Latest World Health Organization Classification Research Articles

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.

Molecular pathophysiology of germline mutations in acute myeloid leukemia.

Germline (GL) predisposition to acute myeloid leukemia (AML) has been established as an independent disease entity in the latest World Health Organization classification. Following the American College of Medical Genetics and Genomics guidelines, GL variants were interpreted as causal if they were classified as "pathogenic." GL predisposition can be divided into three groups with different phenotypes, and play an important role in the pathogenesis of adult-onset AML. The clinical course and age of onset of myeloid neoplasms varied considerably for each gene. For example, patients with GATA2 GL variants develop AML before the age of 30 along with bone marrow failure, whereas those with DDX41 GL variants tend to develop AML after the age of 50 without any preceding hematological abnormalities or organ dysfunction. A comprehensive analysis of adult-onset myelodysplastic syndromes in transplant donors showed a 7% frequency of pathogenic GL variants, with DDX41 being the most frequent gene mutation at approximately 3.8%. Future research on GL predisposition at any age of myeloid neoplasm onset will assist in early and accurate diagnosis, development of effective treatment strategies, and selection of suitable donors for stem cell transplantation.

Delineating the Biomarker Potential and Therapeutic Significance of MicroRNAs in IDH-wildtype Glioblastoma as Defined by the WHO CNS5 Criteria

The World Health Organization (WHO) CNS5 classification, updated in 2021, has brought about a significant transformation in the diagnosis and treatment of IDH-wildtype glioblastoma, a subgroup of aggressive brain tumors. This new system, which incorporates molecular markers alongside traditional tissue analysis, provides a more refined approach that facilitates the identification of distinct glioblastoma subtypes with unique genetic profiles. Examples of these subtypes include IDH-mutant astrocytoma, IDH-mutant and 1p/19q-deleted oligodendroglioma, and IDH-wildtype glioblastoma. Despite advancements in genetics and targeted therapies, the treatment of these malignant tumors remains an ongoing quest. Therefore, the need for more specific diagnostic and therapeutic approaches is undeniable. MicroRNAs (miRNAs) are emerging as molecules that molecular biology has brought to the medical world in this context. These tiny molecules act as master regulators of gene expression and hold immense potential for glioblastoma diagnosis, prognosis prediction, and biomarker development. Recent research has highlighted the potential of miRNAs as therapeutic strategies, attracting scientific interest to this point. This review examines the current relationships of miRNAs in the context of IDH-wildtype glioblastoma within the framework of the WHO CNS5 classification. Utilizing extensive databases, this article investigates the intricate relationship between genetic abnormalities defined in the latest WHO classification and dysregulated miRNAs. By analyzing proposed molecular biomarkers and associated miRNA dysregulation, we aim to pave the way for the development of personalized miRNA-based therapies for this aggressive cancer type.

Diagnostic Biomarkers in Renal Cell Tumors According to the Latest WHO Classification: A Focus on Selected New Entities.

The fifth edition of the World Health Organization (WHO) classification for urogenital tumors, released in 2022, introduces some novelties in the chapter on renal epithelial tumors compared to the previous 2016 classification. Significant changes include the recognition of new disease entities and adjustments in the nomenclature for certain pathologies. Notably, each tumor entity now includes minimum essential and desirable criteria for reliable diagnosis. This classification highlights the importance of biological and molecular characterization alongside traditional cytological and architectural features. In this view, immunophenotyping through immunohistochemistry (IHC) plays a crucial role in bridging morphology and genetics. This article aims to present and discuss the role of key immunohistochemical markers that support the diagnosis of new entities recognized in the WHO classification, focusing on critical topics associated with single markers, in the context of specific tumors, such as the clear cell capillary renal cell tumor (CCPRCT), eosinophilic solid and cystic renal cell carcinoma (ESC-RCC), and so-called "other oncocytic tumors", namely the eosinophilic vacuolated tumor (EVT) and low-grade oncocytic tumor (LOT). Their distinctive characteristics and immunophenotypic profiles, along with insights regarding diagnostic challenges and the differential diagnosis of these tumors, are provided. This state-of-the-art review offers valuable insights in biomarkers associated with novel renal tumors, as well as a tool to implement diagnostic strategies in routine practice.

Molecular classification and intratumoral heterogeneity of gastric adenocarcinoma.

Gastric cancers frequently harbor striking histological complexity and diversity between lesions as well as within single lesions, known as inter- and intratumoral heterogeneity, respectively. The latest World Health Organization Classification of Tumors designated more than 30 histological subtypes for gastric epithelial tumors, assigning 12 subtypes for gastric adenocarcinoma (GAD). Meanwhile, recent advances in genome-wide analyses have provided molecular aspects to the histological classification of GAD, and consequently revealed different molecular traits underlying these histological subtypes. Moreover, accumulating knowledge of comprehensive molecular profiles has led to establishing molecular classifications of GAD, which are often associated with clinical biomarkers for therapeutics and prognosis. However, most of our knowledge of GAD molecular profiles is based on inter-tumoral heterogeneity, and the molecular profiles underlying intratumoral heterogeneity are yet to be determined. In this review, recently established molecular classifications of GAD are introduced in the aspect of pathological diagnosis and are discussed in the context of intratumoral heterogeneity.

CLINICAL CASE OF KERATOACANTHOMA

Keratoacanthoma is a common, rapidly growing skin tumour that has long been considered benign due to its staged course and ability to spontaneously regress. However, according to the latest World Health Organization classification, keratoacanthoma is classified as a well-differentiated form of squamous cell carcinoma.
 Despite its long history keratoacanthoma remains a subject of controversy with regard to epidemiology, diagnosis, prognosis, and treatment.
 The etiology and pathogenesis of keratoacanthoma are also not clearly defined. However, a number of factors have been identified that are highly likely to lead to the development of a tumour. In particular, these are ultraviolet and X-ray radiation, thermal and traumatic injuries, chemical carcinogens, genetic and immunological predictors, human papillomaviruses and certain drugs (sorafenib, infliximab, etc.).
 Clinically, keratoacanthoma appears on the skin as a single or multiple crater-like nodule. Dermoscopy can be used for early diagnosis and differentiation from other tumour formations. The choice of therapy varies widely and depends on the location, stage of development, and size of the tumour.
 The publication presents a number of cases which demonstrate the clinical, dermoscopic, and histological picture of keratoacanthomas.
 Case presentation. Patient A, 44 years old, skin with signs of photodamage. A single dense nodule, up to 0.5 cm in diameter, on the anterior surface of the right lower leg. It appeared and grew rapidly over the past month.
 Dermoscopy with photographic fixation was performed. A non-pigmented dome-shaped lesion with central yellow-brown keratinous masses, sporadic haemorrhages, and white structureless areas was observed. The vascular pattern was represented by looped, glomerular and helical vessels in a radial arrangement. The lesion was surgically excised. A pathohistological study was carried out. The conclusion was a well-differentiated squamous cell carcinoma of the skin.
 In typical cases, the diagnosis of keratoacanthoma is not difficult. However, the combination with other skin lesions can distort the clinical picture. For example, in Patient B, keratoacanthoma developed against the background of seborrheic keratosis. In such cases, the use of dermoscopy can provide additional clues to the diagnosis and, accordingly, influence treatment methods.
 Considering keratoacanthoma as a well-differentiated squamous cell carcinoma, surgical excision is preferred. The metastatic potential of this tumour is not significant, but in high-risk areas such as the lip or ear, it can reach 30%. At the same time, surgery reduces the risk of local recurrence. Other approaches include electrodissection and curettage, cryodestruction, intratumoural administration of methotrexate, 5-fluorouracil, bleomycin, and photodynamic therapy. These methods are appropriate in cases where the size or location of the tumour do not allow achieving the desired aesthetic effect.
 Conclusions: 1. Keratoacanthoma is a well-differentiated squamous cell carcinoma with a low potential for metastasis. 2. Central yellow-brown keratinous masses, sporadic haemorrhages, white structureless areas, in combination with looped and glomerular vessels in radial disposition seen during dermoscopy of a nodule, may be a sign of keratoacanthoma. 3. The choice of treatment method for keratoacanthoma depends on its location and size; surgical excision of the tumour should be preferred.

Advances of pathological diagnosis and molecular pathology of lung neuroendocrine neoplasms

The pathological classification and diagnostic criteria for lung neuroendocrine neoplasms (NENs) in the 2021 World Health Organization (WHO) lung tumor classification are similar to the prior classifications. However, the advances on the molecular studies of lung NENs have shown that both small cell lung carcinoma and large cell neuroendocrine carcinoma are highly heterogeneous tumors with neuroendocrine characteristics and can be subclassified based on the features of genomics or transcriptomics, which are valuable in the diagnosis of lung NENs subtypes and patient treatment. In addition, it is necessary to interpret emerging concepts such as "lung neuroendocrine tumor G3" and "histological transformation" from pathological perspectives, as well as to know the novel neuroendocrine biomarkers such as INSM1 and POU2F3. This article summarized the diagnostic changes and the advances of molecular pathology of lung NENs based on the latest WHO classification and molecular research.

Comprehensive Clinical-Pathologic Assessment of Malignant Phyllodes Tumors: Proposing Refined Diagnostic Criteria.

The latest World Health Organization classification of breast tumors recommends diagnosing malignant phyllodes tumors (MPTs) when all 5 morphologic features are present: permeative borders, marked stromal cellularity, marked stromal cytologic atypia, ≥10 mitoses per 10 high-power fields (HPF), and stromal overgrowth. We assessed the performance of this recommendation to capture MPTs and features predictive of distant metastasis in a multi-institutional retrospective study. Of 65 MPTs, most cases had at least focally permeative borders (58, 89%), with marked stromal cellularity in 40 (61.5%), marked atypia in 38 (58.5%), ≥10 mitoses per 10 HPF in 50 (77%), and stromal overgrowth in 56 (86%). Distant metastases were observed in 20 (31%) patients (median follow-up 24.5mo, 1 to 204). Only 13 of 65 (20%) cases had all 5 morphologic features, while only 7 of 20 (35%) cases with distant metastases had all 5 features. In univariate analysis, only marked stromal atypia ( P =0.004) and cellularity ( P =0.017) were associated with decreased distant metastasis-free survival. In multivariate Cox regression, the combination of stromal overgrowth, marked stromal cellularity, and atypia (C-index 0.721, 95% CI: 0.578, 0.863) was associated with decreased distant metastasis-free survival. The current World Health Organization recommendation will miss a significant number of MPTs with distant metastases. We propose refined diagnostic criteria for MPTs: (1) stromal overgrowth combined with ≥1 feature(s) (marked cellularity, marked atypia, or ≥10 mitoses per 10 HPF), or (2) in the absence of stromal overgrowth, marked cellularity combined with ≥1 feature(s) (permeative borders, marked atypia, or ≥10 mitoses per 10 HPF).

Urothelial carcinoma; an overview of histology, molecular subtypes, and clinical implications based on the latest WHO classification

The incidence of urothelial carcinoma is increasing worldwide (including in Iran). Bladder cancer can be classified in various manners according to the standardized histomorphology set by the World Health Organization (WHO). Various genetic modifications occurring at the DNA level and the resulting variations in RNA expression give rise to different subcategories that have important implications for diagnosis, prognosis, and treatment. The molecular basis of these morphologic variances is now better understood because of recent developments in molecular biology. With updates on the genetic and clinical characteristics, we highlight the histologic traits of the divergent differentiation and subtypes recognized by the most recent WHO classification (5th edition). Molecular subtypes of lower and upper tract cancer can be used to characterize their clinical behaviors and determine therapeutic responses to neoadjuvant chemotherapy. In this overview article, we also present a preliminary analysis of our ongoing data collection on molecular features of urothelial carcinoma.

Diffusion histogram profiles predict molecular features of grade 4 in histologically lower-grade adult diffuse gliomas following WHO classification 2021

ObjectivesIn the latest World Health Organization classification 2021, grade 4 adult diffuse gliomas can be diagnosed with several molecular features even without histological evidence of necrosis or microvascular proliferation. We aimed to explore whole tumor histogram-derived apparent diffusion coefficient (ADC) histogram profiles for differentiating between the presence (Mol-4) and absence (Mol-2/3) of grade 4 molecular features in histologically lower-grade gliomas.MethodsBetween June 2019 and October 2022, 184 adult patients with diffuse gliomas underwent MRI. After excluding 121 patients, 18 (median age, 64.5 [range, 37–84 years]) Mol-4 and 45 (median 40 [range, 18–73] years) Mol-2/3 patients with histologically lower-grade gliomas were enrolled. Whole tumor volume-of-interest-derived ADC histogram profiles were calculated and compared between the two groups. Stepwise logistic regression analysis with Akaike’s information criterion using the ADC histogram profiles with p values < 0.01 and age at diagnosis was used to identify independent variables for predicting the Mol-4 group.ResultsThe 90th percentile (p < 0.001), median (p < 0.001), mean (p < 0.001), 10th percentile (p = 0.014), and entropy (p < 0.001) of normalized ADC were lower, and kurtosis (p < 0.001) and skewness (p = 0.046) were higher in the Mol-4 group than in the Mol-2/3 group. Multivariate logistic regression analysis revealed that the entropy of normalized ADC and age at diagnosis were independent predictive parameters for the Mol-4 group with an area under the curve of 0.92.ConclusionADC histogram profiles may be promising preoperative imaging biomarkers to predict molecular grade 4 among histologically lower-grade adult diffuse gliomas.Clinical relevance statementThis study highlighted the diagnostic usefulness of ADC histogram profiles to differentiate histologically lower grade adult diffuse gliomas with the presence of molecular grade 4 features and those without.Key Points• ADC histogram profiles to predict molecular CNS WHO grade 4 status among histologically lower-grade adult diffuse gliomas were evaluated.• Entropy of ADC and age were independent predictive parameters for molecular grade 4 status.• ADC histogram analysis is useful for predicting molecular grade 4 among histologically lower-grade gliomas.

Epigenetic Regulation in Primary CNS Tumors: An Opportunity to Bridge Old and New WHO Classifications.

Originally approved in 1979, a specific grading classification for central nervous system (CNS) tumors was devised by the World Health Organization (WHO) in an effort to guide cancer treatment and better understand prognosis. These "blue books" have since undergone several iterations based on tumor location, advancements in histopathology, and most recently, diagnostic molecular pathology in its fifth edition. As new research methods have evolved to elucidate complex molecular mechanisms of tumorigenesis, a need to update and integrate these findings into the WHO grading scheme has become apparent. Epigenetic tools represent an area of burgeoning interest that encompasses all non-Mendelian inherited genetic features affecting gene expression, including but not limited to chromatin remodeling complexes, DNA methylation, and histone regulating enzymes. The SWItch/Sucrose non-fermenting (SWI/SNF) chromatin remodeling complex is the largest mammalian family of chromatin remodeling proteins and is estimated to be altered in 20-25% of all human malignancies; however, the ways in which it contributes to tumorigenesis are not fully understood. We recently discovered that CNS tumors with SWI/SNF mutations have revealed an oncogenic role for endogenous retroviruses (ERVs), remnants of exogenous retroviruses that integrated into the germline and are inherited like Mendelian genes, several of which retain open reading frames for proteins whose expression putatively contributes to tumor formation. Herein, we analyzed the latest WHO classification scheme for all CNS tumors with documented SWI/SNF mutations and/or aberrant ERV expression, and we summarize this information to highlight potential research opportunities that could be integrated into the grading scheme to better delineate diagnostic criteria and therapeutic targets.

Precursors, pathways of carcinogenesis and molecular markers of vulvar squamous cell carcinoma. Literature review

The review analyzes and summarizes the results of the studies on the pathogenesis of vulvar squamous cell carcinoma and its diagnostic features, reviews precursors and molecular subtypes of carcinomas. Despite the relatively low incidence of this tumor, over the past few decades, there has been an upward trend in its incidence, including the incidence among young women. According to the latest World Health Organization classification of lower genital tumors from 2020, vulvar squamous cell carcinoma is divided into human papillomavirus (HPV) associated and HPV-independent. While these carcinomas are often morphologically similar, their mechanisms of carcinogenesis, precursors, and clinical outcomes are different. Just the detection of virus DNA in a tumor is not enough to establish HPV status. Meanwhile immunohistochemical detection of the expression of p16 and p53 proteins allows not only to separate two pathogenetic pathways of carcinogenesis, but also to identify its molecular subtypes. The data on the possible use of p16 and p53 expression as the disease prognosis molecular markers have been obtained. Currently, the tactics of treatment and monitoring patients does not depend on the HPV status of carcinoma; however, the results of recent studies suggest that women with HPV positive vulvar cancer have significantly higher survival rates and a lower risk of recurrence. Understanding the mechanisms of carcinogenesis and improving its diagnosis will advance the assessment of the individual risk of the progression of precancerous lesions, as well as the outcome and the occurrence of tumor recurrence.

A prognostic estimation model based on mRNA-sequence data for patients with oligodendroglioma.

The diagnosis of oligodendroglioma based on the latest World Health Organization Classification of Tumors of the Central Nervous System (WHO CNS 5) criteria requires the codeletion of chromosome arms 1p and 19q and isocitrate dehydrogenase gene (IDH) mutation (mut). Previously identified prognostic indicators may not be completely suitable for patients with oligodendroglioma based on the new diagnostic criteria. To find potential prognostic indicators for oligodendroglioma, we analyzed the expression of mRNAs of oligodendrogliomas in Chinese Glioma Genome Atlas (CGGA). We collected 165 CGGA oligodendroglioma mRNA-sequence datasets and divided them into two cohorts. Patients in the two cohorts were further classified into long-survival and short-survival subgroups. The most predictive mRNAs were filtered out of differentially expressed mRNAs (DE mRNAs) between long-survival and short-survival patients in the training cohort by least absolute shrinkage and selection operator (LASSO), and risk scores of patients were calculated. Univariate and multivariate analyses were performed to screen factors associated with survival and establish the prognostic model. qRT-PCR was used to validate the expression differences of mRNAs. A total of 88 DE mRNAs were identified between the long-survival and the short-survival groups in the training cohort. Seven RNAs were selected to calculate risk scores. Univariate analysis showed that risk level, age, and primary-or-recurrent status (PRS) type were statistically correlated with survival and were used as factors to establish a prognostic model for patients with oligodendroglioma. The model showed an optimal predictive accuracy with a C-index of 0.912 (95% CI, 0.679-0.981) and harbored a good agreement between the predictions and observations in both training and validation cohorts. We established a prognostic model based on mRNA-sequence data for patients with oligodendroglioma. The predictive ability of this model was validated in a validation cohort, which demonstrated optimal accuracy. The 7 mRNAs included in the model would help predict the prognosis of patients and guide personalized treatment.

LOT and HOT … or not. The proliferation of clinically insignificant and poorly characterised types of renal neoplasia

The classification of malignant tumours is influenced by both immunohistochemical and molecular genetic findings. This is highlighted in the latest World Health Organization classification of renal neoplasia, which has a tumour category of 'tumours that are molecularly defined'. This implies that the defining molecular features are integral to tumourigenesis, which may not necessarily be the case. Renal oncocytoma is recognised as a benign tumour with variable morphology and immunoexpression. A variant of these tumours is hybrid oncocytic chromophobe tumour, which has features of both oncocytoma and chromophobe renal cell carcinoma and may, on rare occasions, show malignant behaviour. Recent reports have proposed two further entities with eosinophilic cytoplasm and varying nuclear pleomorphism, designated low grade oncocytic tumour (LOT) and eosinophilic vacuolated tumour (EVT), formally known as high grade oncocytic tumour (HOT). The diagnosis of these apparently benign tumours was made on the basis of morphological and immunohistochemical features. More recently it has been claimed that the mutations in the mTOR pathway are also a diagnostic feature and it is further suggested that these mutations are key to the pathogenesis of these tumours. As is seen in oncocytoma, immunohistochemical expression of tumours included in series of LOT and EVT is variable. The mutations in the mTOR pathway, where detected, were not constant, with any combination of mTOR, TSC1 and/or TSC2 being involved. A major issue is that in many of the studies full comparative genomic hybridisation results are not presented. In addition it is well recognised that mTOR mutations are seen in a variety of renal tumours. In view of these conflicting results, the rarity of these tumours and their apparent benign nature, raises questions as to why these tumours should be considered specific entities.

La néoplasie myéloïde associée à un réarrangement de PDGFRB : une pathologie rare de diagnostic difficile

In the latest World Health Organization classification (WHO), eosinophilic disorders represent a group of rare pathologic conditions with highly heterogeneous pathophysiology. In this report, we describe a case of myeloid neoplasm associated with eosinophilia and rearrangement of PDGFRB gene in a 67-year-old-male patient hospitalized with cerebellous ataxia. Initial investigations showed a bicytopenia with hypereosinophilia varying from 1.1 to 1.6×109/L. Bone marrow aspiration was rich and showed a heterogeneous distribution of myeloid cells with clusters of promyelocytes and proerythroblasts associated with numerous eosinophils and spindle-shaped mast cells but without excess of blasts, dysplasia nor maturation skewing. These aspects suggested an atypical myeloproliferative neoplasm. Bone marrow biopsy was performed showing also a very high cellularity with area of myeloid and erythroid precursors associated with numerous spindle-shaped mast cells. Diagnoses of unclassified myeloid neoplasm and/or systemic mastocytosis were then proposed. Further chromosome analysis showed a t(5;8) translocation with PDGFRB rearrangement revealed in fluorescent in situ hybridization. Patient was treated with imatinib and intravenous immunoglobulin therapy allowing a significant improvement in neurological symptoms and biological results. Patient condition is currently stable after six lines of treatment. This rare hematopoietic neoplasm displays unusual histological and cytological features and can mimic other myeloproliferative neoplasm. Specific cytogenetics analysis should be considered for such cases with hypereosinophilia to select patients that may benefit from targeted therapy.

Primary Neuroendocrine Tumor of the Breast: Current Understanding and Future Perspectives.

Primary neuroendocrine carcinoma of the breast (NECB) is characterized with heterogeneity, rarity, and poor differentiation, which is probably an underestimated subtype of breast cancer, including small cell NECs and large cell NECs. The diagnostic criteria for NECB have been constantly updated as the disease changes and the understanding increases. According to the latest WHO Classification, primary neuroendocrine neoplasm (NEN) of the breast consists of well-differentiated neuroendocrine tumors (NET), extremely aggressive neuroendocrine carcinomas (NEC) as well as invasive breast cancers of no special type (IBCs-NST) with neuroendocrine differentiation. The accurate diagnosis of NECB remains a challenge for its low incidence, which needs multi-disciplinary methods. For the rarity of the disease, there is a lack of large samples and prospective clinical research. For these invasive tumors, there are no standardized therapeutic guidelines or norms, and the treatment often refers to nonspecific breast cancer. In addition, the prognosis of such patients remains unknown. In 2003, the World Health Organization (WHO) listed NECB as an independent entity for the first time, while few features of NECB were clarified. In this review, it presents the WHO Classification, clinicopathologic characteristics, diagnosis, treatment, and prognosis of these patients. In addition, it summarizes the latest studies on molecular features of NECB, aiming to provide new therapeutic perspectives for the disease.

Histopathologic and genetic findings in atypical spindle cell/pleomorphic lipomatous tumors and atypical pleomorphic fibromas.

Spindle cell lipomas, pleomorphic lipomas (SCL/PLs), and pleomorphic fibromas (PF) are tumors with loss of retinoblastoma (RB). The latest World Health Organization classification includes a category of atypical spindle cell/pleomorphic lipomatous tumors (ASPLT), which encompasses tumors in this spectrum that show atypical histopathologic features. We have observed PFs that show similar atypical features. Cases of SCL/PL and PF with atypical features were collected from tissue archives between 2010 and 2019. Genetic alterations were investigated using array comparative genomic hybridization (aCGH). Of 15 cases found, most tumors were dermal based with fibrocytic or fibroadipocytic appearance and occasional lipoblasts. All cases had a high proliferation index with atypical mitotic figures in 71% of cases. Chromosome 13q loss was present in all cases with CGH data. Additional recurrent chromosomal losses included 17p, 16q, 17q, 20p, 4, and 10. No recurrence was found in limited follow-up. ASPLTs are characterized by loss of RB, prominent nuclear pleomorphism, mitotic activity including atypical mitotic figures, and genomic instability with multiple chromosomal aberrations. A similar group of tumors with these histopathologic features lacks lipomatous differentiation, and we propose the diagnosis of atypical PF as a fibromatous variant of ASPLT. Limited clinical follow-up appears benign.

Astroblastoma with Rapid Cyst Expansion and Hemorrhage in an Adult: A Case Report

Astroblastoma is an extremely rare primary brain tumor accounting for 0.45 to 2.8% of all neuroglial tumors and usually occurs in pediatrics and young adults. The natural history of astroblastoma still remains unknown. In the World Health Organization (WHO) classification of tumors of the central nervous system, astroblastoma is classified as other neuroepithelial tumors and standard treatment other than surgery has not been established. As molecular and genetic diagnosis becomes more important in the latest WHO classification of brain tumors, the development of therapeutic options based on the information of molecular genetics are expected. Here we report a case of astroblastoma in a 49-year-old male. Small tumor was discovered by coincidence during his check-up following traffic accident, but three months later, tumor bleeding with cystic enlargement resulted in disturbance of consciousness. Initial diagnosis of low grade astroblastoma with BRAFV600E mutation was made. After 1 year, local tumor recurrence was observed. The histological diagnosis at recurrence was high grade astroblastoma. We here, discuss about diagnosis, treatment and the possibility of usefulness of molecular genetic analysis for astroblastoma with some literature review. (Received 10 August, 2021; Accepted 15 December, 2021; Published 1 April, 2022).

The prognostic significance of further genotyping H3G34 diffuse hemispheric gliomas.

H3G34-mutant diffuse hemispheric glioma (DHG) is recognized as a new, distinct entity in the latest World Health Organization classification for central nervous system tumors and is associated with a particularly aggressive course. The authors performed a systematic review and pooled analysis to investigate the frequency of genetic events in these tumors and to determine whether these events were associated with survival trends. Two electronic databases were accessed to search for relevant data. Included criteria were studies that had individual patient data on H3.3 G34-mutant gliomas. To analyze the impact of genetic events on overall survival, Kaplan-Meier analysis and Cox regression models were used, and corresponding hazard ratios and 95% confidence intervals were computed. In total, 20 studies with 257 H3G34-mutant DHGs were included for integrated analyses. The H3 glycine-to-valine (H3G34V) mutation showed a significantly worse prognosis than the glycine-to-arginine (H3G34R) mutation (median overall survival, 9.9 vs 14.8months; hazard ratio, 3.040; 95% confidence interval, 1.208-7.651; P=.018), and this result remained statistically significant in the multivariate Cox regression model. Among H3G34 DHGs, TP53 mutation was the most common genetic alteration (94.9%), followed by ATRX alterations (87.5%), MGMT methylation (79.5%), and PDGFRA alterations (33.2%). The presence of PDGFRA amplification or EGFR amplification conferred poor survival. After adjusting for age and sex, these alterations were still independent indicators for adverse outcomes. The authors highlight the important role of molecular stratification of H3G34 DHGs, which may help refine our understanding of the natural history of this group of malignant tumors.

Neuroendocrine Neoplasms of the Breast: The Latest WHO Classification and Review of the Literature.

Simple SummaryBreast tumors exhibiting neuroendocrine differentiation are a heterogeneous group of tumors that have been variously defined in previous World Health Organization (WHO) classifications. In the WHO Classification of Tumours, 5th edition, neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs) of the breast, both of which are invasive cancers, are classified as neuroendocrine neoplasms (NENs) of the breast. However, the clinical significance of NE differentiation in breast cancers, especially in NETs of the breast, is not yet fully understood, and a large overlap appears to exist between breast cancers showing NE differentiation and invasive breast cancer of no special type (IBC-NST). While breast NECs show distinct clinical and morphological features, diagnosis of NETs based on the morphological characteristics alone can be challenging; one reason is that breast NETs do not necessarily have the same morphological characteristics as those of NENs arising in other organs. Thus, the heterogeneity of breast tumors with neuroendocrine differentiation and the changes in their classifications over the years have left many open issues that still need to be resolved. In this review, we shall summarize the history of breast “NENs,” including of mixed types of tumors and the characteristics of these tumors, and discuss their differences from NENs arising in other organs.Breast tumors with neuroendocrine (NE) differentiation comprise an uncommon and heterogeneous group of tumors, including invasive breast cancer of no special type (IBC-NST) with NE features, neuroendocrine tumors (NETs), and neuroendocrine carcinoma (NEC). The most recent World Health Organization (WHO) classification in 2019 defined neuroendocrine neoplasms (NENs) of the breast (Br-NENs) as tumors in which >90% of cells show histological evidence of NE differentiation, including NETs (low-grade tumors) and NEC (high-grade). Due to the low prevalence of these tumors and successive changes in their diagnostic criteria over the years, only limited evidence of these tumors exists, derived mainly from case reports and retrospective case series. Breast tumors with NE differentiation are usually treated like the more commonly occurring IBC-NSTs. Immunohistochemistry (IHC) of breast tumors with NE differentiation usually shows a hormone receptor (HR)-positive and human epidermal growth factor type 2 (HER2)-negative profile, so that hormonal therapy with cyclin-dependent kinase (CDK)4/6 inhibitors or other targeted agents would be reasonable treatment options. Herein, we present a review of the literature on breast tumors with NE differentiation as defined in the latest WHO 2019 classification, and discuss the clinical management of these tumors.