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We describe a 46-year-old patient with an IDH-wildtype diffusely infiltrating atypical teratoid/rhabdoid tumour (AT/RT), SHH-1B molecular subtype. The unusual histology and subsequent diagnosis in an adult patient will be discussed.
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Neoplasias Encefálicas , Tumor Rabdoide , Teratoma , Humanos , Tumor Rabdoide/patología , Tumor Rabdoide/genética , Teratoma/patología , Teratoma/genética , Persona de Mediana Edad , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/genética , Masculino , Proteínas Hedgehog/genéticaRESUMEN
Fibroepithelial stromal polyps (FSPs) are benign mesenchymal lesions occurring in the vulvovaginal region. Following the identification of loss of Retinoblastoma 1 (RB1) on immunohistochemical staining in routine practice, we stained a series of FSPs and performed additional fluorescence in situ hybridization (FISH) and copy number variation (CNV) sequencing to detect losses/deletions in the Retinoblastoma transcriptional corepressor 1 (RB1) gene. Fifteen FSP cases were stained for RB1, and subsequently, 9 cases were examined by FISH to detect a loss of RB1 (13q). Next, CNV sequencing was performed to assess genomic alterations. The mean age of the patients was 50 years. Loss of RB1 expression on immunohistochemistry was seen in 13 cases, and heterogeneous RB1 staining in the remaining 2 cases. FISH showed deletion of RB1 in all of the cases. CNV sequencing failed in almost all cases due to a low tumor content. Based on our findings, we hypothesize that FSPs are part of a spectrum of genetically related lesions, namely the 13q/RB1 family of tumors (which includes pleomorphic fibromas and spindle cell/pleomorphic lipomas). Due to the clinical, morphologic, and molecular overlap, we suggest that FSPs are pleomorphic fibromas occurring in the specialized stroma of the genital region.
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PURPOSE: Recent technical advancements in PET imaging have improved sensitivity and spatial resolution. Consequently, clinical nuclear medicine will be confronted with PET images on a previously unfamiliar resolution. To better understand [18F]FDG distribution at submillimetric scale, a direct correlation of radionuclide-imaging and histopathology is required. METHODS: A total of five patients diagnosed with a malignancy of the head and neck were injected with a clinical activity of [18F]FDG before undergoing surgical resection. The resected specimen was imaged using a preclinical high-resolution PET/CT, followed by slicing of the specimen. Multiple slices were rescanned using a micro-PET/CT device, and one of the slices was snap-frozen for frozen sections. Frozen sections were placed on an autoradiographic film, followed by haematoxylin and eosin staining to prepare them for histopathological assessment. The results from both autoradiography and histopathology were co-registered using an iterative co-registration algorithm, and regions of interest were identified to study radiotracer uptake. RESULTS: The co-registration between the autoradiographs and their corresponding histopathology was successful in all specimens. The use of this novel methodology allowed direct comparison of autoradiography and histopathology and enabled the visualisation of uncharted heterogeneity in [18F]FDG uptake in both benign and malignant tissue. CONCLUSION: We here describe a novel methodology enabling the direct co-registration of [18F]FDG autoradiography with the gold standard of histopathology in human malignant tissue. The future use of the current methodology could further increase our understanding of the distribution of radionuclides in surgically excised malignancies and hence, improve the integration of pathology and molecular imaging in a multiscale perspective. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05068687.
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Fluorodesoxiglucosa F18 , Neoplasias , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radiofármacos , Estudios de Factibilidad , Tomografía de Emisión de Positrones/métodosRESUMEN
Due to the increased application of RNA-based next-generation sequencing techniques on bone and soft tissue round cell sarcomas new fusions are frequently found, thereby expanding the molecular landscape of these tumors. In this report, we describe and discuss the finding of an undifferentiated sarcoma of the bone with a round to epithelioid cell phenotype harboring a novel EWSR1-SSX2 fusion. Treatment of this new bone tumor entity according to the Euro Ewing 2012 protocol led to complete pathologic response.
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Neoplasias Óseas/genética , Proteínas de Neoplasias/genética , Proteínas de Fusión Oncogénica/genética , Proteína EWS de Unión a ARN/genética , Proteínas Represoras/genética , Sarcoma/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/patología , Neoplasias Óseas/terapia , Células Epitelioides/patología , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Osteotomía , Sarcoma/patología , Sarcoma/terapia , Análisis de Secuencia de ARN , Translocación Genética , Resultado del TratamientoAsunto(s)
Lipoblastoma , Humanos , Osteogénesis , Factor 1 de Elongación Peptídica , Proteínas de Unión al ADNRESUMEN
RB1 stands as the pioneering discovery in tumour-suppressor genes, marking a pivotal breakthrough in comprehending cancer development. This overview delves into the role of RB1 in both health and disease, exploring its association with the tumourigenesis of various cancers and a distinct subset of soft-tissue neoplasms. Additionally, we discuss the application of immunohistochemistry and fluorescence in situ hybridisation to detect RB1 alterations.
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Neoplasias , Proteínas de Unión a Retinoblastoma , Humanos , Proteínas de Unión a Retinoblastoma/genética , Proteínas de Unión a Retinoblastoma/metabolismo , Neoplasias/genética , Neoplasias/patología , Neoplasias/metabolismo , Ciclo Celular , Patólogos , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Inmunohistoquímica , Hibridación Fluorescente in Situ , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genéticaRESUMEN
Paired-like homeobox 2B (PHOX2B) is a gene essential in the development of the autonomic nervous system. PHOX2B mutations are associated with neurocristopathies-Hirschsprung disease (HSCR) and congenital central hypoventilation syndrome (CCHS)-and peripheral neuroblastic tumours. PHOXB2 plays an important role in the diagnostics of these conditions.Genotyping of a PHOX2B pathogenic variant is required to establish a diagnosis of CCHS. In HSCR patients, PHOX2B immunohistochemical staining has proven to be a valuable tool in identifying this disease. Furthermore, PHOXB2 is a predisposition gene for neuroblastoma, in which PHOX2B immunohistochemical staining can be used as a highly sensitive and specific diagnostic marker. The utility of PHOX2B immunohistochemistry in pheochromocytoma and paraganglioma has also been studied but yields conflicting results.In this review, an overview is given of PHOX2B, its associated diseases and the usefulness of PHOX2B immunohistochemistry as a diagnostic tool.
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Proteínas de Homeodominio , Hipoventilación , Inmunohistoquímica , Neuroblastoma , Factores de Transcripción , Humanos , Proteínas de Homeodominio/genética , Factores de Transcripción/genética , Hipoventilación/congénito , Hipoventilación/diagnóstico , Hipoventilación/genética , Neuroblastoma/diagnóstico , Neuroblastoma/genética , Neuroblastoma/patología , Apnea Central del Sueño/diagnóstico , Apnea Central del Sueño/genética , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/análisis , Enfermedad de Hirschsprung/diagnóstico , Enfermedad de Hirschsprung/genética , Enfermedad de Hirschsprung/patología , Mutación , Neoplasias de las Glándulas Suprarrenales/genética , Neoplasias de las Glándulas Suprarrenales/diagnóstico , Neoplasias de las Glándulas Suprarrenales/patología , Predisposición Genética a la EnfermedadRESUMEN
Myxoid pleomorphic liposarcoma (MPL) is an extremely rare adipocytic tumor, recently recognized as a distinct entity in the 5th edition of the World Health Organization (WHO) Classification of Soft Tissue and Bone Tumors. Predominantly found in the mediastinum of young women, MPLs exhibit a combination of histological features characteristic of myxoid liposarcoma and pleomorphic (lipo)sarcoma. Their unique molecular features distinguish MPLs from other liposarcomas. Unlike myxoid liposarcomas and well-differentiated/dedifferentiated liposarcomas, MPLs lack specific FUS/EWSR1::DDIT3 gene fusions and MDM2/CDK4 gene amplifications, respectively. MPLs are associated with complex karyotypes, further highlighting their distinct genetic profile. They demonstrate aggressive growth patterns, high recurrence rates, and a high tendency to metastasize. These factors contribute to a poor prognosis, with a median survival of approximately 22.6 months. The aim of this review article is to provide a comprehensive summary of previously documented case reports and studies related to MPLs. By shedding light on the intricate details of MPLs, researchers and clinicians can gain valuable insights that may pave the way for improvements in diagnosis, treatment, and patient outcomes in the future.
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Liposarcoma Mixoide , Humanos , Liposarcoma Mixoide/genética , Liposarcoma Mixoide/patología , Liposarcoma/genética , Liposarcoma/patología , Femenino , Neoplasias de los Tejidos Blandos/genética , Neoplasias de los Tejidos Blandos/patologíaRESUMEN
We report an exceptional case of a spindle cell mesenchymal tumor with S100 and CD34 co-reactivity, which harbored a SLMAP::RAF1 fusion. To the best of our knowledge, this is the second case of a spindle cell mesenchymal tumor with S100 and CD34 co-reactivity with this specific fusion. Remarkable is the presence of calcification and heterotopic ossification in the center of our lesion, a feature that, to our knowledge, has not been described yet in RAF1-rearranged spindle cell mesenchymal tumors.
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Coristoma , Osificación Heterotópica , Sarcoma , Neoplasias de los Tejidos Blandos , Humanos , Sarcoma/patología , Osificación Heterotópica/genética , Neoplasias de los Tejidos Blandos/complicaciones , Neoplasias de los Tejidos Blandos/genética , Neoplasias de los Tejidos Blandos/patología , Biomarcadores de TumorRESUMEN
L-2-hydroxyglutaric aciduria (L-2-HGA) is a rare neurometabolic disorder characterized by accumulation of L2-hydroxyglutarate (L-2-HG) due to mutations in the L2HGDH gene. L-2-HGA patients have a significantly increased lifetime risk of central nervous system (CNS) tumors. Here, we present a 16-year-old girl with L-2-HGA who developed a tumor in the right cerebral hemisphere, which was discovered after left-sided neurological deficits of the patient. Histologically, the tumor had a high-grade diffuse glioma phenotype. DNA sequencing revealed the inactivating homozygous germline L2HGDH mutation as well as inactivating mutations in TP53, BCOR and NF1. Genome-wide DNA-methylation analysis was unable to classify the tumor with high confidence. More detailed analysis revealed that this tumor clustered amongst IDH-wildtype gliomas by methylation profiling and did not show the glioma CpG island methylator phenotype (G-CIMP) in contrast to IDH-mutant diffuse gliomas with accumulated levels of D-2-HG, the stereoisomer of L-2-HD. These findings were against all our expectations given the inhibitory potential of 2-HG on DNA-demethylation enzymes. Our final integrated histomolecular diagnosis of the tumor was diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype. Due to rapid tumor progression the patient died nine months after initial diagnosis. In this manuscript, we provide extensive molecular characterization of the tumor as well as a literature review focusing on oncogenetic considerations of L-2-HGA-associated CNS tumors.
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FOS and FOSB proto-oncogens are involved in a wide variety of tumourigenic processes. FOS and FOSB gene rearrangements are observed in epithelioid haemangioma, pseudomyogenic haemangioendothelioma, osteoid osteoma/osteoblastoma/cementoblastoma and proliferative myositis/fasciitis. In this review, we provide an overview of FOS and FOSB, including their functions and the differences between lesions with known FOS/FOSB gene rearrangements. Additionally, we discuss the use of FOS/FOSB immunohistochemistry as a diagnostic tool for these lesions.
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Proteínas Proto-Oncogénicas c-fos , Humanos , Neoplasias Óseas/patología , Transformación Celular Neoplásica , Osteoblastoma/diagnóstico , Osteoblastoma/genética , Osteoblastoma/patología , Proteínas Proto-Oncogénicas c-fos/genética , Neoplasias de los Tejidos Blandos/patologíaRESUMEN
Ubiquitin-specific protease 6 (USP6) rearrangements have been identified in aneurysmal bone cyst, nodular fasciitis, myositis ossificans, fibro-osseous pseudotumour of digits and cellular fibroma of tendon sheath. These entities show clinical as well as histological overlap, suggesting they are all clonal neoplastic belonging to the same biological spectrum and referred to as 'USP6-associated neoplasms'. They all show a characteristic gene fusion formed by juxtaposition of the USP6 coding sequences to the promoter regions of several partner genes, leading to USP6 transcriptional upregulation.
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Quistes Óseos Aneurismáticos , Fascitis , Fibroma , Humanos , Fascitis/patología , Reordenamiento Génico , Quistes Óseos Aneurismáticos/genética , Quistes Óseos Aneurismáticos/patología , Fusión Génica , Ubiquitina Tiolesterasa/genéticaRESUMEN
Atypical spindle cell/pleomorphic lipomatous tumor (ASPLT) is a newly described adipocytic tumor type, recently included as a separate tumor entity in the fifth edition of the World Health Organization (WHO) classification of soft tissue and bone tumors. Here, we describe a case of an ASPLT with a striking pleomorphic hyalinizing angiectatic tumor (PHAT)-like growth pattern and discuss the diagnostical clues, which led to the diagnosis of ASPLT. To our knowledge, a PHAT-like growth pattern has not yet been reported in the setting of ASPLT.
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Lipoma , Liposarcoma , Neoplasias de los Tejidos Blandos , Humanos , Neoplasias de los Tejidos Blandos/patologíaRESUMEN
Inflammatory myofibroblastic tumor (IMT) of the biliary tract is rare, and often difficult to diagnose or to distinguish from other tumors due to its atypical clinical presentation and nonspecific radiological features. Histologically, IMTs are (myo)fibroblastic neoplasms with a prominent inflammatory infiltrate. They are characterized by receptor tyrosine kinase gene rearrangements, most often involving an anaplastic lymphoma kinase (ALK) translocation. The final diagnosis of IMT depends on histopathology and immunohistochemical examination. In this manuscript, we provide a clinical and morphomolecular overview of IMT and the difficulties that may arise in using immunohistochemical and molecular techniques in diagnosing IMT.
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Since the introduction of new molecular techniques, the diagnostic landscape of soft tissue and bone tumors has expanded greatly over the past few years. The use of new molecular techniques has led to the identification of new genetic alterations and, therefore, to a better understanding of tumorigenesis, tumor detection and classification. Furthermore, methylation profiling has emerged as a classification tool for soft tissue and bone tumors. Molecular pathology also plays an important role in the determination of patient prognosis and in the identification of targets that can be used for targeted therapy. As a result, molecular pathology has gained a more prominent role in the daily practice of the surgical pathologist. This review delves into various molecular techniques applied in the surgical pathology of soft tissue and bone tumors. It highlights their applications through the analysis of five specific cases.
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Neoplasias Óseas , Neoplasias de los Tejidos Blandos , Humanos , Neoplasias de los Tejidos Blandos/diagnóstico , Neoplasias de los Tejidos Blandos/genética , Neoplasias de los Tejidos Blandos/patología , Mutación , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/genética , Pronóstico , Patología MolecularRESUMEN
We report an exceptional case of an undifferentiated round and spindle cell sarcoma, occurring in the periprostatic region of a 54-year-old male, with a 'high-grade endometrial stromal sarcoma-like' (HG-ESS) morphology and harboring a ZC3H7B::BCOR gene fusion identified by RNA-based next-generation sequencing. In this report, we describe the striking overlap of morphologic, immunohistochemical and molecular features of this current case and previously reported similar cases with ZC3H7B::BCOR fusion-positive HG-ESS, and discuss the differential diagnosis and possible pathogenesis of this unusual entity.
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Neoplasias Endometriales , Sarcoma Estromático Endometrial , Sarcoma , Femenino , Masculino , Humanos , Persona de Mediana Edad , Neoplasias Endometriales/patología , Sarcoma Estromático Endometrial/genética , Proteínas Proto-Oncogénicas/genética , Proteínas Represoras/genética , Sarcoma/diagnóstico , Sarcoma/genéticaRESUMEN
AIMS: PRRX1-rearranged mesenchymal tumours are a recently identified and rare subgroup of soft tissue neoplasms with distinct morphological features and genetic alterations. This study aims to further investigate the immunohistochemical profile and underlying genetic alterations in these tumours in order to get more insight on their underlying biology and the unique profile of these tumours. METHODS: Two new molecular confirmed cases of PRRX1-rearranged mesenchymal tumours were thoroughly studied with immunohistochemical stainings (RB1, CD34, ALK and pan-TRK), fluorescence in situ hybridisation (FISH) RB1/13q12 and RNA-based next-generation sequencing. RESULTS: Both cases exhibited typical morphological and molecular features, confirming the diagnosis of PRRX1-rearranged mesenchymal tumours. Immunohistochemistry revealed RB1 loss in both cases, which was subsequently confirmed through FISH analysis. Additionally, one case showed focal positivity for CD34, ALK and pan-TRK on immunohistochemistry. CONCLUSIONS: We identified loss of RB1 in two cases of PRRX1-rearranged mesenchymal tumours. This could suggest a potential association with RB1-deficient soft tissue tumours, although further research is necessary. Furthermore, the finding of focal positivity for CD34, ALK and pan-TRK on immunohistochemistry enriches the immunohistochemical profile of these tumours.
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Lipomatous neoplasms are a rare entity in the pediatric population, comprising less than 10% of soft tissue tumors in the first two decades of life. Some characteristics of pediatric adipocytic tumors are analogous to their adult counterparts, some pediatric lipomatous lesions however harbor unique features. In recent years, there have been significant advances in the understanding of the pathogenesis and hence in the classification and treatment of pediatric adipocytic tumors. This literature-based article will provide a review of the presently known clinicopathological, immunohistochemical and molecular features of pediatric lipomatous lesions.
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Case report of malignant pleural mesothelioma with an ALK gene rearrangement, detected by FISH and confirmed by RNA-based next-generation sequencing. The co-occurrence of ALK gene fusions with the more common genetic alterations in CDKN2A, NF2 and BAP1 has, to our best knowledge, not yet been described in malignant mesothelioma. Furthermore, this unexpected finding could suggest a potential target for therapy in this subset of malignant mesotheliomas.
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Quinasa de Linfoma Anaplásico/genética , Proteínas de Ciclo Celular/genética , Mesotelioma Maligno/genética , Proteínas Asociadas a Microtúbulos/genética , Serina Endopeptidasas/genética , Anciano , Disnea/etiología , Humanos , Inmunohistoquímica/métodos , Inmunohistoquímica/estadística & datos numéricos , Masculino , Mesotelioma Maligno/fisiopatología , Transcriptoma/genéticaRESUMEN
We present a case of a progressive symptomatic intramedullary cyst, diagnosed decades after Lipiodol injection. Lipiodol was originally administered intrathecally for the radiologic diagnosis of spinal masses. A link between the lesion and the history of Lipiodol injection was never suspected. Surgical exploration revealed a membrane above the lesion, separating the intradural space in a cranial and caudal compartment. On the level of the cyst, we identified glassy pearls containing a fatty liquid, compatible with Lipiodol deposits. We hypothesize that the syrinx is secondary to the impact of cerebrospinal fluid pulsations on the reactive membrane and that this membrane originated from an arachnoiditis caused by Lipiodol deposits. Lipiodol was indeed abandoned after it was found to cause arachnoiditis and neurologic sequelae. Despite the cessation of its usage, the causal role of Lipiodol in arachnoiditis and spinal cyst formation should still be considered, as symptoms may arise many years after Lipiodol administration.