RESUMEN
Epstein-Barr virus (EBV) is an oncogenic virus associated with various malignancies, including classical Hodgkin lymphoma (cHL). Despite its known association, the specific role of humoral immune response to EBV remains poorly characterized in cHL. To address this, we conducted a study using a custom protein microarray to measure the antibody responses in cHL patients and matched healthy controls recruited from an East-Asian hospital-based case-control study. We identified 16 IgG antibodies significantly elevated in EBV-positive cHL compared with controls, defining an "East-Asian antibody signature of EBV-positive cHL." We evaluated responses against these 16 antibodies in a distinct European population, leveraging data from our previous European cHL case-control study from the UK, Denmark, and Sweden. A subset of antibodies (14/16, 87.5%) from the "East-Asian antibody signature of EBV-positive cHL" exhibited significant associations with cHL in the European population. Conversely, we assessed the "European antibody signature of EBV-positive cHL" identified in our prior study which consisted of 18 EBV antibodies (2 IgA, 16 IgG), in the East-Asian population. A subset of these antibodies (15/18, 83.3%) maintained significant associations with cHL in the East-Asian population. This cross-comparison of antibody signatures underscores the robust generalizability of EBV antibodies across populations. Five anti-EBV IgG antibodies (LMP-1, TK, BALF2, BDLF3, and BBLF1), found in both population-specific antibody signatures, represent a "core signature of EBV-positive cHL." Our findings suggest that the antibody responses targeting these core EBV proteins reflect a specific EBV gene expression pattern, serving as potential biomarkers for EBV-positive cHL independent of population-specific factors.
Asunto(s)
Anticuerpos Antivirales , Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Enfermedad de Hodgkin , Humanos , Enfermedad de Hodgkin/virología , Enfermedad de Hodgkin/inmunología , Herpesvirus Humano 4/inmunología , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Femenino , Masculino , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/virología , Estudios de Casos y Controles , Persona de Mediana Edad , Adulto , Proteoma/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Anciano , Adulto Joven , Análisis por Matrices de ProteínasRESUMEN
This review focuses on mature T cells, natural killer (NK) cells, and stroma-derived neoplasms in the fifth edition of the World Health Organization classification of hematolymphoid tumors, including changes from the revised fourth edition. Overall, information has expanded, primarily due to advancements in genomic understanding. The updated classification adopts a hierarchical format. The updated classification relies on a multidisciplinary approach, incorporating insights from a diverse group of pathologists, clinicians, and geneticists. Indolent NK-cell lymphoproliferative disorder of the gastrointestinal tract, Epstein-Barr virus-positive nodal T- and NK-cell lymphoma, and several stroma-derived neoplasms of lymphoid tissues have been newly introduced or included. The review also provides guidance on how the fifth edition of the World Health Organization classification of hematolymphoid tumors can be applied in routine clinical practice.
RESUMEN
Mucoepidermoid carcinoma (MEC) is often seen in salivary glands and can harbor MAML2 translocations (MAML2+). The translocation status has diagnostic utility as an objective confirmation of the MEC diagnosis, for example, when distinction from the more aggressive adenosquamous carcinoma (ASC) is not straightforward. To assess the diagnostic relevance of MAML2, we examined our 5-year experience in prospective testing of 8106 solid tumors using RNA-seq panel testing in combinations with a two-round Delphi-based scenario survey. The prevalence of MAML2+ across all tumors was 0.28% (n = 23/8106) and the majority of MAML2+ cases were found in head and neck tumors (78.3%), where the overall prevalence was 5.9% (n = 18/307). The sensitivity of MAML2 for MEC was 60% and most cases (80%) were submitted for diagnostic confirmation; in 24% of cases, the MAML2 results changed the working diagnosis. An independent survey of 15 experts showed relative importance indexes of 0.8 and 0.65 for "confirmatory MAML2 testing" in suspected MEC and ASC, respectively. Real-world evidence confirmed that the added value of MAML2 is a composite of an imperfect confirmation test for MEC and a highly specific exclusion tool for the diagnosis of ASC. Real-world evidence can help move a rare molecular-genetic biomarker from an emerging tool to the clinic.
Asunto(s)
Carcinoma Mucoepidermoide , Neoplasias de las Glándulas Salivales , Carcinoma Mucoepidermoide/diagnóstico , Carcinoma Mucoepidermoide/genética , Carcinoma Mucoepidermoide/patología , Proteínas de Unión al ADN/genética , Humanos , Proteínas Nucleares/genética , Proteínas de Fusión Oncogénica/genética , Estudios Prospectivos , Neoplasias de las Glándulas Salivales/diagnóstico , Neoplasias de las Glándulas Salivales/genética , Neoplasias de las Glándulas Salivales/patología , Transactivadores/genética , Factores de Transcripción/genética , Translocación GenéticaRESUMEN
BACKGROUND: Extranodal natural killer T-cell lymphoma (NKTCL; nasal type) is an aggressive malignancy with a particularly high prevalence in Asian and Latin American populations. Epstein-Barr virus infection has a role in the pathogenesis of NKTCL, and HLA-DPB1 variants are risk factors for the disease. We aimed to identify additional novel genetic variants affecting risk of NKTCL. METHODS: We did a genome-wide association study of NKTCL in multiple populations from east Asia. We recruited a discovery cohort of 700 cases with NKTCL and 7752 controls without NKTCL of Han Chinese ancestry from 19 centres in southern, central, and northern regions of China, and four independent replication samples including 717 cases and 12â650 controls. Three of these independent samples (451 cases and 5301 controls) were from eight centres in the same regions of southern, central, and northern China, and the fourth (266 cases and 7349 controls) was from 11 centres in Hong Kong, Taiwan, Singapore, and South Korea. All cases had primary NKTCL that was confirmed histopathologically, and matching with controls was based on geographical region and self-reported ancestry. Logistic regression analysis was done independently by geographical regions, followed by fixed-effect meta-analyses, to identify susceptibility loci. Bioinformatic approaches, including expression quantitative trait loci, binding motif and transcriptome analyses, and biological experiments were done to fine-map and explore the functional relevance of genome-wide association loci to the development of NKTCL. FINDINGS: Genetic data were gathered between Jan 1, 2008, and Jan 23, 2019. Meta-analysis of all samples (a total of 1417 cases and 20â402 controls) identified two novel loci significantly associated with NKTCL: IL18RAP on 2q12.1 (rs13015714; p=2·83â×â10-16; odds ratio 1·39 [95% CI 1·28-1·50]) and HLA-DRB1 on 6p21.3 (rs9271588; 9·35â×â10-26 1·53 [1·41-1·65]). Fine-mapping and experimental analyses showed that rs1420106 at the promoter of IL18RAP was highly correlated with rs13015714, and the rs1420106-A risk variant had an upregulatory effect on IL18RAP expression. Cell growth assays in two NKTCL cell lines (YT and SNK-6 cells) showed that knockdown of IL18RAP inhibited cell proliferation by cell cycle arrest in NKTCL cells. Haplotype association analysis showed that haplotype 47F-67I was associated with reduced risk of NKTCL, whereas 47Y-67L was associated with increased risk of NKTCL. These two positions are component parts of the peptide-binding pocket 7 (P7) of the HLA-DR heterodimer, suggesting that these alterations might account for the association at HLA-DRB1, independent of the previously reported HLA-DPB1 variants. INTERPRETATION: Our findings provide new insights into the development of NKTCL by showing the importance of inflammation and immune regulation through the IL18-IL18RAP axis and antigen presentation involving HLA-DRB1, which might help to identify potential therapeutic targets. Taken in combination with additional genetic and other risk factors, our results could potentially be used to stratify people at high risk of NKTCL for targeted prevention. FUNDING: Guangdong Innovative and Entrepreneurial Research Team Program, National Natural Science Foundation of China, National Program for Support of Top-Notch Young Professionals, Chang Jiang Scholars Program, Singapore Ministry of Health's National Medical Research Council, Tanoto Foundation, National Research Foundation Singapore, Chang Gung Memorial Hospital, Recruitment Program for Young Professionals of China, First Affiliated Hospital and Army Medical University, US National Institutes of Health, and US National Cancer Institute.
Asunto(s)
Biomarcadores de Tumor/genética , Proliferación Celular , Subunidad beta del Receptor de Interleucina-18/genética , Linfoma Extranodal de Células NK-T/genética , Células T Asesinas Naturales/patología , Asia , Biomarcadores de Tumor/metabolismo , Estudios de Casos y Controles , Línea Celular Tumoral , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Interleucina-18/metabolismo , Subunidad beta del Receptor de Interleucina-18/metabolismo , Desequilibrio de Ligamiento , Linfoma Extranodal de Células NK-T/inmunología , Linfoma Extranodal de Células NK-T/metabolismo , Linfoma Extranodal de Células NK-T/patología , Células T Asesinas Naturales/inmunología , Células T Asesinas Naturales/metabolismo , Fenotipo , Pronóstico , Sitios de Carácter Cuantitativo , Medición de Riesgo , Factores de Riesgo , Transducción de Señal , TranscriptomaRESUMEN
Metaplastic thymomas are rare biphasic thymic tumors that are characteristically well-circumscribed, confined to the thymus, and follow a benign to indolent clinical course. Their relationship to other thymic neoplasms remains unclear, and their molecular characteristics have not been defined. We report for the first time recurrent translocation events in metaplastic thymomas involving the Yes Associated Protein 1 (YAP1) and Mastermind Like Transcriptional Coactivator 2 (MAML2) genes. Eight metaplastic thymomas were retrieved from two institutions' archives over a 21-year period. Paraffin-embedded material from all cases underwent targeted DNA-based hybrid capture next-generation sequencing. Cases showing no somatic alterations subsequently underwent targeted RNA sequencing. Allele-specific real-time polymerase chain reaction was performed to detect GTF2I c.74146970T>A (p.L424H) mutations. All cases showed characteristic histologic features of metaplastic thymoma and demonstrated no local recurrence or distant metastatic disease at 1-22 years of follow-up. Six of eight cases were successfully sequenced, all showing YAP1-MAML2 fusions; in four cases the fusions were detected by DNA sequencing and in two cases by RNA sequencing. Two distinct products were identified: 5' YAP1 exon 1 fused to 3' MAML2 exons 2-5 or 5' YAP1 exons 1-5 fused to 3' MAML2 exons 2-5. All cases underwent allele-specific real-time polymerase chain reaction and demonstrated no GTF2I L424H mutations. Metaplastic thymoma is a distinct, clinically indolent thymic epithelial neoplasm characterized by YAP1-MAML2 fusion and lacking the GTF2I mutations found in Type A and AB thymomas.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Biomarcadores de Tumor/genética , Neoplasias Glandulares y Epiteliales/genética , Timoma/genética , Neoplasias del Timo/genética , Transactivadores/genética , Factores de Transcripción/genética , Adulto , Boston , Femenino , Fusión Génica , Predisposición Genética a la Enfermedad , Hong Kong , Humanos , Masculino , Metaplasia , Persona de Mediana Edad , Neoplasias Glandulares y Epiteliales/patología , Timoma/patología , Neoplasias del Timo/patología , Proteínas Señalizadoras YAPRESUMEN
Immunodeficiency-associated lymphoproliferative disorders (IA-LPDs) are pathologically and clinically heterogeneous. In many instances, similar features are shared by a spectrum of IA-LPDs in clinically diverse settings. However, the World Health Organization (WHO) classifies IA-LPDs by their immunodeficiency setting largely according to the paradigm of posttransplant lymphoproliferative disorders but with inconsistent terminology and disease definitions. The field currently lacks standardization and would greatly benefit from thinking across immunodeficiency categories by adopting a common working vocabulary to better understand these disorders and guide clinical management. We propose a 3-part unifying nomenclature that includes the name of the lesion, associated virus, and the specific immunodeficiency setting for all IA-LPDs. B-cell lymphoproliferative disorders (LPDs) are usually Epstein-Barr virus (EBV)+ and show a spectrum of lesions, including hyperplasias, polymorphic LPDs, aggressive lymphomas, and, rarely, indolent lymphomas. Human herpes virus 8-associated LPDs also include polyclonal and monoclonal proliferations. EBV- B-cell LPDs and T- and NK-cell LPDs are rare and less well characterized. Recognition of any immunodeficiency is important because it impacts the choice of treatment options. There is an urgent need for reappraisal of IA-LPDs because a common framework will facilitate meaningful biological insights and pave the way for future work in the field.
Asunto(s)
Síndromes de Inmunodeficiencia/complicaciones , Trastornos Linfoproliferativos/etiología , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/patología , Infecciones por Herpesviridae/complicaciones , Infecciones por Herpesviridae/patología , Herpesvirus Humano 4/aislamiento & purificación , Herpesvirus Humano 8/aislamiento & purificación , Humanos , Síndromes de Inmunodeficiencia/clasificación , Síndromes de Inmunodeficiencia/patología , Células Asesinas Naturales/patología , Trastornos Linfoproliferativos/clasificación , Trastornos Linfoproliferativos/patología , Linfocitos T/patologíaRESUMEN
In 2008, we presented three cases of ALK-positive histiocytosis as a novel systemic histiocytic proliferation of early infancy with hepatosplenomegaly and dramatic hematological disturbances. This series of 10 cases (including the original three cases) describes an expanded clinicopathological spectrum and the molecular findings of this histiocytic proliferation. Six patients had disseminated disease: five presented in early infancy with eventual disease resolution, and the sixth presented at 2 years of age and died of intestinal, bone marrow, and brain involvement. The other four patients had localized disease involving nasal skin, foot, breast, and intracranial cavernous sinus - the first three had no recurrence after surgical resection, while the cavernous sinus lesion showed complete resolution with crizotinib therapy. The lesional histiocytes were very large, with irregularly folded nuclei, fine chromatin, and abundant eosinophilic cytoplasm, sometimes with emperipolesis. There could be an increase in foamy histiocytes and Touton giant cells with time, resembling juvenile xanthogranuloma. Immunostaining showed that the histiocytes were positive for ALK, histiocytic markers (CD68, CD163) and variably S100, while being negative for CD1a, CD207, and BRAF-V600E. Next-generation sequencing-based anchored multiplex PCR (Archer® FusionPlex®) performed in six cases identified KIF5B-ALK gene fusion in five and COL1A2-ALK fusion in one. There was no correlation of gene fusion type with disease localization or dissemination. The clinicopathological spectrum of ALK-positive histiocytosis is broader than originally described, and this entity is characterized by frequent presence of KIF5B-ALK gene fusion. We recommend that every unusual histiocytic proliferative disorder, especially disseminated lesions, be tested for ALK expression because of the potential efficacy of ALK inhibitor therapy in unresectable or disseminated disease.
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Proliferación Celular , Fusión Génica , Histiocitos/enzimología , Histiocitosis/genética , Proteínas de Fusión Oncogénica/genética , Adolescente , Adulto , Proliferación Celular/efectos de los fármacos , Preescolar , Crizotinib/uso terapéutico , Femenino , Predisposición Genética a la Enfermedad , Histiocitos/patología , Histiocitosis/tratamiento farmacológico , Histiocitosis/enzimología , Histiocitosis/patología , Hong Kong , Humanos , Lactante , Recién Nacido , Masculino , Fenotipo , Inhibidores de Proteínas Quinasas/uso terapéutico , Singapur , Resultado del Tratamiento , VictoriaRESUMEN
The classification of tumors is essential in the diagnosis and clinical management of patients with malignant neoplasms. The World Health Organization (WHO) provides a globally applicable classification scheme of neoplasms and it was updated several times. In this review, we briefly outline the cornerstones of the upcoming 5th edition of the World Health Organization Classification of Haematolymphoid Tumours on lymphoid neoplasms. As is adopted throughout the 5th edition of the WHO classification of tumors of all organ systems, entities are listed by a hierarchical system. For the first time, tumor-like lesions have been included in the classification, and modifications of nomenclature for some entities, revisions of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities are presented along with mesenchymal lesions specific to the stroma of lymph nodes and the spleen. In addition to specific outlines on constitutional and somatic genetic changes associated with given entities, a separate chapter on germline predisposition syndromes related to hematologic neoplasms has been added.
Asunto(s)
Organización Mundial de la Salud , HumanosRESUMEN
The purpose of this review is to give an overview on the conceptual framework and major developments of the upcoming 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid tumours (WHO-HAEM5) and to highlight the most significant changes made in WHO-HAEM5 compared with the revised 4th edition (WHO-HAEM4R) of lymphoid and stromal neoplasms. The changes from the revised 4th edition include the reorganization of entities by means of a hierarchical system that is realized throughout the 5th edition of the WHO classification of tumors of all organ systems, a modification of nomenclature for some entities, the refinement of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities. For the first time, tumor-like lesions, mesenchymal lesions specific to lymph node and spleen, and germline predisposition syndromes associated with the lymphoid neoplasms are included in the classification.
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Linfoma , Neoplasias , Humanos , Linfoma/diagnóstico , Organización Mundial de la SaludRESUMEN
Fibrin-associated large B-cell lymphoma is a rare microscopic-sized tumor, typically representing an unexpected finding at sites rich in chronic fibrin deposition. It is associated with Epstein-Barr virus, and has been reported to occur in a wide variety of anatomic sites and clinical scenarios. We report a case arising in a thyroid hyperplastic nodule, only the second case reported in this location. Notably, this is only the fourth case of fibrin-associated large B-cell lymphoma that is not associated with Epstein-Barr virus. We provide a literature review on the clinico-pathological characteristics and outcome of this newly characterized indolent lymphoma type, which has only recently been separated out from the pathologically similar but highly aggressive large B-cell lymphoma associated with chronic inflammation.
Asunto(s)
Infecciones por Virus de Epstein-Barr , Linfoma de Células B Grandes Difuso , Nódulo Tiroideo , Humanos , Herpesvirus Humano 4 , Fibrina , Linfoma de Células B Grandes Difuso/patología , Hiperplasia/complicacionesRESUMEN
BACKGROUND: Solitary fibrous tumor can exhibit a broad morphologic spectrum, such as presence of epithelioid tumor cells, adipose cells and multinucleated giant cells. This report describes an unusual morphologic variant characterized by adenofibromatous features, all occurring in the sinonasal region. METHODS: Four cases of the adenofibromatous variant of solitary fibrous tumor were retrieved from the surgical pathology and consultation files in Queen Elizabeth Hospital, Hong Kong. Histologic examination, immunohistochemical study and reverse-transcription polymerase chain reaction (RT-PCR) were performed. RESULTS: The patients were adults who presented with an obstructive mass of the nasal septum, nasal cavity or nasolacrimal sac. Histologic examination showed a circumscribed biphasic tumor with intermingling of glandular structures and spindle cells, reminiscent of mammary fibroadenoma. Bland-looking spindle cells formed short, irregularly oriented fascicles, admixed with variable amount of collagen fibers. The glandular component comprised ducts and seromucinous acini with a lobular architecture, indicating that it represented exuberant hyperplasia of indigenous glands rather than part of the neoplastic process. Demonstration of CD34 and STAT6 immunoreactivity in the spindle cells and NAB2::STAT6 gene fusion by polymerase chain reaction supports the diagnosis of solitary fibrous tumor. CONCLUSION: This study reports four cases of sinonasal solitary fibrous tumor with adenofibromatous features, furthermore expanding the morphologic spectrum of this tumor.
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Neoplasias de Cabeza y Cuello , Hemangiopericitoma , Senos Paranasales , Tumores Fibrosos Solitarios , Adulto , Humanos , Hemangiopericitoma/genética , Tumores Fibrosos Solitarios/genética , Tumores Fibrosos Solitarios/patología , Fusión Génica , Senos Paranasales/patología , Biomarcadores de Tumor/análisisRESUMEN
Lymphadenopathy is a common occurrence in IgG4-related disease; it can appear before, concurrent with, or after the diagnosis of this disease, which is characterized by tumefactive sclerosing inflammatory lesions predominantly affecting extranodal sites, such as the pancreas, salivary gland, and lacrimal gland. Although multiple lymph node groups are commonly involved, constitutional symptoms are absent. The lymph nodes can show a broad morphologic spectrum, including multicentric Castleman disease-like (type I), follicular hyperplasia (type II), interfollicular expansion (type III), progressive transformation of germinal centers (type IV), and inflammatory pseudotumor-like (type V). All are characterized by an increase in IgG4+ plasma cells (>100 per high power field) and IgG4/IgG ratio (>40%). IgG4-related lymphadenopathy is both an underdiagnosed and overdiagnosed entity. The former is because of the fact that this entity has not been characterized until recently, while the latter results from pathologists' enthusiasm in diagnosing "new" entities and the lack of specificity of the morphologic and immunophenotypic features of IgG4-related lymphadenopathy. It is prudent to render this diagnosis only for patients with known IgG4-related disease or in the presence of corroborating clinical and laboratory findings (such as elderly men, systemic lymphadenopathy, elevated serum IgG4, IgG, and IgE but not IgM and IgA, and low titers of autoantibodies). Outside these circumstances, a descriptive diagnosis of "reactive lymphoid hyperplasia with increased IgG4+ cells" accompanied by a recommendation for follow-up will be appropriate because IgG4-related disease will likely ensue only in a minority of such patients.
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Enfermedades Autoinmunes/patología , Inmunoglobulina G/sangre , Ganglios Linfáticos/patología , Enfermedades Linfáticas/patología , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/metabolismo , Biomarcadores/sangre , Enfermedad de Castleman/diagnóstico , Diagnóstico Diferencial , Centro Germinal , Humanos , Enfermedades Linfáticas/inmunología , Enfermedades Linfáticas/metabolismo , Linfoma de Células T/diagnósticoRESUMEN
Merkel cell carcinoma is an uncommon primary neuroendocrine neoplasm of the skin that may exhibit divergent differentiation. However, rhabdomyosarcomatous differentiation has only been rarely described and takes the form of isolated rhabdomyoblasts. We describe a case of cutaneous Merkel cell carcinoma with biphasic morphology imparted by discrete patches of embryonal rhabdomyosarcoma-like spindle cells alternating with islands of neuroendocrine small round cells, justifying a designation of "Merkel cell carcinosarcoma." The former component showed positive immunostaining for desmin and myogenin; and the later component, pan-cytokeratin, cytokeratin 20, synaptophysin, and chromogranin. The patient was an elderly man who presented with a temporal skin mass, and the biphasic morphology was evident in the recurrence and metastasis that developed 2 months after incomplete excision of the skin lesion.
Asunto(s)
Carcinoma de Células de Merkel/patología , Rabdomiosarcoma Embrionario/patología , Neoplasias Cutáneas/patología , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Carcinoma de Células de Merkel/metabolismo , Carcinoma de Células de Merkel/cirugía , Resultado Fatal , Humanos , Masculino , Recurrencia Local de Neoplasia , Neoplasias Primarias Múltiples , Rabdomiosarcoma Embrionario/metabolismo , Rabdomiosarcoma Embrionario/cirugía , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/cirugíaRESUMEN
Spindle cell/sclerosing rbabdomyosarcoma (RMS) is a recently characterized variant of RMS with several distinct molecular subtypes. We describe an example occurring in the tongue of a 10-year-old boy with a novel DCTN1::ALK fusion. The tumor exhibited infiltrative growth and was comprised of fascicles and focally whorls of spindle cells with eosinophilic cytoplasm, in a collagenous or myxoid stroma. Moderate cytologic atypia, mitotic activity (2/10 HPFs), and perineural invasion were identified. The tumor cells expressed actin, desmin, MyoD1, myogenin, and ALK. An in-frame fusion between DCTN1 exon 26 and ALK exon 20 was detected by RNA sequencing, which was confirmed by split reads and supported by FISH studies. The tumor showed an indolent behavior with local recurrence 3 years after excision. This study broadens the molecular spectrum of spindle cell/sclerosing RMS and this molecular aberration may represent a potential therapeutic target for unresectable or disseminated disease.
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Rabdomiosarcoma , Actinas , Biomarcadores de Tumor/genética , Niño , Complejo Dinactina , Humanos , Masculino , Proteínas Tirosina Quinasas Receptoras , Rabdomiosarcoma/genética , Rabdomiosarcoma/patología , Rabdomiosarcoma/terapiaRESUMEN
Burkitt lymphoma (BL) is an aggressive form of B cell lymphoma that can affect children and adults. The study of BL led to the identification of the first recurrent chromosomal aberration in lymphoma, t(8;14)(q24;q32), and subsequent discovery of the central role of MYC and Epstein-Barr virus (EBV) in tumorigenesis. Most patients with BL are cured with chemotherapy but those with relapsed or refractory disease usually die of lymphoma. Historically, endemic BL, non-endemic sporadic BL and the immunodeficiency-associated BL have been recognized, but differentiation of these epidemiological variants is confounded by the frequency of EBV positivity. Subtyping into EBV+ and EBV- BL might better describe the biological heterogeneity of the disease. Phenotypically resembling germinal centre B cells, all types of BL are characterized by dysregulation of MYC due to enhancer activation via juxtaposition with one of the three immunoglobulin loci. Additional molecular changes commonly affect B cell receptor and sphingosine-1-phosphate signalling, proliferation, survival and SWI-SNF chromatin remodelling. BL is diagnosed on the basis of morphology and high expression of MYC. BL can be effectively treated in children and adolescents with short durations of high dose-intensity multiagent chemotherapy regimens. Adults are more susceptible to toxic effects but are effectively treated with chemotherapy, including modified versions of paediatric regimens. The outcomes in patients with BL are good in high-income countries with low mortality and few late effects, but in low-income and middle-income countries, BL is diagnosed late and is usually treated with less-effective regimens affecting the overall good outcomes in patients with this lymphoma.
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Linfoma de Burkitt , Infecciones por Virus de Epstein-Barr , Linfoma , Adolescente , Adulto , Humanos , Niño , Linfoma de Burkitt/epidemiología , Linfoma de Burkitt/metabolismo , Linfoma de Burkitt/patología , Herpesvirus Humano 4 , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/epidemiología , Linfocitos BRESUMEN
Pediatric tumors are uncommon, yet are the leading cause of cancer-related death in childhood. Tumor types, molecular characteristics, and pathogenesis are unique, often originating from a single genetic driver event. The specific diagnostic challenges of childhood tumors led to the development of the first World Health Organization (WHO) Classification of Pediatric Tumors. The classification is rooted in a multilayered approach, incorporating morphology, IHC, and molecular characteristics. The volume is organized according to organ sites and provides a single, state-of-the-art compendium of pediatric tumor types. A special emphasis was placed on "blastomas," which variably recapitulate the morphologic maturation of organs from which they originate. SIGNIFICANCE: In this review, we briefly summarize the main features and updates of each chapter of the inaugural WHO Classification of Pediatric Tumors, including its rapid transition from a mostly microscopic into a molecularly driven classification systematically taking recent discoveries in pediatric tumor genomics into account.
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Neoplasias Encefálicas/clasificación , Niño , Genómica , Humanos , Organización Mundial de la SaludRESUMEN
This overview of the fifth edition of the WHO classification of thymic epithelial tumors (including thymomas, thymic carcinomas, and thymic neuroendocrine tumors [NETs]), mediastinal germ cell tumors, and mesenchymal neoplasms aims to (1) list established and new tumor entities and subtypes and (2) focus on diagnostic, molecular, and conceptual advances since publication of the fourth edition in 2015. Diagnostic advances are best exemplified by the immunohistochemical characterization of adenocarcinomas and the recognition of genetic translocations in metaplastic thymomas, rare B2 and B3 thymomas, and hyalinizing clear cell carcinomas. Advancements at the molecular and tumor biological levels of utmost oncological relevance are the findings that thymomas and most thymic carcinomas lack currently targetable mutations, have an extraordinarily low tumor mutational burden, but typically have a programmed death-ligand 1high phenotype. Finally, data underpinning a conceptual advance are illustrated for the future classification of thymic NETs that may fit into the classification scheme of extrathoracic NETs. Endowed with updated clinical information and state-of-the-art positron emission tomography and computed tomography images, the fifth edition of the WHO classification of thymic epithelial tumors, germ cell tumors, and mesenchymal neoplasms with its wealth of new diagnostic and molecular insights will be a valuable source for pathologists, radiologists, surgeons, and oncologists alike. Therapeutic perspectives and research challenges will be addressed as well.
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Adenocarcinoma , Neoplasias Pulmonares , Neoplasias del Timo , Células Germinativas/patología , Humanos , Mediastino/patología , Neoplasias del Timo/patología , Organización Mundial de la SaludRESUMEN
We herein present an overview of the upcoming 5th edition of the World Health Organization Classification of Haematolymphoid Tumours focussing on lymphoid neoplasms. Myeloid and histiocytic neoplasms will be presented in a separate accompanying article. Besides listing the entities of the classification, we highlight and explain changes from the revised 4th edition. These include reorganization of entities by a hierarchical system as is adopted throughout the 5th edition of the WHO classification of tumours of all organ systems, modification of nomenclature for some entities, revision of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities, as well as inclusion of tumour-like lesions, mesenchymal lesions specific to lymph node and spleen, and germline predisposition syndromes associated with the lymphoid neoplasms.