Current World Health Organization Classification Research Articles

A Multicenter Study on Hepatocellular Adenomas in Korea: Clinicopathological and Imaging Features With an Emphasis on β-Catenin Mutated Subtype.

The clinicopathologic and imaging features of hepatocellular adenomas (HCAs) in Asian population remain unclear. We aimed to analyse clinicopathologic and imaging features of HCAs in Korea and propose an imaging-based method to differentiate β-catenin mutated HCA (βHCA) from other subtypes. This retrospective multicenter study included pathologically confirmed HCAs from three tertiary institutions in Korea between 2010 and 2023. HCA subtypes were determined according to the current World Health Organization classification using immunohistochemical staining. Two abdominal radiologists reviewed computed tomography and magnetic resonance imaging scans. The clinical characteristics and imaging features of HCA subtypes were compared. A scoring system for βHCA was developed and validated using development (January 2010-April 2021) and validation (May 2021-March 2023) cohorts. 121 patients (47 men; mean age, 39.0 years ±13.5) with 138 HCAs were included. HCAs displayed characteristic clinicopathologic features, including a high proportion of male (38.8%) and obese patients (35.5%), with the inflammatory subtype being the most common (38.4%) and a low percentage of patients using oral contraceptive (5.0%). Each HCA subtype demonstrated distinct clinical and imaging features. The scoring system incorporating tumour heterogeneity and iso to high hepatobiliary phase signal intensity on MRI for differentiating βHCA exhibited high performance in both the development (AUC 0.92, 95% CI: 0.87-0.97) and the validation cohort (AUC 0.91, 95% CI: 0.77-1.00). This comprehensive analysis of clinicopathologic and imaging features of HCAs in Korea contributes to the characterisation of HCAs across different geographical regions. The imaging-based scoring system effectively differentiates βHCA.

Evaluation of ploidy and the DNA index by flow cytometry in central nervous system tumors: a review.

Research on central nervous system tumors (CNSTs) has a significant impact on the diagnosis and prognosis of patients. Currently, CNSTs are classified according to the schema proposed by the World Health Organization (WHO), which considers clinical, histopathological, and molecular characteristics, highlighting the importance of tumor biology for accurate diagnosis and optimal treatment approaches. Despite these advances, assessing DNA ploidy-a marker of tumor aggressiveness-remains complex in CNSTs. This review investigates the utility of DNA index (DNAi) and DNA ploidy analysis by flow cytometry in diagnosing CNSTs and prognosing their outcomes. We systematically reviewed studies in the PubMed database from 1990 to the present using the keywords "DNA Index", "Brain", "Flow cytometry", and "Ploidy". We identified 151 studies, 36 of which met our inclusion criteria. We found considerable variation in sample sizes and methodological variation across the studies. Discrepancies between the reported DNAi and ploidy values were observed. Aneuploidy is generally associated with more aggressive tumors, although exceptions exist. Higher DNAi levels correlate with increased malignancy, notably in glioblastomas, astrocytomas, and meningiomas, whereas diploid astrocytomas and oligodendrogliomas are associated with shorter survival rates. DNA ploidy assessment via flow cytometry could predict CNST behavior, yet methodological issues with tissue selection, adequate control samples, and technique variability remain. DNAi and ploidy assessments show promise as prognostic markers in CNSTs. However, the standardization of flow cytometry protocols and alignment with the current WHO classification schema are essential steps to integrate ploidy analysis in routine CNST assessment.

Racial distribution of molecularly classified brain tumors.

In many cancers, specific subtypes are more prevalent in specific racial backgrounds. However, little is known about the racial distribution of specific molecular types of brain tumors. Public data repositories lack data on many brain tumor subtypes as well as diagnostic annotation using the current World Health Organization classification. A better understanding of the prevalence of brain tumors in different racial backgrounds may provide insight into tumor predisposition and development, and improve prevention. We retrospectively analyzed the racial distribution of 1709 primary brain tumors classified by their methylation profiles using clinically validated whole genome DNA methylation. Self-reported race was obtained from medical records. Our cohort included 82% White, 10% Black, and 8% Asian patients with 74% of patients reporting their race. There was a significant difference in the racial distribution of specific types of brain tumors. Blacks were overrepresented in pituitary adenomas (35%, P < .001), with the largest proportion of FSH/LH subtype. Whites were underrepresented at 47% of all pituitary adenoma patients (P < .001). Glioblastoma (GBM) IDH wild-type showed an enrichment of Whites, at 90% (P < .001), and a significantly smaller percentage of Blacks, at 3% (P < .001). Molecularly classified brain tumor groups and subgroups show different distributions among the three main racial backgrounds suggesting the contribution of race to brain tumor development.

Update on Pathologic Conditions, Imaging Findings, Prevention, and Management of Human Papillomavirus-related Neoplasms.

Human papillomavirus (HPV) is the most common sexually transmitted infection that proliferates in the squamous epithelium and is the most common source of viral-related neoplasms. Low-risk subtypes (HPV-6 and -11) cause respiratory papillomas (laryngeal, tracheal, and bronchial) and condyloma acuminata of the penis, anus, and perineal region (anogenital warts). High-risk subtypes (HPV-16, -18, -31, and -33) are responsible for oropharyngeal squamous cell carcinoma (SCC) that involves the tongue base, tonsils, posterior pharyngeal wall, and larynx and malignancies of the anogenital region (cancers of the cervix, vagina, vulva, penis, and anal canal). Recent studies have increasingly shown a favorable treatment response and substantial differences in the overall prognosis associated with HPV-associated oropharyngeal cancers. Given this fact, oropharyngeal, cervical, and penile SCCs are classified as HPV-associated and HPV-independent cancers in the current World Health Organization classification. Imaging is essential in the early detection, diagnosis, and staging of HPV-associated cancers. Imaging also helps assess treatment response and postoperative complications and is used for long-term surveillance. HPV-associated oropharyngeal SCCs have well-defined borders and solid and cystic nodal metastases at imaging. Updated screening and vaccination guidelines are currently available that have great potential to decrease the overall disease burden and help control this worldwide public health concern. Novel therapeutic strategies, such as immunotherapies, are being explored, and imaging biomarkers that can predict treatment response and prognosis are being investigated; radiologists play a pivotal role in these efforts. ©RSNA, 2024 Supplemental material is available for this article.

Giant cell carcinoma of the urinary bladder

We present the clinicopathological features of 23 cases of the giant cell subtype of urothelial carcinoma, a rare subtype of bladder cancer recognized in the current World Health Organization classification of urological tumors. Histologically, the architectural pattern of the tumor varied from infiltrating to the solid expansile pleomorphic tumor with giant, bizarre, anaplastic cells. Typical or atypical mitotic figures were frequently present in all cases. Between 10 and 30% of the tumor had a giant cell component. All cases were associated with conventional high-grade urothelial carcinoma, with areas of squamous cell divergent differentiation and micropapillary carcinoma present in six and two cases, respectively. In one case each had sarcomatoid, nested, small cell, or glandular divergent differentiation. At diagnosis, 35% of patients had advanced disease and 12% had distant metastases. When comparing giant cell urothelial carcinoma with conventional urothelial carcinoma in a matched analysis, differences in overall and cancer-specific survival were observed, particularly in the T1 stage category. Immunohistochemical staining showed a similar profile of urothelial lineage with frequent positive expression of uroplakin II, GATA3, CK20, CK7, and S100P in both giant cell and conventional urothelial carcinomas. High Ki67 proliferation (range, 60–90%; mean, 71%) and nuclear p53 accumulation (mutant profile; range, 50–90%; mean, 64%) were observed. Using the 22C3 assay, the expression of PD-L1 was found to be variable in two cases, and beta-HCG was negative. In conclusion, giant cell carcinoma is a subtype of urothelial carcinoma associated with advanced clinical stage and a trend to lower survival rates.

HGG-19. H3- AND IDH-WILDTYPE DIFFUSE PAEDIATRIC-TYPE HIGH-GRADE GLIOMA WITHMYCN-AMPLIFICATION: AN INDICATION CRITERION FOR LI-FRAUMENI SYNDROME TESTING

Abstract BACKGROUND: In the current World Health Organization (WHO) Classification of Tumors of the Central Nervous System (CNS) (5th edition), the introduction of a molecular layer to the integrated diagnosis not only helps to characterize and prognosticate paediatric CNS tumors but the molecular alteration may predict a potential therapeutic option with a targeted agent. Furthermore, certain gene alterations may be a presage of germline alterations or cancer predisposition syndromes, portending significant implications to the index patients and their families. We report a 5-year-old boy diagnosed with non-metastatic left hemispheric H3-wildtype and IDH-wildtype diffuse paediatric-type high-grade glioma with MYCN-amplification, who was subsequently found to have Li-Fraumeni syndrome. He presented with a 3-day history of facial asymmetry, unsteady gait and right sided weakness. There was no family history of malignancy. Initial MRI revealed a restricting and enhancing solid cystic lesion (5.9 x 4.3 x 5.8cm) in the left frontal-temporal-parietal region. Tumor debulking was performed. Histopathological examination by the local pathologist revealed features of high-grade glioma. Second pathology review with next generation sequencing confirmed H3-wildtype and IDH-wildtype diffuse paediatric-type high-grade glioma with MYCN-amplification and TP53 p.Y103* mutation. He was started on focal radiotherapy and oral temozolomide but succumbed to local and metastatic progressive disease. After genetic counselling, his DNA extracted from blood was sent for targeted exome sequencing and germline mutation of TP53 was demonstrated. Cascade screening of the family members were negative of TP53 mutation. Guerrini-Rousseau et al reported that 57% (n=7) of H3-wildtype and IDH-wildtype diffuse paediatric-type high-grade glioma with MYCN-amplification harboured germline TP53 pathogenic variants. This case further highlights the importance of screening of Li-Fraumeni syndrome in patient with H3-wildtype and IDH-wildtype diffuse paediatric-type high-grade glioma with MYCN-amplification even in the absence of a family history.

Morphologic Features of Invasion in Lung Adenocarcinoma: Diagnostic Pitfalls.

Reproducibility of pulmonary invasive adenocarcinoma diagnosis is poor when applying the World Health Organization (WHO) classification. In this article, we aimed first to explain by 3-dimensional morphology why simple pattern recognition induces pitfalls for the assessment of invasion as applied in the current WHO classification of pulmonary adenocarcinomas. The underlying iatrogenic-induced morphologic alterations in collapsed adenocarcinoma in situ overlap with criteria for invasive adenocarcinoma. Pitfalls in seemingly acinar and papillary carcinoma are addressed with additional cytokeratin 7 and elastin stains. In addition, we provide more stringent criteria for a better reproducible and likely generalizable classification.

Mixed-Grade Urothelial Carcinoma: Insights Into Clinical Behavior and Prognostic Implications Compared to Pure Low-Grade and High-Grade Urothelial Carcinomas.

Low-grade urothelial carcinoma (LGUC) and high-grade urothelial carcinoma (HGUC) are distinguished based on architectural and cytological features, with the anticipation that HGUC exhibits more aggressive behavior and a worse prognosis compared to LGUC. The current World Health Organization classification recognizes mixed-grade urothelial carcinoma (MGUC, for the purposes of this study) as a separate category that behaves like LGUC if the high-grade component is <5% and states that any tumor with ≥5% high-grade component should be graded as HGUC. To evaluate the risk of tumor recurrence, grade, and stage progression of MGUC compared to LGUC and HGUC. A total of 150 de novo noninvasive polypoid urothelial carcinomas (41 cases of MGUC, 59 of LGUC, and 50 of HGUC) were included. Tumor recurrence, grade, and stage progression were compared among the MGUC, LGUC, and HGUC cases. Tumor recurrence was observed in 14 of 41 (34.2%) of MGUC, 33 of 59 (55.9%) of LGUC, and 28 of 50 (56%) of HGUC. Grade progression occurred in 5 of 41 (12.2%) of MGUC cases and 5 of 59 (8.5%) of LGUC cases. No stage progression was observed in LGUC or MGUC cases, while 7 of 50 (14%) of HGUC cases showed stage progression. MGUC was associated with lower odds and hazard of recurrence compared to LGUC. The rate of grade progression was higher in MGUC and occurred after a shorter interval compared to LGUC. MGUC showed a prognosis closer to LGUC. Our study supports the current recommendation to classify tumors with <5% high-grade component as MGUC, as these tumors display clinical characteristics and outcomes close to that of pure LGUC.

Neoplastic Progression in Macroscopic Precursor Lesions of the Pancreas.

Macroscopic precursor lesions of the pancreas represent a complex clinical management problem. Molecular characterization of pancreatic cysts has helped to confirm and refine clinical and pathologic classifications of these lesions, inform our understanding of tumorigenesis in the pancreas, and provide opportunities for preoperative diagnosis. To review the pathologic classification of macroscopic cystic lesions of the pancreas: intraductal papillary mucinous neoplasms (IPMNs), mucinous cystic neoplasms (MCNs), intraductal oncocytic papillary neoplasms (IOPNs), and intraductal tubulopapillary neoplasms (ITPNs), and to describe our current state of understanding of their molecular underpinnings, relationship to invasive carcinomas, and implications for diagnosis and prognostication. We assessed the current primary literature and current World Health Organization Classification of Digestive System Tumours. Macroscopic cystic lesions of the pancreas are morphologically and molecularly diverse. IPMNs and MCNs share mucinous cytoplasm with papillae. MCNs are defined by ovarian-type stroma. IOPNs have granular eosinophilic cytoplasm, prominent nucleoli, and complex, arborizing papillae. ITPNs demonstrate complex, back-to-back tubules and anastomosing papillae and lack prominent intracellular mucin. IPMNs and MCNs are characterized by driver mutations in KRAS/GNAS (IPMNs) and KRAS (MCNs), with later driver events in RNF43, CDKN2A, SMAD4, and TP53. In contrast, IOPNs and ITPNs have recurrent rearrangements in PRKACA/PRKACB and MAPK-associated genes, respectively. The recurrent alterations described in cysts provide an opportunity for diagnosis using aspirated cyst fluid. Molecular characterization of IPMNs shows a striking spatial and mutational heterogeneity, challenging traditional models of neoplastic development and creating challenges to interpretation of cyst fluid sequencing results.

Pediatric spinal ependymoma with chromothripsis of chromosome 6: a case report and review of the literature

BackgroundEpendymomas are the third most common central nervous system tumor in the pediatric population; however, spinal ependymomas in children are rare. Ependymomas affecting the spinal cord most frequently occur in adults of 20–40 years of age. The current World Health Organization classification system for ependymomas is now composed of ten different entities based on histopathology, location, and molecular studies, with evidence that the new classification system more accurately predicts clinical outcomes.Case presentationWe present the case of a 16-year-old Caucasian female patient with a history of type 2 neurofibromatosis with multiple schwannomas, meningioma, and spinal ependymoma. Chromosome analysis of the harvested spinal ependymoma tumor sample revealed a 46,XX,−6,+7,−22,+mar[16]/46,XX[4] karyotype. Subsequent OncoScan microarray analysis of the formalin-fixed paraffin-embedded tumor sample confirmed + 7, −22 and clarified that the marker chromosome represents chromothripsis of the entire chromosome 6 with more than 100 breakpoints. Fluorescent in situ hybridization and microarray analysis showed no evidence of MYCN amplification. The final integrated pathology diagnosis was spinal ependymoma (central nervous system World Health Organization grade 2 with no MYCN amplification.ConclusionThis case adds to the existing literature of pediatric patients with spinal ependymomas and expands the cytogenetic findings that may be seen in patients with this tumor type. This case also highlights the value of cytogenetics and microarray analysis in solid tumors to provide a more accurate molecular diagnosis.

Thoracic SMARCA4-deficient undifferentiated tumor: current knowledge and future perspectives.

Thoracic SMARCA4-deficient undifferentiated tumor is a newly recognized disease entity characterized as a high-grade malignant neoplasm with an undifferentiated or rhabdoid phenotype. The tumor was initially identified as a subtype of thoracic sarcoma with SMARCA4 loss, but further investigation resulted in its classification as a subtype of epithelial malignancies in the current World Health Organization classification. SMARCA4-deficient undifferentiated tumor is highly aggressive and has a poor prognosis. Because of its rarity, an optimal treatment strategy has not yet been identified. In this review, we summarize the literature on SMARCA4-deficient undifferentiated tumor in terms of its clinical characteristics, diagnosis, treatment strategy and future perspectives.

Clinical Features and Treatment Outcomes of Grey Zone Lymphoma (GZL), Unclassifiable B-Cell Lymphoma with Features Intermediate between Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma - a Real-Life Multicenter Study By the Croatian Cooperative Group for Hematologic Diseases (KroHem)

GZL with features between classical Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL) is a rare entity originally introduced in the 2008 World Health Organization (WHO) classification. GZL has been included in KroHem Lymphoma Treatment Guidelines since 2012. The recommended treatment was induction with escalated BEACOPP (escBEACOPP) in those below 60 y and ABVD in those above 60 y, both in combination with rituximab (R) and consolidation with radiotherapy (RT) for patients with limited or autologous stem cell transplantation (ASCT) in those with advanced-stage disease. We conducted a comprehensive retrospective analysis of GZL patients treated in KroHem centers to evaluate clinical features, treatment outcomes and prognostic factors. GZL diagnoses were confirmed by a hematopathologist from a designated expert center, according to current WHO classification at time of diagnosis. Twenty-three patients were evaluable for analysis, 20 diagnosed de novo, and 3 in relapse (2 after HL, 1 after DLBCL). Fourteen patients (60%) were male; median age was 39 and range 18-78 y. Thirteen (57%) presented with mediastinal GZL (MGZL) and 10 (43%) with non-MGZL (NMGZL). NMGZL patients were older (median 55 versus 31 y, p = 0.0157) and had more frequently high NCCN-IPI scores (9/10 vs 5/13, p = 0.0288). Twelve front-line patients received R-escBEACOPP, 4 DA-R-EPOCH, 1 R-ABVD and 3 R-CHOP-like regimen. Of the 3 patients diagnosed in relapse, 2 were treated with R-ICE and 1 with R-CHOP. Ten patients were irradiated and 9 underwent ASCT as consolidation in 1 st remission. Stem-cell collection was successful in all planned patients, albeit 70% with plerixafor. Sixteen (80%) front-line patients responded to immunochemotherapy, 2 progressed during consolidation. At the end of treatment, 13 patients were in complete and 1 in partial remission for a response rate of 70%. Of the 3 relapsing patients, 2 treated with R-ICE responded, underwent ASCT and are in continuous remission. One patient died of toxicity after ASCT in 1 st remission. After a median survivors follow-up time of 42 months, 6 front-line patients have died and additional 3 progressed. Overall survival (OS) at 4 y is 65% and event-free survival (EFS) 52%. MGZL and NMGZL patients had similar outcomes; OS at 4 y was 69% and 64% (p=0.637) and EFS 52% vs. 50% (p=0.88) respectively. Performance status was a statistically significant prognostic factor (OS at 4 y ECOG grade 0-1 90% vs. ECOG grade 2-4 17%, p&amp;lt;0.001; EFS at 4 y 67% vs. 17% p=0.044). Sex influenced EFS (male 70%, female 33% at 4 years, p=0.050), but not OS (69% vs. 61% p=0.667). Age (&amp;lt; 60 y &amp;gt;), presence of bulky or extranodal disease, stage, anemia, LDH or B2M level did not significantly influence outcomes. Patients treated with R-escBEACOPP had numerically superior outcomes (OS at 4 y 81% vs. 44%, p=0.167; EFS at 4 y 64% vs 38%, p=0.293). Despite the small number of patients, the difference was statistically significant in patients with MGZL; EFS at 4 y was 71% in the group treated with R-escBEACOPP vs 0% in the group treated with other regimens (p=0.021) and OS 100% vs. 0% (p&amp;lt;0.001). In contrast, patients with NMGZL treated with R-escBEACOPP had numerically inferior outcomes in comparison to those treated with other regimens (p=0.127 for OS and p=0.388 for EFS). In conclusion, our data confirm the validity of differentiating between MGZL and NMGZL. MGZL patients might benefit from aggressive therapies designed for HL, such as escBEACOPP, in combination with rituximab. Consolidation with ASCT is feasible, but most patients will need plerixafor to collect sufficient stem cells. Different regimens, as used for DLBCL, should be preferred in NMGZL patients.

Cytologic features of mesenchymal, melanocytic and haematolymphoid tumours of the central nervous system and metastases.

The current World Health Organization (WHO) classification of central nervous system (CNS) tumours includes several neoplasms that, while occurring in this location, are more frequently seen extracranially. These include mesenchymal, melanocytic and haematolymphoid neoplasms, as well as metastases. A few of these entities are exclusive of the CNS and have no extracranial counterpart. Despite their diverse histogenesis, these neoplasms share a peculiar predilection for involving meningeal structures. In fact, in the context of an intraoperative pathologic consultation of a meningeal tumour, virtually all these entities should be considered as potential diagnoses. Metastases in the CNS are very common. Most are carcinomas that cytologically resemble their site of origin. Loss of differentiation with cell dissociation and anaplasia and presence of accompanying fibrillary brain parenchyma can be a source of diagnostic problems. In this review, we intend to show the most relevant cytologic features of these tumours, and it is especially aimed at their analysis during intraoperative studies.

THU084 Corticotroph Tumor Type Influences Clinical Presentation In Patients With Nonfunctioning Pituitary Neuroendocrine Tumors

Abstract Disclosure: N. Al-Shamkhi: None. B. Edén Engström: None. O. Gudjonsson: None. J. Wikström: None. O. Casar-Borota: None. E. Rask: None. Introduction: According to the current World Health Organization classification of endocrine tumors the classification of non-functioning pituitary neuroendocrine tumors (NF-PitNET) is based on pituitary cell lineages, defined by immunohistochemical expression of anterior pituitary hormones and pituitary specific transcription factors. The second most common NF-PitNET type, after silent gonadotroph tumors, are silent corticotroph tumors that are regarded as a potentially more aggressive type. If there is indication for treatment, the first-line treatment is transsphenoidal surgery. Some, but not all studies have shown a higher degree of preoperative pituitary failure or more frequent postoperative pituitary failure in patients with silent corticotroph tumors compared to the other NF-PitNET. Objectives: We compared patients with silent corticotroph and silent gonadotroph tumors, and explored whether tumor type and radiological findings were associated with pre- or postoperative pituitary failure. Design and method: One hundred patients who underwent surgery for NF-PitNET at the same tertiary center were included. Data regarding age at surgery, sex, pre- and postoperative pituitary function and tumor type, were collected after chart review. Preoperative MRI examinations were revised regarding tumor volume and Knosp classification. Results: The majority, 72% (72/100) were classified as silent gonadotroph tumors followed by 18% (18/100) silent corticotroph tumors. Patients with silent corticotroph tumors were younger at surgery, P=0.003. There were no differences regarding sex, preoperative tumor volume, invasive growth on MRI, defined as Knosp grade &amp;gt; 3, pituitary failure or prolactin elevation between the two tumor types. Binary logistic regression showed that having a silent corticotroph tumor, P=0.04, odds ratio 5.7 (CI: 1.06-30.71), higher age at surgery, P=0.003, odds ratio 1.07 (CI: 1.02-1.13), and a larger preoperative tumor volume, P=0.01, odds ratio 1.18 (CI: 1.04-1.33), were all factors associated with an increased likelihood of having postoperative pituitary failure. Sex, invasive growth and preoperative prolactin elevation were not significant predictors of postoperative pituitary failure in the binary logistic regression. Conclusion: The results indicate that silent corticotroph tumors influence the clinical presentation of NF-PitNET. Patients with silent corticotroph tumors were significantly younger at surgery, and demonstrated an increased likelihood of postoperative pituitary failure. Presentation: Thursday, June 15, 2023

Prevalence and genotype distribution of human papillomavirus in cervical adenocarcinoma (usual type and variants): A systematic review and meta-analysis.

Cervical glandular neoplasms represent a heterogeneous group of tumors for which a comprehensive overview of the involvement of high-risk human papillomaviruses (HPV) in pathogenesis is still lacking. We first searched MEDLINE (PubMed), Embase, and Scopus databases (until October 2022), and systematically reviewed available literature. We then quantitatively estimated both pooled and genotype-specific prevalence of HPV DNA as well as the influence of various factors (e.g., geographical region, histological subtype, tissue/sample type) on computed effect size by means of random effects meta-analysis. In total, 379 studies comprising 17 129 cases of cervical adenocarcinoma were identified. The pooled HPV prevalence was 78.4% (95% confidence interval [95% CI]: 76.2-80.3) with a significant between-study heterogeneity (I2 = 79.4%, Q test p < 0.0001). Subgroup analyses indicated that the effect size differed substantially by geographical region (from 72.5% [95% CI: 68.7-76.1] in Asia to 86.8% [95% CI: 82.2-90.3] in Oceania) (p < 0.0001) and histological subtype of cancer (from 9.8% [95% CI: 5.5-17] in gastric-type to 85% [95% CI: 79.6-89.2] in usual-type cervical adenocarcinoma) (p < 0.0001). HPV16 and HPV18 were by far the most frequently detected viral strains with specific prevalence of 49.8% (95% CI: 46.9-52.6) and 45.3% (95% CI: 42.8-47.8), respectively. When stratified by continent or histologic variant, these genotype-specific results varied in a relatively limited manner. Altogether, these findings support that all histological subtypes of cervical adenocarcinoma are etiologically linked to high-risk HPV but to varying degrees. Therefore, a dual-criteria classification taking into account accurately both morphological and virological aspects could be an interesting evolution of the current binary World Health Organization classification, better reflecting the pathogenic diversity of the disease.

Pediatric brain tumors

Pediatric central nervous system (CNS) tumors differ in their relative frequency, location, histology, biological behavior and prognosis from tumors in adults. Accurate neuropathological classification of CNS tumors is essential for therapeutic decisions and inclusion in therapy optimization studies. Tissue samples are analyzed by standardized conventional histological, immunohistological and molecular pathological methods and diagnosed according to the current World Health Organization (WHO) classification for CNS tumors (2021). By identifying characteristic genetic alterations and specific epigenetic signatures, the precision in the classification of pediatric brain tumors has significantly improved in recent years. The WHO classification allows aworldwide uniform, standardized classification of brain tumors and forms the basis for comparability of international epidemiological and clinical data. In some tumor types, such as childhood gliomas and embryonal tumors, key molecules and signaling pathways have been identified in recent years that represent starting points for new mechanism-based therapeutic modalities in the treatment of these patients.

Frequent nuclear β-catenin expression in pulmonary enteric-type adenocarcinoma according to the current World Health Organization criteria.

Based on the current World Health Organization classification criteria, five of 3895 consecutive cases of surgically resected primary lung carcinomas (0.13%) categorized as enteric-type were analyzed. Three cases completely comprised tumor cells that resemble colorectal adenocarcinoma, while the other two cases exhibited features of conventional adenocarcinomas admixed with enteric components. Immunohistochemically, all patients expressed at least three of the five intestinal markers: CDX2, CK20, HNF4α, MUC2, and SATB2. None of the patients expressed TTF-1 and NKX3.1. Three cases showed nuclear accumulation of β-catenin, indicating activation of the Wnt/β-catenin signaling pathway; APC mutations were detected in one of these cases. TP53 mutations were detected in three cases. Mutated EGFR or ALK fusions were not detected. Our study demonstrates that pulmonary enteric-type adenocarcinomas share immunohistochemical features and genetic alterations with colorectal adenocarcinomas, which are characterized by frequent activation of the Wnt/β-catenin signaling pathway and a lack of actionable mutations.

A unique case of a fulminant clonal CD8-positive T-cell lymphoproliferative disorder with CNS involvement

BackgroundThis is a unique case that describes the presentation, investigations, and disease trajectory of a fatal, clonal CD8-positive T-cell lymphoproliferative disorder in an otherwise healthy and immunocompetent patient with Epstein-Barr virus seronegative status. Central nervous system involving T-cell lymphoproliferative disorders are rare and typically encountered in the setting of immunocompromise. These disorders are often associated with aggressive cytomorphological features and characteristic magnetic resonance imaging patterns, which were not seen in this case.Case presentationHere we describe a case of a 65 year-old male presenting with neuropsychiatric symptoms, truncal ataxia, and falls who’s bone marrow, cerebrospinal fluid, and brain biopsy were consistent with a clonal CD8-positive T-cell lymphoproliferative disorder that did not meet existing World Health Organization criteria for classification as T-cell lymphoma. The patient was treated with intrathecal methotrexate resulting in transient improvement of his symptoms followed by disease progression and death related to aspiration.ConclusionsThis case highlights the importance of urgent and comprehensive work-up in patients with clinical features suggestive of lymphoma with central nervous system involvement, despite atypical imaging features and lack of cytomorphological features satisfying current World Health Organization classification criteria.

Cytological features of diffuse and circumscribed gliomas.

The current World Health Organization classification of gliomas is based on morphological, genetic, and molecular parameters. In this review, we intend to present the most relevant cytological features of these tumours, with a particular focus on their analysis during intraoperative studies. Rapid diagnosis is required in this context, and at present it is not possible to evaluate the genetic or molecular profile of a tumour intraoperatively. New terminology and diagnostic parameters have been introduced, but the essence of intraoperative recognition remains the same. The main challenge in astrocytoma IDH-mutant, grade 2 is recognising the tissue as neoplastic. Since glioma grades 3 and 4 are assigned based on histological and genetic variables that are not necessarily measurable on cytology, the term high-grade glioma is often used for intraoperative diagnosis. Oligodendroglioma, IDH-mutant and 1p/19q-codeleted shows peculiar cytological findings as well as the common subtypes of glioblastoma IDH-wildtype (giant cell, epithelioid, gliosarcoma and small cell). Many of the paediatric-type-diffuse gliomas have been described very recently and there are no cytological reports of proven cases. Finally, pilocytic astrocytoma, pleomorphic xanthoastrocytoma, subependymal giant cell astrocytoma, chordoid glioma, and astroblastoma MN1-altered constitute the group of circumscribed astrocytic gliomas. They are remarkable entities that the pathologist must be able to recognise since most are low-grade neoplasms that can show atypical morphological features.

A remarkable and aggressive aneurysmal bone cyst ravaging the femoral shaft, advancing to lung metastases: An extremely rare case

Aneurysmal bone cysts (ABCs) are relatively uncommon tumor-like lesions that require careful management. Reporting such cases is crucial to highlight the importance of understanding the physiopathology and treatment options associated with ABCs. Literature-based writing emphasizes the significance of reporting cases like the one presented here. The aneurysmal bone cyst, classified as a Tumor Rich in Giant Cells according to the latest World Health Organization (WHO) classification of soft tissue and bone tumors, has posed several hypotheses and challenge. This aggressive form and rare localization of this lesion necessitates thorough discussions regarding its management.We present a compelling case of a 37-year-old patient, without any specific pathological history, with a giant diaphyseal aneurysmal bone cyst located in the right femur. Remarkably, the lesion had been progressing for a decade, leading to extensive destruction of the entire femoral diaphysis despite undergoing previous surgical interventions. The patient's unique circumstances highlight the unpredictable behavior and destructive potential of aneurysmal bone cysts in rare anatomical locations.This case underscores the need for a comprehensive understanding of aneurysmal bone cysts and their management. The utilization of denosumab, an inhibitor of the RANK/RANKL system, as a medical treatment in conjunction with surgery resulted in a favorable therapeutic response, including a reduction in tumor mass. The current WHO classification, recognizing ABCs as Tumors Rich in Giant Cells, consolidates previous hypotheses and enables the development of new therapeutic protocols. The integration of surgery and medical treatment holds promise for improving outcomes in patients with aneurysmal bone cysts. In conclusion, advancements in understanding the physiopathology and treatment options are crucial for developing effective therapeutic protocols to these aggressive forms of ABCs.