RESUMO
Giant cell tumors (GCTs) with high mobility group AT-Hook 2 ( HMGA2 )::nuclear receptor corepressor 2 ( NCOR2 ) fusion are rare mesenchymal tumors of controversial nosology, which have been anecdotally reported to respond to CSFR1 inhibitors. Here, we performed a comprehensive study of 6 GCTs with HMGA2::NCOR2 fusion and explored their relationship with other giant cell-rich neoplasms. Tumors occurred in 4 females and 2 males ranging in age from 17 to 32 years old (median 24). Three lesions originated in subcutaneous soft tissue and 3 in bone. Tumor size ranged from 20 to 33 mm (median 27 mm). The lesions had a nodular/multinodular architecture and were composed of sheets of mononuclear "histiocytoid" cells with uniform nuclei intermingled with multinucleated giant cells. Mitotic activity was low and nuclear atypia and metaplastic bone were absent. Variable findings included necrosis, cystic degeneration, lymphocytic infiltrate (sometimes forming nodules), and xanthogranulomatous inflammation. On immunohistochemistry, all cases focally expressed pan-keratin and were negative with SATB2 and H3.3G34W. Whole RNA-sequencing was performed in all cases of GCT with HMGA2::NCOR2 fusion and a subset of giant cell-rich tumors (tenosynovial-GCT, n = 19 and "wild-type" GCT of soft tissue, n = 9). Hierarchical clustering of RNA-sequencing data showed that GCT with HMGA2::NCOR2 fusion formed a single cluster, independent of the other 2 entities. Methylome profiling showed similar results, but the distinction from "wild-type" GCT of soft tissue was less flagrant. Gene expression analysis showed similar levels of expression of the CSF1/CSFR1 axis between GCT with HMGA2::NCOR2 fusion and tenosynovial-GCT, supporting their potential sensitivity to CSFR1 inhibitors. Clinical follow-up was available for 5 patients (range: 10 to 64 mo; median 32 mo). Three patients (60%) experienced local recurrences, whereas none had distant metastases or died of disease. Overall, our study confirms and expands previous knowledge on GCT with HMGA2::NCOR2 fusion and supports its inclusion as an independent entity.
Assuntos
Biomarcadores Tumorais , Tumores de Células Gigantes , Masculino , Feminino , Humanos , Adolescente , Adulto Jovem , Adulto , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , Tumores de Células Gigantes/patologia , Imuno-Histoquímica , Osso e Ossos/patologia , Epigênese Genética , Correpressor 2 de Receptor Nuclear/genéticaRESUMO
PURPOSE: The purpose of this study was to analyze the imaging features of extraskeletal osteosarcomas (ESOS) on computed tomography (CT) and magnetic resonance imaging (MRI) and to investigate their associations with overall survival (OS) using uni- and multivariable survival analyses. MATERIALS AND METHODS: This two-center retrospective study included all consecutive adult patients between 2008 and 2021 with histopathologically-proven ESOS who underwent pre-treatment CT and/or MRI. Clinical and histological characteristics, ESOS presentation on CT and MRI, treatment and outcomes were reported. Survival analyses were performed using Kaplan-Meier analysis and Cox regressions. Associations between imaging features and OS were searched using uni- and multivariable analyses. RESULTS: Fifty-four patients were included (30/54 [56%] men, median age: 67.5 years). Twenty-four died of ESOS (median OS: 18 months). ESOS were mostly deep-seated (46/54, 85%) in the lower limb (27/54, 50%) with a median size of 95 mm (interquartile range: 64, 142; range: 21-289 mm). Mineralization was seen on 26/42 (62%) patients, mainly gross-amorphous (18/26; 69%). ESOS were generally highly heterogeneous on T2-weighted images (38/48; 79%) and contrast-enhanced (CE) T1-weighted images (29/40; 72%), with necrosis (39/40; 97%), well-defined or focally infiltrative margins (39/47; 83%), with moderate peritumoral edema (39/47; 83%) and rim-like peripheral enhancement (17/40; 42%). Size, location, mineralization on CT, signal intensity heterogeneity on T1-, T2- and CE-T1-weighted images and hemorragic signal on MRI were associated with poorer OS (range of log-rank P = 0.0069-0.0485). At multivariable analysis, hemorragic signal and signal intensity heterogeneity on T2-weighted images remained predictive for poorer OS (hazard ratio [HR] = 2.68, P = 0.0299; HR = 9.85, P = 0.0262, respectively) CONCLUSION: ESOS typically presents as mineralized heterogeneous and necrotic soft tissue tumor with a possible rim-like enhancement and limited peritumoral abnormalities. MRI may help estimate outcome of patients with ESOS.
Assuntos
Neoplasias Ósseas , Osteossarcoma , Neoplasias de Tecidos Moles , Adulto , Masculino , Humanos , Idoso , Feminino , Estudos Retrospectivos , Osteossarcoma/diagnóstico por imagem , Osteossarcoma/terapia , Neoplasias de Tecidos Moles/patologia , Tomografia Computadorizada por Raios X , Imageamento por Ressonância Magnética/métodos , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/terapiaRESUMO
This article provides an overview of the current knowledge regarding diagnostic imaging of patients with soft-tissue sarcomas, which is a heterogeneous group of rare mesenchymal malignancies. After an initial contextualization, diagnostic flow-chart based on initial radiological findings of soft-tissue masses (with specific focus on adipocytic soft-tissue tumors [STTs], hemorragic STTs and retroperitoneal STTs) are provided considering relevant results from novel researches, guidelines, and experts' viewpoints, with the aim to help radiologists and clinicians in their practice. Particularly, the central place of sarcoma reference centers in the diagnostic and therapeutic management is highlighted, as well as the pivotal role that radiologists should play to correctly identify patients with soft-tissue sarcoma at the initial stage of the disease. Indications and methods for performing imaging-guided biopsies are also discussed, as well as clues to improve soft-tissue sarcoma grading with conventional and quantitative imaging.
Assuntos
Sarcoma , Neoplasias de Tecidos Moles , Humanos , Adulto , Imageamento por Ressonância Magnética/métodos , Sarcoma/diagnóstico por imagem , Sarcoma/patologia , Biópsia , Neoplasias de Tecidos Moles/diagnóstico por imagem , Neoplasias de Tecidos Moles/patologia , AlgoritmosRESUMO
Microstructural changes after an ischemic stroke (IS) have mainly been described in white matter. Data evaluating microstructural changes in gray matter (GM) remain scarce. The aim of the present study was to evaluate the integrity of GM on longitudinal data using mean diffusivity (MD), and its influence on post-IS cognitive performances. A prospective study was conducted, including supra-tentorial IS patients without pre-stroke disability. A cognitive assessment was performed at baseline and 1 year, including a Montreal Cognitive Assessment, an Isaacs set test, and a Zazzo cancelation task (ZCT): completion time and number of errors. A 3-T brain MRI was performed at the same two time-points, including diffusion tensor imaging for the assessment of GM MD. GM volume was also computed, and changes in GM volume and GM MD were evaluated, followed by the assessment of the relationship between these structural changes and changes in cognitive performances. One hundred and four patients were included (age 68.5 ± 21.5, 38.5% female). While no GM volume loss was observed, GM MD increased between baseline and 1 year. The increase of GM MD in left fronto-temporal regions (dorsolateral prefrontal cortex, superior and medial temporal gyrus, p < 0.05, Threshold-Free Cluster Enhancement, 5000 permutations) was associated with an increase time to complete ZCT, regardless of demographic confounders, IS volume and location, GM, and white matter hyperintensity volume. GM integrity deterioration was thus associated with processing speed slowdown, and appears to be a biomarker of cognitive frailty. This broadens the knowledge of post-IS cognitive impairment mechanisms.
Assuntos
AVC Isquêmico , Substância Branca , Humanos , Feminino , Masculino , Substância Cinzenta/diagnóstico por imagem , Imagem de Tensor de Difusão , Velocidade de Processamento , Estudos Prospectivos , Substância Branca/diagnóstico por imagem , Encéfalo/diagnóstico por imagemRESUMO
Round cell sarcomas represent a diagnostic challenge for pathologists due to the poorly differentiated pattern of these high-grade tumors. Their diagnosis often requires large immunohistochemical panels and the use of molecular pathology. These tumors are largely dominated by Ewing sarcomas, but new families are now well characterized, including in decreasing frequency order in bone, BCOR-altered sarcomas, NFATc2-rearranged sarcomas, mesenchymal chondrosarcomas and more rarely CIC-rearranged sarcomas and myoepithelial tumors. This progress report presents microscopic, immunohistochemical and molecular features of these tumors previously named by the inappropriate term "Ewing-like" sarcomas, in order to enable any pathologist to perceive the morphological features of these sarcomas, to select the immunohistochemical panel that will lead to the diagnosis and to better guide the molecular approach needed to establish the final diagnosis.
Assuntos
Neoplasias Ósseas , Sarcoma de Células Pequenas , Sarcoma , Neoplasias de Tecidos Moles , Biomarcadores Tumorais , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Humanos , Proteínas de Fusão Oncogênica/genética , Sarcoma/diagnóstico , Sarcoma/genética , Sarcoma de Células Pequenas/diagnóstico , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/patologiaRESUMO
BACKGROUND. A recently introduced digital breast tomosynthesis (DBT) device allows acquisition of DBT spot compression views with a small paddle during DBT acquisition. OBJECTIVE. The purpose of this study was to evaluate the impact on diagnostic performance of obtaining a DBT spot compression view for assessment of equivocal DBT findings. METHODS. This retrospective study included 102 women (mean age, 60 years) in whom a DBT spot compression view was obtained to characterize an equivocal finding on DBT at the performing radiologist's discretion. The DBT examinations were performed from December 14, 2018, to December 18, 2019. Two fellowship-trained breast radiologists and one breast imaging fellow, who were aware of the location of the equivocal lesions, independently reviewed the examinations. Readers first assigned a BI-RADS category using standard DBT views and then immediately assigned a category using the DBT spot compression view. BI-RADS categories 2 and 3 were considered negative, and categories 4A and greater were considered positive. Histology and at least 1 year of imaging follow-up served as the reference standard. Intrareader agreement for one reader and interreader agreement among all readers were evaluated with kappa coefficients. Diagnostic performance was compared between DBT with and DBT without spot compression views by use of McNemar tests. RESULTS. Intrareader agreement increased from 0.43 to 0.72, and interreader agreement increased from 0.21 to 0.45 on the basis of kappa coefficients for DBT without and with spot compression views. Eighteen cancers were present. Compared with standard DBT views, DBT spot compression views yielded significantly increased accuracy for all three readers (75% vs 90%, 74% vs 94%, 72% vs 94%); significantly increased specificity for all three readers (69% vs 90%, 75% vs 94%, 68% vs 93%); and significantly increased sensitivity for one reader (67% vs 94%) without significant change in sensitivity for the two other readers (89% vs 100%, 100% vs 89%). Radiation dose was 1.97 mGy for the DBT spot compression view versus 1.78-1.81 mGy for standard DBT craniocaudal and medio-lateral oblique views. CONCLUSION. Use of the DBT spot compression view increased intrareader agreement, interreader agreement, and diagnostic accuracy (primarily owing to improved specificity); the supplemental dose for the spot compression view was slightly higher than that for a standard DBT view. CLINICAL IMPACT. DBT spot compression may help characterize equivocal DBT findings, reducing further workup for benign findings.
Assuntos
Neoplasias da Mama , Mamografia , Mama/diagnóstico por imagem , Neoplasias da Mama/diagnóstico por imagem , Feminino , Humanos , Mamografia/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
Normal-appearing white matter (NAWM) is a hub of plasticity, but data relating to its influence on post-ischemic stroke (IS) outcome remain scarce. The aim of this study was to evaluate the relationship between NAWM integrity and cognitive outcome after an IS. A longitudinal study was conducted including supra-tentorial IS patients. A 3-Tesla brain MRI was performed at baseline and 1 year, allowing the analyses of mean fractional anisotropy (FA) and mean diffusivity (MD) in NAWM masks, along with the volume of white matter hyperintensities (WMH) and IS. A Montreal Cognitive Assessment (MoCA), an Isaacs set test, and a Zazzo's cancellation task were performed at baseline, 3 months and 1 year. Mixed models were built, followed by Tract-based Spatial Statistics (TBSS) analyses. Ninety-five patients were included in the analyses (38% women, median age 69 ± 20). FA significantly decreased, and MD significantly increased between baseline and 1 year, while cognitive scores improved. Patients who decreased their NAWM FA more over the year had a slower cognitive improvement on MoCA (ß = - 0.11, p = 0.05). The TBSS analyses showed that patients who presented the highest decrease of FA in various tracts of white matter less improved their MoCA performances, regardless of WMH and IS volumes, demographic confounders, and clinical severity. NAWM integrity deteriorates over the year after an IS, and is associated with a cognitive recovery slowdown. The diffusion changes recorded here in patients starting with an early preserved white matter structure could have long term impact on cognition.
Assuntos
AVC Isquêmico , Leucoaraiose , Substância Branca , Idoso , Idoso de 80 Anos ou mais , Cognição , Imagem de Tensor de Difusão , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Substância Branca/diagnóstico por imagemRESUMO
OBJECTIVES: Due to COVID-19, a lockdown took place between March 17 and May 1, 2020, in France. This study evaluates the impact of the lockdown on the diagnosis and staging of breast cancers in a tertiary cancer centre. METHODS: Our database was searched for all consecutive invasive breast cancers diagnosed in our institution during the lockdown (36 working days), during equivalent periods of 36 working days before and after lockdown and a reference period in 2019. The number and staging of breast cancers diagnosed during and after lockdown were compared to the pre-lockdown and reference periods. Tumour maximum diameters were compared using the Mann-Whitney test. Proportions of tumour size categories (T), ipsilateral axillary lymph node invasion (N) and presence of distant metastasis (M) were compared using Fisher's exact test. RESULTS: Compared to the reference period (n = 40 in average), the number of breast cancers diagnosed during lockdown (n = 32) decreased by 20% but increased by 48% after the lockdown (n = 59). After the lockdown, comparatively to the reference period, breast cancers were more often symptomatic (86% vs 57%; p = 0.001) and demonstrated bigger tumour sizes (p = 0.0008), the rates of small tumours (T1) were reduced by 38%, locally advanced cancers (T3, T4) increased by 80% and lymph node invasion increased by 64%. CONCLUSION: The COVID-19 lockdown was associated with a 20% decrease in the number of diagnosed breast cancers. Because of delayed diagnosis, breast cancers detected after the lockdown had poorer prognosis with bigger tumour sizes and higher rates of node invasion. KEY POINTS: ⢠The number of breast cancer diagnosed in a large tertiary cancer centre in France decreased by 20% during the first COVID-19 lockdown. ⢠Because of delayed diagnosis, breast cancers demonstrated bigger tumour size and more frequent axillary lymph node invasion after the lockdown. ⢠In case of a new lockdown, breast screening programme and follow-up examinations should not be suspended and patients with clinical symptoms should be encouraged to seek attention promptly.
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Neoplasias da Mama , COVID-19 , Axila/patologia , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Controle de Doenças Transmissíveis , Feminino , Humanos , Metástase Linfática , Estadiamento de Neoplasias , SARS-CoV-2RESUMO
Background and Purpose- The aim of the present study was to evaluate the relationship between normal-appearing white matter (NAWM) integrity and postischemic stroke recovery in 4 main domains including cognition, mood, gait, and dependency. Methods- A prospective study was conducted, including patients diagnosed for an ischemic supratentorial stroke on a 3T brain MRI performed 24 to 72 hours after symptom onset. Clinical assessment 1 year after stroke included a Montreal Cognitive Assessment, an Isaacs set test, a Zazzo cancelation task, a Hospital Anxiety and Depression scale, a 10-meter walking test, and a modified Rankin Scale (mRS). Diffusion tensor imaging parameters in the NAWM were computed using FMRIB (Functional Magnetic Resonance Imaging of the Brain) Diffusion Toolbox. The relationships between mean NAWM diffusion tensor imaging parameters and the clinical scores were assessed using linear and ordinal regression analyses, including the volumes of white matter hyperintensities, gray matter, and ischemic stroke as radiological covariates. Results- Two hundred seven subjects were included (66±13 years old; 67% men; median National Institutes of Health Stroke Scale score, 3; interquartile range, 2-6). In the models including only radiological variables, NAWM fractional anisotropy was associated with the mRS and the cognitive scores. After adjusting for demographic confounders, NAWM fractional anisotropy remained a significant predictor of mRS (ß=-0.24; P=0.04). Additional path analysis showed that NAWM fractional anisotropy had a direct effect on mRS (ß=-0.241; P=0.001) and a less important indirect effect mediating white matter hyperintensity burden. Similar results were found with mean diffusivity, axial diffusivity, and radial diffusivity. In further subgroup analyses, a relationship between NAWM integrity in widespread white matter tracts, mRS, and Isaacs set test was found in right hemispheric strokes. Conclusions- NAWM diffusion tensor imaging parameters measured early after an ischemic stroke are independent predictors of functional outcome and may be additional markers to include in studies evaluating poststroke recovery.
Assuntos
Isquemia Encefálica/diagnóstico por imagem , Recuperação de Função Fisiológica , Acidente Vascular Cerebral/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Atividades Cotidianas , Afeto , Idoso , Anisotropia , Isquemia Encefálica/fisiopatologia , Isquemia Encefálica/psicologia , Cognição , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/psicologia , Imagem de Tensor de Difusão , Feminino , Marcha , Transtornos Neurológicos da Marcha/etiologia , Transtornos Neurológicos da Marcha/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/psicologiaRESUMO
Background The substantia nigra (SN) is suspected to be affected after remote infarction, in view of its large array of connections with the supratentorial brain. Whether secondary involvement of SN worsens overall clinical outcome after a supratentorial stroke has not previously been studied. Purpose To assess longitudinal changes in SN R2* by using MRI in the setting of ipsilesional supratentorial infarct and the relationship of SN signal change to clinical outcome. Materials and Methods Participants prospectively included from 2012 to 2015 were evaluated at 24-72 hours (baseline visit) and at 1 year with MRI to quantify R2*. The SN was segmented bilaterally to calculate an R2* asymmetry index (SN-AI); greater SN-AI indicated greater relative R2* in the ipsilateral compared with contralateral SN. The 95th percentile of R2* (hereafter, SN-AI95) was compared according to infarct location with mixed linear regression models. We also conducted voxel-based comparisons of R2* and identified individual infarcted voxels associated with high SN-AI95 through voxel-based lesion-symptom mapping. Multivariable regression models tested the association between SN-AI95 and clinical scores. Results A total of 181 participants were evaluated (127 men, 54 women; mean age ± standard deviation, 64.2 years ± 13.1; 75 striatum infarcts, 106 other locations). Visual inspection, SN-AI95, and average maps consistently showed higher SN R2* at 1 year if ipsilateral striatum was infarcted than if it was not (SN-AI95, 4.25 vs -0.88; P < .001), but this was not observed at baseline. The striatal location of the infarct was associated with higher SN-AI95 at 1 year independently from infarct volume, SN-AI95 at baseline, microbleeds, age, and sex (ß = 4.99; P < .001). Voxel-based lesion-symptom mapping confirmed that striatum but also insula, internal capsule, and external capsule were associated with higher SN-AI95 at 1 year. SN-AI95 was an independent contributor of poor motor outcome (Box and Block Test, ß = -.62 points; P = .01). Conclusion In patients with stroke, greater substantia nigra R2*, likely reflective of greater iron content, can be observed at 1 year ipsilateral from remote infarcts of specific location, which is associated with worse motor function. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Vernooij in this issue.