World Health Organization Classification Research Articles

Posterior Fossa Stereotactic Biopsy with Leksell Vantage Frame-Case Series and Review of Literature.

Background: Stereotactic biopsy of posterior fossa lesions, which are often inoperable, enables a safe trajectory and provides tissue samples for accurate diagnosis, which is crucial for correct treatment since the latest World Health Organization Classification of Tumors of the Central Nervous System from 2021 places immense emphasis on molecular diagnostics. Stereotactic biopsy using the Leksell Vantage headframe is, due to its rigid design, extremely accurate, but stiffer, making the procedure more challenging and the learning curve steeper. Methods: This retrospective analysis demonstrates the introduction of the new Leksell Vantage headframe in day-to-day practice at the University Medical Center in Maribor, Slovenia, in demanding procedures of posterior fossa biopsies, and also provides a review of the literature available on the topic with emphasis on the technical aspect of posterior fossa biopsy using the Leksell Vantage headframe in adults. Results: In the observed series of three patients with posterior fossa lesions, all biopsies were representative, despite tissue samples being small, providing conclusive histopathologic reports (glioblastoma, rosette-forming glioneuronal tumor and metastasis of melanoma) with additional molecular diagnostics. After the initial biopsy case, the preoperative planning times and procedure times were shortened as we learnt about the importance of a tailored approach from the first case. In all cases, the biopsy was performed under local anesthesia with patients being awake throughout surgery. Conclusions: The rigid Leksell Vantage headframe makes access to the posterior fossa tougher when compared to its predecessors. However, the procedure is very accurate but requires precise preoperative planning and a customized approach when placing the headframe.

Resource availability for CNS tumor diagnostics in the Asian Oceanian region: A survey by the Asian Oceanian Society of Neuropathology committee for Adapting Diagnostic Approaches for Practical Taxonomy in Resource-Restrained Regions (AOSNP-ADAPTR).

The shift toward a histo-molecular approach in World Health Organization classification of central nervous system tumors (WHO CNS5) emphasizes the critical role of molecular testing, such as next-generation sequencing (NGS) and DNA methylation profiling, for accurate diagnosis. However, implementing these advanced techniques is particularly challenging in resource-constrained countries. To address this, the Asian Oceanian Society of Neuropathology committee for Adapting Diagnostic Approaches for Practical Taxonomy in Resource-Restrained Regions (AOSNP-ADAPTR) was initiated to help pathologists in resource-limited regions to implement WHO CNS5 diagnoses using simpler diagnostic tools, mainly immunohistochemistry. An online survey by this group assessed the in-house/local availability of diagnostic resources and outsourcing capabilities across the Asian Oceanian region, covering 19 countries. Of 318 responding centers, the availability of molecular techniques in-house/locally was limited in lower middle-income countries (LMICs), with 29% having fluorescence in situ hybridization, 10.7% Sanger sequencing, and only 9.4% NGS. DNA methylation was largely unavailable in-house/locally in of LMICs, while in the whole region, its availability stood at a meager 4.4%. Though outsourcing for all diagnostic tests was an easily accessible alternative, outsourcing for NGS and DNA methylation was uncommon because of the financial burden on patients being a significant obstacle. The survey categorized centers into five resource levels (RLs) based on the in-house/local access to diagnostic techniques, which highlighted the variability and disparity in diagnostic capabilities across the region. High-income countries had 80% of centers with advanced RL IV, V resources, in contrast to LMICs, where 70.5% of centers fell into RL I-III. This comprehensive evaluation emphasizes the need for tailored resource level guidelines, with the aim of improving diagnostic accuracy and treatment as well as advocating better healthcare infrastructure in resource-constrained areas. However, the survey's reliance on responses from better-resourced centers may underestimate challenges in lower-resource settings, stressing the need for broader outreach and support.

Prognostic impact of expression of CD2, CD25, and/or CD30 in/on mast cells in systemic mastocytosis: a registry study of the European Competence Network on Mastocytosis.

Expression of CD2, CD25 and/or CD30 in extracutaneous mast cells (MC) is a minor diagnostic criterion for systemic mastocytosis (SM) in the classification of the World Health Organization and International Consensus Classification. So far, it remains unknown whether expression of these antigens on MC is of prognostic significance in SM. We performed a retrospective multi-center study of patients with SM using the data set of the registry of the European Competence Network on Mastocytosis, including 5034 patients with various MC disorders. The percentage of CD2-, CD25+ and/or CD30+ MC was considerably lower in patients with indolent SM compared to patients with advanced SM, including aggressive SM and MC leukemia. Whereas CD25 and CD30 expression in MC could not be associated with prognosis, we found that lack of CD2 expression in MC is associated with a significantly reduced overall survival (OS) in patients with SM (p < 0.0001). Lack of CD2 was also associated with the presence of extramedullary involvement affecting the spleen, liver, and/or lymph nodes (odds ratio 2.63 compared to SM with CD2+ MC). Together, lack of CD2 expression in MC is a prognostic marker and indicator of reduced OS and extramedullary disease expansion in patients with SM.

Sialoblastomas With Solid Pattern Have FGFR2 Mutations and an Unfavorable Prognosis.

Although sialoblastoma (SBL) is defined as a low-grade malignant salivary gland anlage neoplasm in the 2022 World Health Organization (WHO) Classification of Head and Neck Tumors, its histology, genetics, and behavior remain controversial due to the rarity of the tumor. Here, we performed the first comprehensive clinical, histologic, and molecular analyses of 8 SBLs to better understand their pathogenesis and prognosis. This cohort consisted of 5 boys and 3 girls, with ages ranging from birth to 9 years at diagnosis. Tumors occurred in the parotid (4), cheek (3), and submandibular glands (1). Histologically, 5 tumors primarily presented as a solid pattern consisting of primitive basaloid epithelial cells, often with necrosis. Three tumors exhibited a non-solid pattern, with 1 tumor mainly showing epithelial-myoepithelial carcinoma (EMC)-like histology, whereas the other 2 tumors exhibited basal cell adenoma (BCA)-like histology. All 5 solid SBLs harbored FGFR2 mutations, and 1 also harbored mutations in PALB2, AR, and MAP2K1. In contrast, non-solid pattern tumors were characterized by HRAS mutations or significant β-catenin nuclear positivity. All 5 solid tumors recurred, 3 of them developed distant metastases, and 2 died 40 and 44 months after diagnosis. Three non-solid tumors showed no evidence of disease recurrence at 49, 144, and 132 months, suggesting a relatively favorable prognosis. Overall, SBLs can be stratified into solid and non-solid patterns, with solid pattern tumors usually having FGFR2 mutations, increasing the risk of recurrence and metastasis. This stratification underscores the importance of genetic and morphologic profiling for predicting the prognosis of SBLs.

Mixed neuroendocrine-non-neuroendocrine neoplasm of the colon treated with laparoscopic resection and adjuvant chemotherapy: a case report.

Mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) of the colon is rare with a poor prognosis. Since the first description of a mixed neoplasm 100years ago, the nomenclature has evolved, most recently with the 2022 World Health Organization(WHO) classification system. We describe our experience of a case of locoregionally advanced MiNEN of the descending colon treated with curative laparoscopic resection and adjuvant chemotherapy. The patient is a 72year old woman who presented with haematochezia. Initial clinical diagnosis was poorly differentiated adenocarcinoma of the descending colon, cT2N0M0, cStage I. Laparoscopic partial colectomy of the descending colon with D3 lymph node dissection and intracorporeal overlap anastomosis was performed. The pathological diagnosis however, returned mixed adenocarcinoma-neuroendocrine carcinoma (MANEC) of the descending colon, pT4aN1bM0, pStage IIIB, a subgroup of MiNEN: 70% was neuroendocrine carcinoma (NEC), whilst poorly differentiated mucinous carcinoma constituted 30% of the tumour. She completed 4 courses of irinotecan plus cisplatin (IP) adjuvant chemotherapy and is currently recurrence-free at postoperative year 2. The clinical course of MiNEN depends on the biology of the two components, both of which must be pathologically characterised. Even quantitatively discrete components should be carefully subtyped as their prognostic relevance is undetermined.

Leukopenia and thrombocytopenia in dengue patients presenting in the emergency department of a tertiary center in Nepal: a cross-sectional study

IntroductionDengue viruses cause either symptomatic infections or asymptomatic seroconversion. Symptomatic dengue has a wide clinical spectrum ranging from self-limiting infection to severe manifestations, mostly characterized by plasma leakage with or without hemorrhage. World Health Organization classification in 2009 classified dengue into dengue without warning signs, dengue with warning signs, and severe dengue. This study aimed to determine patient characteristics and hematological parameters (leukopenia, and thrombocytopenia) in patients with dengue infection in the emergency department of a tertiary center.MethodsA cross-sectional study was conducted among 252 patients with dengue confirmed by serological testing against dengue-specific nonstructural protein 1 (NS1) antigen and immunoglobulin M (IgM) by enzyme-linked immunosorbent assay from September to November 2022 who presented in the emergency department of a tertiary hospital in Nepal after ethical approval was obtained. Dengue was categorized according to the World Health Organization 2009 classification. Hematological parameters were recorded by reviewing patients’ laboratory records. Data analysis was done using descriptive statistical parameters and a chi-square test.ResultsDengue without warning signs was present in 166 (65.87%) patients, while dengue with warning signs and severe dengue was present in 68 (26.89%) and 18 (7.14%) patients, respectively. Leukopenia (< 4000 cells/mm3) was present among 163 (64.68%) patients. The lowest recorded leukocyte count was 1440. Similarly, thrombocytopenia (< 150000 cells/mm3) was present among 102 patients (40.48%). The lowest recorded platelet count was 26,000 cells/mm3. A significant association was found between the severity of dengue infection and leukopenia (χ2 13.268, p-value 0.001) and thrombocytopenia (χ2 43.924, p value < 0.001).ConclusionsMonitoring of warning signs and clinical parameters is important for identifying the progression of dengue infection to the critical phase. Leukopenia and thrombocytopenia are present among many dengue-infected patients presenting in the emergency department. The severity of the disease will usually only be apparent around defervescence, which often coincides with the onset of the critical phase. Leukopenia and thrombocytopenia could indicate progression to severe disease during emergency department admission.

VTE incidence shortens survival in IDH-WT glioblastoma.

Venous thromboembolisms (VTE's) are the second leading cause of death in cancer patients. While previous analyses have demonstrated VTE rates are greater in GBM patients using smaller patient cohorts in high-grade glioma, since the release of the update 5 th edition of the World Health Organization (WHO) classification a systematic analysis in a large-scale cohort of patients with IDH-wildtype GBM with clinical outcomes is lacking. This study utilizes the online database, TriNetx, to build patient cohorts for outcomes analysis. TriNetX is a database comprised of over 50 healthcare organization patient information that is quarriable by CPT, ICD, RxNorm, and other proprietary codes. Patient cohort demographics were used for propensity score matching. Risk ratios, odds ratios, hazard ratios, and Kaplan Meier curves were utilized for primary outcomes including survival and time-to-event analyses. 24% of patients with GBM experienced at least 1 VTE or PE after their diagnosis. Compared to a population of patients with no cancer history with an index event of an inpatient visit, patients with GBM were at 20.4 (12.23-34.17) and 5.96 (3.85-9.23) times higher risk of experiencing a VTE/PE at 1- and 5-year follow-up, respectively. Sex differences were not seen between VTE/PE rates and survival after VTE/PE at 1- and 5-year follow-up (p>0.05). Lastly, patients with GBM and a VTE/PE after diagnosis experienced worse survival at 1- and 5-year follow-up compared to those without a VTE/PE (p<0.0001 and p = 0.0014, respectively). Patients with GBM experience increased risks of thrombotic events after diagnosis. These risks are not sex-dependent but do affect overall survival.

Prognostic risk factors of pneumonia associated with COVID-19 in patients with lymphoma.

Patients with hematological malignancies have an elevated risk of developing pneumonia after contracting COVID-19. Lymphoma is the most prevalent hematologic malignancy. It is critical to identify patients at high risk of contracting COVID-19-associated pneumonia. From January 11-31, 2023, we distributed questionnaires to patients diagnosed with lymphoma according to 2016 World Health Organization diagnostic and classification criteria. COVID-19 infection was confirmed based on symptoms and laboratory tests. Pneumonia was confirmed using computed tomography scans. In total, 257 patients were included in this study; 221 patients (86.0%) had COVID-19 infection and 61 (27.6%) of these had pneumonia. Patients with B-cell non-Hodgkin lymphoma (B-NHL) had a significantly higher pneumonia incidence than patients with other lymphoma types (31.8% vs. 27.6%, P=0.005). Higher incidence of pneumonia was observed in patients receiving anti-CD20 therapy (30.0% vs. 16.3%, P=0.048) and Bruton's tyrosine kinase (BTK) inhibitor therapy (51.3% vs. 22.5%, P=0.001). B-NHL (hazard ratio [HR]=3.7, 95% confidence interval [CI] 1.4-10.0, P=0.009), anti-CD20 therapy (HR=2.3, 95% CI 1.0-5.2, P=0.050), BTK inhibitor (HR=3.6, 95% CI 1.8-7.4, P<0.001), active therapy (HR=3.0, 95% CI 1.5-5.7, P=0.001), and lack of disease remission (HR=3.7, 95% CI 1.8-7.4, P=0.001) were high-risk factors for developing pneumonia. Anti-PD-1 therapy was a protective factor against pneumonia development (HR=0.2, 95% CI 0.05-0.9, P=0.034). In multivariable analysis, BTK inhibitor (HR=3.5, 95% CI 1.6-8.0, P=0.003), active therapy (HR=3.3, 95% CI 1.6-6.8, P=0.001), and disease non-remission (HR=2.9, 1.3-6.4, P=0.007) were independent risk factors for pneumonia development after COVID-19 infection in patients with lymphoma. Patients with lymphoma receiving BTK inhibitors, undergoing active therapy, and lacking disease remission exhibited a higher risk for pneumonia associated with COVID-19.

Lipomatous ependymoma with ZFTA: RELA fusion-positive: A case report

BACKGROUND Ependymoma with lipomatous differentiation is a rare type of ependymoma. The ZFTA fusion-positive supratentorial ependymoma is a novel tumor type in the 2021 World Health Organization classification of central nervous system tumors. ZFTA fusion-positive lipomatous ependymoma has not been reported to date. CASE SUMMARY We reported a case of a 15-year-old Chinese male who had a sudden convulsion lasting approximately six minutes. Magnetic resonance imaging showed a round cystic shadow of approximately 1.9 cm × 1.5 cm × 1.9 cm under the right parieto-occipital cortex. Microscopic examination showed characteristic perivascular pseudorosettes and adipose differentiation in the cytoplasm. Immunohistochemical staining showed that the tumor cells were negative for cytokeratin, NeuN, Syn and p53, but positive for GFAP, vimentin and S-100 protein. Significant punctate intracytoplasmic EMA immunoreactivity was observed. The level of Ki-67 was about 5%. Genetic analysis revealed ZFTA: RELA fusion. A craniotomy with total excision of the tumor was performed. The follow-up time was 36 months, no evidence of disease recurrence was found in magnetic resonance imaging. CONCLUSION Based on these findings, the patient was diagnosed as a ependymoma with ZFTA fusion and lipomatous differentiation. This case report provides information on the microscopic morphological features of ependymoma with ZFTA fusion and lipomatous differentiation, which can help pathologists to make a definitive diagnosis of this tumor.

Revisiting Age-Related Normative Hearing Levels in Korea.

Hearing level reference values based on the results of recent audiometry have not been established for the general population of South Korea. This study aimed to evaluate the mean hearing levels of each age group and to measure the annual progression of hearing loss. We used the database of the eighth and ninth Korea National Health and Nutrition Examination Survey from 2020 to 2022, and included participants with normal tympanic membranes and without occupational noise exposure. Mean hearing levels were calculated by averaging hearing levels at 0.5 kHz, 1 kHz, 2 kHz, and 4 kHz. Hearing loss was defined as a hearing level exceeding 25 dB in the better ear, and severity of hearing loss was classified as moderate, moderately severe, severe, and profound, following the World Health Organization classification. Hearing levels and the proportions of patients with hearing loss increased with age. Hearing levels were 9.11 ± 6.28 dB, 13.33 ± 7.85 dB, 19.90 ± 10.30 dB, and 31.95 ± 13.37 dB in those in their 40s, 50s, 60s, and 70s, respectively, and the proportions of patients with hearing loss were 1.81%, 7.51%, 25.32%, and 63.94%, respectively. The annual increase in hearing level was 0.71 dB, and increases were greater at higher frequencies. Hearing loss was also worse in men. The present study provides reference values for normal hearing levels by age group, and indirectly reveals the progression of age-related hearing loss. Based on the results, physicians will be able to provide appropriate advice regarding hearing levels and the need for monitoring in the elderly.

Advances in Therapy for Urothelial and Non-Urothelial Subtype Histologies of Advanced Bladder Cancer: From Etiology to Current Development.

Urothelial carcinoma (UC) is the most common histological subtype of bladder tumors; however, bladder cancer represents a heterogeneous group of diseases with at least 40 distinct histological subtypes. Among these, the 2022 World Health Organization classification of urinary tract tumors identifies a range of less common subtypes of invasive UC, formerly known as variants, which are considered high-grade tumors, including squamous cell, small-cell, sarcomatoid urothelial, micropapillary, plasmacytoid, and urachal carcinomas, and adenocarcinoma. Their accurate histological diagnosis is critical for risk stratification and therapeutic decision-making, as most subtype histologies are associated with poorer outcomes than conventional UC. Despite the importance of a precise diagnosis, high-quality evidence on optimal treatments for subtype histologies remains limited owing to their rarity. In particular, neoadjuvant and adjuvant chemotherapy have not been well characterized, and prospective data are scarce. For advanced-stage diseases, clinical trial participation is strongly recommended to address the lack of robust evidence. Advances in molecular pathology and the development of targeted therapies and immunotherapies have reshaped our understanding and classification of bladder cancer subtypes, spurring efforts to identify predictive biomarkers to guide personalized treatment strategies. Nevertheless, the management of rare bladder cancer subgroups remains challenging because they are frequently excluded from clinical trials. For localized disease, curative options such as surgical resection or radiotherapy are available; however, treatment options become more limited in recurrence or metastasis, where systemic therapy is primarily used to control disease progression and palliate symptoms. Herein, we present recent advances in the management of urothelial and non-urothelial bladder cancer subtypes and also explore the current evidence guiding their treatment and emphasize the challenges and perspectives of future therapeutic strategies.

Unveiling Rare Breast Neoplasms: Diagnostic Challenges and Insights

Breast neoplasm encompasses a diversified range of different diseases characterized by unique biological and pathological features, clinical presentation, response to treatments, clinical behavior, and outcome. The histological variability has profound prognostic implications, thus playing a pivotal role in diagnosing breast neoplasm. Special histologies can occur rarely, and most information on outcomes and treatments is mainly derived from small series and case reports. Thus, reporting such unusual occurrences is of utmost importance. This is a retrospective study of four years in which 11 cases of breast neoplasm diagnosed on histopathology were assessed. The clinical details were acquired from an electronic search. The hematoxylin and eosin and immunohistochemistry slides were retrieved from the archives to review the histopathological features. The patient’s age ranged from 32 to 72 years (median: 51 years). Eleven unusual cases of breast neoplasms were diagnosed and categorized according to the latest World Health Organisation (WHO) classification. These cases include rare and salivary gland type tumors (2 cases), neuroendocrine neoplasms (1 case), hamartomas of the breast (2 cases), fibroblastic and myofibroblastic tumors of the breast (1 case), peripheral nerve sheath tumor (1 case) and hematolymphoid tumors of the breast (4 cases). The management of unusual breast cancer histotypes represents a real challenge in daily clinical practice. Our data suggest that these variants are distinct clinicopathological entities with unique hormonal receptor statuses. The occurrence of such entities is rare, and they demonstrate different clinical behaviors and responses to treatment, suggesting that a few genomic-specific events might also drive them. Therefore, it is important to indulge in future research on such rare breast neoplasms.

Prognostic Implications of the Bethesda System in Fine-Needle Aspiration for Follicular Thyroid Carcinoma.

Fine-needle aspiration is an effective tool for sampling thyroid nodules; its results are classified according to the Bethesda System for Reporting Thyroid Cytopathology (BSRTC), whose categories define malignancy risks. To compare the histologic outcomes and disease-free survival (DFS) with the preceding BSRTC categories, we hypothesized that the initial cytologic categories may reflect long-term outcomes in follicular thyroid carcinoma (FTC), similar to those observed in papillary thyroid carcinoma. This retrospective study enrolled 134 patients with FTC who underwent preoperative cytology between April 2011 and December 2020. Results were classified into 6 categories according to the BSRTC: nondiagnostic, benign, atypia of uncertain significance (AUS), follicular neoplasm (FN), suspicious for malignancy, or malignant. Overall, 8 of 134 patients (6.0%) were categorized as having a nondiagnostic FTC, 35 of 134 (26.1%) as benign, 51 of 134 (38.1%) as AUS, and 40 of 134 (29.9%) as FN. No lesions were classified as suspicious for malignancy or malignant. The nondiagnostic, AUS, and FN categories were associated with a progressively higher risk of vascular invasion, disease recurrence, and high-risk FTC, based on the 2022 World Health Organization classification (P for trend = .01, .01, and .01, respectively). Disease-free survival was lower in the FN group (log-rank P = .01). The initial BSRTC results may reflect not only the risk of malignancy but also the presence of vascular invasion and poor prognosis when the thyroid nodule is diagnosed as FTC. These results may provide prognostic information for therapeutic decision-making and clinical management of FTC.

Glioma Image-Level and Slide-Level Gene Predictor (GLISP) for Molecular Diagnosis and Predicting Genetic Events of Adult Diffuse Glioma.

The latest World Health Organization (WHO) classification of central nervous system tumors (WHO2021/5th) has incorporated molecular information into the diagnosis of each brain tumor type including diffuse glioma. Therefore, an artificial intelligence (AI) framework for learning histological patterns and predicting important genetic events would be useful for future studies and applications. Using the concept of multiple-instance learning, we developed an AI framework named GLioma Image-level and Slide-level gene Predictor (GLISP) to predict nine genetic abnormalities in hematoxylin and eosin sections: IDH1/2, ATRX, TP53 mutations, TERT promoter mutations, CDKN2A/B homozygous deletion (CHD), EGFR amplification (EGFRamp), 7 gain/10 loss (7+/10-), 1p/19q co-deletion, and MGMT promoter methylation. GLISP consists of a pair of patch-level GLISP-P and patient-level GLISP-W models, each pair of which is for a genetic prediction task, providing flexibility in clinical utility. In this study, the Cancer Genome Atlas whole-slide images (WSIs) were used to train the model. A total of 108 WSIs from the Tokyo Women's Medical University were used as the external dataset. In cross-validation, GLISP yielded patch-level/case-level predictions with top performances in IDH1/2 and 1p/19q co-deletion with average areas under the curve (AUCs) of receiver operating characteristics of 0.75/0.79 and 0.73/0.80, respectively. In external validation, the patch-level/case-level AUCs of IDH1/2 and 1p/19q co-deletion detection were 0.76/0.83 and 0.78/0.88, respectively. The accuracy in diagnosing IDH-mutant astrocytoma, oligodendroglioma, and IDH-wild-type glioblastoma was 0.66, surpassing the human pathologist average of 0.62 (0.54-0.67). In conclusion, GLISP is a two-stage AI framework for histology-based prediction of genetic events in adult gliomas, which is helpful in providing essential information for WHO 2021 molecular diagnoses.

DEK::AFF2 fusion-associated middle ear non-keratinizing squamous cell carcinoma: A case report

BACKGROUND Primary squamous cell carcinoma (SCC) of the middle ear is rare, with non-keratinizing basaloid types being exceptionally uncommon. Distinguishing these cancers, often caused by viral factors (e.g. , human papillomavirus or Epstein-Barr virus), or specific genetic alterations (e.g. , bromodomain-containing protein 4-nuclear protein in testis fusion gene or Ewing sarcoma breakpoint region 1 gene fused with FLI chromosomal rearrangement), from other cranial conditions, is difficult. The recently identified DEK::AFF2 non-keratinizing SCC (NKSCC) is a novel subtype, fitting the World Health Organization classification of head and neck neoplasms. Less than 30 cases have been reported, highlighting the need for further studies. CASE SUMMARY A 55-year-old female patient first exhibited signs of illness over 10 years ago with persistent discomfort in the left external auditory canal, accompanied by skin irritation and bleeding. One month prior to seeking professional help, she experienced hearing loss and a sensation of obstruction in the affected ear, intermittently accompanied by ringing sounds, but no dizziness. An unusual mass was detected in the left auditory canal, confirmed through biopsy as moderately differentiated epithelial squamous cancer cells. This led to her admission to our hospital, where the final diagnosis confirmed as “NKSCC linked to a positive DEK::AFF2 fusion”. The patient underwent surgical excision, followed by three cycles of local radiation therapy. Yet, metastasis to the lumbar vertebrae occurred 19 months post-treatment, followed by neck lymph node swelling detected three months after a physical examination. The patient died nine months later despite surgical removal of the metastatic lesion. CONCLUSION DEK::AFF2 gene fusion-associated NKSCC of the middle ear carries a grim prognosis and presents an emerging challenge.

The Significance of Detecting an Unusual Myeloblast Immunophenotype in a Presumptive Clinical Diagnosis of Myelodysplastic Syndromes.

Blasts in myelodysplastic syndromes (MDSs) typically have a primitive myeloid immunophenotype (CD34+CD117+CD13+CD33+HLA-DR+). On rare occasions, blasts were found to be CD34 negative or minimally expressed in a presumptive MDS. To investigate the occurrence of these cases, and to examine any unique molecular genetic features, and clinical relevance. Over 2000 flow cytometry immunophenotyping tests for MDS performed during a 5-year period were retrospectively reviewed. Chronic myelomonocytic leukemia and overt acute myeloid leukemia (AML) (≥20% blasts) were excluded. Approximately 800 cases had abnormal myeloblasts consistent with myeloid neoplasms; 96% of cases showed a typical primitive phenotype, but 31 patients (4%) had unusual blasts that were either completely or partially negative for CD34. Of the latter, recurrent genetic abnormalities were identified in 13 (42%) including 10 with nucleophosmin 1 (NPM1) mutation, 1 with lysine methyltransferase 2A (KMT2A) rearrangement, and 2 with t(3;5)(q25.3;q35.1)/NPM1::myeloid leukemia factor 1 (MLF1). These cases were classified as MDS prior to the 2022 classifications, but 9 of 13 (69%) and 7 of 13 (52%) cases would be reclassified as AML according to the 5th edition of the World Health Organization classification and the International Consensus Classification, respectively. Eight cases (26%) had multihit tumor protein p53 (TP53) mutation, and 6 of them were ultimately diagnosed as or quickly evolved to pure erythroid leukemia. Of the remaining 10 cases, 4 uncharacteristically had no detectable molecular genetic abnormalities. Our data show that, if a presumptive MDS shows a nonprimitive blast phenotype, caution is needed to rule out AML with recurrent genetic abnormality with an oligoblastic presentation, high-risk myeloid neoplasms with double-hit TP53 mutation with abnormal erythroid proliferation, and MDS with molecular-genetic and clinical features more akin to AML.

Pediatric lymphomas: overview and diagnostic challenges.

Only 10% of new lymphoma diagnoses in the USA occur in children < 15years. Although the same diagnostic criteria apply to both adult and pediatric lymphomas, there are important differences in some lymphoma subtypes. These differences are recognized by the World Health Organization (WHO) with the recent 2022 classification of pediatric tumors including pediatric hematopoietic tumors. Here, we review the WHO classification scheme for pediatric lymphomas and summarize the diagnostic criteria, recent genetic findings, and differences from their adult counterparts for some subtypes including those yet to be included as a definitive subtype. In general, there are differences in relatively frequency, genetic mutation, and prognosis with the pediatric counterpart often having better prognosis. Emerging B-cell lymphomas with recurrent gene alterations such as IRF4 rearrangement and 11q gain/loss chromosomal alterations will be reviewed. The overlapping pathological, clinical, and molecular features between pediatric-type follicular lymphoma (PTFL) and pediatric nodal marginal zone lymphoma (PNMZL) suggesting one disease with broad morphological spectrum will be discussed. The pathogenetic role of EBV in subclassifying Burkitt lymphoma is highlighted. The revised classification of the EBV-positive lymphoproliferative disorders in children is discussed. This review will focus on novel findings, areas of special interest, and diagnostic challenges in pediatric lymphomas.

A reproducibility study on invasion in small pulmonary adenocarcinoma according to the WHO and a modified classification, supported by biomarkers.

Evaluating invasion in non-mucinous adenocarcinoma (NMA) of the lung is crucial for accurate pT-staging. This study compares the World Health Organization (WHO) with a recently modified NMA classification. A retrospective case-control study was conducted on small NMA pT1N0M0 cases with a 5-year follow-up. Seventy cases were reviewed by 42 pulmonary pathologists first according to the WHO classification and after tutorial according to a modified classification. A third round was conducted based on feedback from 41 peers of previous rounds. Additionally, orthogonal biomarker analysis was performed. In the first two rounds, 42 pathologists from 13 countries assessed all 70 cases, while 36 pathologists evaluated 41 non-unanimous cases in the third round. Kappa values for invasiveness increased in rounds 1, 2, and 3 to 0.27, 0.45 and 0.62, respectively. In contrast to low variation in total tumor size measurements (6%), a marked increase in invasive tumor size variation was observed (42%), which was associated with high uncertainty. In the third round 10 cases were non-invasive, all without recurrence. The modified classification showed in the 3rd round marked reduction of the variation in pT staging compared to the current WHO classification. Proliferation rate, tumor mutational burden, and transcriptomic profiles supported the distinction between invasive cases and non-invasive cases of the modified classification. The modified classification demonstrates essentially higher reproducibility compared to the current WHO classification in NMA. The modified classification proves valuable in identifying low-risk lesions that are entirely non-invasive, and is supported by biomarker analysis.

The Prevalence and Diagnostic Patterns of Oral and Maxillofacial Lesions: A Seven-Year, Retrospective, Single-Center Cone Beam Computed Tomography and Histopathology Study in Saudi Arabia.

Objective: To determine the prevalence of oral and maxillofacial lesions among patients at King Abdulaziz University from January 2016 to December 2022. Methods: This cross-sectional observational study included patients diagnosed with oral and maxillofacial intra-bony lesions based on radiological findings and confirmed by histopathological examination. The lesions were classified according to the fourth edition of the World Health Organization Classification of Head and Neck Tumors. Results: This study included 237 patients with a mean age of 31.53 ± 14.97 years, of which 45.1% were female. Most patients (46.7%) had mandibular lesions, followed by maxillary lesions (35.9%). Only 2.95% of the tumors were malignant. Odontogenic cysts were the most prevalent (65.40%), with radicular cysts and keratocytes being the most common types. The most prevalent tumor types were odontoma and ameloblastoma. The most malignant lesion was multiple myeloma. Conclusions: Our findings reveal that mandibular cystic lesions predominated, and emphasize the low incidence of malignancy in the study population. They provide valuable insights into the oral and maxillofacial lesion landscape at a high-volume tertiary care center.

Reclassification of Acute Myeloid Leukemia According to the 2022 World Health Organization Classification and the International Consensus Classification Using Open-Source Data.

In 2022, the revised WHO classification and International Consensus Classification (ICC) for myeloid neoplasms were published. We examined the impact of these guidelines on AML diagnoses alongside the 2022 European LeukemiaNet (ELN) recommendations on risk stratification. We included 450 adult patients with newly diagnosed AML (non-acute promyelocytic leukemia) from the cBioPortal open-source dataset. Diagnoses and risk stratifications were revised based on the new guidelines and compared with the 2017 WHO classification. Survival analyses were performed using Cox regression. Among the patients included, 190 (42.2%) had consistent diagnoses across the three classifications, whereas 225 (50.0%) had inconsistent diagnoses. The two major WHO 2017 subtypes, AML not otherwise specified (AML-NOS) and AML with myelodysplasia-related changes (AML-MRC), were further subdivided according to the WHO 2022 and ICC. The ICC had the highest prognostication power among the three classifications. Subgroup analysis according to the different definitions of myelodysplasia-related AML and the introduction of AML with mutatedTP53 (AML-TP53) showed that the differentiation of AML-TP53 was beneficial. The update from ELN 2017 to ELN 2022 resulted in significant transitions in a subset of patients. The updated diagnostic classification and ELN risk stratification (i.e., the ICC and ELN 2022) showed a straightforward relationship. This study presents an integrative comparative analysis of past and current guidelines for AML diagnosis and risk classification based on open-source data. The ICC diagnostic criteria are clinically significant for determining AML prognosis. In line with the changing treatment paradigm for AML, future research is needed to continuously validate diagnostic and risk stratification systems.