World Health Organization Classification Research Articles

Seromucinous tumors of ovary: A case series

Seromucinous neoplasms are new category of ovarian epithelial tumor in the 2014 revised World Health Organization classification. Surface epithelial neoplasms are the most common ovarian tumors. Based on the degree of stratification and the presence or absence of invasion, these epithelial proliferations are further divided into benign, borderline, and malignant categories. Benign tumors are divided into three subtypes: cystadenoma (cystic areas), cystadenofibroma (cystic and fibrous areas), and adenofibroma (predominantly fibrous sections). Serous adenofibromas are rare variant of serous surface epithelial tumors. They affect females between the ages of 15 and 65 and make up 1.7% of all benign ovarian tumors. Serous tumor with a solid, fibrous component is designated as serous cystadenofibroma in which both serous and mucinous components are closely intermixed. Seromucinous adenofibroma is a benign cystic neoplasm composed of glands and cysts lined by an admixture of bland mullerian type epithelium which includes ciliated, endocervical type mucinous, and endometroid. They have a characteristic prominent fibromatous hypocellular stroma which helps differentiate it from the commoner cystadenoma. Seromucinous borderline tumors is 10% -20% of all epithelial ovarian tumors. Develops in younger age, usually bilateral in upto 40%, associated with endometriosis. We discuss about four different cases of seromucinous tumor reported in our institute.

Immune Deficiency/Dysregulation Associated Lymphoid Proliferations, EBV+ In Persons Living With HIV.

The 5th edition of the World Health Organization Classification of Hematolymphoid Tumors recently defined immune deficiency/dysregulation (IDD)-associated-lymphoid-proliferations in HIV settings, where information is scarce, often gone under or misdiagnosed. To describe the clinical picture, histopathology, and outcomes of IDD-associated-lymphoidproliferations Epstein-Barr virus+ (EBV) in people living with HIV without organ transplantation, antiretroviral therapy (ART) treated. HIV+ patients diagnosed with IDD-associated-lymphoid-proliferations seen at an academic medical center in Mexico from 2016 to 2019 were included. Immunohistochemical studies, in situ hybridization, and polymerase chain reaction analysis for EBV and LMP1 gene deletions were performed and correlated with clinical data. We included 27 patients, all men who have sex with men, median age 36 years (interquartile range [IQR] 22-54). The median baseline CD4+ T cells were 113/mL (IQR 89-243), the CD4+/CD8+ ratio was 0.15 (IQR: 0.09-0.22), and the HIV viral load was 184,280 copies/mL (IQR: 76,000-515,707). Twenty patients (74.07%) had IDD-associated-lymphoid-proliferations hyperplasia plasma cell type EBV+, 3 (11.1%) had hyperplasia mononucleosis-like type (IM-type), 1 patient (3.70%) had florid follicular hyperplasia, 3 (11.1%) IDD-associated-lymphoid-proliferations polymorphic type, and there were 22 cases (81.4%) of synchronic Kaposi Sarcoma. Two patients were diagnosed with Hodgkin lymphoma following a second positron emission tomography-computed tomography scan-guided biopsy. The median follow-up was 228 weeks (IQR 50-269); 6 patients died (22.2%) of causes unrelated to IDD-associated-lymphoid-proliferations related. IDD-associated-lymphoid-proliferations EBV+ occured in severely immunosuppressed HIV+ patients, a high percentage of whom had concomitant Kaposi sarcoma. The prognosis was good in patients treated only with ART.

T2-FLAIR Mismatch Sign Predicts DNA Methylation Subclass and CDKN2A/B Status in IDH-Mutant Astrocytomas.

DNA methylation profiling stratifies isocitrate dehydrogenase (IDH)-mutant astrocytomas into methylation low- and high-grade groups. We investigated the utility of the T2-fluid-attenuated inversion recovery (T2-FLAIR) mismatch sign for predicting DNA methylation grade and cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) homozygous deletion, a molecular biomarker for grade 4 IDH-mutant astrocytomas, according to the 2021 World Health Organization classification. Preoperative MRI scans of IDH-mutant astrocytomas subclassified by DNA methylation profiling (n = 71) were independently evaluated by two radiologists for the T2-FLAIR mismatch sign. The diagnostic utility of T2-FLAIR mismatch in predicting methylation grade, CDKN2A/B status, copy number variation, and survival was analyzed. The T2-FLAIR mismatch sign was present in 21 of 45 (46.7%) methylation low-grade and 1 of 26 (3.9%) methylation high-grade cases (P < 0.001), resulting in 96.2% specificity, 95.5% positive predictive value, and 51.0% negative predictive value for predicting low methylation grade. The T2-FLAIR mismatch sign was also significantly associated with intact CDKN2A/B status (P = 0.028) with 87.5% specificity, 86.4% positive predictive value, and 42.9% negative predictive value. Overall multivariable Cox analysis showed that retained CDKN2A/B status remained significant for progression-free survival (P = 0.01). Multivariable Cox analysis of the histologic grade 3 subset, which was nearly evenly divided by CDKN2A/B status, copy number variation, and methylation grade, showed trends toward significance for DNA methylation grade with overall survival (P = 0.045) and CDKN2A/B status with progression-free survival (P = 0.052). The T2-FLAIR mismatch sign is highly specific for low methylation grade and intact CDKN2A/B in IDH-mutant astrocytomas.

Microsecretory adenocarcinoma of the hard palate: a case report and literature review

Microsecretory adenocarcinoma (MSA) is a new type of salivary gland neoplasm identified in the 2022 World Health Organization Classification of Head and Neck Tumour (Skalova et al., Head Neck Pathol 16:40-53, 2022) and is characterized by a unique set of histomorphologic and immunohistochemical features and a recurrent MEF2C::SS18 fusion. MSA was initially misdiagnosed as another salivary gland tumour due to its similar morphology; until recently, only fewer than 50 cases were reported. We present a case of MSA of the hard palate with diverse architectural growth patterns, bland cytological features, abundant basophilic intraluminal secretions and fibromyxoid stroma. The tumour cells were positive for the SOX10, S100, and p63 protein and negative for the p40 protein according to immunohistochemistry. SS18 gene rearrangement was demonstrated via break-apart fluorescence in situ hybridization. We also provided a comprehensive literature review and integrated the clinicopathological features, immunophenotype, and molecular alterations of the disease. A comprehensive understanding of MSA enables us to accurately distinguish and categorize MSA from other salivary gland tumours with analogous morphologies.

Interpretation of lymphoid proliferations and lymphomas associated with immune deficiency and dysregulation in the 5th edition WHO classification of haematolymphoid tumours

The fifth edition of the World Health Organization (WHO) classification of lymphohematopoietic system tumors updated the terminology, types of lesions, diagnostic criteria, nomenclature, and other aspects of lymphoid proliferations and lymphomas associated with immune deficiency and dysregulation. The important updates and main changes in this section were briefly introduced, in order to guide the precise classification of lymphoid proliferations and lymphomas associated with immune deficiency and dysregulation, and standardize pathological reports.

Myelodysplastic/Myeloproliferative Neoplasms with Features Intermediate between Primary Myelofibrosis and Chronic Myelomonocytic Leukemia: Case Series and Review of the Entity

Diagnosis of myeloid neoplasm is currently performed according to the presence of a predetermined set of clinical, morphological, and molecular diagnostic criteria agreed upon by a consensus of experts. Even strictly adhering to these criteria, it is possible to encounter patients who present features that are not easily ascribable to a single disease category. This is the case, e.g., of patients with de novo myeloid neoplasms with features intermediate between primary myelofibrosis (PMF) and chronic myelomonocytic leukemia (CMML). In this study, we retrospectively searched the pathological database of IRCCS Humanitas Research Hospital to identify cases of chronic myeloid neoplasm with monocytosis with a driver mutation of classic myeloproliferative neoplasms (MPN) and showing morphological MPN features. For each case, we assessed all epidemiological, clinical, histopathological, and molecular data. Then, we carried out a literature review, searching for cases with features similar to those of our patients. We retrieved a total of 13 cases presenting such criteria (9 from the literature review and 4 from our institution); in all of them, there was a coexistence of clinical, histopathological, and molecular myelodysplastic and myeloproliferative features. To date, according to current classifications (World Health Organization and International Consensus Classification), given the presence/absence of essential features for PMF or CMML, these patients should be formally diagnosed as myelodysplastic/myeloproliferative neoplasm unclassified/not otherwise specified (U/NOS). This review aims to summarize the features of these difficult cases and discuss their differential diagnosis and their classification according to the novel classifications and the existing literature on overlapping myeloid neoplasms.

Linking physiology and demographics, non-ocular pathology and pharmaceutical drug use to standard OCT measures of the inner retina: The PPP project.

To assess the associations between physiology and demographics, non-ocular pathology and pharmaceutical drug use against peri-papillary retinal nerve fibre layer thickness (pRNFL T) and other optical coherence tomography (OCT) inner retinal measures in normal, healthy eyes. A retrospective, cross-sectional study of 705 consecutive participants with bilateral normal, healthy optic nerves and maculae. PRNFL Ts, vertical cup/disc ratio (CDR), cup volume and macular ganglion cell layer-inner plexiform layer (GCL-IPL) Ts were extracted from Cirrus OCT scans, then regressed against predictor variables of participants' physiology and demographics (eye laterality, refraction, intraocular pressure [IOP], age, sex, race/ethnicity, etc.) and non-ocular pathology and pharmaceutical drug use according to the World Health Organisation classifications. Associations were assessed for statistical significance (p < 0.05) and clinical significance (|β| > 95% limits of agreement for repeated measures). A multitude of non-ocular pathology and pharmaceutical drug use were statistically and clinically significantly associated with deviations in standard OCT inner retinal measures, exceeding the magnitude of other factors such as age, IOP and race/ethnicity. Thinner inner retina and larger optic nerve cup measures were linked to use of systemic corticosteroids, sex hormones/modulators, presence of vasomotor/allergic rhinitis and other diseases and drugs (up to -29.3 [-49.88, -8.72] μm pRNFL T, 0.31 [0.07, 0.54] vertical CDR, 0.29 [0.03, 0.54] mm3 cup volume and -10.18 [-16.62, -3.74] μm macular GCL-IPL T; all p < 0.05). Thicker inner retina and smaller optic nerve cup measures were diffusely associated with use of antineoplastic agents, presence of liver or urinary diseases and other diseases and drugs (up to 67.12 [64.92, 69.31] μm pRNFL T, -0.31 [-0.53, -0.09] vertical CDR, -0.06 [-0.11, 0] mm3 cup volume and 28.84 [14.51, 43.17] μm macular GCL-IPL T; all p < 0.05). There are a multitude of systemic diseases and drugs associated with altered OCT inner retinal measures, with magnitudes far exceeding those of other factors such as age, IOP and race/ethnicity. These systemic factors should at least be considered during OCT assessments to ensure precise interpretation of normal versus pathological inner retinal health.

Clinical implications of the 2022 WHO classification on the multidisciplinary management of PitNETS patients.

The review explores the 2022 update to the World Health Organization (WHO) classification of pituitary adenomas, now referred to as pituitary neuroendocrine tumors (PitNETs), and his possible impact on the clinical management of PitNET patients. The review highlights the differences and the evolution from the 2017 to 2022 version, with the current classification considering the lineage of the tumor cells, cell type, hormones produced, and other auxiliary characteristics for a comprehensive histological classification. The revision in terminology reflects a broader perspective on neuroendocrine neoplasia. The new approach based on transcription factors, hormone expression and other biomarkers has allowed a major revision of the nomenclature and a more accurate classification of pituitary adenomas. Furthermore, in some cases this approach is also assuming a prognostic value, useful in clinical practice. However, despite this elaborate classification and stratification, the review points out the lack of a robust grading or staging system and suggests the need for further research and validation of diagnostic methods. Despite these limitations, the revised classification presents a significant step towards understanding and managing PitNETs patients.

Navigating The 2022 International Consensus and World Health Organization Classifications of Hematopathology: A Call for Unified Diagnostic Language.

In 2022, 2 distinct guidelines for the diagnosis of myeloid neoplasms became available: the 5th edition of the World Health Organization guideline (WHO2022) solely and the International Consensus Classification (ICC). Despite major overlap, there are important differences that can have important implications. To explore the current opinions and diagnostic practices of hemato-oncologists and hematopathologists across the United States. An online anonymous survey was created using REDCap, and a secure link was shared via email to fellowship program leaderships and via posts on social media. A total of 310 responses were obtained. Only 33 of 309 respondents (10.7%) reported using solely the 2016 World Health Organization guideline to make diagnoses, whereas 167 of 309 (54%) supplemented it with other guidelines. The rest were either not sure (17; 5.5%), used WHO2022 solely (46; 14.9%), or used ICC solely (6; 1.9%). The choice of guideline was not related to region (P = .15), practice setting (P = .86), or hospital size (P = .22). More than 90% reported it is a source of confusion in clinical diagnosis, management, trial design, and other areas. Overall, our study found that having 2 distinct guidelines could be a source of confusion for physicians and calls for a unified diagnostic language.

Study of histopathological spectrum of ovarian tumors in a tertiary care hospital in India

Abstract Background: Ovarian tumors rank as the third leading cause of mortality among female genital tract malignancies. This study examined the histopathological spectrum of ovarian neoplasms based on our center’s 2020 World Health Organization (WHO) classification. Materials and Methods: This descriptive study was carried out over 5 years at our tertiary healthcare hospital, including 406 cases of ovarian neoplasms. After proper fixation and gross examination, sections were routinely processed and examined. The histopathological spectrum of ovarian neoplasms was analyzed according to the 2020 WHO classification. Results: Out of the 406 cases studied, 329 (81.03%) were benign, 65 (16.01%) were malignant, and 12 (2.95%) were borderline. The cases included 326 (80.29%) surface epithelial tumors, 58 (14.28%) germ cell tumors, 19 (4.68%) sex cord-stromal tumors, and 2 (0.49%) metastatic tumors. The majority of ovarian tumors (n = 340, 83.74%) occurred in the 20–60 years age group. Conclusion: The study reveals that benign tumors were more prevalent than malignant ones, with serous tumors being the most common among the benign cases. We observed a higher incidence of malignancy in women over the age of 40. Therefore, early and accurate histological diagnosis is crucial for initiating an appropriate management plan.

Peripartum anesthesia management and outcomes of patients with congenital heart disease: a single-center retrospective analysis (2009–2023)

BackgroundAdvances in medicine have enabled more patients with congenital heart disease (CHD) to become pregnant. However, these patients face significant challenges during the peripartum period. Current peripartum anesthesia guidelines for CHD patients mainly rely on case reports and small series. MethodsIn this retrospective study at a high-volume tertiary care center, we analyzed peripartum anesthetic approaches, postpartum hemorrhage (PPH) incidence, and maternal outcomes in CHD patients stratified by the modified World Health Organization (mWHO) classification. ResultsAmong 85 473 deliveries between 2009 and 2023, 409 occurred in 282 patients with CHD. Cesarean deliveries were significantly more frequent in mWHO class III, p=0.005. Labor epidural analgesia was the most common analgesic modality for vaginal deliveries (epidural rate was 71.1% with no differences between mWHO classes). Anesthesia management for cesarean deliveries varied significantly by class p<0.001. While spinal anesthesia was predominant in classes I and II, combined spinal-epidural anesthesia was more common in class III. PPH incidence was 6.4%, with no significant difference across classes, and no association was found between mWHO class severity and PPH risk (OR 0.97; 95% CI; 0.93 to 1.02, p=0.2). Higher mWHO classes correlated with significantly higher intensive care unit (ICU) admission rates, longer hospital stays, and one-year cardiac hospitalizations. ConclusionIn this retrospective study on the peripartum anesthetic management and outcomes of CHD patients stratified by mWHO class, cases with greater mWHO class were more likely to deliver preterm, by cesarean delivery, with a combined spinal-epidural anesthetic and an arterial line placement for that cesarean delivery. They overall had a longer hospital stay and were more likely to be admitted to the ICU. However, the overall risk of PPH did not increase with mWHO class severity.

Pathological Diagnosis and Genetic Alterations of Meningioma

Meningiomas, renowned for their histological diversity, are one of the most prevalent brain tumors. Some meningiomas show unusual histomorphology, especially in intraoperative rapid diagnosis. Therefore, clinical and radiological information is crucial for pathological diagnosis. Before the 2021 World Health Organization Classification of Tumors of the Central Nervous System(5th edition), pathological diagnosis relied solely on histopathological features. However, this classification introduced new diagnostic criteria for anaplastic meningiomas, which now include TERT promoter mutations and the homozygous deletion of CDKN2A/B, indicating the necessity of genetic analysis. Some rhabdoid and papillary meningiomas have BAP1 alterations, which tend to demonstrate an aggressive clinical course and may represent a phenotype of BAP1-related tumor predisposition syndrome. Heterozygous deletion of CDKN2A/B and loss of H3 p.K28me3(K27me3)are also associated with poor prognosis. Although some immunohistochemical markers like MTAP may serve as surrogates for the homozygous deletion of CKKN2A/B, genetic analysis is required to confirm TERT promoter mutations. Therefore, in routine clinical practice, neurosurgeons and pathologists prioritize appropriate formalin fixation to facilitate genetic analysis using pathological specimens.

Elucidating hematological profile and electrolyte balance in oral cancer patients.

Oral cancer is a serious health issue in both the developing and developed worlds, and it is one of the most common forms of cancer of the head and neck. In accordance with the 2017 World Health Organization classification, oral cancer can affect any part of the mouth, including the buccal mucosa, the front two-thirds of the tongue, the lip, the palate, the vestibule, the alveolus, the floor of the mouth, and the gingivae. Hematology and electrolyte balance have been proposed as tumor indicators and paths into cancer's genesis. Examining the patient's blood count and electrolyte levels in order to better understand their oral cancer. Electrolyte abnormalities are common in cancer patients and may be caused by the disease itself or by treatment. Hyponatremia is the most frequent electrolyte problem in cancer patients, and it is typically caused by the syndrome of improper ADH secretion. Although electrolyte problems are associated with a worse prognosis for cancer patients, timely and effective therapy has the potential to enhance both short- and long-term results and quality of life. Hematological tests on patients with oral cancer, including differential cell count, white blood cell count, and hemoglobin level. Compared to healthy controls, oral cancer patients show statistically significant differences in a number of biochemical parameters, including electrolytes (sodium, P<0.05; potassium, P=0.89; chloride, P<0.05); differential count (neutrophils, P<0.05; basophils, P<0.05). A significant risk factor for cancer patients is an electrolyte imbalance, which has been linked to inappropriate anti-diabetic hormone release. Clinicians will find these shifts in electrolytic level helpful in diagnosing and tracking oral cancer. Potentially malignant oral disorders and Oral squamous cell carcinoma may be better predicted using a combination of TLC, neutrophil, and lymphocyte counts, as shown in this study.

Mammary analogue secretory carcinoma involving submandibular gland: Diagnostic pitfall with review of literature

ABSTRACT Mammary analogue secretory carcinoma (MASC) is a recently defined entity among salivary gland tumors. MASC bores a striking resemblance to secretory carcinoma of breast along with the characteristics of ETV6–NTRK3 translocation. Hence, the entity was designated as MASC and was formally included in the 4th edition of World Health Organization classification of head and neck tumors in 2017. To the best of our knowledge, around 12 cases of MASC have been described in the Indian literature. MASC commonly involves parotid gland (70%). Involvement of submandibular gland is still rarer (7%). Prognosis of MASC is comparable to other low grade salivary gland malignancies; however, aggressive behavior has also been reported in few cases. This case is one of the very few reported cases describing MASC with detailed clinical, cytology, and microscopy findings along with special stains and immunohistochemistry.

Chronic myelomonocytic leukemia with ring sideroblasts/SF3B1 mutation presents with low monocyte count and resembles myelodysplastic syndromes with-RS/SF3B1 mutation in terms of phenotype and prognosis.

Chronic myelomonocytic leukemia (CMML) and myelodysplastic syndromes (MDS) with ring sideroblasts (RS) or SF3B1 mutation (MDS-RS/SF3B1) differ in many clinical features, but share others, such as anemia. RS and SF3B1 mutation can also be found in CMML. We compared CMML with and without RS/SF3B1 and MDS-RS/SF3B1 considering the criteria established by the 2022 World Health Organization classification. A total of 815 patients were included (CMML, n=319, CMML-RS/SF3B1, n=172 and MDS-RS/SF3B1, n=324). The percentage of RS was ≥15% in almost all CMML-RS/SF3B1 patients (169, 98.3%) and most (125, 72.7%) showed peripheral blood monocyte counts between 0.5 and 0.9 x109/L and low risk prognostic categories. CMML-RS/SF3B1 differed significantly from classical CMML in the main clinical characteristics, whereas it resembled MDS-RS/SF3B1. At a molecular level, CMML and CMML-RS/SF3B1 had a significantly higher frequency of mutations in TET2 (mostly multi-hit) and ASXL1 (p=0.013) and CMML had a significantly lower frequency of DNMT3A and SF3B1 mutations compared to CMML/MDS-RS/SF3B1. Differences in the median overall survival among the three groups were statistically significant: 6.75 years (95% confidence interval [CI] 5.41-8.09) for CMML-RS/SF3B1 vs. 3.17 years (95% CI 2.56-3.79) for CMML vs. 16.47 years (NA) for MDS-RS/SF3B1, p<0.001. Regarding patients with CMML and MDS, both with SF3B1 mutation, survival did not significantly differ. CMML had a higher risk of transformation to acute myeloid leukemia (24% at 8 years, 95%CI 19%-30%). CMML-RS/SF3B1 mutation resembles MDS-RS/SF3B1 in terms of phenotype and clearly differs from CMML. The presence of ≥15% RS and/or SF3B1 in CMML is associated with a low monocyte count. SF3B1 mutation clearly improves the prognosis of CMML.

Assessing the Safety of a Novel Monoclonal Antibody Cocktail for Postexposure Prophylaxis in Category III Animal Exposures.

TwinRab™ is a novel life-saving biological containing two monoclonal antibodies (docaravimab and miromavimab) essential for all age victims of category III animal exposures. It effectively neutralizes rabies and similar viruses at the exposure site until the body generates vaccine-induced antibodies. This postmarketing surveillance study assesses the safety of TwinRab™ in current postexposure prophylaxis (PEP) use and aims to reinforce its safety data for future applications. The prospective, open-label observational study was conducted on patients with the World Health Organization category III animal exposures at a government hospital in a northern region of India, by a suspected rabid animal. The study protocol included administering TwinRab™ (40 IU/kg) and a full course of anti-rabies vaccination as PEP. Out of 405 participants, 404 completed the study as per the protocol. Adverse events (AEs) occurred in 12.35% of cases, with 9.88% local AEs (primarily pain and tenderness) and 2.47% systemic AEs (fever, malaise, and myalgia). All AEs were mild and resolved without complications. Most participants (88.9%) and investigators (89.1%) rated TwinRab™'s tolerability as excellent. The present study demonstrates the evidence of a satisfactory safety profile along with better tolerability of TwinRab™ (40 IU/kg) for category III animal exposures and supports its continued usage.

Risk of malignancy and overall survival associated with the diagnostic categories in the World Health Organization Reporting System for Pancreaticobiliary Cytopathology.

The World Health Organization (WHO) classification system revised the Papanicolaou Society of Cytopathology (PSC) system for reporting pancreaticobiliary cytopathology. To better stratify intraductal and/or cystic neoplasms by cytologic grade, the neoplastic, other category was replaced by two new categories: pancreaticobiliary neoplasm, low-risk/grade (PaN-Low) and pancreaticobiliary neoplasm, high-risk/grade (PaN-High). Low-grade malignancies were placed in the malignant category, and benign neoplasms were placed in the benign/negative for malignancy category. An institutional pathology database search identified patients who underwent endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for pancreatic lesions from January 2015 to April 2022. The absolute risk of malignancy (ROM) was determined by histologic and/or clinical follow-up of at least 6 months, and overall survival rates were calculated across diagnostic categories, comparing the WHO and PSC systems. In total, 1012 cases were reviewed and recategorized. The ROM for the WHO system was 8.3% for insufficient/inadequate/nondiagnostic, 3.2% for benign/negative for malignancy, 24.6% for atypical, 9.1% for PaN-Low, 46.7% for PaN-High, 75% for suspicious for malignancy, and 100% for malignant. Comparatively, the ROM for the PSC system was 7.4% for nondiagnostic, 3.0% for negative for malignancy, 23.1% for atypical, 0% for neoplastic, benign, 7.3% for neoplastic, other, 75% for suspicious for malignancy, and 100% for malignant. The WHO system demonstrated superior stratification for overall survival. The WHO system significantly improves the stratification of ROM and overall survival across diagnostic categories by introducing the PaN-Low and PaN-High categories and reassigning low-grade malignancies to the malignant category. Analyzing EUS-FNA samples with the WHO system provides critical insights for guiding clinical management.

Mantle Cell Lymphoma: Evolving Frontline Treatment Strategies

Mantle cell lymphoma (MCL) is a mature B-cell non-Hodgkin lymphoma (NHL) that accounts for 3-10% of new NHL cases in Canada. The clinical course of MCL is heterogeneous, ranging from indolent behavior that does not require therapy for years, to highly aggressive disease with limited prognosis. As such, the 2022 International Consensus Classification (ICC) and World Health Organization (WHO) classifications subdivide MCL into two categories: 1) indolent MCL, which is characterized by blood involvement, splenomegaly without nodal involvement, or low-burden nodal involvement (mutated immunoglobulin heavy chain [IGHV], SOX11 negative, low Ki67 proliferative index); and 2) aggressive MCL, which is characterized by pleomorphic and blastoid morphologic appearance, TP53 aberrancy, high Ki67, and unmutated IGHV. While traditionally, patients with MCL had a median overall survival (OS) of only 3 to 5 years, there has been significant improvement over the last two decades, owing to chemoimmunotherapy with rituximab, cytarabine-based induction regimens, addition of consolidative autologous stem cell transplant (ASCT), rituximab maintenance, and the advent of novel targeted therapies (including Bruton kinase inhibitors [BTKi], venetoclax, and lenalidomide) in the relapsed setting. Despite these advances, MCL remains incurable even with aggressive therapy, and most patients will invariably relapse. As such, prospective studies integrating novel therapies with either a chemotherapy backbone or evaluating chemotherapy-free regimens are ongoing, aiming to improve outcomes and reduce toxicities. This review summarizes the current understanding of disease prognostication, treatment options, and novel therapeutic strategies that will reshape the treatment paradigm of MCL in the near future.

Pediatric-type diffuse low-grade gliomas.

The World Health Organization's 5th edition classification of Central Nervous System (CNS) tumors differentiates diffuse gliomas into adult and pediatric variants. Pediatric-type diffuse low-grade gliomas (pDLGGs) are distinct from adult gliomas in their molecular characteristics, biological behavior, clinical progression, and prognosis. Various molecular alterations identified in pDLGGs are crucial for treatment. There are four distinct entities of pDLGGs. All four of these tumor subtypes exhibit diffuse growth and share overlapping histopathological and imaging characteristics. Molecular analysis is essential for differentiating these lesions.

Diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters (DGONC), new name and new problems: an illustration of one case with atypical morphology and biology

A novel histomolecular tumor of the central nervous system (CNS), the “diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters (DGONC),” has recently been identified, based on a distinct DNA methylation profile and has been added to the 2021 World Health Organization Classification of CNS Tumors. This glioneuronal tumor mainly affects the supratentorial area in children and recurrently presents with a monosomy of chromosome 14. Herein, we report the case of a DNA-methylation based diagnosis of DGONC having atypical features, such as pseudo-rosettes and the absence of a chromosome 14 monosomy, thus rendering its diagnosis very challenging. Because of the wide variety of morphologies harbored by DGONC, a large range of differential diagnoses may be hypothesized from benign to malignant. Interestingly, the current case, like one previously reported, exhibited a co-expression of OLIG2, synaptophysin and SOX10, without GFAP immunopositivity. This particular immunophenotype seems to be a good indicator for a DGONC diagnosis. The classification of DGONC amongst glioneuronal or embryonal tumors is still debated. The clinical (a pediatric supratentorial tumor), morphological (from a benign oligodendroglioma-like tumor with microcalcifications and possible neuropil-like islands to a malignant embryonal tumor with a possible spongioblastic pattern), and immunohistochemical (co-expression of OLIG2 and synaptophsyin) profiles resemble CNS, neuroblastoma, FOXR2-activated and may potentially bring them together in a future classification. Further comprehensive studies are needed to conclude the cellular origin of DGONC and its prognosis.