Distinct Disease Entity Research Articles

Future directions in myelodysplastic syndromes/neoplasms and acute myeloid leukaemia classification: from blast counts to biology.

Myelodysplastic syndromes/neoplasms (MDS) and acute myeloid leukaemia (AML) are neoplastic haematopoietic cell proliferations that are diagnosed and classified based on a combination of morphological, clinical and genetic features. Specifically, the percentage of myeloblasts in the blood and bone marrow is a key feature that has historically separated MDS from AML and, together with several other morphological parameters, defines distinct disease entities within MDS. Both MDS and AML have recurrent genetic abnormalities that are increasingly influencing their definitions and subclassification. For example, in 2022, two new MDS entities were recognised based on the presence of SF3B1 mutation or bi-allelic TP53 abnormalities. Genomic information is more objective and reproducible than morphological analyses, which are subject to interobserver variability and arbitrary numeric cut-offs. Nevertheless, the integration of genomic data with traditional morphological features in myeloid neoplasm classification has proved challenging by virtue of its sheer complexity; gene expression and methylation profiling also can provide information regarding disease pathogenesis, adding to the complexity. New machine-learning technologies have the potential to effectively integrate multiple diagnostic modalities and improve on historical classification systems. Going forward, the application of machine learning and advanced statistical methods to large patient cohorts can refine future classifications by advancing unbiased and robust previously unrecognised disease subgroups. Future classifications will probably incorporate these newer technologies and higher-level analyses that emphasise genomic disease entities over traditional morphologically defined entities, thus promoting more accurate diagnosis and patient risk stratification.

Symptom management in isocitrate dehydrogenase mutant glioma

Abstract According to the 2021 World Health Organization classification of CNS tumors, gliomas harboring a mutation in isocitrate dehydrogenase (mIDH) are considered a distinct disease entity, typically presenting in adult patients before the age of 50 years. Given their multiyear survival, patients with mIDH glioma are affected by tumor and treatment-related symptoms that can have a large impact on the daily life of both patients and their caregivers for an extended period of time. Selective oral inhibitors of mIDH enzymes have recently joined existing anticancer treatments, including resection, radiotherapy, and chemotherapy, as an additional targeted treatment modality. With new treatments that improve progression-free and possibly overall survival, preventing and addressing daily symptoms becomes even more clinically relevant. In this review we discuss the management of the most prevalent symptoms, including tumor-related epilepsy, cognitive dysfunction, mood disorders, and fatigue, in patients with mIDH glioma, and issues regarding patient’s health-related quality of life and caregiver needs in the era of mIDH inhibitors. We provide recommendations for practicing healthcare professionals caring for patients who are eligible for treatment with mIDH inhibitors.

Distinct clinical profiles and patient outcomes in aCML and CNL.

The classification of atypical chronic myeloid leukemia (aCML) and chronic neutrophilic leukemia (CNL) as a single disease entity remains a topic of debate. To elucidate the characteristics of both entities, this retrospective cohort study was conducted, encompassing 36 cases of aCML and 18 cases of CNL. We discovered that aCML and CNL presented distinct blood counts, genetics, molecular profiles and outcomes. Specifically, hemoglobin levels (P < 0.001) and platelet counts (P < 0.001) were significantly lower in aCML cases than in CNL cases, with no significant difference in mean white blood cells (P = 0.637). The proportion of abnormal karyotypes was higher in aCML cases compared with CNL cases (P = 0.010). Notably, we found that aCML and CNL showed distinct gene expression profiles by transcriptome sequencing technology. The median follow-up duration for the entire cohort was 8months (rang 0.4 to 36.6months), and the median overall survival (OS) was significantly shorter in aCML cases (7.3months, 95%CI 5.4 to 20.5months) than in CNL cases (median OS not reached). The one-year OS rate for aCML patients was 31.0% (9/29), compared to 92.9% (13/14) for CNL patients. In conclusion, our study supports the notion that aCML and CNL are indeed distinct disease entities characterized by unique hematological features and clinical outcomes.

Hippocampal dentate granule cells in temporal lobe epilepsy: A morphometry and transcriptomic study.

The dentate gyrus (DG) plays a critical role in hippocampal circuitry, providing a "gate-like" function to the downstream cornu ammonis (CA) sectors. Despite this critical role, pathologies in DG are less commonly described than those in the CA sectors in the diagnosis of mesial temporal lobe epilepsy (mTLE). To elucidate the role of the DG in mTLE, we analysed hippocampal sclerosis (HS), no-HS, non-TLE epilepsy control, and non-epilepsy control cohorts using morphometry and gene expression profiling techniques. Morphometry techniques analysed DG cell spacing, nucleus size, and nucleus circularity. Our data show distinct DG morphometry and RNA expression profiles between HS and No-HS. Dentate granule cells are more dispersed in patients with HS, and the DG shows an elevated expression of the complement system, apoptosis, and extracellular matrix remodelling-related RNA. We also observe an overall decrease in neurogenesis-related RNA in HS DG. Interestingly, regardless of the pathological diagnosis, the DG morphometry correlates with post-operative outcomes. Increased cell spacing is observed in the DG of mTLE cases that achieve seizure freedom post-operatively. This study reveals the possible prognostic value of DG morphometry, as well as supporting the notion that HS and no-HS TLE may be distinct disease entities with differing contributing mechanisms.

A Rose by Any Other Name: The Long Intricate History of Localized Aggressive Periodontitis.

This review addresses the recent World Workshop Consensus Conference (WWCC) decision to eliminate Localized Aggressive Periodontitis (LAgP) in young adults as a distinct form of periodontitis. A "Consensus" implies widespread, if not unanimous, agreement among participants. However, a significant number of attendees were opposed to the elimination of the LAgP classification. The substantial evidence supporting a unique diagnosis for LAgP includes the (1) incisor/molar pattern of disease, (2) young age of onset, (3) rapid progression of attachment and bone loss, (4) familial aggregation across multiple generations, and (5) defined consortium of microbiological risk factors including Aggregatibacter actinomycetemcomitans. Distinctive clinical signs and symptoms of LAgP are presented, and the microbial subgingival consortia that precede the onset of signs and symptoms are described. Using Bradford-Hill guidelines to assess causation, well-defined longitudinal studies support the unique microbial consortia, including A. actinomycetemcomitans as causative for LAgP. To determine the effects of the WWCC elimination of LAgP on research, we searched three publication databases and discovered a clear decrease in the number of new publications addressing LAgP since the new WWCC classification. The negative effects of the WWCC guidelines on both diagnosis and treatment success are presented. For example, due to the localized nature of LAgP, the practice of averaging mean pocket depth reduction or attachment gain across all teeth masks major changes in disease recovery at high-risk tooth sites. Reinstating LAgP as a distinct disease entity is proposed, and an alternative or additional way of measuring treatment success is recommended based on an assessment of the extension of the time to relapse of subgingival re-infection. The consequences of the translocation of oral microbes to distant anatomical sites due to ignoring relapse frequency are also discussed. Additional questions and future directions are also presented.

Novel Targeted Agents in Advanced and Recurrent Low-Grade Serous Ovarian Cancer: A Silver Lining in the Therapy of a Chemoresistant Disease?

Low-grade serous ovarian carcinoma (LGSOC) is a rare subtype of epithelial ovarian cancer, characterized by a unique molecular background and specific clinical behavior. A growing body of molecular data underscores LGSOC as a distinct disease entity; however, clinical evidence on the optimal treatment regimens for LGSOC remains limited due to the low incidence of the disease. Consequently, treatment recommendations for LGSOC are still often derived from findings on the more common high-grade serous ovarian carcinoma (HGSOC) and typically focus on radical cytoreductive surgery and platinum-based chemotherapy. Since LGSOCs typically exhibit only limited responsiveness to platinum-based chemotherapy, the clinical management of advanced and recurrent LGSOCs remains a significant therapeutic challenge and often results in limited treatment options and suboptimal outcomes. Recent advances in molecular profiling and the identification of new, promising targets, such as the mitogen-activated protein kinase (MAPK) pathway, offer hope for improving both the prognosis and health-related quality of life in affected patients. Given the high unmet clinical need to establish new therapeutic standards beyond cytotoxic chemotherapy, this review aims to summarize the most promising molecular targets and emerging targeted agents.

Systemic Mastocytosis: State of the Art.

Since identification of Systemic mastocytosis (SM) as a distinct disease entity by the World Health Organisation (WHO), there has been a wealth of new research in therapeutic targeting of the pathogenic C-KIT D816V mutation. Avapritinib, the first licensed drug in SM capable of disease modification alongside the increasingly potent, oral and highly selective KIT tyrosine kinase inhibitors (TKIs) Bezuclastinib and now Elenestinib have enabled the prospect of long-term remissions. Studies have shown improved survival and symptomatic control in patients with SM. Of great triumph, this has been achieved in an outpatient setting with apparent tolerable and minimal toxicity. The importance of molecular profiling is being demonstrated in administering combination therapies for SM with an associated haematological neoplasm (AHN), allowing more personalised and streamlined treatment regimes. This review focuses on current management strategies of SM, focusing on state-of-the-art directed therapies, the evidence behind their use with presentation of two clinical cases to highlight key messages.

Ageing-related tau astrogliopathy severely affecting the substantia nigra.

Astrocytic tau pathology is a major feature of tauopathies and ageing-related tau astrogliopathy (ARTAG). The substantia nigra (SN) is one of the important degenerative areas in tauopathies with parkinsonism. Nigral tau pathology is usually reported as neuronal predominant with less prominent astrocytic involvement. We aimed to identify cases with prominent astrocytic tau pathology in the SN. We use the term nigral tau-astrogliopathy (NITAG) to describe cases showing an unusually high density of ARTAG with less neuronal tau pathology in the SN. We collected clinical information and studied the distribution of tau pathology, morphological features and immunostaining profiles in three cases. Three cases, all males with parkinsonism, were identified with the following clinicopathological diagnoses: (i) atypical parkinsonism with tau pathology reminiscent to that in postencephalitic parkinsonism (69-year-old); (ii) multiple system atrophy (73-year-old); (iii) traumatic encephalopathy syndrome/chronic traumatic encephalopathy (84-year-old). Double-labelling immunofluorescence confirmed co-localization of GFAP and phosphorylated tau in affected astrocytes. Staining profiles of NITAG revealed immunopositivity for various phosphorylated tau antibodies. Some astrocytic tau lesions were also seen in other brainstem regions and cerebral grey matter. We propose NITAG is a rare neuropathological feature, and not a distinct disease entity, in the frame of multiple system ARTAG, represented by abundant tau-positive astrocytes in various brain regions but having the highest density in the SN. The concept of NITAG allows the stratification of cases with various background pathologies to understand its relevance and contribution to neuronal dysfunction.

Risk prediction for clonal cytopenia: multicenter real-world evidence

AbstractClonal cytopenia of undetermined significance (CCUS) represents a distinct disease entity characterized by myeloid-related somatic mutations with a variant allele fraction of ≥2% in individuals with unexplained cytopenia(s) but without a myeloid neoplasm (MN). Notably, CCUS carries a risk of progressing to MN, particularly in cases featuring high-risk mutations. Understanding CCUS requires dedicated studies to elucidate its risk factors and natural history. Our analysis of 357 patients with CCUS investigated the interplay between clonality, cytopenia, and prognosis. Multivariate analysis identified 3 key adverse prognostic factors: the presence of splicing mutation(s) (score = 2 points), platelet count of <100 × 109/L (score = 2.5), and ≥2 mutations (score = 3). Variable scores were based on the coefficients from the Cox proportional hazards model. This led to the development of the clonal cytopenia risk score (CCRS), which stratified patients into low- (score of <2.5 points), intermediate- (score of 2.5 to <5), and high-risk (score of ≥5) groups. The CCRS effectively predicted 2-year cumulative incidence of MN for low- (6.4%), intermediate- (14.1%), and high-risk (37.2%) groups, respectively, by the Gray test (P < .0001). We further validated the CCRS by applying it to an independent CCUS cohort of 104 patients, demonstrating a c-index of 0.64 (P = .005) in stratifying the cumulative incidence of MN. Our study underscores the importance of integrating clinical and molecular data to assess the risk of CCUS progression, making the CCRS a valuable tool that is practical and easily calculable. These findings are clinically relevant, shaping the management strategies for CCUS and informing future clinical trial designs.

Desquamative Lesions Of Gingiva – Clinicopathologic Presentation And Review Of Literature

Desquamative gingivitis (DG) is a descriptive clinical term signifying epithelial detachment of the oral masticatory mucosa, presenting as "peeling gums." this usually manifests as a sign and symptoms rather than a distinct disease entity, often associated with various underlying mucocutaneous conditions.

Retrospective Study of Clinicopathologic Features and Outcome of Colonic Cancer in Relation to Primary Tumor Location

Abstract Background Colon cancer is one of the most common cancers worldwide and outcomes of colon cancer are different according to the primary tumor location and could be considered as distinct disease entities of the same organ. Objectives Analyzing and comparing clinical, epidemiological, pathologic features and outcome of colon cancer according to primary location whether the patients are right sided colon cancer (RSCC) and left sided colon cancer (LSCC) patients in different situations. Patients and Methods This is a retrospective, descriptive and analytical study conducted between January 1st, 2013 and January 1st 2019. One hundred and fifty patients diagnosed with colon cancer were enrolled in GIT unit, Department of Clinical Oncology, Ain Shams University Hospital. Results In our study right sided colon cancer patients were more females and clinically presented with higher frequency of anaemia (P value = 0.001) and perforation (P value = 0.02). Left sided colon cancer on the other side were more males (P value = 0.032) and was associated with more constipation (P value &amp;lt;0.001) and intestinal obstruction (P value = 0.085). RSCC was more associated mucinous adenocarcinoma, more advanced T stage (T4), lymphovascular invasion, larger tumor sizes and more poorly differentiated tumor. LSCC was associated with more advanced stage and lymph node positivity. Right side tumor has highest disease-free survival period which is 34.63 months (95% confidence interval [CI] 28.39-40.86) comparing with the left side tumor which was 24.94 months (95% confidence interval [CI] 19.61-30.27). left side tumor has highest progressive free survival period which is 4.77 months (95% confidence interval [CI] 3.33-8.22) comparing with the right-side tumor which was 2.21 months (95% confidence interval [CI] 0.63-3.79). Conclusion RSCCs and LSCCs show different characteristics in clinical presentation and prognostic features, so we can consider the side of tumor is helpful in determining the behavior and the outcome of the disease. We can consider RSCC and LSCC as two separate disease entities.

Exploring the Comorbidity, Pathophysiology, and Integrated Treatment Strategies of Hypertension and Depression

Hypertension and depression are widely prevalent conditions with substantial comorbidity. Hypertension, characterized by persistently elevated arterial pressure, is associated with significant cardiovascular morbidity and mortality. Depression, a multifactorial mood disorder, adversely affects mental and physical health through mechanisms involving neuroinflammation, neurotransmitter imbalances, and hormonal dysregulation. The association between these disorders has been recognized since the mid-20th century.Historical medical literature from ancient Chinese and Indian systems identified symptoms indicative of hypertension, later classified as a distinct disease entity by Fredrick Akbar Mahomed in the 19th century. Notable epidemiological studies have elucidated the significant relationship between hypertension and depression, particularly among medical students and other high-risk populations.Research indicates that common pathophysiological mechanisms, including sympathetic nervous system overactivity, chronic inflammation, and endothelial dysfunction, underlie the comorbidity of hypertension and depression. Elevated levels of norepinephrine, proinflammatory cytokines, and oxidative stress contribute to the expression or worsening of both conditions. Shared genetic and environmental factors further compound this relationship, highlighting the need for integrated treatment strategies.Pharmacological interventions, including angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, have shown potential to improve mental health outcomes in patients with comorbid hypertension and depression. However, inconsistent findings regarding the impact of antihypertensive medications on depression necessitate further investigation. The comorbidity of these conditions complicates treatment adherence, leading to poorer health outcomes and increased healthcare costs.The clinical implications of this unidirectional or bidirectional comorbidity are considerable, affecting quality of life, treatment adherence, and overall health outcomes. Integrated care approaches, incorporating lifestyle modifications and combined pharmacological treatments, have shown promise in improving compliance and outcomes.Despite extensive research, limitations persist, including difficulties in establishing causality, inconsistent diagnostic criteria, and the influence of confounding variables. Future research should focus on clarifying the bidirectional relationship between these conditions, the impact of social determinants, and the efficacy of various treatment modalities. Identifying high-risk populations and refining intervention strategies are crucial for improving clinical outcomes in patients with comorbid hypertension and depression.This paper aims to review the current literature regarding the association and comorbidity of hypertension and depression.Abbreviations: ACE: Angiotensin-Converting Enzyme; ARBs: Angiotensin Receptor Blockers; DBP: Diastolic Blood Pressure; mm Hg: Millimeters of Mercury; QoL: Quality of Life; SBP: Systolic Blood Pressure

Clinical Characteristics and Special Considerations in the Management of Rare Melanoma Subtypes.

Rare histologic subtypes of melanoma, including acral, mucosal, uveal, and desmoplastic melanomas, only make up 5% of all diagnosed melanomas and are often underrepresented in large, randomized trials. Recent advancements in systemic therapy have shown marked improvement in pathologic response rates, improving progression-free and overall survival among cutaneous melanoma patients, but there are limited data to demonstrate improved survival among rarer subtypes of melanoma. Acral melanoma has a poor response to immunotherapy and is associated with worse survival. Mucosal melanoma has a large variability in its presentation, a poor prognosis, and a low mutational burden. Uveal melanoma is associated with a high rate of liver metastasis; recent adoption of infusion and perfusion therapies has demonstrated improved survival among these patients. Desmoplastic melanoma, a high-risk cutaneous melanoma, is associated with high locoregional recurrence rates and mutational burden, suggesting this melanoma may have enhanced response to immunotherapy. While these variants of melanoma represent distinct disease entities, this review highlights the clinicopathologic characteristics and treatment recommendations for each of these rare melanomas and highlights the utility of modern therapies for each of them.

TAFRO Syndrome: Guidance for Managing Patients Presenting Thrombocytopenia, Anasarca, Fever, Reticulin Fibrosis, Renal Insufficiency, and Organomegaly

TAFRO syndrome is an inflammatory disorder of unknown etiology characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly. Despite great advancements in research on the TAFRO syndrome in the last decade, its diagnosis and treatment are still challenging for most clinicians because of its rarity and severity. Since the initial proposal of the TAFRO syndrome as a distinct disease entity in 2010, two independent diagnostic criteria have been developed. Although these are different in the concept of whether TAFRO syndrome is a subtype of idiopathic multicentric Castleman disease or not, they are similar except for the magnitude of lymph node histopathology. Because there have been no specific biomarkers, numerous diseases must be ruled out before the diagnosis of TAFRO syndrome is made. The standard of care has not been fully established, but interleukin-6 blockade therapy with siltuximab or tocilizumab and anti-inflammatory therapy with high-dose corticosteroids are the most commonly applied for the treatment of TAFRO syndrome. The other immune suppressive agents or combination cytotoxic chemotherapies are considered for patients who do not respond to the initial treatment. Whereas glowing awareness of this disease improves the clinical outcomes of patients with TAFRO syndrome, further worldwide collaborations are warranted.

Evaluation of changes caused by HR-HPV infection in squamous cell carcinoma of the head and neck using Raman microspectroscopy in combination with multivariate statistical analysis

Abstract Introduction: Squamous cell carcinoma of the head and neck region (HNSCC), with a positive status for high oncogenic potential human papillomavirus (HR-HPV), represents a clinically distinct disease entity compared to HPV-independent cases. Patients exhibit variations in prognosis and proposed therapy regimens. A prompt and reliable diagnosis of the presence of HPV infection could optimize the treatment for these patients. Currently employed treatment methods are long-term, expensive, and lack specificity, especially when administered separately. Material and methods: The research objective of this study is to explore significant differences in the Raman spectra of biological samples taken from patients with HNSCC, facilitating the confirmation of HPV virus presence. Study groups were delineated based on histopathological diagnosis and molecular biology tests, confirming the biological activity of the virus and the presence of the HR-HPV form with a diagnosis of a specific subtype. Results: To identify high oncogenic potential human papillomavirus (HR-HPV) infection as a crucial factor in squamous cell carcinoma of the head and neck region, an effective automatic data analysis system was established, relying on Raman microspectroscopy and multivariate analysis. Our results showed clear ranges of the Raman spectrum that differentiated between HPV-associated and non-HPV-associated cancers. Conclusions: In conclusion, our experience shows a great diagnostic potential of Raman confocal microscopy with multidimensional statistical analysis. In the future, the use of this method may allow for the creation of an effective and automated HR-HPV detection system in neoplastic tissue.

Myelin Oligodendrocyte Glycoprotein-Antibody Associated Disease: An Updated Review of the Clinical Spectrum, Pathogenetic Mechanisms and Therapeutic Management.

Clinical syndromes associated with antibodies against myelin oligodendrocyte glycoprotein (MOG) are now recognized as a distinct neurological disease entity, and are gaining increasing attention. The pathogenic mechanisms underlying MOG-antibody disease (MOGAD) remain incompletely understood. Case series, facilitated by registries, and observational studies over the past few years have shed increasing light on the clinical aspects and therapeutic approaches of MOGAD. MOGAD may manifest with a variety of clinical syndromes, including acute disseminated encephalomyelitis (ADEM), autoimmune encephalitis, optic neuritis (ON) and transverse myelitis (TM). MOGAD can be either monophasic or relapsing. This review aims to provide a comprehensive updated description of the clinical spectrum, paraclinical features, and prognosis of MOG-antibody disease, as well as summarize its therapeutic considerations. Randomized clinical trials, standardized diagnostic criteria and treatment guidelines are the steps forward.

Idiopathic Ileocolonic Intussusception in the Elderly: Case Report and Literature Review

Background: Adult intussusception is rare, in sharp contrast to childhood intussusception. It’s often considered a distinct disease entity from the paediatric intussusception because of dissimilarities in the aetiology, clinical presentation and management options. Operative treatment is mandatory for the management of colonic intussusception in the adult patient as many cases are associated with bowel tumours. Case presentation: An 86-year-old male retired civil servant presented with clinical and radiological features of ileocolonic intussusception. He had extended right hemicolectomy. The histology revealed an idiopathic ileocolic intussusception without an associated bowel tumour. He made an uneventful recovery and was discharged on the 8th day after surgery. Conclusion: Adult intussusception is not only rarer than the childhood disease, but requires mandatory surgical operation for treatment. This case involving an elderly patient in his 9th decade of life is reported to highlight the deviation from the usual pattern of presentation of this disease in an adult patient.

Pathogenesis of Alopecia Areata and Vitiligo: Commonalities and Differences.

Both alopecia areata (AA) and vitiligo are distinct, heterogenous, and complex disease entities, characterized by nonscarring scalp terminal hair loss and skin pigment loss, respectively. In AA, inflammatory cell infiltrates are in the deep reticular dermis close to the hair bulb (swarm of bees), whereas in vitiligo the inflammatory infiltrates are in the epidermis and papillary dermis. Immune privilege collapse has been extensively investigated in AA pathogenesis, including the suppression of immunomodulatory factors (e.g., transforming growth factor-β (TGF-β), programmed death-ligand 1 (PDL1), interleukin-10 (IL-10), α-melanocyte-stimulating hormone (α-MSH), and macrophage migration inhibitory factor (MIF)) and enhanced expression of the major histocompatibility complex (MHC) throughout hair follicles. However, immune privilege collapse in vitiligo remains less explored. Both AA and vitiligo are autoimmune diseases that share commonalities in pathogenesis, including the involvement of plasmacytoid dendritic cells (and interferon-α (IFN- α) signaling pathways) and cytotoxic CD8+ T lymphocytes (and activated IFN-γ signaling pathways). Blood chemokine C-X-C motif ligand 9 (CXCL9) and CXCL10 are elevated in both diseases. Common factors that contribute to AA and vitiligo include oxidative stress, autophagy, type 2 cytokines, and the Wnt/β-catenin pathway (e.g., dickkopf 1 (DKK1)). Here, we summarize the commonalities and differences between AA and vitiligo, focusing on their pathogenesis.

Idiopathic Ileocolonic Intussusception in the Elderly: Case Report and Literature Review

Background: Adult intussusception is rare, in sharp contrast to childhood intussusception. It’s often considered a distinct disease entity from the paediatric intussusception because of dissimilarities in the aetiology, clinical presentation and management options. Operative treatment is mandatory for the management of colonic intussusception in the adult patient as many cases are associated with bowel tumours. Case presentation: An 86-year-old male retired civil servant presented with clinical and radiological features of ileocolonic intussusception. He had extended right hemicolectomy. The histology revealed an idiopathic ileocolic intussusception without an associated bowel tumour. He made an uneventful recovery and was discharged on the 8th day after surgery. Conclusion: Adult intussusception is not only rarer than the childhood disease, but requires mandatory surgical operation for treatment. This case involving an elderly patient in his 9th decade of life is reported to highlight the deviation from the usual pattern of presentation of this disease in an adult patient.

Abstract P13: Genetic and epigenetic characterization of B-cell chronic lymphocytic leukemia with IG::BCL3-translocation provides evidence for a distinct biological entity

Abstract IG translocations occur in various B-cell neoplasms and result in the deregulation of (onco)genes due to their juxtaposition with regulatory elements in the immunoglobulin loci, predominantly the immunoglobulin heavy chain (IGH) locus (14q32). Some of these IGH translocations are pathognomonic for distinct disease entities, like those involving MYC, BCL2 or CCND1 in Burkitt, Follicular or Mantle Cell Lymphomas, respectively. In Chronic Lymphocytic Leukemia (CLL), the BCL3 gene (19q13), a transcriptional coactivator of the nuclear factor-kappaB (NF-κB) family, is a known partner gene in these translocations. Two subsets of IG::BCL3 translocation-positive B-cell neoplasms have been described that exhibit differences in chromosomal aberrations, IGHV mutation status, and histopathology [Martín-Subero et al. 2007]. In CLL, IG::BCL3 translocation is linked to a younger age at diagnosis, a more aggressive clinical course, and an atypical tumor cell phenotype [Michaux et al. 1997; Au et al. 2002]. A total of 89 B-cell neoplasms, primarily diagnosed as CLL, displaying IG::BCL3 translocation detected by fluorescence in situ hybridization (FISH), were examined. Analysis of DNA methylation and copy number aberrations (CNA) was conducted for 86 IGH::BCL3-translocated B-cell neoplasms using 850K EPIC BeadChip array data. Evaluation of chromosomal aberrations typical for CLL was moreover performed by FISH and the IGHV mutation status was determined. IGH::BCL3 breakpoint junctions were sequenced in 23 samples using targeted capture and whole-genome sequencing approaches. RNA expression of BCL3 was assessed using the HTG mRNA pan B-cell panel. In UMAP analysis of DNA methylation, CLLs with IG::BCL3 translocation exhibited segregation from other CLLs, irrespective of IGH translocations. Supervised analysis revealed global hypomethylation of B-cell neoplasms with IG::BCL3 translocation compared to other CLL. A total of 66/69 CLLs with IG::BCL3 translocation showed an unmutated IGHV status (96%). Copy number determination using BeadChip data (n=86) and FISH analysis (n=85) showed a significantly higher incidence of trisomy 12 in IG::BCL3-translocated cases compared to the general CLL population (p=0.011). Breakpoint sequencing indicated IG::BCL3 junctions to be recurrently associated with aberrant class-switch recombination at the IGH locus, involving IGHA (n=11/23), IGHG (n=5/23) and IGHM segments (n=5/23). Breakpoints at the BCL3 locus displayed two groups. 80 cases (all CLL) were located upstream of BCL3 and two other B-cell neoplasms (NHL, DLBCL) were located downstream of BCL3. BCL3 expression analysis in 15 IG::BCL3-translocated CLLs confirmed its transcriptional upregulation compared to the general CLL population. Our genetic and epigenetic analyses support the view that CLL with IG::BCL3 translocation may constitute a genetically and epigenetically distinct subtype of B-cell neoplasms, diverging from the typical CLL. Citation Format: Cosima Drewes, Cristina López, Nnamdi Okeke, Sina Hillebrecht, Petra Schütz, Anja Fischer, Anja Mottok, Susanne Bens, Christof Schneider, Stephan Stilgenbauer, Eugen Tausch, Reiner Siebert. Genetic and epigenetic characterization of B-cell chronic lymphocytic leukemia with IG::BCL3-translocation provides evidence for a distinct biological entity [abstract]. In: Proceedings of the Blood Cancer Discovery Symposium; 2024 Mar 4-6; Boston, MA. Philadelphia (PA): AACR; Blood Cancer Discov 2024;5(2_Suppl):Abstract nr P13.