Genomic profiling of pleomorphic rhabdomyosarcoma reveals a genomic signature distinct from that of embryonal rhabdomyosarcoma.

Pleomorphic rhabdomyosarcoma (PRMS) is a rare and highly aggressive sarcoma, occurring mostly in the deep soft tissues of middle-aged adults and showing a variable degree of skeletal muscle differentiation. The diagnosis is challenging as pathologic features overlap with embryonal rhabdomyosarcoma (ERMS), malignant Triton tumor, and other pleomorphic sarcomas. As recurrent genetic alterations underlying PRMS have not been described to date, ancillary molecular diagnostic testing is not useful in subclassification. Herein, we perform genomic profiling of a well-characterized cohort of 14 PRMS, compared to a control group of 23 ERMS and other pleomorphic sarcomas (undifferentiated pleomorphic sarcoma and pleomorphic liposarcoma) using clinically validated DNA-targeted Next generation sequencing (NGS) panels (MSK-IMPACT). The PRMS cohort included eight males and six females, with a median age of 53 years (range 31-76 years). Despite similar tumor mutation burdens, the genomic landscape of PRMS, with a high frequency of TP53 (79%) and RB1 (43%) alterations, stood in stark contrast to ERMS, with 4% and 0%, respectively. CDKN2A deletions were more common in PRMS (43%), compared to ERMS (13%). In contrast, ERMS harbored somatic driver mutations in the RAS pathway and loss of function mutations in BCOR, which were absent in PRMS. Copy number variations in PRMS showed multiple chromosomal arm-level changes, most commonly gains of chr17p and chr22q and loss of chr6q. Notably, gain of chr8, commonly seen in ERMS (61%) was conspicuously absent in PRMS. The genomic profiles of other pleomorphic sarcomas were overall analogous to PRMS, showing shared alterations in TP53, RB1, and CDKN2A. Overall survival and progression-free survival of PRMS were significantly worse (p < 0.0005) than that of ERMS. Our findings revealed that the molecular landscape of PRMS aligns with other adult pleomorphic sarcomas and is distinct from that of ERMS. Thus, NGS assays may be applied in select challenging cases toward a refined classification. Finally, our data corroborate the inclusion of PRMS in the therapeutic bracket of pleomorphic sarcomas, given that their clinical outcomes are comparable.

Rhabdomyosarcoma: Updates on classification and the necessity of molecular testing beyond immunohistochemistry.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and adolescents under the age of 20. The current World Health Organization (WHO) classification for soft tissue and bone tumors recognizes 4 distinct subtypes of RMS based on clinicopathological and molecular genetic features: embryonal, alveolar, spindle cell/sclerosing and pleomorphic subtypes. However, with the increased use of molecular techniques, the classification of rhabdomyosarcoma has been evolving rapidly. New subtypes such as osseus RMS harboring TFCP2/NCOA2 fusions or RMS arising in inflammatory rhabdomyoblastic tumor have been emerging within the last decade, adding to the complexity of diagnosing skeletal muscle tumors. This review article provides an overview of classically recognized distinctive subtypes as well as new, evolving subtypes and discusses important morphologic, immunophenotypic and molecular genetic features of each subtype including recommendations for a diagnostic approach of malignant skeletal muscle neoplasms.

Rabdomiossarcoma de ovário em paciente jovem: Relato de caso / Ovarian rhabdomyosarcoma in a young patient: report of case

O sarcoma de partes moles mais comum na infância é o rabdomiossarcoma. Entretanto a localização ovariana é extremamente rara. Acredita-se que este tumor se origina de células imaturas destinadas a compor o músculo esquelético, porém pode surgir em locais onde tipicamente não há músculo esquelético. O diagnóstico do Rabdomiossarcoma primário de ovário pode causar um dilema entre os clínicos, cirurgiões e patologistas, por se tratar de um tumor muito raro. Após o diagnóstico, é necessária a investigação de possíveis metástases. Este caso trata de uma paciente de 17 anos, submetida a parto cesáreo e, no intraoperatório, foi observado aumento de volume, inespecífico, de ovário direito sendo optado por não abordar naquele momento. De antecedentes pessoais, apresentava ooforectomia esquerda aos 13 anos, por Tumor de células da granulosa juvenil e lobectomia inferior esquerda por malformação adenomatosa cística aos 7 anos. Deu entrada no Pronto Socorro 17 dias após dar à luz com queixa de febre, vômitos e dor abdominal. Foi realizada ultrassonografia de urgência, onde foi visualizada massa sólida em fossa ilíaca direita medindo 14,0 x 11,2 x 10,8 cm. Realizada laparotomia exploradora com anexectomia direita e cito-redução subótima do tumor. O resultado anátomo-patológico demonstrou neoplasia maligna fusocelular com áreas de necrose em ovário. A complementação com o estudo imunohistoquímico concluiu rabdomiossarcoma embrionário. Ela voltou a procurar atendimento no Pronto Socorro dois meses após a abordagem com queixa de vômitos biliosos e epigastralgia. Realizou tomografia computadorizada que identificou recidiva do tumor. Durante a internação, evoluiu com quadro de tromboembolismo pulmonar agudo. Diante disso, foi iniciada terapia com enoxaparina em dose plena e quimioterapia com esquema VAC (Vincristina, Doxorrubicina e Ciclofosfamida). Entretanto, ela apresentou insuficiência de múltiplos órgãos, que culminou com o óbito da paciente. O curso clínico desse caso mostra a rápida progressão e letalidade dessa neoplasia. Além da histopatologia, a idade, o tamanho do tumor, a ressecabilidade, o subtipo histopatológico, a presença de metástase no momento do diagnóstico e a invasão linfonodal influenciam no curso clínico da doença. Palavras-chave: Neoplasias ovarianas. Rabdomiossarcoma. Ovário.

Evolving classification of rhabdomyosarcoma.

Rhabdomyosarcomas comprise the single largest category of soft tissue sarcomas in children and adolescents in the United States, occurring in 4.5 million people aged below 20 years. Based on the clinicopathological features and genetic abnormalities identified, rhabdomyosarcomas are classified into embryonal, alveolar, spindle cell/sclerosing and pleomorphic subtypes. Each subtype shows distinctive morphology and has characteristic genetic abnormalities. This review discusses the evolution of the classification of rhabdomyosarcoma to the present day, together with a discussion of key histomorphological and genetic features of each subtype and the diagnostic approach to these tumours.

Novel EWSR1::UBP1 fusion expands the spectrum of spindle cell rhabdomyosarcomas.

Over the last decade, the development of next-generation sequencing techniques has led to the molecular dismantlement of adult and pediatric sarcoma, with the identification of multiple gene fusions associated with specific subtypes and currently integrated into diagnostic classifications. In this report, we describe and discuss the identification of a novel EWSR1-UBP1 gene fusion in an adult patient presenting with multi-metastatic sarcoma. Extensive pathological, transcriptomic, and genomic characterization of this tumor in comparison with a cohort of different subtypes of pediatric and adult sarcoma revealed that this fusion represents a novel variant of spindle cell rhabdomyosarcoma with features of TFCP2-rearranged subfamily.

DEVOLUTION-A method for phylogenetic reconstruction of aneuploid cancers based on multiregional genotyping data.

Phylogenetic reconstruction of cancer cell populations remains challenging. There is a particular lack of tools that deconvolve clones based on copy number aberration analyses of multiple tumor biopsies separated in time and space from the same patient. This has hampered investigations of tumors rich in aneuploidy but few point mutations, as in many childhood cancers and high-risk adult cancer. Here, we present DEVOLUTION, an algorithm for subclonal deconvolution followed by phylogenetic reconstruction from bulk genotyping data. It integrates copy number and sequencing information across multiple tumor regions throughout the inference process, provided that the mutated clone fraction for each mutation is known. We validate DEVOLUTION on data from 56 pediatric tumors comprising 253 tumor biopsies and show a robust performance on simulations of bulk genotyping data. We also benchmark DEVOLUTION to similar bioinformatic tools using an external dataset. DEVOLUTION holds the potential to facilitate insights into the development, progression, and response to treatment, particularly in tumors with high burden of chromosomal copy number alterations.

Establishment and characterization of NCC-ssRMS2-C1: a novel patient-derived cell line of spindle cell/sclerosing rhabdomyosarcoma.

Spindle cell/sclerosing rhabdomyosarcoma (ssRMS) is a rare subtype of rhabdomyosarcoma (RMS) that has fascicular spindle cell and/or sclerosing morphology. SsRMS has a diverse molecular background and is categorized into three groups: congenital/infantile ssRMS with a gene fusion involving the NCOA2 and VGLL2, ssRMS with the MYOD1 mutation, and ssRMS with no recurrent identifiable genetic alterations. Because ssRMS is a newly defined disease concept of RMS, the optimal treatment methods have not been determined. This results in unfavorable prognosis and consequently signals the urgent need for continuous research. Patient-derived cell lines are essential tools in basic and translational research. However, only two ssRMS cell lines with the MYOD1 mutation have been reported to date. Thus, we established a novel ssRMS cell line named NCC-ssRMS2-C1 using a surgically resected tumor tissue from an adult ssRMS patient. NCC-ssRMS2-C1 cells retained the copy number alterations corresponding to the original tumor and are categorized into the group with no recurrent identifiable genetic alterations. NCC-ssRMS2-C1 cells demonstrated constant proliferation, spheroid formation, and capability for invasion in vitro, reflecting the malignant features of the original tumor tissue. In a drug screening test, ssRMS demonstrated remarkable sensitivity to romidepsin, trabectedin, actinomycin D, and bortezomib. Hence, we conclude that the NCC-ssRMS2-C1 cell line is the first ssRMS cell line which belongs to the group with no recurrent identifiable genetic alterations, and it will be a useful resource in both basic and translational studies for ssRMS.

Pathology of childhood rhabdomyosarcoma: A consensus opinion document from the Children's Oncology Group, European Paediatric Soft Tissue Sarcoma Study Group, and the Cooperative Weichteilsarkom Studiengruppe.

The diagnosis and classification of rhabdomyosarcoma (RMS) has undergone several shifts over the last 30 years. While the main diagnostic categories remained the same, changes in the histologic criteria necessary for diagnosis, as well as varied reliance on immunohistochemical and molecular data over time, have created confusion, particularly regarding how these shifts impacted risk stratification and enrollment onto clinical trials. The goal of this report is to review the evolution and current status of RMS diagnosis, focusing on diagnostic criteria in the Children's Oncology Group (COG), the European Paediatric Soft Tissue Sarcoma Group (EpSSG), and the Cooperative Weichteilsarkom Studiengruppe (CWS). In addition, we emphasize research tools used to classify RMS and address biological questions within current clinical trials run by each group. The INternational Soft Tissue SaRcoma ConsorTium (INSTRuCT) initiative will maximize potential to optimize risk stratification by recognizing and accounting for differences in historical data and current practices.

SRF-FOXO1 and SRF-NCOA1 Fusion Genes Delineate a Distinctive Subset of Well-differentiated Rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) encompasses a heterogenous collection of tumors in which new groups have recently been identified that improved the World Health Organization (WHO) classification. While performing RNA-sequencing in our routine practice, we identified 3 cases of well-differentiated RMS harboring new fusion genes. We also analyzed these tumors through array-comparative genomic hybridization. Clinically, these tumors were deep paraspinal tumors, occurring in neo-nat and young children. The patients underwent resection and adjuvant therapy. At the time of last follow-up (ranging from 12 to 108 mo), they were alive without disease. Histologically, these tumors consisted of well-differentiated rhabdomyoblastic proliferations with nuclear atypia, infiltrative borders, and a specific growth pattern. These tumors harbored new fusion genes involving SRF and either FOXO1 or NCOA1. We compared the expression profiles of these 3 tumors to the expression data of a series of 33 skeletal muscle tumors including embryonal RMSs, alveolar rhandomyosarcomas, RMSs with VGLL2 fusions, RMSs with the myoD1 mutation, EWSR1/FUS-TFCP2 epithelioid and spindle cell RMSs of the bone, and rhabdomyomas with PTCH1 loss. According to clustering analyses, the 3 SRF-fused tumors formed a distinct group with a specific expression profile different from that of the other types of skeletal muscle tumors. Array-comparative genomic hybridization showed a recurrent gain of chromosome 11. These 3 tumors define a new group of RMS associated with a fusion of the SRF gene. FOXO1 rearrangements, usually used to confirm the diagnosis of alveolar RMS and identify poor-outcome RMSs, were identified in a nonalveolar RMS for the first time.

Integrative clinical and biopathology analyses to understand the clinical heterogeneity of infantile rhabdomyosarcoma: A report from the French MMT committee.

BACKGROUND: Rhabdomyosarcoma (RMS) in infants is a particular entity with various clinical presentations and outcomes. To better understand the clinical heterogeneity of RMS in infants, an integrative clinical, histological, and molecular analysis was performed. METHODS: From 1989 to 2015, 37 infants aged less than 6 months with a diagnosis of RMS and archival tumor materials were identified in France. Clinical data, central pathologic review, and molecular profile including RNA sequencing were analyzed. RESULTS: Nineteen patients (51%) had embryonal RMS (ERMS) (including three highly differentiated ERMS with PTCH deletion), eight (22%) had spindle cell RMS (SRMS) (three VGLL2-, one NTRK-, and two (B)RAF-fusions), six (16%) had alveolar RMS (ARMS) (all FOXO1- or PAX3-fusion), two had unclassified RMS, and two poorly differentiated RMS were retrospectively diagnosed as rhabdoid tumors (RT) with loss of INI1 expression. The two RT patients died of rapid disease progression. Five-year event-free (EFS) and overall survival (OS) for RMS were 62% (95%CI, 47-82) and 52% (95%CI, 37-72). Eleven patients (31%) relapsed and four (11%) had primary refractory disease (all ERMS). In univariate analysis, EFS and OS were only associated with histology subtype, with 100% survival of known fusion-positive SRMS. RNA cluster expression showed three main clusters: ARMS, ERMS, and "VGLL2-fusion" cluster, consisting of SRMS and ERMS. CONCLUSIONS: Biopathology findings from this study support the different prognosis of infantile RMS. New fusion-positive SRMS has a very good outcome which may allow more conservative treatment in the future.

The current landscape of rhabdomyosarcomas: an update.

Rhabdomyosarcomas are malignancies associated with a rhabdomyoblastic phenotype which can be demonstrated morphologically or by immunohistochemistry for MYOD1 and myogenin. Rhabdomyosarcomas are currently subdivided into 4 types in the 2013 WHO classification of tumors of soft tissue and bone, including embryonal rhabdomyosarcoma, alveolar rhabdomyosarcoma, spindle cell/sclerosing rhabdomyosarcoma, and pleomorphic rhabdomyosarcoma. Recent studies have significantly impacted this classification with the emergence of three distinct new subtypes of rhabdomyosarcomas, namely rhabdomyosarcoma with MYOD1 mutations, rhabdomyosarcoma with TFCP2 fusions, and rhabdomyosarcoma with VGLL2/NCOA2 fusions. Although all these tumors share the terminology "rhabdomyosarcoma," their morphology, clinical behavior, and underlying molecular alterations are dramatically different. Finally, the presence of a rhabdomyoblastic phenotype within a tumor is by no means a diagnostic of a rhabdomyosarcoma, as this may be seen in many other mesenchymal malignancies, such as mesenchymal chondrosarcomas, malignant peripheral nerve sheaths tumors, and biphenotypic sinonasal sarcomas. In this review, we present the main clinical, morphological, and molecular features of these tumors and discuss the evolution of the current classification.

[Clinicopathological characteristics and therapeutic effects of adult rhabdomyosarcoma patients].

Objective: This study aimed to investigate the clinicopathological characteristics and prognosis of adult rhabdomyosarcoma (RMS) patients. Methods: The clinical data of 34 adult RMS patients were retrospectively analyzed. Based on their intervention and treatment, patients were divided into operation group (n=7), chemotherapy group (n=8) and operation plus chemotherapy group (n=19). The clinical characteristics and treatment outcomes of the three groups were compared. Results: A statically significant difference was found in IRSG surgical-pathological stage among the three groups (P=0.026), while no significant difference existed in gender, age of disease onset, primary site, tumor size, pathological subtypes and IRSG risk group in the three groups (all P>0.05). In the operation group, three CR, one PR, one SD and two PD were achieved and one CR, one PR, one SD and five PD were obtained in the chemotherapy group. While in the chemotherapy plus operation group, four CR, twelve PR, one SD and two PD were achieved. A significant difference was found in response (P=0.043) and median overall survival (OS) (P=0.036) among the three groups, which were 44.7, 26.9 and 53.6 months, respectively. Conclusions: Pleomorphic RMS was the main histological subtype for adult RMS patients, and the prognosis for adult RMS was usually poorer than that for pediatric RMS patients. Single therapeutic approach could not achieve satisfactory outcomes, while multimodal treatment consisted of surgery, chemotherapy and radiotherapy are helpful to improve the prognosis of adult patients with RMS.

Gene Co-Expression Networks Restructured Gene Fusion in Rhabdomyosarcoma Cancers.

Rhabdomyosarcoma is subclassified by the presence or absence of a recurrent chromosome translocation that fuses the FOXO1 and PAX3 or PAX7 genes. The fusion protein (FOXO1-PAX3/7) retains both binding domains and becomes a novel and potent transcriptional regulator in rhabdomyosarcoma subtypes. Many studies have characterized and integrated genomic, transcriptomic, and epigenomic differences among rhabdomyosarcoma subtypes that contain the FOXO1-PAX3/7 gene fusion and those that do not; however, few investigations have investigated how gene co-expression networks are altered by FOXO1-PAX3/7. Although transcriptional data offer insight into one level of functional regulation, gene co-expression networks have the potential to identify biological interactions and pathways that underpin oncogenesis and tumorigenicity. Thus, we examined gene co-expression networks for rhabdomyosarcoma that were FOXO1-PAX3 positive, FOXO1-PAX7 positive, or fusion negative. Gene co-expression networks were mined using local maximum Quasi-Clique Merger (lmQCM) and analyzed for co-expression differences among rhabdomyosarcoma subtypes. This analysis observed 41 co-expression modules that were shared between fusion negative and positive samples, of which 17/41 showed significant up- or down-regulation in respect to fusion status. Fusion positive and negative rhabdomyosarcoma showed differing modularity of co-expression networks with fusion negative (n = 109) having significantly more individual modules than fusion positive (n = 53). Subsequent analysis of gene co-expression networks for PAX3 and PAX7 type fusions observed 17/53 were differentially expressed between the two subtypes. Gene list enrichment analysis found that gene ontology terms were poorly matched with biological processes and molecular function for most co-expression modules identified in this study; however, co-expressed modules were frequently localized to cytobands on chromosomes 8 and 11. Overall, we observed substantial restructuring of co-expression networks relative to fusion status and fusion type in rhabdomyosarcoma and identified previously overlooked genes and pathways that may be targeted in this pernicious disease.

MYOD1-mutant spindle cell and sclerosing rhabdomyosarcoma: an aggressive subtype irrespective of age. A reappraisal for molecular classification and risk stratification.

Sclerosing and spindle cell rhabdomyosarcoma is a rare histologic subtype, designated in the latest WHO classification as a stand-alone pathologic entity. Three genomic groups have been defined: an infantile subset of spindle cell rhabdomyosarcoma harboring VGLL2-related gene fusions, a MYOD1-mutant subset commonly associated with sclerosing morphology, and a subset lacking recurrent genetic abnormalities. In this study, we focus on MYOD1-mutant rhabdomyosarcoma to further define their clinicopathologic characteristics and behavior in a larger patient cohort. We investigated 30 cases of MYOD1-mutant rhabdomyosarcoma (12 previously reported and 18 newly diagnosed) with an age range of 2-94 years, including 15 children. All cases showed morphology within the spectrum of spindle cell/sclerosing rhabdomyosarcoma (8 cases showing pure sclerosing morphology, 8 cases  showing pure spindle cell morphology and 14 cases showing a hybrid phenotype of spindle, sclerosing and primitive undifferentiated areas). All tumors harbored either homozygous or heterozygous MYOD1 (p.L122R) exon 1 mutations. In 10 (33%) cases, a co-existent PIK3CA mutation was identified. Hot-spot mutations in NRAS and HRAS were each identified in a single case, respectively. Follow-up was available on 22 (73%) patients with a median duration of 28 months. Local recurrence was seen in 12 (55%) and distant recurrence in 12 (55%) cases, despite multimodality chemoradiation therapy. At last follow-up, 15 (68%) patients died of the disease, one patient was alive with disease and five had no evidence of disease. The prognosis was equally poor in pediatric and adult patients. In conclusion, MYOD1 mutation defines an aggressive rhabdomyosarcoma subset, with poor outcome and response to therapy, irrespective of age. Given that this distinct molecular subtype is characterized by an aggressive biologic behavior compared to other genetic subtypes of spindle and sclerosing rhabdomyosarcoma, the MYOD1 genotype should be used as a molecular marker in both subclassification and prognostication of rhabdomyosarcoma.

Current Treatment of Pediatric Bladder and Prostate Rhabdomyosarcoma.

PURPOSE OF REVIEW: Rhabdomyosarcoma (RMS) is the most common sarcoma diagnosed in the first 20 years of life; bladder/prostate (BP) RMS accounts for 5% of all cases. Through efforts from multiple cooperative study groups, survival has improved significantly. This article aims to review the complex RMS classification system and treatment of BP RMS, with a focus on developing aspects of treatment. RECENT FINDINGS: Recent advancements in technology are responsible for most of the progress in RMS treatment. PET-CT scanning has been shown to be superior to conventional metastatic workup. The use of proton beam therapy and brachytherapy to reduce the side effects of radiation is also showing promise. All cooperative oncology groups agree on surgical biopsy for diagnosis and staging of BP RMS. Patients are then grouped and risk classified before receiving chemotherapy. Regardless of local control strategy, oncologic outcomes appear to be similar for BP RMS. Alternative treatment strategies, which remain unproven, include brachytherapy and proton therapy.

Transfer learning on fused multiparametric MR images for classifying histopathological subtypes of rhabdomyosarcoma.

This paper presents a deep-learning-based CADx for the differential diagnosis of embryonal (ERMS) and alveolar (ARMS) subtypes of rhabdomysarcoma (RMS) solely by analyzing multiparametric MR images. We formulated an automated pipeline that creates a comprehensive representation of tumor by performing a fusion of diffusion-weighted MR scans (DWI) and gadolinium chelate-enhanced T1-weighted MR scans (MRI). Finally, we adapted transfer learning approach where a pre-trained deep convolutional neural network has been fine-tuned based on the fused images for performing classification of the two RMS subtypes. We achieved 85% cross validation prediction accuracy from the fine-tuned deep CNN model. Our system can be exploited to provide a fast, efficient and reproducible diagnosis of RMS subtypes with less human interaction. The framework offers an efficient integration between advanced image processing methods and cutting-edge deep learning techniques which can be extended to deal with other clinical domains that involve multimodal imaging for disease diagnosis.

Laryngeal Rhabdomyosarcoma in a dog: case report / Rabdomiossarcoma na laringe em cão: relato de caso

The larynx is part of the upper respiratory tract and is responsible for phonation. It allows air to pass between the pharynx and the trachea, but prevents food from entering the airways. Laryngeal neoplasms, including rhabdomyosarcomas, are uncommon in dogs. However, these tumors can trigger numerous progressive clinical signs related to respiratory difficulty and altered phonation. The diagnosis of laryngeal cancer should be made based on the history and symptoms of the patient, combined with complementary tests. The treatment of choice is surgical excision, combined or not with chemotherapy. In view of the low incidence of laryngeal cancer, the objective of the present work was to describe a case of laryngeal rhabdomyosarcoma detected during necropsy of an adult dog and diagnosed by histopathology, in addition to raising awareness about the importance of the diagnosis and early therapy for the quality of life and survival of affected patients. The results showed that the location of the tumor impaired its early diagnosis. Although malignant, the animal did not develop metastases as has been described in the literature.(AU)

A laringe é um dos órgãos que compõem o trato respiratório superior, sendo também responsável pela fonação. Permite a passagem do ar entre a faringe e traqueia, mas impede que alimentos adentrem as vias aéreas. As neoplasias laringeanas, incluindo os rabdomiossarcomas, são incomuns em cães, porém, quando presentes, desencadeiam inúmeros sinais clínicos progressivos relacionados à dificuldade respiratória e à alteração na fonação. O diagnóstico das neoplasias na laringe deve ser baseado no histórico e na sintomatologia do paciente, associado a exames complementares. O tratamento de eleição é a exérese cirúrgica, concomitante ou não com a quimioterapia. Desse modo, diante da baixa incidência desse tipo neoplásico, inclusive na laringe, o objetivo do atual trabalho é descrever o caso de rabdomiossarcoma em laringe, detectado durante o exame de necropsia de um cão adulto e diagnosticado por histopatologia, bem como conscientizar sobre a importância do diagnóstico e da terapêutica precoce na qualidade de vida e sobrevida dos afetados. De acordo com a descrição do caso, pode-se admitir que a localização da neoplasia prejudicou o diagnóstico precoce e que, apesar de esta ser maligna, não houve metástases conforme descrição na literatura.(AU)

[Soft tissue tumors : Epidemiology, classification and staging]. / Weichteiltumoren : Epidemiologie, Klassifikation und Stadieneinteilung.

Benign, intermediate and malignant soft tissue tumors can be differentiated histologically. Furthermore, the tumors can be subdivided according to their linear differentiation. In the new World Health Organization (WHO) classification of soft tissue tumors from 2013 changes have been made relating to the allocation of known entities, e. g. undifferentiated sarcomas have been formed into a new subgroup and are no longer assigned to the fibrohistiocytic tumors. The term malignant fibrous histiocytoma has been replaced by the undifferentiated sarcoma. Furthermore, two new subgroups were incorporated, the nerve sheath tumors and gastrointestinal stromal tumors. These were previously included in the tumor classification of other organ systems. These changes in the new classification are related to the rapid increase in knowledge of the genetics and the cell biology of soft tissue tumors. Malignant soft tissue tumors only represent 1% of all malignant tumors in adults. The largest subgroup of soft tissue tumors in adults is the adipocytic tumors. The liposarcoma, which belongs to this subgroup is one of the most common malignant soft tissue tumors in adults. In childhood malignant soft tissue tumors represent 15% of malignant tumors and rhabdomyosarcoma is the most common malignant soft tissue tumor.

Update on molecular findings in rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is the most common malignant soft tissue tumour in children and adolescents. Histologically RMS resembles developing fetal striated skeletal muscle. RMS is stratified into different histological subtypes which appear to influence management plans and patient outcome. Importantly, molecular classification of RMS seems to more accurately capture the true biology and clinical course and prognosis of RMS to guide therapeutic decisions. The identification of PAX-FOXO1 fusion status in RMS is one of the most important updates in the risk stratification of RMS. There are several genes close to PAX that are frequently altered including the RAS family, FGFR4, PIK3CA, CTNNB1, FBXW7, and BCOR. As with most paediatric blue round cell tumours and sarcomas, chemotherapy is the key regimen for RMS therapy. Currently there are no direct inhibitors against PAX-FOXO1 fusion oncoproteins and targeting epigenetic cofactors is limited to clinical trials. Failure of therapy in RMS is usually related to drug resistance and metastatic disease. Through this review we have highlighted most of the molecular aspects in RMS and have attempted to correlate with RMS classification, treatment and prognosis.