (21.6% of the total). The least affected age group was the 0-10 group with only one patient (3.3%). Women accounted for 16 cases of the total 33 benign neoplasias (55% of the total). Of the 33 benign tumour, 18 were in males (54.5% of all benign tumours) and 15 were in females (45.5%). Total 60 operated cases). Of these, 32 were pleomorphic adenomas (53.3%) and 1 was an adenolymphoma (1.6%). the total number of malignant tumours confirmed by HPE were 27 (45%). Of these, most numerous was adenoid cystic carcinoma in 8 cases (13.3%). squamous cell carcinoma and muco epidermoid carcinoma were found in 6 cases each (10%). There were 4 and 3 cases of adenocarcinoma (6.6%) and acinic cell carcinoma (5%) respectively. The parotid glands were also the sole location for the 3 acinic cell carcinomas. No tumours were found in the sublingual gland. The majority of the tumours found in the parotid gland were benign tumours, mainly pleomorphic adenomas with 24 cases (75% of the total parotid tumours). Conclusions: The tumours were equally distributed between males and females. The tumours were most commonly found in the third to fifth decades of life. The most common benign tumour and the most common tumour overall was pleomorphic adenoma making up 54.5% of all tumours. Surgical excision was the most commonly done treatment. The most commonly done surgical procedure was superficial parotidectomy.

Unusual Presentation: Nephroblastoma/Wilms tumor in an Adult – A Case Report

Abstract Introduction/Objective Nephroblastoma/Wilms tumor is a common renal tumor primarily observed in children, and its occurrence in adults is exceedingly rare. This rarity contributes to the diagnostic challenges encountered in adults. Here, we present a case of a 32-year-old male diagnosed with biphasic nephroblastoma/Wilms tumor in the kidney, with liver and lung metastases. Methods/Case Report A 32-year-old male, without significant past medical history, presented with the chief complaint of abdominal pain for 2-3 weeks. Imaging studies revealed a substantial 17.5 cm kidney lesion accompanied by numerous lung and liver lesions. A liver biopsy indicated a small blue cell tumor, morphologically and immunophenotypically, (positive WT1) resembling nephroblastoma, with a strong suspicion of metastasis. Subsequent kidney biopsy confirmed a small blue cell malignant tumor demonstrating biphasic features, including blastema and epithelial components forming tubular structures similar to the liver biopsy, predominantly showing the blastemal component. The renal tumor biopsy supported the diagnosis of nephroblastoma. Despite chemotherapy, the patient passed away two months after the initial liver tumor biopsy. Results (if a Case Study enter NA) NA Conclusion Diagnosing nephroblastoma in adults poses significant challenges, particularly when initial presentations involve metastases. The occurrence of pediatric tumors in adulthood, though rare, should be considered in the diagnostic process after exhausting other possibilities. It is also important to note that the clinical presentation of pediatric tumors in adults may deviate from typical patterns. While Wilm’s tumor commonly presents as a painless, palpable abdominal mass in pediatric cases, adults may exhibit abdominal pain as the predominant symptom, as present in our case.

Audit of oral neoplasms in children and young adults in Nigeria

BackgroundOrofacial neoplasms in children and young adults may differ significantly from those observed in adults. Our aim was to describe the epidemiological characteristics of histologically diagnosed orofacial neoplasms among children and young adults in Nigeria.MethodsThis was a multicenter cross-sectional study across geopolitical zones in Nigeria. Annual reports of clinical information and surgical biopsies submitted at the Oral Pathology Laboratory, clinic day registries, surgical day case registries and operative theatre registries were retrieved from January 2008 to March 2024. The relevant demographic data were obtained for each patient. The study subjects were categorized by age into children, adolescents and young adults. Tissue involvement was classified as soft tissue involvement, bony involvement or both soft tissue and bony involvement. The site and behaviour of the lesions were subdivided according to the ICD-10 codes. Statistical analysis was performed via the R programming language.ResultsA total of 1889 cases were observed during the period under review, with a mean age of 15 years. Cases were more common in females (52%) and in young adults (47%). Most cases were benign neoplasms (85%), and bony affectation (54%) was slightly predominant. Odontogenic tumours (38%) and fibro-osseous lesions (20%) were the most common category of lesions observed, whereas salivary gland tumours (2.2%) and neoplasms of epithelial origin (2.5%) were the least common. Neoplasms in children involved mostly soft tissues, whereas those in adolescents and young adults had a preference for bone (p < 0.001). In all age groups, benign lesions were mostly observed in the mouth and pharynx. For malignant lesions, in children, the bones of the skull and face were mostly involved, whereas in adolescents, the mandible was the predominant site (p < 0.001). In children, mesenchymal neoplasms were the most prevalent category of lesions, whereas in both adolescents and young adults, odontogenic tumours were more common. The proportion of malignant neoplasms in males was significantly greater than that in females (p < 0.001).ConclusionThis study revealed that although most biopsied orofacial lesions were more often benign, the proportion of malignant neoplasms in this population was greater than that previously reported.

Imaging Recommendations for Diagnosis, Staging, and Management of Primary Central Nervous System Neoplasms in Adults

Central nervous system (CNS) neoplasms are a vast and diverse group of tumors in adults with variable prognoses depending on histology and increasingly understood molecular features. There has been a major paradigm shift in the approach towards these neoplasms ever since the implications of these molecular features have been recognized. Gliomas are the major group of primary CNS neoplasms in adults, and glioblastomas are a significant cause of morbidity and mortality, especially in older patients. Apart from gliomas, meningiomas and pituitary tumors are other major groups. This review aims to elucidate the role of imaging in the screening, diagnosis, management, and follow-up of major primary CNS neoplasms, with an elaborate discussion on the role of artificial intelligence and advanced imaging techniques and future directions likely to play a pivotal role in this ever-evolving subspecialty of oncology.

Association between ABO blood groups and hematological myeloid neoplasms in adolescents and adults.

Prior research suggests a potential link between ABO blood types and susceptibility to various malignancies. The correlation between ABO blood types and hematological myeloid neoplasms, however, remains inadequately explored. This study investigates the association between ABO blood groups and the incidence of hematological myeloid neoplasms in adolescents and adults. In this retrospective clinical study, 1,022 adolescent and adult cases of myeloid neoplasms diagnosed at our institution were initially considered. After excluding conditions potentially linked to ABO blood types from prior studies, 792 eligible cases were analyzed. These cases were categorized based on disease subtypes and compared with a control group for blood type distribution. Our findings reveal a significantly higher prevalence of blood type A in patients with myeloid neoplasms compared to the control group, except for chronic myelocytic leukemia and myeloproliferative neoplasms. Conversely, the prevalence of blood type AB in myeloid neoplasms was notably lower than in the control group. The study suggests a potential association between ABO blood types and the risk of developing hematological myeloid neoplasms in adolescents and adults. Further research is warranted to elucidate the underlying mechanisms of this relationship.

Clonal monocytosis of renal significance

Clonal monocytosis reflects a preneoplastic or neoplastic sustained increase in the absolute monocyte count in the absence of reactive causes. Causes of clonal monocytosis include clonal cytopenias with monocytosis and acute and chronic myeloid neoplasms. Chronic myelomonocytic leukemia is a prototypical myelodysplastic/myeloproliferative overlap neoplasm in adults, characterized by sustained peripheral blood monocytosis. Renal abnormalities, including acute kidney injury and chronic kidney disease, are frequent in patients with chronic myelomonocytic leukemia and are predictors of worse outcomes. In addition, acute kidney injury/chronic kidney disease often limits eligibility for allogeneic stem cell transplantation or enrollment in clinical trials. In this review, we highlight clonal monocytosis-related etiologies that give rise to acute kidney injury and chronic kidney disease, with special emphasis on chronic myelomonocytic leukemia and lysozyme-induced nephropathy. Monocytes produce lysozyme, which, in excess, can accumulate in and damage the proximal renal tubular epithelium. Early identification of this etiology and a timely reduction in monocyte counts can salvage renal function. Other etiologies of renal injury associated with clonal monocytosis include direct renal infiltration by monocytes, renal extramedullary hematopoiesis, myeloproliferative neoplasm-associated glomerulopathy, autoimmune (membranous nephropathy, minimal change disease) and paraneoplastic manifestations, thrombotic microangiopathy, obstructive nephropathy due to myeloproliferation, and urate nephropathy due to tumor lysis syndrome. We propose to group these mechanistic etiologies of renal injury as clonal monocytosis of renal significance and provide guidance on their diagnosis and management.

Locoregional Treatments in Peritoneal Metastasis from Gastric Cancer

Background: Liver cancer is among the top five causes of cancer death globally. Hepatocellular Carcinoma (HCC) accounts for up to 90% of primary liver neoplasms in adults. The incidence of thyroid me-tastasis from HCC is rare and estimated from 0.8 to 12%. This report describes a 51-year-old man presenting with hypercalcemia and known metastatic HCC with new metastasis to the thyroid gland. Case Report: A 51-year-old male was admitted due to symptomatic hypercalcemia. His medical history included HCC with metastasis to the retroperitoneal lymph nodes diagnosed one year prior. Computed tomography revealed an enlarging liver mass, diffuse lymphadenopathy and many osseous lytic lesions. Ultrasound of the neck revealed abnormal right cervical lymph nodes and a heterogeneous mass replacing the right thyroid gland. Biopsy of the right cervical lymph node immunohistochemical stained positive for PAN-K, Glypican-3, HepPar1 and Anti-Arginase and negative for p40 and CEA-poly, supporting the diagnosis for metastatic HCC. His hospital course was complicated by dysphagia, spontaneous bacterial peritonitis and acute-on-chronic liver failure. Despite aggressive resuscitation, he continued to decline and ultimately pursued hospice care. Conclusion: This case illustrates the need to have a high index of suspicion for thyroid metastasis in HCC patients presenting with a new-onset cervical mass, dysphagia or hypercalcemia. Metastatic cancer to the thyroid gland is generally considered a poor prognostic factor, as seen in this case with the rapid decline. This case demonstrates an extremely rare presentation of HCC with metastasis to the thyroid gland.

Brain Metastases in Differentiated Thyroid Cancer: Clinical Presentation, Diagnosis, and Management.

Background: Brain metastases (BM) are the most common intracranial neoplasms in adults and are a significant cause of morbidity and mortality. The brain is an unusual site for distant metastases of thyroid cancer; indeed, the most common sites are lungs and bones. In this narrative review, we discuss about the clinical characteristics, diagnosis, and treatment options for patients with BM from differentiated thyroid cancer (DTC). Summary: BM can be discovered before initial therapy due to symptoms, but in most patients, BM is diagnosed during follow-up because of imaging performed before starting tyrosine kinase inhibitors (TKI) or due to the onset of neurological symptoms. Older male patients with follicular thyroid cancer (FTC), poorly differentiated thyroid cancer (PDTC), and distant metastases may have an increased risk of developing BM. The gold standard for detection of BM is magnetic resonance imaging with contrast agent administration, which is superior to contrast-enhanced computed tomography. The treatment strategies for patients with BM from DTC remain controversial. Patients with poor performance status are candidates for palliative and supportive care. Neurosurgery is usually reserved for cases where symptoms persist despite medical treatment, especially in patients with favorable prognostic factors and larger lesions. It should also be considered for patients with a single BM in a surgically accessible location, particularly if the primary disease is controlled without other systemic metastases. Additionally, stereotactic radiosurgery (SRS) may be the preferred option for treating small lesions, especially those in inaccessible areas of the brain or when surgery is not advisable. Whole brain radiotherapy is less frequently used in treating these patients due to its potential side effects and the debated effectiveness. Therefore, it is typically reserved for cases involving multiple BM that are too large for SRS. TKIs are effective in patients with progressive radioiodine-refractory thyroid cancer and multiple metastases. Conclusions: Although routine screening for BM is not recommended, older male patients with FTC or PDTC and distant metastases may be at higher risk and should be carefully evaluated for BM. According to current data, patients who are suitable for neurosurgery seem to have the highest survival benefit, while SRS may be appropriate for selected patient.

Clinical utility of a blood based assay for the detection of IDH1.R132H-mutant gliomas

Glioma represents the most common central nervous system neoplasm in adults. Current classification scheme utilizes molecular alterations, particularly IDH1.R132H, to stratify lesions into distinct prognostic groups. Identification of the single nucleotide variant through traditional tissue biopsy assessment poses procedural risks and does not fully reflect the heterogeneous and evolving tumor landscape. Here, we introduce a liquid biopsy assay, mt-IDH1dx. The blood-based test allows minimally invasive detection of tumor-derived extracellular vesicle RNA using only 2 ml plasma volume. We perform rigorous, blinded validation testing across the study population (n = 133), comprising of IDH1.R132H patients (n = 80), IDH1 wild-type gliomas (n = 44), and age matched healthy controls (n = 9). Results from our plasma testing demonstrate an overall sensitivity of 75.0% (95% CI: 64.1%–84.0%), specificity 88.7% (95% CI: 77.0%–95.7%), positive predictive value 90.9%, and negative predictive value 70.1% compared to the tissue gold standard. In addition to fundamental diagnostic applications, the study also highlights the utility of mt-IDH1dx platform for blood-based monitoring and surveillance, offering valuable prognostic information. Finally, the optimized workflow enables rapid and efficient completion of both tumor tissue and plasma testing in under 4 hours from the time of sampling.

Imaging Recommendations for Diagnosis, Staging, and Management of Central Nervous System Neoplasms in Adults: CNS Metastases.

To identify cancer patients at a higher risk of developing CNS metastases and to evaluate associated prognostic factors. Review of imaging referral guidelines, response criteria, interval imaging assessment, modality of choice, as well as the association of clinical, serological, and imaging findings as per various cancer societies. Quantitative response assessment of target and non-target brain metastases as well as an interval imaging protocol set up based on primary histological diagnosis and therapy status are discussed as per various cancer societies and imaging programs. Predictive factors in the primary tumor as well as independent variables of brain metastases like size, number, and response to therapy are necessary in management. The location of CNS metastases, symptomatic disease, as well as follow up imaging findings form a skeletal plan to prognosticate the disease, keeping in mind all the available new advanced therapy options of surgery, radiation, and immunotherapy that improve patient outcome significantly.

Shared Care Planning for a pregnant patient with uveal melanoma treated with interventional radiotherapy (brachytherapy)

Introduction: Uveal melanoma (UM) is the most prevalent primary intraocular tumor in adulthood, with an important risk of metastasis, notably to the liver, rendering standard chemotherapy ineffective. Cases of UM onset during pregnancy are rare but can exhibit accelerated tumor growth. For these cases the best conservative treatment is interventional radiotherapy (IRT) also known as brachytherapy (BT). It is a form of radiotherapy that demonstrates efficacy comparable to the more common enucleation, while mitigating any risks of intrauterine toxicity. Objective: We reported the case of M., a 39-year-old pregnant patient, diagnosed with UM and undergoing brachytherapy treatment. Our aim is to make pertinent ethical considerations about: a. The ethical and clinical approach favouring a treatment strategy that preserves the affected organ and its functionality, b. The advance care planning process conducted within a multidisciplinary team. Case discussion: With the objective of preserving the mother’s health and ensuring the protection of the foetus, the team unanimously agreed, through a collaborative decision-making process, to proceed with the viable brachytherapy intervention. This approach results in a lower burden and maximizes benefits for both the patient and the unborn child. Conclusions: Considering a holistic evaluation, especially considering the patient’s pregnancy, the multidisciplinary approach proves fundamental. Collaboration between bioethicists and health-care professionals facilitated the development of a shared document for healthcare ethics planning, expressing the team’s ethical-clinical considerations.

Prevalence of Hospitalizations for Malignant Brain Neoplasms in Adults in the Last 5 Years in the Brazilian Territory

Prevalence of Hospitalizations for Malignant Brain Neoplasms in Adults in the Last 5 Years in the Brazilian Territory

Current status of precision oncology in adult glioblastoma.

The concept of precision oncology, the application of targeted drugs based on comprehensive molecular profiling, has revolutionized treatment strategies in oncology. This review summarizes the current status of precision oncology in glioblastoma (GBM), the most common and aggressive primary brain tumor inadults with a median survival below 2 years. Targeted treatments without prior target verification have consistently failed. Patients with BRAF V600E-mutated GBM benefit from BRAF/MEK-inhibition, whereas targeting EGFR alterations was unsuccessful due to poor tumor penetration, tumor cell heterogeneity, and pathway redundancies. Systematic screening for actionable molecular alterations resulted in low rates (< 10%) of targeted treatments. Efficacy was observed in one-third and currently appears to be limited to BRAF-, VEGFR-, and mTOR-directed treatments. Advancing precision oncology for GBM requires consideration of pathways instead of single alterations, new trial concepts enabling rapid and adaptive drug evaluation, a focus on drugs with sufficient bioavailability in the CNS, and the extension of target discovery and validation to the tumor microenvironment, tumor cell networks, and their interaction with immune cells and neurons.

A green and highly sensitive microwell spectrofluorimetric method with high throughput for the determination of pemigatinib based on dual fluorescence enhancement by photoinduced electron transfer blocking and micellization: Application to the analysis of tablets, content uniformity testing, and human plasma.

Pemigatinib (PGT) is a recently FDA-approved small molecule kinase inhibitor used for the treatment of relapsed or refractory myeloid/lymphoid neoplasms in adults. This study introduces the development of a first microwell spectrofluorimetric method (MW-SFM) for quantifying PGT in FDA-approved tablets and plasma samples. The method utilized the enhancement of PGT's weak native fluorescence by blocking photoinduced electron transfer (PET) and micellization with sodium lauryl sulfate (SLS). The MW-SFM was performed in 96-microwell plates, and fluorescence signals were measured using a fluorescence microplate reader with excitation at 290 nm and emission at 350 nm. The method exhibited a linear range of 2-250 ng mL-1, and a limit of quantitation was 6.5ng mL-1. The accuracy and precision of the method were confirmed with recovery rates ranging from 96.5% to 102.8% and relative standard deviations of 1.52% to 3.51%. The MW-SFM successfully analyzed Pemazyre® tablets, assessed content uniformity, and analyzed PGT-spiked human plasma samples. The greenness of the MW-SFM was verified using three different metric tools. In conclusion, the proposed MW-SFM is a valuable tool in supporting quality assessment of dosage forms, conducting pharmacokinetic studies, and monitoring therapeutic outcomes.

Radioligand therapies in meningioma - evidence and future directions.

Meningiomas are the most common intracranial neoplasms in adults. While most meningiomas are cured by resection, further treatment by radiotherapy may be needed, particularly in WHO grade 2 and 3 tumors which have an increased risk of recurrence, even after conventional therapies. Still, there is an urgent need for novel therapeutic strategies after exhaustion of local treatment approaches. Radionuclide therapies combine the specificity of tumor-specific antibodies or ligands with the cytotoxic activity of radioactive emitters. Alongside, integrated molecular imaging allows for a non-invasive assessment of predictive biomarkers as treatment targets. Whereas the concept of "theranostics" has initially evolved in extracranial tumors such as thyroid diseases, neuroendocrine tumors, and prostate cancer, data from retrospective case series and early phase trials underscore the potential of this strategy in meningioma. This review aims to explore the available evidence of radionuclide treatments and ongoing clinical trial initiatives in meningioma. Moreover, we discuss optimal clinical trial design and future perspectives in the field, including compound- and host-specific determinants of the efficacy of "theranostic" treatment approaches.

PROGNOSTIC MODELS FOR CHRONIC LYMPHOCYTIC LEUKEMIA (CLL): A TEN-YEAR SYSTEMATIC REVIEW

Background: CLL is the most common malignant neoplasm of aging adults in Western populations. CLL is a hematology malignancy defined by the continuous proliferation of monoclonal B lymphocytes in bone marrow, peripheral blood, and lymphoid organs that have a specific immunophenotype. Clinical outcomes for patients with CLL are heterogeneous, leading to the development of prognostic factors. CLL-IPI is a commonly used tool for predicting outcomes. The aim: This study aims to determine the prognostic models for CLL. Methods: By comparing itself to the standards set by the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020, this study was able to show that it met all of the requirements. So, the experts were able to make sure that the study was as up-to-date as it was possible to be. For this search approach, publications that came out between 2014 and 2024 were taken into account. Several different online reference sources, like Pubmed, SAGEPUB, and ScienceDirect, were used to do this. It was decided not to take into account review pieces, works that had already been published, or works that were only half done. Results: In the PubMed database, the results of our search brought up 27 articles, whereas the results of our search on SAGEPUB brought up 415 articles, our search on ScienceDirect brought up 742 articles. In the end, we included four research that met the criteria. Conclusion: In conclusion, of the five models, the CLL-IPI shows the best predictive performances. However, further research is needed.

Features and Factors Associated With Myeloid Neoplasms After Chimeric Antigen Receptor T-Cell Therapy

This case-control study examines the incidence and risks of myeloid neoplasms in adults treated for B-cell lymphoproliferative disorders or multiple myeloma.

The Prognostic Role of Volumetric MRI Evaluation in the Surgical Treatment of Glioblastoma

Background: Glioblastoma is the most common primary brain neoplasm in adults, with a poor prognosis despite a constant effort to improve patient survival. Some neuroradiological volumetric parameters seem to play a predictive role in overall survival (OS) and progression-free survival (PFS). The aim of this study was to analyze the impact of the volumetric areas of contrast-enhancing tumors and perineoplastic edema on the survival of patients treated for glioblastoma. Methods: A series of 87 patients who underwent surgery was retrospectively analyzed; OS and PFS were considered the end points of the study. For each patient, a multidisciplinary revision was conducted in collaboration with the Neuroradiology and Neuro-Oncology Board. Manual and semiautomatic measurements were adopted to perform the radiological evaluation, and the following quantitative parameters were retrospectively analyzed: contrast enhancement preoperative tumor volume (CE-PTV), contrast enhancement postoperative tumor volume (CE-RTV), edema/infiltration preoperative volume (T2/FLAIR-PV), edema/infiltration postoperative volume (T2/FLAIR-RV), necrosis volume inside the tumor (NV), and total tumor volume including necrosis (TV). Results: The median OS value was 9 months, and the median PFS value was 4 months; the mean values were 12.3 and 6.9 months, respectively. Multivariate analysis showed that the OS-related factors were adjuvant chemoradiotherapy (p &lt; 0.0001), CE-PTV &lt; 15 cm3 (p = 0.03), surgical resection &gt; 95% (p = 0.004), and the presence of a “pseudocapsulated” radiological morphology (p = 0.04). Conclusions: Maximal safe resection is one of the most relevant predictive factors for patient survival. Semiautomatic preoperative MRI evaluation could play a key role in prognostically categorizing these tumors.

Transcriptomic and epigenetic dissection of spinal ependymoma (SP-EPN) identifies clinically relevant subtypes enriched for tumors with and without NF2 mutation

Ependymomas encompass multiple clinically relevant tumor types based on localization and molecular profiles. Tumors of the methylation class “spinal ependymoma” (SP-EPN) represent the most common intramedullary neoplasms in children and adults. However, their developmental origin is ill-defined, molecular data are scarce, and the potential heterogeneity within SP-EPN remains unexplored. The only known recurrent genetic events in SP-EPN are loss of chromosome 22q and NF2 mutations, but neither types and frequency of these alterations nor their clinical relevance have been described in a large, epigenetically defined series. Transcriptomic (n = 72), epigenetic (n = 225), genetic (n = 134), and clinical data (n = 112) were integrated for a detailed molecular overview on SP-EPN. Additionally, we mapped SP-EPN transcriptomes to developmental atlases of the developing and adult spinal cord to uncover potential developmental origins of these tumors. The integration of transcriptomic ependymoma data with single-cell atlases of the spinal cord revealed that SP-EPN display the highest similarities to mature adult ependymal cells. Unsupervised hierarchical clustering of transcriptomic data together with integrated analysis of methylation profiles identified two molecular SP-EPN subtypes. Subtype A tumors primarily carried previously known germline or sporadic NF2 mutations together with 22q loss (bi-allelic NF2 loss), resulting in decreased NF2 expression. Furthermore, they more often presented as multilocular disease and demonstrated a significantly reduced progression-free survival as compared to SP-EP subtype B. In contrast, subtype B predominantly contained samples without NF2 mutation detected in sequencing together with 22q loss (monoallelic NF2 loss). These tumors showed regular NF2 expression but more extensive global copy number alterations. Based on integrated molecular profiling of a large multi-center cohort, we identified two distinct SP-EPN subtypes with important implications for genetic counseling, patient surveillance, and drug development priorities.

Clinicopathological Features of Primary Renal Mesenchymal Neoplasms in Adults: A Cross-sectional Study

Introduction: Renal mesenchymal tumours are a subset of primary renal tumours arising from the mesenchymal tissue in the kidney. They are a heterogeneous group of mostly benign tumours that exhibit varied behaviours and molecular characteristics. Aim: To analyse the wide spectrum of histological subtypes, their unique clinical presentation, and pathological features of primary renal mesenchymal neoplasms. Materials and Methods: This was a retrospective crosssectional observational clinicopathological study conducted in Department of General Pathology, Christian Medical College, tertiary care hospital, Vellore, Tamil Nadu, India, looking at data of adult Primary Renal Mesenchymal Tumours (PRMT) for a 15- year period between January 2006 and March 2021. Clinical details such as age, presenting symptoms, and tumour size were obtained from the hospital information system. Histopathology and immunohistochemical slides were reviewed for all the cases. Additional Immunohistochemistry (IHC) and molecular studies were performed for the undifferentiated sarcomas. The tumours were categorised into three groups as recommended by the World Health Organisation (WHO) 2020 classification of soft-tissue tumours based on biological behaviour: benign, intermediate, and malignant. Continuous variables are expressed as mean and Standard Deviation (SD). Comparison of categorical variables between groups was performed using the Chi-squared test. Continuous variables between groups were compared using the Student’s t-test for significance. A p-value of less than 0.05 was considered statistically significant. Results: Of the 2164 nephrectomies performed for neoplastic conditions, 97 (4.5%) were diagnosed as renal mesenchymal tumours. There were 59 (60.8%) benign, 10 (10.3%) with intermediate biologic behaviour and 28 (28.9%) malignant tumours. The mean ages at presentation were 40.5 years for benign, 43.4 years for intermediate, and 41 years for malignant tumours, respectively. Haematuria was seen in 11 of 38 (29%) intermediate grade and malignant tumours and in only 6 of 59 (10%) benign tumours, a difference that was statistically significant (p-value=0.017). Malignant tumours 24 of 28 (86%) were more likely to be larger (&gt;7 cm) when compared to benign tumours 28 of 59 (47%) at the time of presentation (p-value=0.027). Classical angiomyolipomas constituted 53/59 (90%) of the benign tumours. Of the 10 intermediate grade tumours, epithelioid angiomyolipomas and solitary fibrous tumours were the most common, accounting for 50% and 30% of the intermediate group, respectively. Undifferentiated small round cell sarcoma was the most common malignant neoplasm, making up 12/28 (43%) of the malignant tumours. Conclusion: The present study found that renal mesenchymal tumours constitute a small but unique group of renal tumours. They are predominantly benign, but up to a quarter are malignant. Malignant tumours tend to be larger and more often present with haematuria. The present study highlights the importance of IHC in the diagnosis of intermediate and malignant mesenchymal tumours and the requirement of exhaustive molecular studies individually tailored to the immuno-profile of malignant tumours.