World Health Organization Classification Research Articles

Molecular Classification of Large B-Cell Lymphoma and High-Grade B-Cell Lymphoma Cases and Association with Outcomes in Morocco

Background: High-grade B-cell lymphoma with c-MYC and BCL2 and/or BCL6 rearrangements (HGBL-DHL/THL) is a recently identified category in the most recent World Health Organization (WHO) classification. For all tumors displaying the appearance of diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma (HGBL), it is necessary to perform fluorescence in situ hybridization (FISH) in order to achieve an accurate diagnosis. The findings of FISH and immunohistochemistry (IHC) examinations from 50 DLBCL/HGBL samples obtained from Hassan II University Hospital in Fez/Morocco are reported. Methods: This retrospective study included 50 patients diagnosed with DLBCL/HGBL over a period of nine years (2013–2022) and treated with RCHOP chemotherapy protocol. All patients underwent a histological study followed by an immunohistochemical study to confirm the diagnosis and to classify patients according to cell of origin into non-GCB and GCB subtypes; then, a cytogenetic study using FISH was performed to classify patients according to the presence or absence of rearrangements in the c-MYC, BCL2 and BCL6 genes. A comparison was made between the molecular subtypes of DLBCL/HGBL in relation to clinicopathological features and outcomes. Results: Among the 50 cases studied in our population, we found 5 cases of HGBL with DLBCL morphology and 45 cases of DLBCL, which consisted of 13 cases (28.89%) of GCB subtype and 32 cases (71.11%) of non-GCB subtype based on the immunohistochemistry Hans algorithm. After FISH testing of all cases, we found three cases of double-hit lymphoma (DHL) and one case of triple-hit lymphoma (THL). Thus, HGBL-DHL/THL accounted for 8% of the cases. Furthermore, two cases were detected with only one rearrangement in the BCL2 gene and one case harboring a rearrangement in the BCL6 gene. DHL and THL patients and patients with a single rearrangement (BCL2 or BCL6) have a worse prognosis than patients with no rearrangement. Conclusions: DHL and THL are an aggressive entity of HGBL with poorer outcomes in comparison to DLBCL/HGBL NOS. First-line treatment with the RCHOP chemotherapy protocol may not be effective for all aggressive DLBCL cases. More targeted treatment is crucial for better patient outcomes.

Recurrent symptomatic intracranial hemorrhage in high-grade astrocytoma with piloid features: illustrative case.

High-grade astrocytoma with piloid features (HGAP) is a novel condition introduced in the 2021 World Health Organization classification. Given that it has been recently classified, reports clarifying its clinical features or diagnostic criteria are lacking, especially in cases of atypical presentation. Herein, the authors present a rare case of HGAP with repeated symptomatic hemorrhages. A woman in her 20s presented with an acute headache and vertigo. Computed tomography and magnetic resonance imaging revealed a 2.5 × 2.8 × 2.3-cm hemorrhagic cerebellar mass with calcifications. After moderate improvement of her symptoms, she developed recurrent hemorrhage, and the tumor size increased (3.0 × 3.6 × 4.0 cm) 18 days later, necessitating resection. Pathological and molecular analyses confirmed the diagnosis of HGAP with an FGFR1-TACC1 fusion, MTAP/CDKN2A/B deletion, and SETD2 rearrangement. Radiologically, the presence of calcification and cystic components and the absence of perilesional edema were atypical features of previously reported HGAP. Although recurrent symptomatic intracranial hemorrhages are rare in HGAP, enhancing lesions on magnetic resonance imaging suggest the need for resection to obtain tissue for molecular diagnosis and guide adjuvant treatment strategies. https://thejns.org/doi/10.3171/CASE24395.

Severe bleeding events among critically ill patients with haematological malignancies.

Bleeding events are common complications in critically ill patients with haematological malignancies. The objective of this study was to assess the incidence and identify determinants of ICU-acquired severe bleeding events in critically ill patients with haematological malignancies. We conducted a single-center retrospective study including all adult patients with a history of haematological malignancy requiring unplanned ICU admission over a 12-year period (2007-2018). The primary endpoint was the occurrence of ICU-acquired (i.e. after the first 24h in the ICU) severe bleeding events, as defined as grades 3 or 4 of the World Health Organization classification. A total of 1012 patients were analysed, mainly with a diagnosis of lymphoma (n = 434, 42.9%) and leukaemia or myelodysplastic syndrome (n = 266, 26.3%). Most patients were recently diagnosed (n = 340, 33.6%) and under active cancer treatment within the last 3 months (n = 604, 59.7%). The main cause for admission was infection (n = 479, 47.3%), but a significant proportion of patients were admitted for a primary haemorrhage (n = 99, 10%). ICU-acquired severe bleeding events occurred in 109 (10.8%) patients after 3.0 days [1.0-7.0] in the ICU. The main source of bleeding was the gastrointestinal tract (n = 44, 40.3%). Patients experiencing an ICU-acquired severe bleeding event displayed prolonged in-ICU length of stay (9.0 days [1.0-6.0] vs. 3.0 [3.5-15.0] in non-bleeding patients, p < 0.001) and worsened outcomes with increased in-ICU and in-hospital mortality rates (55% vs. 18.3% and 65.7% vs. 33.1%, respectively, p < 0.001). In multivariate analysis, independent predictors of ICU-acquired severe bleeding events were chronic kidney disease (cause-specific hazard 2.00 [1.19-3.31], p = 0.008), a primary bleeding event present at the time of ICU admission (CSH 4.17 [2.71-6.43], p < 0.001), non-platelet SOFA score (CSH per point increase 1.06 [1.01-1.11], p = 0.02) and prolonged prothrombin time (CSH per 5-percent increase 0.90 [0.85-0.96], p = 0.001) on the day prior to the event of interest. Major bleeding events are common complications in critically ill patients with haematological malignancies and are associated with a worsened prognosis. We identified relevant risk factors of bleeding which may prompt closer monitoring or preventive measures.

Diagnostic issues in neuroendocrine neoplasms ofthe lung.

Bronchopulmonary neuroendocrine neoplasms (BP-NENs) account for approximately 30% of all NENs. Although BP-NENs and NENs of the gastroenteropancreatic organs (GEP-NENs) share morphological and molecular features, they differ in terms of their terminology and classification. Bronchopulmonary neuroendocrine tumors (BP-NETs) have classically been termed as carcinoid and grouped into typical (TC) and atypical carcinoid (AC) based on the presence or absence of necrosis and mitotic count. In the most recent World Health Organization (WHO) classification for NENs of endocrine organs (WHO 2022), BP-NETs-NET G1 and G2-are introduced as synonyms of TC and AC, respectively. However, the Ki-67 index, which defines the grade of NETs in digestive organs, is only discussed in the descriptive text and not included into the criteria for classification of BP-NENs. In addition, well-differentiated NENs with high mitotic counts which correspond toNET G3 in the GEP organ system are not defined. This review discusses the role of Ki-67 for aproper classification of BP-NETs/carcinoids.

Molecular Markers in the World Health Organization Classification of Head and Neck Tumors, Fifth Edition.

The past decade has seen exponential advancements in molecular markers and the genetics of tumors, recognizing the limitations of conventional histopathology for grading, classification, and prognostication. Such advances have resulted in changes to classification systems, for example, with the incorporation of objective molecular and genetic information into the 2021 World Health Organization (WHO) classification of central nervous system tumors. The fifth edition of the WHO classification of head and neck tumors (HN5) (beta online version, 2022) also introduced major changes based on molecular markers, including additions, deletions, and reclassifications of entities, with the idea of being more objective and standardized. These changes are highly relevant to therapy decisions, prognosis, and clinical research and for patients with resistant diseases to explore options in clinical trials. The HN5, for the first time, included a radiologist as a member of the writing team to incorporate pertinent imaging findings into the classification. It is important for the radiologist, as an integral part of the multidisciplinary team, to be up to date about these changes for a better understanding of tumor biology, to integrate this into their clinical practice, and to provide more value in their interpretations. The authors provide a basic understanding of pathology and genetics for the radiologist, highlighting the molecular changes in epithelial (including squamous cell) and nonepithelial tumors of the head and neck. The authors also highlight newly recognized and reclassified tumor entities and provide a brief discussion on the genetic tumor syndromes. ©RSNA, 2024 Supplemental material is available for this article. See the invited commentary by Junn and Baugnon in this issue.

Differential diagnosis between low-risk and high-risk thymoma: Comparison of diagnostic performance of radiologists with and without deep learning model.

There are few CT-based deep learning (DL) studies on thymoma according to the World Health Organization classification. To develop a CT-based DL model to distinguish between low-risk and high-risk thymoma and to compare the diagnostic performance of radiologists with and without the DL model. 159 patients with 160 thymomas were included. A fine-tuning VGG16 network model with Adam optimizer was used, followed by k-fold cross validation. The dataset consisted of three axial slices, including the maximum tumor size from the CT volume data. The data were augmented 50 times by rotation, zoom, shear, and horizontal/vertical flip. Three independent networks for the CT dataset were considered, and the result was determined by voting. Three radiologists independently diagnosed thymomas with and without the model. The area under the curve (AUC) of the diagnostic performance was compared using receiver operating characteristic analysis. Accuracy of the DL model was 71.3%. Diagnostic performance of the radiologists was as follows: AUC and accuracy without the DL model, 0.61-0.68 and 61.9%-69.3%; and with the DL model, 0.66-0.69 and 68.1%-70.0%, respectively. AUC of the diagnostic performance showed no significant differences between radiologists with and without the DL model. The DL model tended to increase the diagnostic accuracy, but AUC was not significantly improved. Diagnostic performance of the DL was comparable to that of radiologists. The DL model assistance tended to increase diagnostic accuracy.

What's new in neuropathology 2024: CNS WHO 5th edition updates.

The fifth edition of the World Health Organization (WHO) Classification of Central Nervous System (CNS) Tumors was released in 2021, just five years following the updated fourth edition. Advanced molecular testing such as next-generation sequencing, RNA fusion analysis, and DNA methylation profiling has led to more precise grading and classification of pre-existing tumor types as well as the recognition of new ones. Herein, we outline the major updates of the 2021 WHO Classification of CNS tumors, with emphasis on the expanded molecular characterization of CNS tumors.

Mesenchymal Non-Meningothelial Tumors of the CNS: Evolving Molecular Landscape and Implications for Neuroradiologists.

The World Health Organization Classification of Tumors of the Central Nervous System (WHO CNS5) significantly revised the terminology and diagnostic criteria of "mesenchymal non-meningothelial" tumors of CNS to better align with the classification of these soft tissue tumors outside the CNS. The CNS chapter only covers the entities with distinct histological or molecular characteristics that occur exclusively or primarily in the CNS. These tumors usually arise from the meninges and are rarely intraparenchymal in origin, mainly in the supratentorial compartment. These tumors are grouped into three main categories: soft tissue, chondro-osseous, and notochordal. Soft tissue tumors, the largest group, are further divided into fibroblastic, vascular, and skeletal muscle subtypes. Notably, a new subcategory for "tumors of uncertain differentiation" has been introduced, encompassing three new histomolecular entities: FET::CREB fusion-positive, CIC-rearranged sarcoma, and primary intracranial sarcoma, DICER1-mutant. Emerging entities like dural angioleiomyomas and spindle cell neoplasms with NTRK-rearrangements have been reviewed, although not introduced in WHO CNS5. Given the often non-specific histology and immunophenotype of mesenchymal nonmeningothelial tumors of uncertain differentiation, molecular techniques have become indispensable for accurate diagnosis. This review provides a comprehensive overview of primary mesenchymal non-meningothelial CNS tumors, including their clinical, radiological, histopathological, and molecular characteristics and treatment strategies.ABBREVIATIONS: ALK: Anaplastic lymphoma kinase; ATF1: activating transcriptase factor-1; CREB: cAMP response element-binding protein; CREM: cAMP response element modulator; CIC: Capicua transcriptional receptor; EWSR1: Ewing sarcoma RNA binding protein; FUS: fused in sarcoma; NAB2: nerve growth factor-inducible protein A binding protein 2; STAT6: signal transducer and activator of transcription 6; WHO: World Health Organization WHO CNS5: World Health Organization Classification of Tumors of the Central Nervous System, fifth edition.

Impact on natural history of atypical meningioma after changes in 2016 edition of the world health organization (WHO) classification of central nervous system tumors: a literature review.

Meningiomas and their WHO histological diagnostic criteria is complex, especially for grade 2 tumors presenting a interobserverdiscordance as high as 12.2%. The 2016 edition of the WHO Classification of CNS tumors recommended brain invasion as a stand-alone grading criterion for diagnosing an atypical grade 2 meningioma (AM). To provide an overview of the classification of 2016 WHO impact on the natural history of atypical meningioma (AM) relative to previous classification. To achieve this goal, we selected articles from the period 2017-2024 in Medline search on atypical meningiomas and analyzed them after following the following criteria: 1) reports with confirmed histopathological diagnosis according to WHO 2016 and or 2021 criteria; 2) series and case reports; 3) detailed and individualized clinical outcomes for AM; and 4) papers written in English; after that a total of 3445 patients reported in 67 manuscripts from worldwide centers from 2017 to March 2024 were analyzed. The patient's age at the time of surgery ranged from 1month to 97years (mean 52.28 ± 18.7years). The most common tumor site was the convexity, accounting for 67.8%, followed by the skull base in 30.6%, ventricle in 1%, and spine in 0.6%; Gross total resection (GTR) was performed in 71.25% and subtotal resection (STR) in 28.75%; 1021 patients (29.63%) underwent adjuvant radiotherapy, and 22 patients (0.6%) were treated with adjuvant chemotherapy; tumor recurrence was reported in 1221 patients (35.44%) and 859 deaths (24.93%). 1) AM prevalence in females; 2) AM age distribution similar to the distribution of meningiomas in general; 3) AM recurrence rate of 35.44%, despite the high rate of GTR, which was higher than previously reported; 4) deepening knowledge in molecular mechanism of tumor progression will provide alternative therapeutic approaches for AM.

Outcomes of Obese Patients Undergoing Primary Total Knee Arthroplasty: Trends Over 30 Years.

The rates of obesity among patients undergoing total knee arthroplasty (TKA) have substantially increased. In addition, obesity is a well-established risk factor for complications after TKA. The purpose of this study was to analyze trends in body mass index (BMI) and complication risk among obese patients undergoing primary TKA treated at a single institution over 3 decades. Utilizing an institutional total joint registry, 13,919 primary TKAs performed to treat osteoarthritis between 1990 and 2019 were identified. Patients were stratified by BMI according to the World Health Organization (WHO) classification into 3 groups: non-obese (BMI, <30 kg/m2), WHO Class-I and II obese (BMI, 30 to 39.9 kg/m2), and WHO Class-III obese (BMI, ≥40 kg/m2). Trends in BMI and survivorship free from reoperation, revision, and periprosthetic joint infection (PJI) were analyzed over time while controlling for age, sex, and the Charlson Comorbidity Index. Over the study period, there was a 90% increase in the prevalence of Class-II obesity (13% to 25%) and a 300% increase in Class-III obesity (3% to 12%). Analysis of the entire cohort demonstrated a decrease in the 2-year risk of any reoperation, any revision, and PJI (p < 0.05 for all) with time. The risk decreased significantly over time for non-obese patients for any reoperation (p = 0.029) and any revision (p = 0.004) and for Class-III obese patients for any reoperation (p = 0.038) and any revision (p = 0.012), but it remained stable for Class-I and II obese patients. The risk of PJI decreased from 1990 to 2019 for non-obese patients (p = 0.005), but there were no significant changes in PJI risk for any obesity group. Despite increasing rates of obesity among our patients who underwent TKA, we observed decreasing risks of reoperation, revision, and PJI over time. The risks of reoperation and revision declined among non-obese patients, remained stable for Class-I and II obese patients, and declined for Class-III obese patients. The PJI risk declined for non-obese patients over the study period, but no such decline occurred for any category of obesity. Despite the decreasing risks of reoperation and revision, further work is needed to improve PJI risk in obese patients. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

From Voxel to Gene: A Scoping Review on MRI Radiogenomics' Artificial Intelligence Predictions in Adult Gliomas and Glioblastomas-The Promise of Virtual Biopsy?

Gliomas, including the most severe form known as glioblastomas, are primary brain tumors arising from glial cells, with significant impact on adults, particularly men aged 45 to 70. Recent advancements in the WHO (World Health Organization) classification now correlate genetic markers with glioma phenotypes, enhancing diagnostic precision and therapeutic strategies. This scoping review aims to evaluate the current state of deep learning (DL) applications in the genetic characterization of adult gliomas, addressing the potential of these technologies for a reliable virtual biopsy. We reviewed 17 studies, analyzing the evolution of DL algorithms from fully convolutional networks to more advanced architectures (ResNet and DenseNet). The methods involved various validation techniques, including k-fold cross-validation and external dataset validation. Our findings highlight significant variability in reported performance, largely due to small, homogeneous datasets and inconsistent validation methods. Despite promising results, particularly in predicting individual genetic traits, the lack of robust external validation limits the generalizability of these models. Future efforts should focus on developing larger, more diverse datasets and integrating multidisciplinary collaboration to enhance model reliability. This review underscores the potential of DL in advancing glioma characterization, paving the way for more precise, non-invasive diagnostic tools. The development of a robust algorithm capable of predicting the somatic genetics of gliomas or glioblastomas could accelerate the diagnostic process and inform therapeutic decisions more quickly, while maintaining the same level of accuracy as the traditional diagnostic pathway, which involves invasive tumor biopsies.

Analysis of clinicopathological characteristics and prognostic factors in 54 metaplastic breast carcinoma patients from northwest China

Objective: Metaplastic breast carcinoma (MBC) is a special type of morphologically heterogeneous and aggressively invasive breast cancer. MBC is characterized by the transformation of tumor epithelium into squamous epithelium and/or mesenchymal components, including differentiation into spindle cells, chondrocytes, and osteocytes. Due to its rarity and invasiveness, there is a paucity of research on MBC prognosis. Furthermore, there are currently no treatment guidelines for MBC. This study analyzed the clinicopathological characteristics, immunophenotype, and prognostic features of MBC. Our aim was to better characterize MBC, thereby identifying potential prognostic factors and new treatment methods. Moreover, we also describe an MBC case treated experimentally with anti-vascular targeted therapy. Material and Methods: We retrospectively analyzed clinical pathological data on 54 female patients with MBC from Shaanxi Provincial People’s Hospital and the XiJing Hospital of Air Force Medical University. These cases were diagnosed with MBC between January 1st, 2013, and October 1st, 2018. All patients were from the northwest region of China. The gross morphological, histological, and immunohistochemical features of MBC were analyzed. Kaplan–Meier analysis was used to calculate the survival rate, and univariate analysis was performed to identify significant prognostic factors. In addition, the treatment of an MBC patient with anti-angiogenic therapy was described, and a relevant literature review was conducted. Results: MBC was diagnosed in 32 left breasts and 22 right breasts from 54 women aged 21–76 years (median age of 57 years). The maximum tumor diameter ranged from 0.6 to 14 cm (average of 4.1 cm). Of the 54 patients, 47 underwent surgical treatment, with lymph node metastasis found in 17.0% (8/47). According to the World Health Organization classification criteria for breast tumors, the study cohort consisted of 15 cases of squamous cell carcinoma, ten cases of spindle cell carcinoma, nine cases of carcinoma with associated stromal differentiation, 18 cases of mixed carcinoma, and two cases of adenocarcinoma with squamous differentiation. Based on the American Joint Committee on Cancer clinical staging criteria, the patients were classified as Stage I (10 cases, 18.5%), Stage II (26 cases, 48.1%), Stage III (11 cases, 20.4%), and Stage IV (7 cases, 13.0%). Immunohistochemical analysis revealed that 94.4% of patients had triple-negative breast cancer (TNBC), 47 cases showed mutant tumor protein 53 (TP53) expression, 29 cases showed positive epidermal growth factor receptor (EGFR) expression, 43 cases showed positive E-cadherin expression, and 37 cases showed positive Cluster of Differentiation 24 expression. The Ki-67 index ranged from 20% to 90%. Univariate analysis showed that the Ki-67 index was not significantly associated with either progression-free survival (PFS) or overall survival (OS) in MBC patients. Patients with negative axillary lymph nodes had significantly better PFS and OS than those with positive nodes (P &lt; 0.05), and patients with clinical stage I-II disease had better PFS and OS than those with stage III-IV disease (P &lt; 0.05). Patients treated with anthracycline-containing chemotherapy had significantly better PFS than those who did not receive chemotherapy. Univariate analysis revealed that the high expression of EGFR correlated with worse PFS (P &lt; 0.05). The type of surgical approach employed did not affect the prognosis of MBC patients. Following the application of anti-angiogenic therapy, a rapid partial response was observed in an MBC patient with carcinoma and associated stromal differentiation. This patient subsequently underwent surgery and radiation therapy and has now achieved over 6 years of PFS. Conclusion: MBC is a heterogeneous group of tumors with high malignancy and poor prognosis. The large majority is TNBC and exhibits unique immune phenotypes. The poor PFS of MBC patients may be related to EGFR expression, which could become a potential therapeutic target in these patients. Surgery remains the primary treatment method for MBC. The present study found that sentinel lymph node biopsy was feasible in appropriate patients, and that chemotherapy regimens incorporating anthracycline-class drugs did not appear to improve OS. Anti-angiogenic therapy holds promise as a potentially effective treatment approach for MBC, and the optimization of systemic treatment strategies should be a priority in the management of these patients.

Spectrum of blue nevus-like lesions, including blue nevus, pigmented epithelioid melanocytoma & animal-type melanoma

Blue nevus-like lesions constitute a category of melanocytic lesions clinically identified by their blue coloration. Histologically, they exhibit two primary features: a dermal location and intense pigmentation. The latest World Health Organization (WHO) classification categorizes blue melanocytic lesions into benign entities (dermal melanocytoses, blue nevus, and deep penetrating nevus), melanocytic tumors with low to intermediate malignant potential (pigmented epithelioid melanocytoma, PEM), and malignant lesions (blue nevus-like melanoma and melanoma arising in blue nevus).Clinically, blue nevi are enduring and stable lesions, displaying a structureless blue pigmentation both clinically and dermatoscopically, with a straightforward histologic diagnosis. Conversely, lesions with recent onset and/or rapid growth are more commonly associated with diagnoses falling within the intermediate part of the spectrum or with melanoma. These lesions often present with a blue color along with additional features such as black blotches, irregular vessels, and irregular pigmented globules. They typically emerge de novo without recognizable precursors, they pose significant challenges for patient management.Melanoma on a blue nevus is an exceedingly rare entity with only a few cases described to date. Histologically, differentiating between lesions with intermediate malignant potential and melanoma is always challenging, necessitating a comprehensive evaluation of all morphologic findings of the lesion.

The prognostic effect of blast count in TP53 mutant myeloid neoplasms –the Minnesota experience

In 2022, the World Health Organization (WHO) and International Consensus Classification (ICC) recognized TP53 as an entity-defining alteration in myeloid neoplasms, yet with differing criteria that could lead to discrepant diagnoses and affect clinical trial eligibility. We studied 67 patients with TP53 mutant myeloid neoplasms, reclassifying them using both criteria. While most cases fulfill the criteria for TP53 mutant defined entities, most discrepancies were found in cases with ≥20% blasts. Patients were stratified into three groups based on blast count (<10%, 10–19%, and ≥20%) which revealed comparable clinicopathologic features, genetic characteristics, and outcomes. Notably, patients with ≥10% blasts had shorter overall survival compared to those with <10% blasts (8.1 vs. 12.4 months; p = 0.03). This study is among the few to examine TP53 mutant myeloid neoplasms as a single entity and suggests that the 10% blast count threshold could serve as a gateway to a more harmonized classification for these patients.

Imaging Features and World Health Organization Classification of Rare Breast Tumors.

Breast radiologists encounter unusual lesions, which may not be well described in the literature. Previously based on histologic and molecular classifications, the World Health Organization (WHO) classification of tumors has become increasingly multidisciplinary. Familiarity with imaging features and basic pathology of infrequent breast lesions, as well as their current classification according to the WHO, may help the radiologist evaluate biopsy results for concordance and help direct the management of uncommon breast lesions. This review article provides a case-based review of imaging features and WHO histologic classification of rare breast tumors.

Conduction System Hamartoma: Autopsy Case Series.

Conduction system hamartoma is a benign hamartomatous lesion arising from Purkinje and Purkinje-like cells of the heart. We aimed to investigate the cases that we detected during postmortem histopathological examination. The histopathology reports of the cases autopsied between 2012 and 2022 were reviewed retrospectively. The cases were evaluated in terms of histopathological features, demographic data, autopsy findings, causes of death, microbiological results, and accompanying cardiac anomalies. There was a total of 4 cases. The female-to-male ratio was 3/1. The mean age of the cases was 5.8 months. The heart weight was found within the normal range when evaluated according to age and gender. Microscopy revealed sharply demarcated cell groups or layers with histiocyte-like cells with foamy cytoplasm. Congenital heart disease and lung infection were given as causes of death in all cases. The lesion, which was previously called histiocytoid cardiomyopathy and many different names, is known as "conduction system hamartoma" in the latest World Health Organization classification (5th edition). Being aware of this entity that causes fatal arrhythmias and sudden cardiac deaths is important for pathologists. Autopsy findings should be evaluated by taking extra samples from the heart if necessary, especially in suspected cases below 2 years of age.

The 2023 WHO updates on skin tumors: advances since the 2018 edition.

Pathology is pivotal in diagnosing skin tumors, and the precision of diagnosis is crucial to devise customized treatment plans and enhance patient care in dermatology. The latest edition of the World Health Organization's classification of skin tumors serves as a comprehensive compendium, summarizing and categorizing all recent advancements in both anatomical-pathological and molecular aspects of cutaneous neoplasms. Several relevant advances have been introduced and new entities have been described. While the fundamental structure of the classification remains unchanged, notable additions include three new sections aimed at providing a more exhaustive description of skin lesions: nail unit tumors, skin metastases, and genetic tumor syndromes associated with skin malignancies. Recent strides in molecular pathology have led to significant breakthroughs in decoding the underlying mechanisms of various skin tumors, ranging from adnexal neoplasms to hematolymphoid neoplasms, soft tissue tumors, and melanocytic lesions. Of particular importance is the evolution in our understanding of melanocytic neoplasms, with the introduction of the term "melanocytoma" reserved for lesions exhibiting "intermediate" biological behavior and characterized by specific molecular mutations. The pathologic diagnosis process integrates morphological, immunohistochemical, and molecular features, playing a crucial role in clinical decision-making. The WHO classification serves as a valuable tool in promoting multidisciplinarity in the management of cutaneous neoplasms with the aim of translating novel pathological discoveries into more effective treatments. This review aims to distill the major updates introduced by the new classification, providing a synthesis of the latest scientific insights.

Myxoid pleomorphic liposarcoma.

Myxoid pleomorphic liposarcoma (MPL) is an extremely rare adipocytic tumor, recently recognized as a distinct entity in the 5th edition of the World Health Organization (WHO) Classification of Soft Tissue and Bone Tumors. Predominantly found in the mediastinum of young women, MPLs exhibit a combination of histological features characteristic of myxoid liposarcoma and pleomorphic (lipo)sarcoma. Their unique molecular features distinguish MPLs from other liposarcomas. Unlike myxoid liposarcomas and well-differentiated/dedifferentiated liposarcomas, MPLs lack specific FUS/EWSR1::DDIT3 gene fusions and MDM2/CDK4 gene amplifications, respectively. MPLs are associated with complex karyotypes, further highlighting their distinct genetic profile. They demonstrate aggressive growth patterns, high recurrence rates, and a high tendency to metastasize. These factors contribute to a poor prognosis, with a median survival of approximately 22.6 months. The aim of this review article is to provide a comprehensive summary of previously documented case reports and studies related to MPLs. By shedding light on the intricate details of MPLs, researchers and clinicians can gain valuable insights that may pave the way for improvements in diagnosis, treatment, and patient outcomes in the future.

Multi-pool chemical exchange saturation transfer MRI in glioma grading, molecular subtyping and evaluating tumor proliferation.

To evaluate the performance of multi-pool Chemical exchange saturation transfer (CEST) MRI in prediction of glioma grade, isocitrate dehydrogenase (IDH) mutation, alpha-thalassemia/mental retardation syndrome X-linked (ATRX) loss and Ki-67 labeling index (LI), based on the fifth edition of the World Health Organization classification of central nervous system tumors (WHO CNS5). 95 patients with adult-type diffuse gliomas were analyzed. The amide, direct water saturation (DS), nuclear Overhauser enhancement (NOE), semi-solid magnetization transfer (MT) and amine signals were derived using Lorentzian fitting, and asymmetry-based amide proton transfer-weighted (APTwasym) signal was calculated. The mean value of tumor region was measured and intergroup differences were estimated using student-t test. The receiver operating curve (ROC) and area under the curve (AUC) analysis were used to evaluate the diagnostic performance of signals and their combinations. Spearman correlation analysis was performed to evaluate tumor proliferation. The amide and DS signals were significantly higher in high-grade gliomas compared to low-grade gliomas, as well as in IDH-wildtype gliomas compared to IDH-mutant gliomas (all p < 0.001). The DS, MT and amine signals showed significantly differences between ATRX loss and retention in grade 2/3 IDH-mutant gliomas (all p < 0.05). The combination of signals showed the highest AUC in prediction of grade (0.857), IDH mutation (0.814) and ATRX loss (0.769). Additionally, the amide and DS signals were positively correlated with Ki-67 LI (both p < 0.001). Multi-pool CEST MRI demonstrated good potential to predict glioma grade, IDH mutation, ATRX loss and Ki-67 LI.

Imaging in Erdheim-Chester Disease.

Erdheim-Chester disease (ECD) is a rare, multisystemic, inflammatory, non-Langerhans cell histiocytic neoplasm. The discovery of recurrent and somatic mutations in the mitogen-activated protein kinase signaling pathway, most commonly BRAFV600E, has led to a reclassification of ECD from an inflammatory disorder to a neoplastic process. It is now included in the revised 2016 World Health Organization classification of hematopoietic tumors and in the Langerhans group in the revised 2016 Histiocytosis Classification of the Histiocyte Society. When symptomatic, ECD most commonly manifests with bone pain and fatigue. Also, neurologic manifestations, central diabetes insipidus, exophthalmos, and periorbital xanthelasma-like lesions are frequently encountered. Pathologic findings may vary depending on the site of biopsy and may display a spectrum of features. Thus, due to the diverse clinical presentation and variable histologic findings, imaging can often show the first sign of the disease. Radiologic findings are, however, interpreted in conjunction with clinical and histologic findings to establish the diagnosis of ECD. From providing classic findings that facilitate diagnosis to helping radiologists determine the extent of disease and predicting a prognosis, the role of radiology in ECD has evolved with the understanding of the disease itself. Insights into the molecular pathogenesis and the development of targeted therapeutic agents along with approval of vemurafenib and cobimetinib have necessitated revision of the guidelines for the management of ECD. The authors discuss various radiologic findings of ECD and differential diagnoses by using an organ system-based approach and briefly describe the revised consensus recommendations for evaluation, diagnosis, and treatment based on the International Medical Symposia on ECD from a radiologist's perspective. ©RSNA, 2024 Supplemental material is available for this article. The full digital presentation is available online.