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Retinoblastoma is the most common cause of all intraocular pediatric malignancies. It is caused by the loss of RB1 tumor suppressor gene function, although some tumors occur due to MYCN oncogene amplification with normal RB1 genes. Nearly half of all retinoblastomas occur due to a hereditary germline RB1 pathogenic variant, most of which manifest with bilateral tumors. This germline RB1 mutation also predisposes to intracranial midline embryonal tumors. Accurate staging of retinoblastoma is crucial in providing optimal vision-, eye-, and life-saving treatment. The AJCC Cancer Staging Manual has undergone significant changes, resulting in a universally accepted system with a multidisciplinary approach for managing retinoblastoma. The authors discuss the role of MRI and other diagnostic imaging techniques in the pretreatment assessment and staging of retinoblastoma. A thorough overview of the prevailing imaging standards and evidence-based perspectives on the benefits and drawbacks of these techniques is provided. Published under a CC BY 4.0 license. Test Your Knowledge questions for this article are available in the supplemental material.
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Oncólogos , Oftalmólogos , Neoplasias de la Retina , Retinoblastoma , Niño , Humanos , Diagnóstico por Imagen , Mutación , Estadificación de Neoplasias , Neoplasias de la Retina/diagnóstico por imagen , Neoplasias de la Retina/genética , Retinoblastoma/diagnóstico por imagen , Retinoblastoma/genéticaRESUMEN
Lynch syndrome (LS) is the most common cause of inherited colorectal cancer and the increases risk of developing extracolonic cancers. We present the first case of pediatric-onset LS with recurrent adenomatous colonic polyps presenting with rectal prolapse. This case highlights the importance of considering polyposis syndromes such as LS as possible diagnoses for pediatric patients who present with colorectal adenomatous polyps, as well as the need to consider immunohistochemical staining of polyps for mismatch repair protein expression in pediatric populations to rule out LS as a diagnosis. We demonstrate the need to consider pediatric patients in LS guidelines.
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Congenital infections with SARS-CoV-2 are uncommon. We describe two confirmed congenital SARS-CoV-2 infections using descriptive, epidemiologic and standard laboratory methods and in one case, viral culture. Clinical data were obtained from health records. Nasopharyngeal (NP) specimens, cord blood and placentas when available were tested by reverse transcriptase real-time PCR (RT-PCR). Electron microscopy and histopathological examination with immunostaining for SARS-CoV-2 was conducted on the placentas. For Case 1, placenta, umbilical cord, and cord blood were cultured for SARS-CoV-2 on Vero cells. This neonate was born at 30 weeks, 2 days gestation by vaginal delivery. RT-PCR tests were positive for SARS-CoV-2 from NP swabs and cord blood; NP swab from the mother and placental tissue were positive for SARS-CoV-2. Placental tissue yielded viral plaques with typical morphology for SARS-CoV-2 at 2.8 × 102 pfu/mL confirmed by anti-spike protein immunostaining. Placental examination revealed chronic histiocytic intervillositis with trophoblast necrosis and perivillous fibrin deposition in a subchorionic distribution. Case 2 was born at 36 weeks, 4 days gestation. RT-PCR tests from the mother and infant were all positive for SARS-CoV-2, but placental pathology was normal. Case 1 may be the first described congenital case with SARS-CoV-2 cultivated directly from placental tissue.
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COVID-19 , Complicaciones Infecciosas del Embarazo , Embarazo , Chlorocebus aethiops , Recién Nacido , Animales , Femenino , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Placenta , Células Vero , Trofoblastos , Complicaciones Infecciosas del Embarazo/diagnóstico , Transmisión Vertical de Enfermedad InfecciosaRESUMEN
BACKGROUND: Hypoxic Ischemic Encephalopathy (HIE) can lead to devastating consequences for the affected infant. Although therapeutic cooling benefits infants with moderate and severe HIE, differentiating mild from moderate-severe HIE may be challenging. The placenta reflects the fetal intrauterine environment and may reveal underlying processes that affect brain injury. AIM: To describe placental histopathology using the Amsterdam Placental Workshop Group Criteria in different grades of HIE. STUDY DESIGN: Retrospective cohort. SUBJECTS: Infants admitted to a tertiary care neonatal intensive care unit with a diagnosis of HIE between 2011 and 2016. OUTCOME MEASURE: Maternal and neonatal clinical variables and placental histopathology using the Amsterdam Placental Workshop Group Criteria were compared between mild and moderate-severe HIE. Mann-Whitney or t-test or ê2 were performed for bivariate associations as appropriate. To explain the relationship between placental pathology and severity of HIE odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated using logistic regression models. RESULTS: Of the 73 infants in the study, 23 had mild and 50 moderate-sever HIE. There was no difference in maternal and neonatal characteristics except for sentinel events which were higher in the moderate- severe group. On placental histopathology, acute inflammation, including fetal inflammatory reaction (FIR) were significantly higher in the moderate-severe group. After adjusting for confounders, FIR remained significantly associated with moderate-severe HIE, ORs 6.29, 95 % CI 1.5-25. CONCLUSION: Our study demonstrates FIR in the placenta is associated with severity of HIE.
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Lesiones Encefálicas , Hipotermia Inducida , Hipoxia-Isquemia Encefálica , Femenino , Humanos , Lactante , Recién Nacido , Embarazo , Lesiones Encefálicas/complicaciones , Hipoxia-Isquemia Encefálica/terapia , Placenta , Estudios RetrospectivosRESUMEN
BACKGROUND: Workload measurement is important to help determine optimal staffing and workload distribution for pathology laboratories. The Level 4 Equivalent (L4E) System is the most widely used Anatomical Pathology (AP) workload measurement tool in Canada. However, it was initially not developed with subspecialties in mind. METHODS: In 2016, a Pan-Canadian Pediatric-Perinatal Pathology Workload Committee (PCPPPWC) was organized to adapt the L4E System to assess Pediatric-Perinatal Pathology workload. Four working groups were formed. The Placental Pathology Working Group was tasked to develop a scheme for fair valuation of placental specimens signed out by subspecialists in the context of the L4E System. Previous experience, informal time and motion studies, a survey of Canadian Pediatric-Perinatal Pathologists, and interviews of Pathologists' Assistants (PA) informed the development of such scheme. RESULTS: A workload measurement scheme with average L4E workload values for examination and reporting of singleton and multiple gestation placentas was proposed. The proposal was approved by the Canadian Association of Pathologist - Association canadienne des pathologistes Workload and Human Resources Committee for adoption into the L4E System. CONCLUSION: The development of a workload measurement model for placental specimens provides an average and fair valuation of these specimen types, enabling its use for resource planning and workload distribution.
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Servicio de Patología en Hospital , Placenta , Femenino , Embarazo , Humanos , Niño , Canadá , Carga de TrabajoRESUMEN
Juvenile dermatomyositis is a rare autoimmune myopathy of childhood, associated with systemic vasculopathy, primarily affecting the capillaries. Panniculitis is seen histologically in about 10% of patients with dermatomyositis; however, its clinical presentation is rare, with only 30 cases presented in the literature to date. The histopathology overlaps with other inflammatory disease states, and is almost identical to the panniculitis seen in lupus erythematous panniculitis. In the cases with both panniculitis and dermatomyositis, skin and muscle inflammation is usually the first clinical manifestation. We present a case of a 16-year-old female with panniculitis as the initial presenting feature of juvenile dermatomyositis in the context of a prior diagnosis of indeterminate colitis.
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Emergomyces canadensis pulmonary infection was incidentally diagnosed in an asymptomatic patient suspected to have metastatic osteosarcoma. Molecular diagnosis was imperative to fungal identification given overlapping histopathological features with histoplasmosis. This report documents a case of isolated pulmonary emergomycosis in an otherwise immunocompetent patient while discussing diagnostic and management pitfalls of this emerging and underdiagnosed infection.
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OBJECTIVE: The objective of this study is to assess the effect of the lockdown measures during the coronavirus disease 2019 (COVID-19) pandemic on pregnancy outcomes of women who were not affected by severe acute respiratory syndrome coronavirus 2 infection. STUDY DESIGN: We used data from the perinatal health program and neonatal databases to conduct a cohort analysis of pregnancy outcomes during the COVID-19 lockdown in the Calgary region, Canada. Rates of preterm birth were compared between the lockdown period (March 16 to June 15, 2020) and the corresponding pre-COVID period of 2015 to 2019. We also compared maternal and neonatal characteristics of preterm infants admitted to neonatal intensive care units (NICUs) in Calgary between the two periods. FINDINGS: A total of 4,357 and 24,160 live births occurred in the lockdown and corresponding pre-COVID period, respectively. There were 366 (84.0 per 1,000 live births) and 2,240 (92.7 per 1,000 live births) preterm births in the lockdown and corresponding pre-COVID period, respectively (p = 0.07). Rates of very preterm and very-low-birth-weight births were lower in the lockdown period compared with the corresponding pre-COVID period (11.0 vs. 15.6 and 9.0 vs. 14.4 per 1,000 live births, p = 0.02 and p = 0.005, respectively). There was no difference in spontaneous stillbirth between the two periods (3.7 vs. 4.1 per 1,000 live birth, p = 0.71). During the lockdown period, the likelihood of multiple births was lower (risk ratio [RR] 0.73, 95% confidence interval [CI]: 0.60-0.88), while gestational hypertension and clinical chorioamnionitis increased (RR 1.24, 95%CI: 1.10-1.40; RR 1.33, 95%CI 1.10-1.61, respectively). CONCLUSION: Observed rates of very preterm and very-low-birth-weight births decreased during the COVID-19 lockdown. Pregnant women who delivered during the lockdown period were diagnosed with gestational hypertension and chorioamnionitis more frequently than mothers in the corresponding pre-COVID period. KEY POINTS: · Lockdown measures to reduce COVID-19 transmission were associated with a lower rate of preterm birth.. · Mental and physical wellbeing of pregnant women were significantly affected by the lockdown measures.. · A comprehensive public health plan to relieve psychosocial stress during pregnancy is required..
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Nacimiento Vivo/epidemiología , Nacimiento Prematuro/epidemiología , Cuarentena , Adulto , COVID-19 , Canadá/epidemiología , Corioamnionitis/epidemiología , Estudios de Cohortes , Femenino , Humanos , Hipertensión Inducida en el Embarazo/epidemiología , Recién Nacido , Recién Nacido de muy Bajo Peso , Pandemias , Embarazo , Embarazo Múltiple , Estudios RetrospectivosRESUMEN
ABSTRACT: Pancreatoblastomas are rare pediatric tumors. In adults, they are exceedingly rare and seem to have a worse prognosis. Most are sporadic, though rare, cases occur in patients with familial adenomatous polyposis. Unlike pancreatic ductal adenocarcinomas, pancreatoblastomas are not believed to arise from dysplastic precursor lesions. Clinical history, along with endoscopic, pathological, and molecular findings, was reviewed for a 57-year-old male patient with an ampullary mass who presented with obstructive jaundice. Microscopic examination showed a pancreatoblastoma subjacent to an adenomatous polyp with intestinal differentiation and low-grade dysplasia. Both tumors had abnormal p53 (complete loss) and nuclear ß-catenin immunostaining. Mutational panel analysis showed an identical CTNNB1 (p.S45P) mutation in both. This case adds to our understanding of the pathogenesis of these rare tumors and suggests that a subset may arise from an adenomatous precursor. In addition, this case is just the second pancreatoblastoma to originate in the duodenal ampulla, and the preceding case suggests that an ampullary location leads to earlier diagnosis. Moreover, this case highlights the difficulty in diagnosing pancreatoblastoma on limited tissue specimens and illustrates the need to include pancreatoblastoma in the differential diagnosis in all tumors in and around the pancreas, including those in adult patients.
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Adenoma , Poliposis Adenomatosa del Colon , Neoplasias Pancreáticas , Masculino , Humanos , Adenoma/genética , Adenoma/patología , Neoplasias Pancreáticas/patología , Poliposis Adenomatosa del Colon/genética , Páncreas/patologíaRESUMEN
The dilated cardiomyopathy with ataxia syndrome (DCMA) is an autosomal recessive mitochondrial disease caused by mutations in the DnaJ heat shock protein family (Hsp40) member C19 (DNAJC19) gene. DCMA or 3-methylglutaconic aciduria type V is globally rare, but the largest number of patients in the world is found in the Hutterite population of southern Alberta in Canada. We provide an update on phenotypic findings, natural history, pathological findings, and our clinical experience. We analyzed all available records for 43 patients diagnosed with DCMA between 2005 and 2015 at the Alberta Children's Hospital. All patients studied were Hutterite and homozygous for the causative DNAJC19 variant (c.130-1G>C, IVS3-1G>C) and had elevated levels of 3-methyglutaconic acid. We calculated a birth prevalence of 1.54 cases per 1000 total births in the Hutterite community. Children were small for gestational age at birth and frequently required supplemental nutrition (63%) or surgical placement of a gastrostomy tube (35%). Early mortality in this cohort was high (40%) at a median age of 13 months (range 4-294 months). Congenital anomalies were common as was dilated cardiomyopathy (50%), QT interval prolongation (83%), and developmental delay (95%). Tissue pathology was analyzed in a limited number of patients and demonstrated subendocardial fibrosis in the heart, macrovesicular steatosis and fibrosis in the liver, and structural abnormalities in mitochondria. This report provides clinical details for a cohort of children with DCMA and the first presentation of tissue pathology for this disorder. Despite sharing common genetic etiology and environment, the disease is highly heterogeneous for reasons that are not understood. DCMA is a clinically heterogeneous systemic mitochondrial disease with significant morbidity and mortality that is common in the Hutterite population of southern Alberta.
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Cardiomiopatía Dilatada , Enfermedades Mitocondriales , Ataxia/genética , Cardiomiopatía Dilatada/diagnóstico , Cardiomiopatía Dilatada/genética , Cardiomiopatía Dilatada/metabolismo , Ataxia Cerebelosa , Fibrosis , Humanos , Errores Innatos del Metabolismo , Enfermedades Mitocondriales/complicaciones , Fenotipo , SíndromeRESUMEN
Background: Cutaneous pseudolymphoma (CPL) refers to a group of benign, reactive processes that mimic cutaneous lymphoma and are associated with a variety of triggering immune stimuli, including arthropod bites, drugs, and foreign bodies. In children, most cases of CPL are due to a variant of Borreliosis that is specific to Eurasia. Cutaneous pseudolymphoma secondary to ear piercing has only been documented in adults. Case Reports: We present the clinical and pathological findings of cutaneous Bcell psuedolymphoma in two adolescent patients (11-year-old female and 15-year-old male) secondary to ear piercing. Conclusion: Our report expands the clinico-pathological spectrum of CPL associated with ear piercing by documenting its occurrence in children.
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Perforación del Cuerpo , Seudolinfoma , Neoplasias Cutáneas , Adolescente , Adulto , Perforación del Cuerpo/efectos adversos , Niño , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Seudolinfoma/diagnóstico , Seudolinfoma/etiología , Seudolinfoma/patología , Piel/patología , Neoplasias Cutáneas/complicacionesRESUMEN
The vitelline circulation normally regresses by about 10 weeks gestation. Vitelline vessel remnants (VVRs) are found in approximately 4-11% of umbilical cords. While these remnants retain an active fetal circulation, this has never been studied. Using an operating microscope, VVRs were catheterized, injected with ink, and then examined grossly and histologically. Over 90% of VVRs are paired thin-walled vessels with afferent and efferent circulation completed within the cord via capillary plexuses and bridging vessels; <10% are single thin-walled arterial vessels running the length of the cord to the placental disc, with their venous return circulation via allantoic umbilical vessels.
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Variación Anatómica , Cordón Umbilical/irrigación sanguínea , Humanos , MicromanipulaciónRESUMEN
BACKGROUND: Pediatric fibroblastic/myofibroblastic tumors (PFMTs) can be challenging to definitively classify. Large case series or diagnostic updates have not been recently published despite identification of molecular alterations that could improve diagnostic accuracy. Our review of the literature found that over two-thirds of the more than 30 types of PFMTs harbor recurrent molecular alterations. We performed an institutional review of PFMTs to highlight limitations of a predominantly morphological classification, and evaluated the utility of a next-generation sequencing assay to aid diagnosis. METHODS: PFMTs identified over a period of 12 years were reviewed, categorized per the new WHO classification, and tested using the Oncomine Childhood Cancer Research Assay. RESULTS: Eighty-seven specimens from 58 patients were reviewed; 50 were chosen for molecular analysis, 16 (32%) lacking definitive classification. We identified alterations, some novel, in 33% of assayed cases. Expected alterations were identified for most known diagnoses and mutations were identified in 6 of 16 tumors (38%) that were initially unclassified. CONCLUSION: We confirmed a significant subset of PFMTs remain difficult to classify using current criteria, and that a combined DNA/RNA assay can identify alterations in many of these cases, improving diagnostic certainty and suggesting a clinical utility for challenging cases.
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Biomarcadores de Tumor/genética , Fibroma/genética , Granuloma de Células Plasmáticas/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Miofibroma/genética , Sarcoma/genética , Neoplasias de los Tejidos Blandos/genética , Adolescente , Niño , Preescolar , Femenino , Fibroma/clasificación , Fibroma/diagnóstico , Fibroma/patología , Granuloma de Células Plasmáticas/clasificación , Granuloma de Células Plasmáticas/diagnóstico , Granuloma de Células Plasmáticas/patología , Humanos , Lactante , Recién Nacido , Masculino , Mutación , Miofibroma/clasificación , Miofibroma/diagnóstico , Miofibroma/patología , Proteínas de Fusión Oncogénica/genética , Estudios Retrospectivos , Sarcoma/clasificación , Sarcoma/diagnóstico , Sarcoma/patología , Neoplasias de los Tejidos Blandos/clasificación , Neoplasias de los Tejidos Blandos/diagnóstico , Neoplasias de los Tejidos Blandos/patología , Organización Mundial de la SaludRESUMEN
Neuroblastoma is the most common cancer in infants younger than 12 months of age, occurring with an incidence of 1 in 100,000 children. The clinical outcome of neuroblastoma ranges from spontaneous regression to treatment-resistant progression and/or metastasis, and accounts for 8-10% of childhood cancer deaths. Segmental chromosomal aberrations, as well as MYCN and ALK amplification, are among factors contributing to an unfavorable genomic profile and high-risk disease classification. Here, we describe a 5-year-old male who presented with a large right renal neuroblastoma tumor having lung and liver metastases. Fluorescence in situ hybridization analysis indicated the presence of >20 copies of the 5' region of the ALK gene in 26% of cells examined. Subsequent copy number assessment did not confirm ALK amplification, but revealed a gain of exons 2-5 of ALK, consistent with increased copy number for the 5' region of the ALK gene. Subsequent array analysis showed the presence of other unfavorable prognostic genomic features, including segmental gain of the 17q region and amplification of the long arm of chromosome 12 harboring CDK4 and MDM2, both reported to be poor prognostic indicators in patients with atypical clinical features in neuroblastoma. Taken together, this report illustrates the importance of careful interpretation of aberrant FISH findings and subsequent use of orthogonal methods to clarify the presence of genomic alterations to successfully determine potential treatment targets.
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Enfermedades Pulmonares , Linfangiectasia , Neumotórax , GTP Fosfohidrolasas , Humanos , Enfermedades Pulmonares/diagnóstico por imagen , Enfermedades Pulmonares/genética , Linfangiectasia/diagnóstico por imagen , Linfangiectasia/genética , Proteínas de la Membrana , Neumotórax/diagnóstico por imagen , Neumotórax/genéticaRESUMEN
Background: Placental abnormalities are associated with inflammation and have been linked to brain injury in preterm infants. We studied the relationship between placental pathology and the temporal profiles of cytokine levels in extremely pre-term infants. Study Design: We prospectively enrolled 55 extremely preterm infants born between June 2017 and July 2018. Levels of 27 cytokines were measured in blood drawn from the umbilical artery at birth and from infants at 1-3 and 21-28 days of life. Placental pathology was grouped as normal (N), inflammation (I), vasculopathy (V), or combined vasculopathy and inflammation (V+I). Results: Complete data was available from 42 patients. Cord blood median levels of cytokines differed between groups with the highest levels observed in group V+I as compared to groups N, I and V for the following: Eotaxin (p = 0.038), G-CSF (p = 0.023), IFN-γ (p = 0.002), IL-1ra (p < 0.001), IL-4 (p = 0.005), IL-8 (p = 0.010), MCP-1 (p = 0.011), and TNFα (p = 0.002). Post-hoc analysis revealed sex differences between and within the placental pathology groups. Conclusion: Specific types of placental pathology may be associated with differential cytokine profiles in extremely pre-term infants. Sampling from cord blood may help assess the pathological status of the placenta and potentially infer outcome risks for the infant.
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Mosaic RASopathies are an emerging group of disorders characterized by mosaic or post-zygotic activating mutations in genes of the RAS/MAPKinase signaling pathway. The phenotype is highly variable, ranging from limited or localized forms to cases with a syndromic presentation with extensive or multiorgan involvement, and also overlaps with other mosaic disorders. While there are several reports of malignancies in patients with mosaic RASopathies, specifically rhabdomyosarcoma and transitional urothelial carcinoma, the lifetime risk and molecular mechanisms that lead to the development of malignancies remain unclear. We report a 22-month-old boy with a somatic RASopathy due to an underlying KRAS p.G12D mutation who presented with a large unilateral epidermal nevus, asymmetric lower limb overgrowth with lytic and sclerotic bone lesions, capillary malformation, bilateral nephrogenic rests and Wilms tumors, and a novel complex renal vascular anomaly that resembles Fibro-Adipose Vascular Anomaly (FAVA). This report further expands the phenotypic spectrum of somatic RASopathies, and discusses the potential phenotypic and pathogenetic overlap with PIK3CA-related overgrowth disorders, specifically CLOVES. The occurrence of a secondary cancer hotspot mutation (FBXW7 p.R479G) in the Wilms tumor, but not the associated nephrogenic rest, moreover suggests that additional driver mutations are involved in the development of Wilms tumor in somatic overgrowth disorders.
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Neoplasias Renales/genética , Riñón/anomalías , Proteínas Proto-Oncogénicas p21(ras)/genética , Malformaciones Vasculares/genética , Tumor de Wilms/genética , Preescolar , Humanos , Lactante , Masculino , Nevo/genéticaRESUMEN
Gardner fibroma (GF) is a benign soft-tissue tumor that is associated with Gardner syndrome and can progress to, or co-occur with, desmoid fibromatosis (DF). Herein, we report a unique case of an 11-year-old boy who presented with a rapidly growing soft-tissue mass after biopsy of a stable fat-rich lesion present in the calf muscles since infancy, with Magnetic resonance imaging findings suggesting an intramuscular adipocytic tumor. The resection showed GF and DF. DF arising from a preexisting GF (the so-called "GF-DF sequence") is a well-documented phenomenon. Although immunohistochemistry was negative for nuclear ß-catenin expression, a CTTNB1 S45F mutation, which has been associated with aggressive behavior in DF, was identified in both components using a next-generation sequencing-based molecular assay. This is the first time a mutation in CTNNB1 has been identified in GF and the GF-DF sequence, thus expanding our knowledge of the molecular pathogenesis of the GF-DF sequence and highlighting the role of molecular testing in pediatric soft-tissue tumors. The histologic findings of an adipocyte-rich intramuscular GF also are unique, expanding the morphological spectrum of GF and adding GF to the differential diagnosis of intramuscular lesions with an adipocytic component.