RESUMO
BACKGROUND: Diagnosis of primary diffuse large B-cell lymphoma of the central nervous system (PCNSL) is challenging and often delayed. MRI imaging, CSF cytology and flow cytometry have a low sensitivity and even brain biopsies can be misleading. We report three cases of PCNSL with various clinical presentation and radiological findings where the diagnosis was suggested by novel CSF biomarkers and subsequently confirmed by brain biopsy or autopsy. CASE PRESENTATIONS: The first case is a 79-year-old man with severe neurocognitive dysfunction and static ataxia evolving over 5 months. Brain MRI revealed a nodular ventriculitis. An open brain biopsy was inconclusive. The second case is a 60-year-old woman with progressive sensory symptoms in all four limbs, evolving over 1 year. Brain and spinal MRI revealed asymmetric T2 hyperintensities of the corpus callosum, corona radiata and corticospinal tracts. The third case is a 72-year-old man recently diagnosed with primary vitreoretinal lymphoma of the right eye. A follow-up brain MRI performed 4 months after symptom onset revealed a T2 hyperintense fronto-sagittal lesion, with gadolinium uptake and perilesional edema. In all three cases, CSF flow cytometry and cytology were negative. Mutation analysis on the CSF (either by digital PCR or by next generation sequencing) identified the MYD88 L265P hotspot mutation in all three cases. A B-cell clonality study, performed in case 1 and 2, identified a monoclonal rearrangement of the immunoglobulin light chain lambda (IGL) and kappa (IGK) gene. CSF CXCL-13 and IL-10 levels were high in all three cases, and IL-10/IL-6 ratio was high in two. Diagnosis of PCNSL was later confirmed by autopsy in case 1, and by brain biopsy in case 2 and 3. CONCLUSIONS: Taken together, 5 CSF biomarkers (IL-10, IL-10/IL-6 ratio, CXCL13, MYD88 mutation and monoclonal IG gene rearrangements) were strongly indicative of a PCNSL. Using innovative CSF biomarkers can be sensitive and complementary to traditional CSF analysis and brain biopsy in the diagnosis of PCNSL, potentially allowing for earlier diagnosis and treatment.
Assuntos
Linfoma Difuso de Grandes Células B , Humanos , Masculino , Idoso , Linfoma Difuso de Grandes Células B/líquido cefalorraquidiano , Linfoma Difuso de Grandes Células B/diagnóstico , Pessoa de Meia-Idade , Feminino , Neoplasias do Sistema Nervoso Central/líquido cefalorraquidiano , Neoplasias do Sistema Nervoso Central/diagnóstico por imagem , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/patologia , Biomarcadores Tumorais/líquido cefalorraquidiano , Encéfalo/patologia , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância MagnéticaRESUMO
Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology.
Assuntos
Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/genética , Metilação de DNA , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Nervoso Central/classificação , Neoplasias do Sistema Nervoso Central/patologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Aprendizado de Máquina não Supervisionado , Adulto JovemRESUMO
Ependymal and choroid plexus tumours arise in anatomically related regions. Their intraoperative differential diagnosis is large and depends on factors such as age, tumour site and clinical presentation. Squash cytology can provide valuable information in this context. Cytological features of conventional ependymomas, subependymomas and myxopapillary ependymomas as well as choroid plexus tumours are reviewed and illustrated. Differential diagnostic considerations integrating morphological and clinical information are discussed.
Assuntos
Neoplasias do Plexo Corióideo , Ependimoma , Humanos , Neoplasias do Plexo Corióideo/patologia , Neoplasias do Plexo Corióideo/diagnóstico , Ependimoma/patologia , Ependimoma/diagnóstico , Citodiagnóstico/métodos , Diagnóstico Diferencial , Plexo Corióideo/patologia , Epêndima/patologia , FemininoRESUMO
Mutations affecting codon 172 of the isocitrate dehydrogenase 2 (IDH2) gene define a subgroup of sinonasal undifferentiated carcinomas (SNUCs) with a relatively favorable prognosis and a globally hypermethylated phenotype. They are also recurrent (along with IDH1 mutations) in gliomas, acute myeloid leukemia, and intrahepatic cholangiocarcinoma. Commonly reported mutations, all associated with aberrant IDH2 enzymatic activity, include R172K, R172S, R172T, R172G, and R172M. We present a case of SNUC with a never-before-described IDH2 mutation, R172A. Our report compares the methylation pattern of our sample to other cases from the Gene Expression Omnibus database. Hierarchical clustering suggests a strong association between our sample and other IDH-mutant SNUCs and a clear distinction between sinonasal normal tissues and tumors. Principal component analysis (PCA), using 100 principal components explaining 94.5% of the variance, showed the position of our sample to be within 1.02 standard deviation of the other IDH-mutant SNUCs. A molecular modeling analysis of the IDH2 R172A versus other R172 variants provides a structural explanation to how they affect the protein active site. Our findings thus suggest that the R172A mutation in IDH2 confers a gain of function similar to other R172 mutations in IDH2, resulting in a similar hypermethylated profile.
Assuntos
Carcinoma , Metilação de DNA , Isocitrato Desidrogenase , Neoplasias do Seio Maxilar , Mutação , Humanos , Isocitrato Desidrogenase/genética , Metilação de DNA/genética , Carcinoma/genética , Carcinoma/patologia , Neoplasias do Seio Maxilar/genética , Neoplasias do Seio Maxilar/patologia , Masculino , Pessoa de Meia-Idade , Feminino , IdosoRESUMO
Glial cell activation is a hallmark of several neurodegenerative and neuroinflammatory diseases. During HIV infection, neuroinflammation is associated with cognitive impairment, even during sustained long-term suppressive antiretroviral therapy. However, the cellular subsets contributing to neuronal damage in the CNS during HIV infection remain unclear. Using post-mortem brain samples from eight HIV patients and eight non-neurological disease controls, we identify a subset of CNS phagocytes highly enriched in LGALS3, CTSB, GPNMB and HLA-DR, a signature identified in the context of ageing and neurodegeneration. In HIV patients, the presence of this phagocyte phenotype was associated with synaptic stripping, suggesting an involvement in the pathogenesis of HIV-associated neurocognitive disorder. Taken together, our findings elucidate some of the molecular signatures adopted by CNS phagocytes in HIV-positive patients and contribute to the understanding of how HIV might pave the way to other forms of cognitive decline in ageing HIV patient populations.
Assuntos
Infecções por HIV , Fagócitos , Sinapses , Encéfalo/patologia , Encéfalo/virologia , Infecções por HIV/complicações , Infecções por HIV/metabolismo , Infecções por HIV/patologia , Humanos , Glicoproteínas de Membrana , Transtornos Neurocognitivos , Neurônios/patologia , Neurônios/virologia , Fagócitos/metabolismo , Fagócitos/patologia , Sinapses/patologia , Sinapses/virologiaRESUMO
Oligodendrogliomas are defined at the molecular level by the presence of an IDH mutation and codeletion of chromosomal arms 1p and 19q. In the past, case reports and small studies described gliomas with sarcomatous features arising from oligodendrogliomas, so called oligosarcomas. Here, we report a series of 24 IDH-mutant oligosarcomas from 23 patients forming a distinct methylation class. The tumors were recurrences from prior oligodendrogliomas or developed de novo. Precursor tumors of 12 oligosarcomas were histologically and molecularly indistinguishable from conventional oligodendrogliomas. Oligosarcoma tumor cells were embedded in a dense network of reticulin fibers, frequently showing p53 accumulation, positivity for SMA and CALD1, loss of OLIG2 and gain of H3K27 trimethylation (H3K27me3) as compared to primary lesions. In 5 oligosarcomas no 1p/19q codeletion was detectable, although it was present in the primary lesions. Copy number neutral LOH was determined as underlying mechanism. Oligosarcomas harbored an increased chromosomal copy number variation load with frequent CDKN2A/B deletions. Proteomic profiling demonstrated oligosarcomas to be highly distinct from conventional CNS WHO grade 3 oligodendrogliomas with consistent evidence for a smooth muscle differentiation. Expression of several tumor suppressors was reduced with NF1 being lost frequently. In contrast, oncogenic YAP1 was aberrantly overexpressed in oligosarcomas. Panel sequencing revealed mutations in NF1 and TP53 along with IDH1/2 and TERT promoter mutations. Survival of patients was significantly poorer for oligosarcomas as first recurrence than for grade 3 oligodendrogliomas as first recurrence. These results establish oligosarcomas as a distinct group of IDH-mutant gliomas differing from conventional oligodendrogliomas on the histologic, epigenetic, proteomic, molecular and clinical level. The diagnosis can be based on the combined presence of (a) sarcomatous histology, (b) IDH-mutation and (c) TERT promoter mutation and/or 1p/19q codeletion, or, in unresolved cases, on its characteristic DNA methylation profile.
Assuntos
Neoplasias Encefálicas/patologia , Isocitrato Desidrogenase/genética , Oligodendroglioma/patologia , Sarcoma/patologia , Adulto , Idoso , Neoplasias Encefálicas/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Oligodendroglioma/genética , Sarcoma/genéticaRESUMO
BACKGROUND: The novel beta-coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), enters the human body via mucosal surfaces of the upper and/or lower respiratory tract. Viral entry into epithelial cells is mediated via angiotensin-converting enzyme 2 (ACE2) and auxiliary molecules, but the precise anatomic site of infection still remains unclear. METHODS: Here, we systematically investigated the main SARS-CoV-2 receptor proteins ACE2 and transmembrane serine protease 2 (TMPRSS2), as well as 2 molecules potentially involved in viral entry, furin and CD147, in formalin-fixed, paraffin-embedded human tissues. Tissue microarrays incorporating a total of 879 tissue cores from conjunctival (n = 84), sinonasal (n = 95), and lung (bronchiolar/alveolar; n = 96) specimens were investigated for protein expression by immunohistochemistry. RESULTS: ACE2 and TMPRSS2 were expressed in ciliated epithelial cells of the conjunctivae and sinonasal tissues, with highest expression levels observed in the apical cilia. In contrast, in the lung, the expression of those molecules in bronchiolar and alveolar epithelial cells was much rarer and only very focal when present. Furin and CD147 were more uniformly expressed in all tissues analyzed, including the lung. Interestingly, alveolar macrophages consistently expressed high levels of all 4 molecules investigated. CONCLUSIONS: Our study confirms and extends previous findings and contributes to a better understanding of potential SARS-CoV-2 infection sites along the human respiratory tract.
Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , Basigina/metabolismo , Furina/metabolismo , Sistema Respiratório/metabolismo , SARS-CoV-2 , Serina Endopeptidases/metabolismo , Internalização do Vírus , COVID-19/metabolismo , COVID-19/virologia , Humanos , Pulmão/metabolismo , Sistema Respiratório/virologiaRESUMO
Synoptic reporting in pathology as opposed to traditional narrative reporting is defined by a laboratory value-like format and use of standardized checklists. It contributes to completeness and comprehensibility of pathology reports and ultimately patient care. As of today, two major institutions publish synoptic reporting templates, the College of American Pathologists (CAP) and the International Collaboration for Cancer Reporting (ICCR). Synoptic protocols are available for all major cancer types and provide not only a standardized terminology and a checklist for completeness of reports, but also facilitate uniform utilization of diagnostic criteria. Additionally, both CAP and ICCR protocols are accompanied by detailed and up-to-date reference lists and thereby represent a valuable source of information even when synoptic reporting is not used. The benefits and challenges of implementation of synoptic reporting are discussed, in particular with regard to reporting in German.
Assuntos
Neoplasias Gastrointestinais , Patologia Clínica , HumanosRESUMO
Reciprocal RUNX1 fusions are traditionally found in up to 10% of acute myeloid leukemia (AML) patients, usually associated with a translocation (8;21)(q22;q22) corresponding to the RUNX1-RUNX1T1 fusion gene. So far, alternative RUNX1 rearrangements have been reported only rarely in AML, and the few reports so far have focused on results based on cytogenetics, fluorescence in situ hybridization, and polymerase chain reaction. Acknowledging the inherent limitations of these diagnostic techniques, the true incidence of rare RUNX1 rearrangements may be underestimated. In this report, we present two cases of adult AML, in which we detected rare RUNX1 rearrangements not by conventional cytogenetics but rather by next-generation panel sequencing. These include t(16;21)(q24;q22)/RUNX1-CBFA2T3 and t(7;21)(p22;q22)/RUNX1-USP42, respectively. In both patients the AML was therapy-related and associated with additional structural and numerical alterations thereby conferring bad prognosis. This is in line with previous reports on rare RUNX1 fusions in AML and emphasizes the clinical importance of their detection. In summary, our report not only confirms the clinical utility of NGS for diagnostics of rare reciprocal rearrangements in AML in a real-life scenario but also sheds light on the variety and complexity within AML. It further emphasizes the need for collection of additional cases for deepening insights on their clinical meaning as well as their frequency.
Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core/genética , Rearranjo Gênico , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Translocação Genética , Idoso , Biomarcadores Tumorais , Linhagem Celular Tumoral , Cromossomos Humanos Par 16 , Cromossomos Humanos Par 21 , Estudos de Associação Genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Hibridização in Situ Fluorescente , Masculino , Proteínas de Fusão Oncogênica/genética , Proteínas Repressoras/genéticaRESUMO
The "isomorphic subtype of diffuse astrocytoma" was identified histologically in 2004 as a supratentorial, highly differentiated glioma with low cellularity, low proliferation and focal diffuse brain infiltration. Patients typically had seizures since childhood and all were operated on as adults. To define the position of these lesions among brain tumours, we histologically, molecularly and clinically analysed 26 histologically prototypical isomorphic diffuse gliomas. Immunohistochemically, they were GFAP-positive, MAP2-, OLIG2- and CD34-negative, nuclear ATRX-expression was retained and proliferation was low. All 24 cases sequenced were IDH-wildtype. In cluster analyses of DNA methylation data, isomorphic diffuse gliomas formed a group clearly distinct from other glial/glio-neuronal brain tumours and normal hemispheric tissue, most closely related to paediatric MYB/MYBL1-altered diffuse astrocytomas and angiocentric gliomas. Half of the isomorphic diffuse gliomas had copy number alterations of MYBL1 or MYB (13/25, 52%). Gene fusions of MYBL1 or MYB with various gene partners were identified in 11/22 (50%) and were associated with an increased RNA-expression of the respective MYB-family gene. Integrating copy number alterations and available RNA sequencing data, 20/26 (77%) of isomorphic diffuse gliomas demonstrated MYBL1 (54%) or MYB (23%) alterations. Clinically, 89% of patients were seizure-free after surgery and all had a good outcome. In summary, we here define a distinct benign tumour class belonging to the family of MYB/MYBL1-altered gliomas. Isomorphic diffuse glioma occurs both in children and adults, has a concise morphology, frequent MYBL1 and MYB alterations and a specific DNA methylation profile. As an exclusively histological diagnosis may be very challenging and as paediatric MYB/MYBL1-altered diffuse astrocytomas may have the same gene fusions, we consider DNA methylation profiling very helpful for their identification.
Assuntos
Neoplasias Encefálicas/genética , Glioma/genética , Proteínas Proto-Oncogênicas c-myb/genética , Proteínas Proto-Oncogênicas/genética , Transativadores/genética , Adulto , Neoplasias Encefálicas/patologia , Criança , Pré-Escolar , Variações do Número de Cópias de DNA , Metilação de DNA , Feminino , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Fusão Oncogênica , Adulto JovemRESUMO
Synoptic reporting in tumour pathology is defined by (1) completeness in terms of data elements as well as (2) a specific, laboratory value-like format. Adoption of synoptic reporting leads to more complete reporting of essential parameters, improved standardisation of diagnostic criteria and terminology, as well as easier retrieval of information. It is therefore associated with a high degree of satisfaction among end users including surgeons and oncologists and contributes to improvement of clinical care. Furthermore, synoptic reporting is an important step towards higher levels of data capture, which facilitate data exchange and analysis for quality assurance, cancer epidemiology and clinical and basic research. Increased interest in and adoption of synoptic reporting on a global level is stimulated by the International Collaboration on Cancer Reporting (ICCR) which publishes freely available, evidence-based datasets for reporting an increasing number of different cancer types. These developments pave the path for increased future application of synoptic reporting across the entire field of oncologic medicine, where it will likely deploy similar benefits to those in pathology. Given that synoptic reporting can be considered the most precise means available for reporting of medical findings, it may be predicted to be critical for the promise of precision medicine to become real.
Assuntos
Neoplasias/patologia , Relatório de Pesquisa/normas , Guias como Assunto , Humanos , Patologistas , Sociedades MédicasRESUMO
PURPOSE: The aim of this study is to identify the micro-mechanical characteristics that define biopsy performance in normal ex vivo animal organs. MATERIALS AND METHODS: Three biopsy systems with differences of needle external diameter, tray height and effective tray length were assessed. Sampling was performed in porcine liver and kidneys with commercially labelled 14G, 16G and 18G, using 2-cm throw needle systems. Five samples were obtained per needle size and per organ, and the experiment was repeated twice for a total of 90 biopsy cores. Samples were analysed and compared in terms of macroscopic aspect, sample length, weight and tissue architecture. RESULTS: The system with the longest effective needle tray (system A) has shown significant superiority (p < 0.001) versus the other systems regarding the mean weight of tissue obtained for all needle sizes. Furthermore, the 14G needle of system A has shown superiority regarding the number of portal spaces and the 16G regarding the length of kidney fragments obtained. CONCLUSION: The outcomes obtained with the different biopsy systems were not equal. The micro-mechanical characteristic that appears to influence the quantity and quality of the obtained tissue is the effective needle tray length and not the needle external diameter or the needle tray height. This information should be taken into account in the future design of biopsy needle systems, particularly when potentially used in the assessment of biomarkers and the characterisation of tumour micro-environment. KEY POINTS: ⢠The amount of obtained tissue mass is not the same among percutaneous biopsy needle systems. ⢠There are different micro-mechanical characteristics that condition the amount of obtained tissue. ⢠The micro-mechanical characteristic that offers more tissue mass for the same calibre is the effective length of the needle tray.
Assuntos
Biópsia com Agulha de Grande Calibre/instrumentação , Nefropatias/diagnóstico , Rim/patologia , Hepatopatias/diagnóstico , Fígado/patologia , Animais , Modelos Animais de Doenças , Desenho de Equipamento , SuínosRESUMO
Tumors with histological features of pilocytic astrocytoma (PA), but with increased mitotic activity and additional high-grade features (particularly microvascular proliferation and palisading necrosis) have often been designated anaplastic pilocytic astrocytomas. The status of these tumors as a separate entity has not yet been conclusively demonstrated and molecular features have only been partially characterized. We performed DNA methylation profiling of 102 histologically defined anaplastic pilocytic astrocytomas. T-distributed stochastic neighbor-embedding (t-SNE) and hierarchical clustering analysis of these 102 cases against 158 reference cases from 12 glioma reference classes revealed that a subset of 83 of these tumors share a common DNA methylation profile that is distinct from the reference classes. These 83 tumors were thus denominated DNA methylation class anaplastic astrocytoma with piloid features (MC AAP). The 19 remaining tumors were distributed amongst the reference classes, with additional testing confirming the molecular diagnosis in most cases. Median age of patients with MC AAP was 41.5 years. The most frequent localization was the posterior fossa (74%). Deletions of CDKN2A/B (66/83, 80%), MAPK pathway gene alterations (49/65, 75%, most frequently affecting NF1, followed by BRAF and FGFR1) and mutations of ATRX or loss of ATRX expression (33/74, 45%) were the most common molecular alterations. All tumors were IDH1/2 wildtype. The MGMT promoter was methylated in 38/83 tumors (45%). Outcome analysis confirmed an unfavorable clinical course in comparison to PA, but better than IDH wildtype glioblastoma. In conclusion, we show that a subset of histologically defined anaplastic pilocytic astrocytomas forms a separate DNA methylation cluster, harbors recurrent alterations in MAPK pathway genes in combination with alterations of CDKN2A/B and ATRX, affects patients who are on average older than those diagnosed with PA and has an intermediate clinical outcome.
Assuntos
Astrocitoma/genética , Neoplasias Encefálicas/genética , Isocitrato Desidrogenase/genética , Transdução de Sinais/genética , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Inibidor p16 de Quinase Dependente de Ciclina/genética , Metilação de DNA/genética , Metilases de Modificação do DNA/metabolismo , Enzimas Reparadoras do DNA/metabolismo , Feminino , Histonas/genética , Histonas/metabolismo , Humanos , Lactente , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Mutação/genética , Estudos Retrospectivos , Proteínas Supressoras de Tumor/metabolismo , Proteína Nuclear Ligada ao X/genética , Adulto JovemRESUMO
AIMS: To assess whether in oligoastrocytomas ATRX deficiency, as a surrogate of the alternative lengthening of telomeres (ALT) pathway, has a role in predicting the presence or absence of loss of heterozygosity (LOH) of 1p and 19q, the genetic signature of oligodendroglial differentiation and a favourable prognostic marker. METHODS AND RESULTS: A series of 54 oligoastrocytomas were investigated by immunohistochemistry as well as microsatellite analysis for LOH 1p19q. Genetic findings were correlated with morphological assessment. CONCLUSIONS: ATRX deficiency was mutually exclusive with LOH. Conversely, ATRX-proficient tumours immunoreactive for R132H-mutant isocitrate dehydrogenase 1 (IDH1) showed a high rate (85%) of LOH. A more oligodendroglioma-like morphology was associated with a higher rate of LOH even in the morphologically ambiguous group of oligoastrocytomas. Our findings support the concept that oligoastrocytomas represent a morphological grey zone, rather than a group of truly 'mixed' or 'intermediate' tumours. More precise classification of diffuse gliomas may also improve grading of borderline cases. We propose an immunohistochemical algorithm for classification of morphologically ambiguous diffuse gliomas.
Assuntos
Isocitrato Desidrogenase , Perda de Heterozigosidade , Repetições de Microssatélites/genética , Oligodendroglioma/classificação , Homeostase do Telômero/genética , Proteína Nuclear Ligada ao X , Adulto , Idoso , Idoso de 80 Anos ou mais , Cromossomos Humanos Par 1/genética , Cromossomos Humanos Par 19/genética , Feminino , Genótipo , Humanos , Imuno-Histoquímica , Isocitrato Desidrogenase/genética , Isocitrato Desidrogenase/metabolismo , Masculino , Pessoa de Meia-Idade , Oligodendroglioma/genética , Oligodendroglioma/metabolismo , Oligodendroglioma/patologia , Análise Serial de Tecidos , Proteína Nuclear Ligada ao X/genética , Proteína Nuclear Ligada ao X/metabolismo , Adulto JovemRESUMO
Thyroid transcription factor 1 (TTF-1) is encoded by the NKX2-1 homeobox gene. Besides specifying thyroid and pulmonary organogenesis, it is also temporarily expressed during embryonic development of the ventral forebrain. We recently observed widespread immunoreactivity for TTF-1 in a case of subependymal giant cell astrocytoma (SEGA, WHO grade I)--a defining lesion of the tuberous sclerosis complex (TSC). This prompted us to investigate additional SEGAs in this regard. We found tumor cells in all 7 specimens analyzed to be TTF-1 positive. In contrast, we did not find TTF-1 immunoreactivity in a cortical tuber or two renal angiomyolipomas resected from TSC patients. We propose our finding of consistent TTF-1 expression in SEGAs to indicate lineage-committed derivation of these tumors from a regionally specified cell of origin. The medial ganglionic eminence, ventral septal region, and preoptic area of the developing brain may represent candidates for the origin of SEGAs. Such lineage-restricted histogenesis may also explain the stereotypic distribution of SEGAs along the caudate nucleus in the lateral ventricles.
Assuntos
Astrocitoma/patologia , Neoplasias Encefálicas/patologia , Proteínas de Ligação a DNA/biossíntese , Adolescente , Adulto , Astrocitoma/metabolismo , Neoplasias Encefálicas/metabolismo , Núcleo Celular/metabolismo , Criança , Pré-Escolar , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Fatores de Transcrição , Adulto JovemAssuntos
Candidíase/diagnóstico , Esofagite/diagnóstico , Infecções por Bactérias Gram-Positivas/diagnóstico , Sarcina/isolamento & purificação , Idoso de 80 Anos ou mais , Candidíase/patologia , Esofagite/patologia , Infecções por Bactérias Gram-Positivas/microbiologia , Infecções por Bactérias Gram-Positivas/patologia , Humanos , MasculinoRESUMO
INTRODUCTION: Desmoplastic small round cell tumor (DSRCT) is an uncommon, embryonic-type neoplasm, typically presenting as an abdominal mass in young men. A single case of DSRCT arising in the peripheral nervous system has been reported previously. METHODS: The clinical course, imaging, electrophysiological, intraoperative, histopathological, molecular findings, and postoperative follow-up are reported. RESULTS: A 43-year-old man presented with slowly progressive right brachial plexopathy. Magnetic resonance imaging revealed an enlarged medial cord with heterogeneous contrast enhancement. Histology showed a "small round cell" neoplasm with a polyphenotypic immunoprofile, including epithelial and mesenchymal markers. A pathognomonic fusion of Ewing sarcoma breakpoint region 1 and Wilms tumor 1 genes (EWSR1/WT1) was present. Treatment involved gross total excision and local radiotherapy. CONCLUSIONS: Our findings confirm the occurrence of DSRCT as a primary peripheral nerve tumor. Despite its usually very aggressive clinical course, prolonged recurrence-free survival may be reached. Histomorphology and immunoprofile of DSRCT may lead to misdiagnosis as small cell carcinoma.
Assuntos
Neuropatias do Plexo Braquial/etiologia , Tumor Desmoplásico de Pequenas Células Redondas/complicações , Neoplasias do Sistema Nervoso Periférico/complicações , Adulto , Neuropatias do Plexo Braquial/diagnóstico , Terapia Combinada , Tumor Desmoplásico de Pequenas Células Redondas/diagnóstico , Tumor Desmoplásico de Pequenas Células Redondas/terapia , Humanos , Imageamento por Ressonância Magnética , Masculino , Neoplasias do Sistema Nervoso Periférico/diagnóstico , Neoplasias do Sistema Nervoso Periférico/terapia , Tomografia por Emissão de Pósitrons , Resultado do TratamentoRESUMO
With respect to localization, oligodendrogliomas are characterized by a marked preponderance of the cerebral hemispheres. Outside these typical sites, any tumor histopathologically reminiscent of oligodendroglioma a priori is likely to represent one of its morphological mimics, including clear cell ependymoma, neurocytoma, pilocytic astrocytoma or glioneuronal tumors. This is particularly relevant as several of the latter are in principle curable by surgery. Among extrahemispherical sites, bona fide oligodendroglioma - as characterized by loss of heterozygosity (LOH) of chromosome arms 1p and 19q - so far has not been documented to occur in the brain stem. Here, we report the case of a 55-year-old female patient with an anaplastic oligodendroglioma (WHO grade III) of the brain stem and cerebellum diagnosed by stereotactic biopsy and featuring combined LOH of 1p and 19q. A morphological peculiarity was a population of interspersed tumor giant cells, a phenomenon that has been referred to as polymorphous oligodendroglioma. Our findings confirm the notion that - although very infrequently - true oligodendrogliomas do occur in the infratentorial compartment.
Assuntos
Neoplasias do Tronco Encefálico/diagnóstico , Cromossomos Humanos Par 19/genética , Cromossomos Humanos Par 1/genética , Oligodendroglioma/diagnóstico , Neoplasias do Tronco Encefálico/genética , Neoplasias do Tronco Encefálico/patologia , Deleção Cromossômica , Feminino , Humanos , Pessoa de Meia-Idade , Oligodendroglioma/genética , Oligodendroglioma/patologiaRESUMO
A polymorphous variant of oligodendroglioma was described by K.J. Zülch half a century ago, and is only very sporadically referred to in the subsequent literature. In particular, no comprehensive analysis with respect to clinical or genetic features of these tumors is available. From a current perspective, the term polymorphous oligodendroglioma (pO) may appear as contradictory in terms, as nuclear monotony is a histomorphological hallmark of oligodendrogliomas. For the purpose of this study, we defined pO as diffusely infiltrating gliomas felt to be of oligodendroglial rather than astrocytic differentiation and characterized by the presence of multinucleate tumor giant cells and/or nuclear pleomorphism. In a total of nine patients, we identified tumors consistent with this working definition. All tumors were high-grade. We characterized these with respect to clinical, histomorphological and genetic features. Despite clinical and genetic heterogeneity, we identified a subset of tumors of bona fide oligodendroglial differentiation as characterized by combined loss of heterozygosity of chromosome arms 1p and 19q (LOH 1p19q). Those tumors that lacked LOH 1p19q showed a high frequency of IDH1 mutations and loss of alpha thalassemia/mental retardation syndrome X-linked gene (ATRX) immunoreactivity, indicating a possible phenotypic convergence of true oligodendrogliomas and gliomas of the alternative lengthening of telomeres (ALT) pathway. p53 alterations were common irrespective of the 1p19q status. Histomorphologically, the tumors featured interspersed bizarre multinucleate giant tumor cells, while the background population varied from monotonous to significantly pleomorphic. Our findings indicate, that a rare polymorphous - or "giant cell" - variant of oligodendroglioma does indeed exist.