What are the Optimal Systemic Treatment Options for Rhabdomyosarcoma?

OPINION STATEMENT: Rhabdomyosarcoma, a soft tissue sarcoma commonly observed in childhood, requires multidisciplinary treatment, including surgical tumor resection, chemotherapy, and radiation therapy. Although long-term survival can be expected in patients with localized rhabdomyosarcoma, the clinical outcomes in patients with metastatic or unresectable rhabdomyosarcoma remain unsatisfactory. To improve the outcomes of rhabdomyosarcoma, it is important to explore effective systemic treatments for metastatic rhabdomyosarcoma. Currently, multiagent chemotherapy comprising vincristine, actinomycin D, and ifosfamide/cyclophosphamide remains standard systemic treatment for rhabdomyosarcoma. On the other hand, new treatment, such as immune checkpoint inhibitors and molecular targeted drugs, have demonstrated superior clinical outcomes compared to those of standard treatments in various type of malignancies. Therefore, it is necessary to assess the efficacies of these treatments in patients with rhabdomyosarcoma. Recent clinical studies have shown efficacies and safeties of temozolomide combined with vincristine/irinotecan, olaratumab combined with doxorubicin or vincristine/irinotecan, and long-term maintenance therapy. Furthermore, basic researches demonstrated new therapeutic targets. Future studies using these approaches are required to assess their clinical significances.

[Combined surgeries for secondary chest wall lesions]. / Kombinirovannye operatsii pri vtorichnom porazhenii grudnoi stenki.

The authors present treatment of rhabdomyosarcoma of the gluteal region with secondary lesion of the lung and chest wall. Features of chest wall defect closure are analyzed.

Preliminary study on the optical diagnosis of orbital rhabdomyosarcoma by Raman spectroscopy.

To investigate the Raman spectral features of orbital rhabdomyosarcoma (ORMS) tissue and normal orbital tissue in vitro, and to explore the feasibility of Raman spectroscopy for the optical diagnosis of ORMS. 23 specimens of ORMS and 27 specimens of normal orbital tissue were obtained from resection surgery and measured in vitro using Raman spectroscopy coupled to a fiber optic probe. The important spectral differences between the tissue categories were exploited for tissue classification with the multivariate statistical techniques of principal component analysis (PCA) and linear discriminant analysis (LDA). Compared to normal tissue, the Raman peak intensities located at 1450 and 1655 cm-1 were significantly lower for ORMS (p < 0.05), while the peak intensities located at 721, 758, 1002, 1088, 1156, 1206, 1340, 1526 cm-1 were significantly higher (p < 0.05). Raman spectra differences between normal tissue and ORMS could be attributed to the changes in the relative amounts of biochemical components, such as nucleic acids, tryptophan, phenylalanine, carotenoid and lipids. The Raman spectroscopy technique together with PCA-LDA modeling provides a diagnostic accuracy of 90.0%, sensitivity of 91.3%, and specificity of 88.9% for ORMS identification. Significant differences in Raman peak intensities exist between normal orbital tissue and ORMS. This work demonstrated for the first time that the Raman spectroscopy associated with PCA-LDA diagnostic algorithms has promising potential for accurate, rapid and noninvasive optical diagnosis of ORMS at the molecular level.

Mandibular rhabdomyosarcoma with TFCP2 rearrangement and osteogenic differentiation: a case misdiagnosed as fibrous dysplasia or low-grade central osteosarcoma.

Rhabdomyosarcoma with TFCP2-related fusions (TFCP2-RMS) is a rare entity that commonly affects young adults with a predilection for skeletal involvement. We herein report a 40-year-old female patient with TFCP2-RMS who was misdiagnosed as fibrous dysplasia or low-grade central osteosarcoma of the mandible by referring institutions. Histologically, the tumor showed dominant spindle cells and focal epithelioid cells with marked immature woven bone formation. Immunophenotypically, in addition to the characteristic expression of myogenic markers, ALK, and cytokeratins, tumor cells also unusually expressed osteogenic markers, such as MDM2 and SATB2. Through fluorescence in situ hybridization, the tumor cells showed EWSR1::TFCP2 gene fusion and no MDM2 gene amplification. This is a rare case of TFCP2-RMS, which was misdiagnosed as low-grade central osteosarcoma due to its presenting immunophenotype of MDM2 and SATB2, as well as extensive osteoid matrix formation.

NF1-Driven Rhabdomyosarcoma Phenotypes: A Comparative Clinical and Molecular Study of NF1-Mutant Rhabdomyosarcoma and NF1-Associated Malignant Triton Tumor.

PURPOSE: Alterations of the NF1 tumor suppressor gene is the second most frequent genetic event in embryonal rhabdomyosarcoma (ERMS), but its associations with clinicopathologic features, outcome, or coexisting molecular events are not well defined. Additionally, NF1 alterations, mostly in the setting of neurofibromatosis type I (NF1), drive the pathogenesis of most malignant peripheral nerve sheath tumor with divergent RMS differentiation (also known as malignant triton tumor [MTT]). Distinguishing between these entities can be challenging because of their pathologic overlap. This study aims to comprehensively analyze the clinicopathologic and molecular spectrum of NF1-mutant RMS compared with NF1-associated MTT for a better understanding of their pathogenesis. METHODS: We investigated the clinicopathologic and molecular landscape of a cohort of 22 NF1-mutant RMS and a control group of 13 NF1-associated MTT. Cases were tested on a matched tumor-normal hybridization capture-based targeted DNA next-generation sequencing. RESULTS: Among the RMS group, all except one were ERMS, with a median age of 17 years while for MTT the mean age was 39 years. Three MTTs were misdiagnosed as ERMS, having clinical impact in one. The most frequent coexisting alteration in ERMS was TP53 abnormality (36%), being mutually exclusive from NRAS mutations (14%). MTT showed coexisting CDKN2A/B and PRC2 complex alterations in 38% cases and loss of H3K27me3 expression. Patients with NF1-mutant RMS exhibited a 70% 5-year survival rate, in contrast to MTT with a 33% 5-year survival. All metastatic NF1-mutant ERMS were associated with TP53 alterations. CONCLUSION: Patients with NF1-mutant ERMS lacking TP53 alterations may benefit from dose-reduction chemotherapy. On the basis of the diagnostic challenges and significant treatment and prognostic differences, molecular profiling of challenging tumors with rhabdomyoblastic differentiation is recommended.

When the second comes first- rhabdomyosarcoma preceding heritable retinoblastoma- a case report.

BACKGROUND: Retinoblastoma (rb) is the most frequent intraocular tumor, accounting for 3% of all childhood cancers. Heritable rb survivors are germline carriers for an RB1 mutation and have a lifelong risk to develop non-ocular second primary tumors (SPTs) involving multiple other organs like the bones, soft tissues, or skin. These SPTs usually become manifest several years succeeding the diagnosis of rb. In our instance, however, a non-ocular SPT presented prior to the diagnosis of heritable rb. CASE PRESENTATION: We report a rare case of a monozygotic twin who presented with primary rhabdomyosarcoma (RMS) preceding the manifestation of heritable rb. The rb was diagnosed when the child developed strabismus while already on therapy for the RMS. The child underwent therapy for both as per defined treatment protocols. The rb regressed well on treatment, but the RMS relapsed and the child developed multiple refractory metastatic foci and succumbed to his disease. CONCLUSIONS: Non-ocular SPTs like sarcomas are usually known to manifest in heritable rb survivors with a lag of two to three decades (earlier if exposure to radiation is present) from the presentation of the rb. However, in our case, this seemed to be reversed with the RMS being manifest at an unusual early age and the rb being diagnosed at a later point in time.

Multifaceted Spindle Cell/Sclerosing Rhabdomyosarcoma With Role of Immunohistochemistry in Avoiding Misdiagnosis: A Multi-Institutional Study of 45 Distinct Tumors.

Background. Spindle cell/sclerosing rhabdomyosarcoma is a rare neoplasm and has an aggressive clinical course. Because of its rarity, we performed a multi-institutional collaboration to comprehend the overarching clinical, histopathological, and immunohistochemical characteristics of a cohort of spindle cell/sclerosing rhabdomyosarcoma. Materials and Methods. Forty-five patients with spindle cell/sclerosing rhabdomyosarcoma were identified. Demographics, clinical, histopathological, and immunohistochemistry data were reviewed and recorded. Results. The patients' age ranged from 1 to 85 years with a male to female ratio of 1.2:1. There were 15 children/adolescents and 30 adults. Eighteen (40%) tumors were located in the head and neck region. Twenty-four (53%) tumors displayed a bimorphic cellular arrangement with hypercellular areas having short, long, and sweeping fascicular and herringbone pattern, and hypocellular areas with stromal sclerosis and associated hyalinized and/or chondromyxoid matrix. Histomorphological differentials considered were leiomyosarcoma, malignant peripheral nerve sheath tumor, fibrosarcoma, nodular fasciitis, liposarcoma, synovial sarcoma, sarcomatoid carcinoma, solitary fibrous tumor, dermatofibrosarcoma protuberans, and schwannoma. Six tumors exhibited marked stromal sclerosis. The myogenic nature was confirmed by immunohistochemistry. Positivity for at least one skeletal muscle-associated marker (MyoD1 and/or myogenin) was observed. Conclusion. Spindle cell/sclerosing rhabdomyosarcoma diagnosis can be challenging as a number of malignant spindle cell neoplasm mimic this entity. Thus a correct diagnosis requires immunohistochemical work up with a broad panel of antibodies. In view of rarity of this neoplasm, further studies on a large cohort of patients with clinical follow-up data are needed for a better understanding of this tumor.

Isolated embryonal rhabdomyosarcoma of the anterior petrous bone in a young child: Focusing on the intra-operative diagnosis and differentials.

OBJECTIVE: Rhabdomyosarcoma is a common soft tissue tumor, but isolated involvement of anterior portion of petrous bone is exceedingly rare. Here, we present a case of embryonal rhabdomyosarcoma involving the anterior petrous without involvement of the mastoid and middle ear. PATIENT: A 6-year-old boy presented with a progressive right side lower motor neuron facial paresis for 1-month duration along with headache and recurrent vomiting episodes. Radiology showed a contrast-enhancing lesion involving the right petrous apex. He underwent craniotomy and excision of the lesion. Based on the frozen section, a diagnosis of rhabdomyosarcoma was rendered, and gross total resection could be achieved. Postoperative course was uneventful. CONCLUSION: Isolated petrous bone involvement of embryonal rhabdomyosarcoma is a rare presentation. Intra-operative frozen section plays a key role in decision making regarding the extent of excision. Hence, a prompt and accurate diagnosis is essential in managing these cases.

Rabdomiossarcoma pleomórfico em adultos: revisão de literatura / Pleomorphic rhabydomyosarcoma in adults: literature review

O rabdomiossarcoma (RMS) pleomórfico (PLM) é um subtipo raro de RMS que afeta principalmente adultos e idosos sendo sua biologia e genética ainda não completamente conhecida ou descrita. Os fatores de risco e suas alterações moleculares também são pouco conhecidos. O tratamento em adultos com RMS PLM ainda não é totalmente padronizado havendo diversas opções de regimes quimioterápicos. O prognóstico dessa patologia é considerado reservado pois, comparado com outros tipos de sarcoma de adultos, tem uma baixa sobrevida global. O seu diagnóstico correto e seu tratamento constituem em desafios na prática clínica oncológica e devido a esses fatores realizamos uma revisão de literatura com dados do Pubmed de 1º de janeiro de 2003 a 31 de dezembro de 2023 para rever epidemiologia, características clínicas, diagnóstico e tratamento dos pacientes com RMS PLM em adultos acima de 18 anos

Pleomorphic rhabdomyosarcoma (RMS) (PLM) is a rare subtype of RMS that mainly affects adults and the elderly, and its biology and genetics are not yet completely known or described. The risk factors and their molecular alterations are also poorly known. Treatment in adults with RMS PLM is not yet fully standardized and there are several options for chemotherapy regimens.The prognosis of this pathology is considered guarded because compared to other types of adult sarcoma, it has a low overall survival rate. in challenges in oncology clinical practice and due to these factors we carried out a literature review with data from Pubmed from January 1, 2003 to December 31, 2023 to review the epidemiology, clinical characteristics, diagnosis and treatment of patients with RMS PLM in adults above 18 years old

Clinical spectrum and clinicopathological correlation of pediatric orbital tumors: 20 years' experience from a tertiary eye care center.

PURPOSE: To study the epidemiological profile of various pediatric orbital tumors and determine their clinicopathological correlation over 20 years. METHODS: A retrospective analysis of all pediatric patients with orbital tumors from the medical records between 1995 and 2015 was done. Tumors were categorized based on their cellular origin. Demographic details, clinical and histopathological diagnoses, frequency, and clinicopathological correlation were studied. RESULTS: A total of 265 pediatric patients with orbital tumors were analyzed, of which 145 (54.7%) patients were males and 120 (45.3%) were females. The mean age was 7 years (median: 6 years; range: 10 days-16 years). The distribution of lesions in each group was as follows: vasculogenic, 76 (28.7%); lipogenic and myxoid, 66 (25%); myogenic, 31 (11.7%); optic nerve and meningeal, 22 (8.3%); lymphoid and lymphoproliferative, 18 (6.8%); secondary orbital tumors, 14 (5.2%); histiocytic, 9 (3.4%); miscellaneous, 9 (3.4%), lacrimal gland, 8 (3%); mesenchymal with neural differentiation, 6 (2%); osseous, 4 (1.5%), and fibrocystic, 2 (0.8%). The most common benign and malignant pediatric orbital tumors were dermoid cysts (65, 24.5%) and rhabdomyosarcoma (31, 11.7%). A statistically significant ( P < 0.0001) clinicopathological correlation was observed in 208 (83.2%) out of 250 biopsy-proven cases. CONCLUSION: Pediatric orbital neoplasms include a broad spectrum of benign and malignant lesions. Vasculogenic tumors constitute the majority of them, followed by lipogenic and myxoid tumors. A thorough knowledge of the incidence, clinical profile, imaging features, and histopathology of specific orbital tumors aids in accurate diagnosis and their successful management.

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.

Perianal rhabdomyosarcoma in an adult: A case report and review of the literature.

Perianal/perineal rhabdomyosarcomas (PRMS) is rare, and the outcome is poor. A 29-year-old female presented with perineal rhabdomyosarcomas revealed metastases to inguinal lymph nodes on the bilateral side. Disease progression was discovered when the patient got adjuvant epirubicin, ifosfamide, and bevacizumab for 2 cycles. After 3 cycles of nivolumab, dacarbazine, cisplatin, and vinblastine therapy, a partial response was identified in the patient. The surgical resection was performed. The patient received neoadjuvant chemotherapy before surgery and was weak after surgery, so he did not receive chemoradiotherapy. The patient succumbed after 11 months postoperatively due to widespread intraabdominal metastasis.

Critical elements of pediatric rhabdomyosarcoma surgery.

Rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children, requires multimodal therapy which is determined by risk group stratification. Local control may be achieved by surgical resection, radiation, or both. Resection may occur upfront or following induction chemotherapy as a delayed primary excision. An R1 resection may allow a reduction in radiation exposure; however, debulking is not indicated nor is excision of residual masses at the end of therapy. Regional lymph node assessment is an important component of surgical care, as positive nodal basins require radiation. Depending on the tumor site and biology, sentinel lymph node biopsy vs biopsy of clinically or radiographically concerning nodes is indicated. Therapeutic lymph node dissection is never indicated. Familiarity with site-specific oncologic principles for RMS and participation in a multidisciplinary team including Pediatric Oncology and Radiation Oncology are necessary components of surgical care to ensure optimal outcomes.

[Clinical analysis of 5 adult laryngeal rhabdomyosarcoma].

Objective:To explore the clinical manifestations,the type of pathology, treatment and prognosis of laryngeal rhabdomyosarcoma, and to enhance the understanding of the clinical characteristics of the disease, while improving the diagnosis rateand reducing the misdiagnosis rate, in order to explore effective diagnosis and treatment methods. Methods:A retrospective analysis was conducted on the clinical data of 5 cases of laryngeal rhabdomyosarcoma treated in the First Affiliated Hospital of Zhengzhou University from May 2015 to May 2021. Results:All 5 cases of laryngeal rhabdomyosarcoma were misdiagnosed in the early stage. with tumors mostly occurring in the vocal cords and appearing as smooth mass. The clinical symptoms were mostly hoarseness. According to pathological classification, three cases were embryonic type, one case was polymorphic type, and one case was spindle type.Three patients died due to tumor recurrence, one patient had multiple systemic metastases, and another patient who underwent surgical resection in the early stage and supplemented with postoperative radiotherapy and chemotherapyhas been followed up to date without recurrence. Conclusion:Laryngeal rhabdomyosarcoma has low incidence rate, high malignancy degree and poor prognosis. It is easy to be misdiagnosed as a benign mass. Extensive surgical resection combined with radiotherapy and chemotherapy should be performed as soon as possible after diagnosis.

A case series of urinary bladder rhabdomyosarcoma in seven dogs.

Background: Juvenile urinary bladder rhabdomyosarcoma (ubRMS) is a known entity; however, literature regarding its clinical behavior and endoscopic features is scarce. The aim of this study was to describe clinical and endoscopic features, and outcomes of ubRMS in dogs. Case Description: Dogs undergoing transurethral endoscopy and with a histological diagnosis of ubRMS were retrospectively collected. Seven dogs with a median age of 18 months (range 6-32 months) were included in this retrospective, multicenter, and descriptive study. Median tumor size was 58 mm (range 30-65 mm), and tumor location was bladder neck in three cases, trigone in two cases, and bladder body in two cases. Two dogs had monolateral ureteral obstruction. Two dogs presented with regional lymphadenopathy and one dog had lung lesions suggestive of metastatic disease. A grape-like mass was reported in four cases and solid in two, with variable consistency (two friables, two firms, and two not reported). Tumor treatments included surgery in three cases, surgery, and adjuvant doxorubicin in one case, and palliative therapy in three cases. The overall median survival time (ST) was 45 days. STs were shorter (range 20-45 days) for dogs treated with palliative care than for dogs treated with curative-intent treatment (range 70-120 days). Conclusion: ubRMS should be considered as a differential diagnosis in young dogs presenting with bladder masses. In this study, ubRMS confirmed its aggressive clinical behavior. Surgery and chemotherapy seem to increase STs but the prognosis remains poor.

Rhabdomyosarcoma or Fibrosarcoma? A Case of Large Ulcerated and Necrotic Lesion on the Forearm of a Newborn.

Congenital infantile fibrosarcoma (CIFS) is a rare malignant soft tissue tumor. The incidence of fibrosarcoma is estimated to be 0.3 per 100 000 population per year, and it accounts for less than 1% of all soft tissue sarcomas. We present a case of a 7-day-old newborn with a large ulcerated and necrotic lesion on the left forearm, which was initially misdiagnosed as rhabdomyosarcoma. Magnetic resonance imaging (MRI) revealed a soft tissue mass with cystic components affecting the forearm and distal humerus muscles. Fine-needle biopsy was performed and initially diagnosed as rhabdomyosarcoma but later confirmed as low-grade fibrosarcoma with positive immunostaining for vimentin. The patient underwent a transhumeral amputation with follow-up chemotherapy at a specialized oncology center. This case underscores the importance of interdisciplinary collaboration and specialized care in managing complex medical conditions in infants. Early detection and appropriate management of these tumors are essential for improving outcomes and reducing morbidity and mortality. Despite the rarity of this case, it serves as a reminder of the importance of considering neoplastic lesions in the differential diagnosis of soft tissue masses in newborns.