Morphology and classification of the myelodysplastic syndromes and their pathologic variants.
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Humans↗
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Results for “Variant classification”
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[Primary mediastinal (thymus) large B-cell lymphoma: clinically defined type of tumors and morphologic variants].
In the WHO lymphoma classification, primary mediastinal (thymic) large B-cell lymphoma (PMVBL) is defined as a subtype of diffuse large B-cell lymphoma (DLBCL) showing typical clinical manifestation. The patterns related to variability of tumor cell morphology were analyzed in the setting of 15 bioptically verified PMVBL cases. In the majority of the cases (n = 12), the tumor showed pleomorphic blastic morphology with individual cell patterns resembling those of polymorphic centroblastoma of the Kiel classification. In addition, some of the cases had clear-cell and/or lacunar appearance (5/12), while distinctive anaplastic appearance was rare (1/12). Other cases (n = 3) showed a monotonous morphology of uniform smaller-sized blasts with monocytoid-like cytoplasm. The described morphologic variants of PMVBL might be related to the known genotypic variability of DLBCL, although monotypic c-Ig expression verified in some of the cases would support post-follicular stage of the tumor cell development. In the absence of clinical data and within the described morphologic variability, it is recommended to prefer a diagnosis of DLBCL and to include the tumor into a clinically defined subtype of PMVBL only in cases with well defined and typical clinical presentation and progression of the disease.
Adolescent↗
Burkitt-type ALL with variant t(2;8) and complex additional rearrangements at diagnosis.
We describe a case of Burkitt-type acute lymphoblastic leukemia (L3 according to the classification FAB) with a variant t(2;8)(p12;q24) and additional chromosomal abnormalities at diagnosis. The karyotype was 47,X,Xq+,t(2;8)(p12;q24),7q+,12p+,+mar. The literature on chromosome rearrangements associated with t(2;8) in L3 leukemias has been reviewed.
Bone Marrow↗
E pluribus unum: The riddle of focal segmental glomerulosclerosis.
A recent consensus conference proposed a new classification for focal segmental glomerulosclerosis (FSGS). Five patterns have been defined: FSGS not otherwise specified, perihilar variant, cellular variant, tip variant, and collapsing variant. In light of the multiplicity of classification schemes in use, the promise of a rational and uniform scheme for FSGS pathology is most welcome. This approach has worked extremely well for the classification of lupus nephritis. It does not necessarily mean, however, that this new classification scheme will help to select treatment protocols according to histopathologic subsets of FSGS. In fact, one renal biopsy examination may show multiple variants and this classification, despite many merits, still lumps categories that should be split and splits categories that should be lumped together. It has become clear that despite its histologic diversity FSGS begins as a podocyte disease that progresses from a cellular to a scar lesion. Recent years have brought about astonishing insight into the complex molecular array of proteins forming the slit diaphragm between podocyte foot processes, a narrow space essential for restricting glomerular permeability to albumin. Concentrating on the podocyte rather than on the glomerular tuft is helpful for abolishing the classic distinction between primary versus secondary forms of FSGS, a distinction that crumbles away with each new evidence of genetic, ischemic, or viral etiologies of FSGS, despite similar lesions. In fact, recent studies focusing on the podocyte changes that occur in various subsets of FSGS have unraveled the striking phenomena of podocyte dedifferentiation and transdifferentiation along with differential expression of cyclin-dependent kinase inhibitors. Interestingly, the latter showed that expression of cyclin-dependent kinase inhibitors p21 and proliferation marker Ki-67 are the same in cellular FSGS, collapsing glomerulopathy, and human immunodeficiency virus-associated FSGS. Taken together these findings lead to a reassuring unitary interpretation of the pluralistic appearance of FSGS by histopathology. Clearly, further studies of the podocyte will lead to improved understanding of FSGS and to improved classification schemes that are grounded in molecular understanding of glomerular injury and that will guide the clinician in the choice of treatment and prognosis.
Animals↗
Congenital H-type urethroanal fistula.
A case of congenital urethroanal fistula with a normal anterior urethra in a male child is reported. The fistula was demonstrated between the prostatic urethra and anorectum. This anomaly is usually associated with an atretic anterior urethra and has been variously described as a variant of a urethral duplication by some authors, and of an anorectal malformation (ARM) by others. We conclude that its rightful classification is as a variant of ARM in which the fistula is a result of persistence of the cloacal duct and corresponds to the anorecto-vestibular fistula with a normal anus (perineal canal) in a female.
Humans↗
Translocation (8;17)(p21;q21), a possible variant of t(15;17), in acute promyelocytic leukemia.
We report a 64-year old man with typical features of acute promyelocytic leukemia (APL) [M3, French-American-British (FAB) classification] in whom a variant, t(8;17)(p21;q21), was detected. This is the second case of the same variant translocation to be reported. The breakpoint on 17q was similar to those described in cases with a standard translocation 15;17. Consequently, this chromosome break or rearrangement at band 17q21, rather than the recipient site of translocation of the deleted material, appears to be of crucial importance in the genesis of APL.
Chromosomes, Human, Pair 15↗
Oncogene lineages of human papillomavirus type 16 E6, E7 and E5 in preinvasive and invasive cervical squamous cell carcinoma.
Human papillomavirus (HPV)16 accounts for about 60% of the HPV infections in invasive cervical cancer (ICC). There are many sequence variations within HPV16, some of which have been associated with different biological properties, although no definite correlations have yet been established. However, the definition 'variant' has been a source of confusion in research and diagnosis, since it is based on all sequence deviations from a randomly selected prototype. This study has sequenced the HPV16 oncogenes E6, E7 and E5 from 61 Swedish cases with cervical intraepithelial neoplasia grade III (CIN III) or ICC. Clustering the sequence variations at the three common sites of variation (nucleotide 350 in E6, which has previously been associated with the progression from CIN III to ICC, and nucleotides 3979 and 4042 in E5) resulted in the distinction of three major oncogene lineages encompassing more than 95% of the cases, and two minor oncogene lineages. Simple comparison of the distribution of the individual variations or oncogene lineages between CIN III and ICC showed no significant difference, but the number of variations in addition to the three common ones was significantly higher in ICC. This novel classification scheme, based on the variations in the E6, E7 and E5 region, is considered to be a major improvement over the classical 'prototype-variant' classification, and can help to clarify the interpretation of HPV sequence data in relation to the progression of cervical cancer.
Carcinoma, Squamous Cell↗
Molecular Landscape and Advanced Diagnostic Technologies for BRAF Mutations in Cancer: From Quantitative PCR and ddPCR to CRISPR-Based Platforms.
BRAF mutations are key oncogenic alterations across multiple malignancies, including melanoma, thyroid carcinoma, colorectal cancer, non-small cell lung cancer, glioma, and hairy cell leukemia. The most prevalent variant, BRAF-V600E, induces constitutive activation of the MAPK signaling pathway, promoting tumor progression and influencing therapeutic responsiveness. Accurate detection of BRAF alterations is therefore essential for molecular classification, prognostic assessment, treatment selection, and resistance surveillance. This review summarizes the molecular heterogeneity of BRAF mutations and critically evaluates current diagnostic methodologies. Conventional approaches such as allele-specific PCR and Sanger sequencing are compared with advanced quantitative platforms, including high-resolution melting analysis, droplet digital PCR, and next-generation sequencing, with emphasis on analytical sensitivity, mutation coverage, and clinical applicability. Emerging technologies such as CRISPR-based assays, rolling circle amplification systems, and nanoparticle-based biosensors and point-of-care diagnostic platforms are also discussed for their potential to enhance ultra-sensitive detection, particularly in liquid biopsy settings. These emerging tools are highlighted for their potential to enable ultra-sensitive, rapid, and decentralized mutation detection, particularly in liquid biopsy settings. Key challenges, including intratumoral heterogeneity, low allele-frequency variants, FFPE-associated artifacts, and clonal evolution under therapeutic pressure, are examined within a translational framework. In addition, we examine critical barriers to clinical implementation, including standardization, cost, and global accessibility of molecular diagnostics, and outline potential solutions through scalable technologies and decentralized testing strategies. We propose that optimal BRAF testing requires a mutation subclass-informed and clinically integrated strategy combining comprehensive baseline profiling with longitudinal molecular monitoring. Future diagnostic paradigms will likely integrate multi-omics data and artificial intelligence (AI)-assisted interpretation to refine precision oncology implementation. Looking forward, we propose that optimal BRAF testing will require integration of multi-omics profiling with AI-assisted interpretation, enabling automated variant classification, real-time clinical decision support, and improved prediction of therapeutic response and resistance.
Humans↗
Classifying the medulloblastoma: insights from morphology and molecular genetics.
Significant advances in the treatment of the medulloblastoma (MB) have been made in the last 30 years, reducing mortality by 2-fold. Further improvements in the cure rate require an increased understanding of the biology of MBs, and this will translate into refinements in their classification. Scrutiny of the cytological variation found among MBs has recently led to the concept of the anaplastic MB, which overlaps the large-cell variant and appears to share its poor prognosis. In contrast, the MB with extensive nodularity, a distinctive nodular/desmoplastic variant occurring in infants, has a better outcome than most MBs in these young patients. Building on cytogenetic studies that have drawn attention to abnormalities on chromosome 17 in over a third of MBs, research shows non-random losses on chromosomes 8, 9, 10, 11 and 16, and gains on chromosomes 1, 7 and 9. Overexpression of ErbB2 receptors and losses on chromosome 17p have been proposed as independent indicators of aggressive behaviour, while high TrkC receptor expression indicates a favourable outcome. There is a strong association between anaplastic/large-cell tumours and MYC amplification, which has previously been linked with aggressive disease, but associations between abnormalities on chromosome 17 and anaplastic/large-cell MBs and between abnormalities in the shh/PTCH pathway and the desmoplastic variant are more controversial. Classification of the MB histopathologically and according to profiles of molecular abnormalities will help both to rationalize approaches to therapy, increasing the cure rate and reducing long-term side-effects, and to suggest novel treatments.
Cerebellar Neoplasms↗
Follicular variant of papillary thyroid carcinoma: genome-wide appraisal of a controversial entity.
The majority of thyroid tumors are classified as papillary (papillary thyroid carcinomas; PTCs) or follicular neoplasms (follicular thyroid adenomas and carcinomas; FTA/FTC) based on nuclear features and the cellular growth pattern. However, classification of the follicular variant of papillary thyroid carcinoma (FVPTC) remains an issue of debate. These tumors contain a predominantly follicular growth pattern but display nuclear features and overall clinical behavior consistent with PTC. In this study, we used comparative genomic hybridization (CGH) to compare the global chromosomal aberrations in FVPTC to the PTC of classical variant (classical PTC) and FTA/FTC. In addition, we assessed the presence of peroxisome proliferator-activated receptor-gamma (PPARG) alteration, a genetic event specific to FTA/FTC, using Southern blot and immunohistochemistry analyses. In sharp contrast to the findings in classical PTC (4% of cases), CGH analysis demonstrated that both FVPTC (59% of cases) and FTA/FTC (36% of cases) were commonly characterized by aneuploidy (P = 0.0002). Moreover, the pattern of chromosomal aberrations (gains at chromosome arms 2q, 4q, 5q, 6q, 8q, and 13q and deletions at 1p, 9q, 16q, 17q, 19q, and 22q) in the follicular variant of PTC closely resembled that of FTA/FTC. Aberrations in PPARG were uniquely detected in FVPTC and FTA/FTC. Our findings suggest a stronger relationship between the FVPTC and FTA/FTC than previously appreciated and support further consideration of the current classification of thyroid neoplasms.
Adult↗
Classification, clinical manifestations, and immunopathological mechanisms of the epithelial variant of paraneoplastic autoimmune multiorgan syndrome: a reappraisal of paraneoplastic pemphigus.
BACKGROUND: Recent studies suggest that paraneoplastic pemphigus (PNP) is a heterogeneous autoimmune syndrome involving several internal organs and that the pathophysiological mechanisms mediating cutaneous, mucosal, and internal lesions are not limited to autoantibodies targeting adhesion molecules. OBJECTIVE: To classify the diverse mucocutaneous and respiratory presentations of PNP and characterize the effectors of humoral and cellular autoimmunity mediating epithelial tissue damage. METHODS: We examined 3 patients manifesting the lichen planus pemphigoideslike subtype of PNP. A combination of standard immunohistochemical techniques, enzyme-linked immunosorbent assay with desmoglein (DSG) baculoproteins, and an immunoprecipitation assay were used to characterize effectors of humoral and cellular autoimmunity in patients with PNP and in neonatal wild-type and DSG3-knockout mice with PNP phenotype induced by passive transfer of patients' IgGs. RESULTS: In addition to the known "PNP antigenic complex," epithelial targets recognized by PNP antibodies included 240-, 150-, 130-, 95-, 80-, 70-, 66-, and 40/42-kd proteins but excluded DSG1 and DSG3. In addition to skin and the epithelium lining upper digestive and respiratory tract mucosa, deposits of autoantibodies were found in kidney, urinary bladder, and smooth as well as striated muscle. Autoreactive cellular cytotoxicity was mediated by CD8(+) cytotoxic T lymphocytes, CD56(+) natural killer cells, and CD68(+) monocytes/macrophages. Inducible nitric oxide synthase was visualized both in activated effectors of cellular cytotoxicity and their targets. Keratin 14-positive basal epithelial cells sloughed from the large airways and obstructed small airways. CONCLUSIONS: The paraneoplastic disease of epithelial adhesion known as PNP in fact represents only 1 manifestation of a heterogeneous autoimmune syndrome in which patients, in addition to small airway occlusion and deposition of autoantibodies in different organs, may display a spectrum of at least 5 different clinical and immunopathological mucocutaneous variants (ie, pemphiguslike, pemphigoidlike, erythema multiforme-like, graft-vs-host disease-like, and lichen planus-like). We suggest that the more encompassing term "paraneoplastic autoimmune multiorgan syndrome," or PAMS, be applied. The pathophysiological mechanisms of PAMS involve both humoral and cellular autoimmunity responses. Epithelial cell membrane antigens other than DSG1 or DSG3 are targeted by effectors of PAMS autoimmunity. Apoptosis of damaged basal cells mediates epithelial clefting, and respiratory failure results possibly from obstruction of small airways with sloughed epithelial cells.
Animals↗
[Results of the polychemotherapy of different variants of lymphosarcomas based on the World Health Organization classification].
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Adolescent↗
[The classification of nervous system tumors].
The paper presents the classification of tumors of the nervous system, which is based on the Second Variant of the International Histological Classification of Tumors of the Nervous System which was developed by the WHO experts in 1993 and on the section "Morphology of Neoplasms" of the International Classification of Diseases, Xth review. These classifications were critically reviewed by taking into account the experience gained by the Laboratory of Pathomorphology, Academician N. N. Burdenko Research Institute, Russian Academy of Medical Sciences. The proposed classification may unify the material of our country's neurosurgical clinics and provide more corrective statistic data.
Humans↗
Phylogenetic position of Rickettsia tsutsugamushi and the relationship among its antigenic variants by analyses of 16S rRNA gene sequences.
The 16S rRNA gene sequences of Rickettsia tsutsugamushi and Rickettsia sibirica were determined by PCR and DNA sequencing. Phylogenetic analysis revealed that R. sibirica is positioned in a cluster of the genus Rickettsia with a similarity value of 98.1-99.6%, whereas R. tsutsugamushi is located apart from the cluster with a similarity value of 90.2-90.6%. This evidence suggests that R. tsutsugamushi should be excluded taxonomically from the genus Rickettsia. The phylogenetic classification of six antigenic variants in R. tsutsugamushi moderately reflected their antigenic relationship known in closely and distantly related strains.
Antigens, Bacterial↗
Automated white blood cell classification revisited.
A novel approach to the problem of automated white blood cell classification is described. Whereas in most earlier attempts the segmentation of the cells has been recognized as the most difficult and most critical step in the sequence of operations resulting in the classification, the method described here eliminates the necessity of the detection of the contour of the nucleus and of the cytoplasm, and is therefore less sensitive to such disturbing factors as the presence of granules, of other cells touching the cell of interest, etc. The multiple sequential threshold method to be described here in two slightly different variants yields a correct classification rate of 94.7% for a 4 class problem (90 cells in the test set), and 91.8% for an 8 class problem (279 cells in the test set). Both experiments include immature cell types.
Densitometry↗
[Comparative analysis of the histological variants of renal cell cancer].
85 cases of renal-cell carcinoma are studied histologically, cytologically and electron-microscopically. Morphological variant was determined according to the classification of N. A. Krayevsky et al. Histological and cytological variants of renal-cell carcinoma, differences of the degree of their differentiation are shown. Electron-microscopically the cell types characteristic of clear-cell and granular-cell variants of a different degree of differentiation are distinguished. Similarity of cell ultrastructure in granular-cell, sarcoma-like and glandular tumour variants is found. The ultrastructural features of nephrocytes and renal tubules in the form of the accumulation of microvilli, cytoplasmic membrane invaginations, desmosomes, basal membrane fragments which are seen as the markers of the tumour organospecificity were preserved in all variants of renal-cell carcinoma studied.
Adult↗
Rapid molecular analysis of the haemagglutinin gene of human influenza A H3N2 viruses isolated in spain from 1996 to 2000.
A simple molecular technique was used for the rapid preliminary genetic characterization of human influenza A H3N2 viruses isolated in Spain from 1996 to 2000. Subtyping, based on RT-PCR, was followed by subtype-specific restriction enzyme fragment length polymorphism (RFLP) analyses of an amplified region of the HA1 domain of the H3 haemagglutinin (HA) gene to distinguish variants differentiated by common amino acid substitutions in HA1. The approach was tested using 135 Spanish H3N2 isolates and included nucleotide sequencing and phylogenetic analyses of a region of the HA1 domain of 41 representative isolates. The viruses were distinguished by haemagglutination inhibition (HI) assays into two antigenically discernible groups, the A/Wuhan/359/95-like and A/Sydney/5/97-like viruses. The results of PCR-RFLP analysis allowed a finer classification into five genetic variant subgroups, corresponding to those distinguished by phylogenetic analyses. This rapid, simple and variant-specific procedure could, therefore, be used to rapidly screen clinical specimens prior to more detailed antigenic and genetic analyses.
Hemagglutinin Glycoproteins, Influenza Virus↗
[Hepatic arterial vascular anatomy and its variants].
PURPOSE: We investigated the frequency of anatomical variants of the hepatic artery, which can influence interventional angiographic procedures. MATERIAL AND METHODS: We reviewed 150 consecutive angiograms performed for the treatment of primary (112) or metastatic (38) liver tumors and evaluated the frequency of anatomical variants of the hepatic artery based on the classification proposed by Michels in 1955, which describes 10 variants. The so-called typical anatomy, which is in fact only found in 55% of cases, is indicated as type I. RESULTS: The typical anatomy (type I variant) was seen in 78 patients (52%) and variants were seen in the other 72 (48%). We found 15 type II variants (10%), 23 type III (15.5%), 1 type IV and 1 type V (0.6%), 3 type VI (2%), 1 type VII (0.6%) and finally 6 type IX (4%). There were no type VIII or X variants, but in 22 patients (14.7%) vascular anatomy did not fit Michaels' classification. DISCUSSION AND CONCLUSIONS: In our series the typical hepatic artery anatomy was found in 52%, which is in agreement with Michels' findings, while the frequency of the individual anatomical variants differed. Not all of the variants reported by Michels were seen in our series and we found 22 patients with different variants. Disagreement might be due to the fact that Michels' was an autoptic series while our patients were cancer patients only and thus variability could be at least partly accounted for by neoplastic neovascularization. We believe that thourough knowledge of the anatomical variants of the hepatic artery is fundamental to angiographic practice, in particular for interventional procedures, because such variants can influence the choice of vascular technique and of materials.
Angiography↗