Primary Alveolar Rhabdomyosarcoma Research Articles

Primary perianal alveolar rhabdomyosarcoma with uncommon metastatic sites: a case report and follow-up using 18F-FDG PET/CT

BackgroundRhabdomyosarcoma (RMS), a rare pediatric soft tissue neoplasm, predominantly develops in late childhood and adolescence with no discernible gender bias. Alveolar rhabdomyosarcoma (ARMS) stems from mesenchymal cells and may develop most frequently in the trunk, extremities, and head/neck areas, while occurrences in the pelvic cavity are less frequent. The manifestation is typically characterized by a high rate of aggressive metastasis and a poor overall survival prognosis.Case reportWe present the case of an 11-year-old girl with ARMS initially presenting with a perianal mass. The diagnostic workup included MRI and PET/CT, which highlighted the tumor’s aggressive nature and metastatic potential. Subsequent metastases to the pleura, lymph nodes, and, less frequently, to the bone were detected using 2-deoxy-2-[fluorine-18]-fluoro-D-glucose positron emission tomography combined with computed tomography (18F-FDG PET/CT) imaging. The patient underwent a multi-regimen chemotherapy protocol but showed an incomplete response, indicating a poor prognosis.ConclusionThis report presents a rare case of ARMS primarily located in the perianal region with multiple metastases, including the uncommon occurrence of bone metastasis, which illustrates the challenges in diagnosing and treating ARMS, emphasizing the need for accurate and early diagnosis, advanced imaging for disease assessment, and more effective treatment strategies. 18F-FDG PET/CT imaging highlights its preeminence in detecting multiple rare metastatic lesions. However, the persistent disease activity despite treatment highlights the need for further research into the biology of ARMS and the development of novel therapeutics to improve patient outcomes.

Primary Alveolar Rhabdomyosarcoma of the Thyroid: A Case Report.

Malignancies in paediatric age group are the second leading cause of death, next only to accidents. The variety of malignancies involving the head and neck region in paediatric age group is bewildering. Rhabdomyosarcoma of thyroid gland is one such entity very rarely seen. We present the case of an adolescent who presented with a neck mass and suffered rapid deterioration. Establishment of final diagnosis was possible only because of a skilfully performed pathological examination which revealed a thyroid gland rhabdomyosarcoma. An alveolar variety of rhabdomyosarcoma presenting in the thyroid gland is extremely rare. To the best of our knowledge, only two cases of the aforementioned are documented as yet. Through this report, we aim at highlighting the possibility of such an occurrence and vigilance on part of the treating surgeon so that timely intervention can be instituted.

Primary alveolar rhabdomyosarcoma of the brain: a case report

BackgroundPrimary brain rhabdomyosarcoma is a rare primary brain malignancy with few case reports. The vast majority of cases of primary brain rhabdomyosarcoma occur in pediatric patients, and immunohistochemistry can distinguish it from embryonal subtypes; however, few cases of primary brain rhabdomyosarcoma in adults have been reported in the literature.Case presentationWe report the case of a 26-year-old White male patient who was found to have primary brain alveolar rhabdomyosarcoma after developing headaches for several months. A brain MRI revealed a mixed cystic and solid tumor along the vermis of the cerebellum. The patient underwent a gross total surgical resection, which confirmed the diagnosis of alveolar rhabdomyosarcoma. Further staging workup for another primary focus or disseminated disease yielded negative results, confirming the diagnosis of primary alveolar rhabdomyosarcoma of the brain.ConclusionThe standard of care for managing this rare type of brain tumor involves surgery with adjuvant chemoradiotherapy. Further studies should be conducted for a better diagnostic and therapeutic understanding.

Primary alveolar rhabdomyosarcoma of the breast skin: a case report and literature review

Alveolar rhabdomyosarcoma is one of the four subtypes of rhabdomyosarcoma identified by the World Health Organization. This type of malignant neoplasms more often affects deep soft tissues of extremities and occurs in young ages, regardless of gender. According to the medical literature, no more than 45 cases of the development of primary cutaneous rhabdomyosarcoma have been reported in the world. In this report, we describe a clinical case of a 40-year-old woman with primary localization of alveolar radbomyosarcoma in the skin of the mammary gland.

Metastasis of a Primary Sinonasal Alveolar Rhabdomyosarcoma to the Testicle in an Adult Patient

Abstract Introduction/Objective Alveolar rhabdomyosarcoma is an aggressive tumor of skeletal muscle differentiation that predominantly affects adolescents and young adults, and is rare over 45 years of age. It has poor prognosis with metastasis, and most commonly spreads to the lymph nodes, bone marrow, and lungs. In this report, we describe a middle-aged patient with a primary sinonasal alveolar rhabdomyosarcoma which metastasized to the right testicle, an unusual metastatic site reported only a few times in literature. Methods/Case Report Our patient is a 53 year old male who presented in 2020 with recurrent epistaxis and bilateral cervical lymphadenopathy over a 2 month period. Maxillofacial CT/MRI imaging revealed a 4-cm sized mass within the left nasal cavity eroding into the ethmoid sinuses. The patient underwent endoscopic sinus surgery of the sinonasal mass, which on histology, appeared as poorly differentiated small round blue cells with numerous mitoses infiltrating as single cells and nests. These cells stained positive for vimentin, myogenin, desmin, and CD56, and negative for AE1/AE3, chromogranin, S-100, CD99, and CD45. The cells showed very high Ki67 proliferation index (70-80%) and tested positive for FOXO1 gene rearrangement, which supported the diagnosis of alveolar rhabdomyosarcoma. The patient completed chemoradiation therapy, and MRI scans over the next 2 years were negative for residual sinonasal tumor. However, the patient returned in 2022 after having undergone a right orchiectomy at an outside hospital for testicular pain, and abdominal CT showed diffuse retroperitoneal lymphadenopathy concerning for metastasis. On histology, the resected testicle showed seminiferous tubules infiltrated and destroyed by sheets of poorly differentiated small round blue cells with fibrous septae separating the nests of tumor cells into alveolar-like spaces with central loss of cohesion. The tumor cells showed the same immunohistochemical staining pattern as the primary sinonasal lesion, thus confirming it to be metastatic alveolar rhabdomyosarcoma. Results (if a Case Study enter NA) NA. Conclusion It is unusual for alveolar rhabdomyosarcomas to occur in adults over 45 years old, and is even rarer for these tumors to metastasize to the testicle. Metastases also only account for 1% of testicular tumors. Our report documents a very rare case of an alveolar rhabdomyosarcoma in a middle-aged adult which metastasized to the testicle after chemoradiation therapy.

Therapeutic targeting of ATR in alveolar rhabdomyosarcoma

Despite advances in multi-modal treatment approaches, clinical outcomes of patients suffering from PAX3-FOXO1 fusion oncogene-expressing alveolar rhabdomyosarcoma (ARMS) remain dismal. Here we show that PAX3-FOXO1-expressing ARMS cells are sensitive to pharmacological ataxia telangiectasia and Rad3 related protein (ATR) inhibition. Expression of PAX3-FOXO1 in muscle progenitor cells is not only sufficient to increase sensitivity to ATR inhibition, but PAX3-FOXO1-expressing rhabdomyosarcoma cells also exhibit increased sensitivity to structurally diverse inhibitors of ATR. Mechanistically, ATR inhibition leads to replication stress exacerbation, decreased BRCA1 phosphorylation and reduced homologous recombination-mediated DNA repair pathway activity. Consequently, ATR inhibitor treatment increases sensitivity of ARMS cells to PARP1 inhibition in vitro, and combined treatment with ATR and PARP1 inhibitors induces complete regression of primary patient-derived ARMS xenografts in vivo. Lastly, a genome-wide CRISPR activation screen (CRISPRa) in combination with transcriptional analyses of ATR inhibitor resistant ARMS cells identifies the RAS-MAPK pathway and its targets, the FOS gene family, as inducers of resistance to ATR inhibition. Our findings provide a rationale for upcoming biomarker-driven clinical trials of ATR inhibitors in patients suffering from ARMS.

Fusion transcripts as liquid biopsy markers in alveolar rhabdomyosarcoma and synovial sarcoma: A report of the Cooperative Weichteilsarkom Studiengruppe (CWS).

The possible application of gene fusion transcripts as tumor-specific noninvasive liquid biopsy biomarkers was investigated in blood plasma from patients with alveolar rhabdomyosarcoma (ARMS) and synovial sarcoma (SS). Patients entered in the CWS Soft-Tissue Sarcoma Registry (SoTiSaR) with tumors positive for fusion genes and available blood/plasma samples were included in our analysis. Cell-free exosomal RNA was extracted and used to detect PAX-FOXO1 or SYT-SSX fusion transcripts by reverse transcription quantitative PCR (RT-qPCR). The analysis included 112 ethylene diamine tetraacetic acid blood samples from 80 patients (65 with ARMS, 15 with SS; 34 with localized, 46 with metastatic disease). For patients with metastatic ARMS, 62% (n=18) of initial liquid biopsies were positive, and 16 (89%) of them showed initial bone marrow (BM) metastases. For all patients with primary localized ARMS, liquid biopsy was negative at diagnosis. Of the 48 plasma samples collected during therapy and follow-up, five were positive. None of the liquid biopsies from patients with SS were positive. This liquid biopsy assay based on the detection of fusion transcripts in cell-free RNA from blood exosomes is suitable for analysis of patients with ARMS. Results showed good correlation with the initial tumor status; liquid biopsy was positive in 94% of patients with metastatic ARMS and initial BM involvement, whereas biopsies from all patients with localized tumors were negative. Prospective validation and optimization of the assay, as well as its application for other markers in diagnostics and monitoring of soft-tissue sarcoma, are ongoing.

Primary alveolar rhabdomyosarcoma of the diaphragm requiring proximal gastrectomy

Primary rhabdomyosarcoma (RMS) of the diaphragm, especially alveolar RMS, is extremely rare. Because of its rarity, no treatment for it has yet been established, but previous studies have reported long-term survival in recipients of a combination therapy with local control, including a total resection and/or radiation therapy concomitant with multiagent chemotherapy. We experienced a case of primary alveolar rhabdomyosarcoma of the diaphragm surrounding the gastric cardia in a 15-year-old, female patient. After administering chemotherapy consisting of vincristine, actinomycin D, and cyclophosphamide (VAC) to shrink the tumor, tumor resection was performed with a proximal gastrectomy and partial resection of the diaphragm, pericardium, and left lung. After receiving postoperative adjuvant chemotherapy with VAC and radiotherapy at a total of 41.4 Gy, the patient has been relapse-free for 18 months. The tumor-induced stenosis at the hilum was corrected, allowing oral intake and markedly improving the patient's nutritional status. Tumor resection with a proximal gastrectomy for primary diaphragmatic RMS surrounding the lower esophagus is recommended both for its efficacy in local control and for allowing the preservation of postoperative gastrointestinal function.

EHMT1 promotes tumor progression and maintains stemness by regulating ALDH1A1 expression in alveolar rhabdomyosarcoma.

Alveolar rhabdomyosarcoma (ARMS) is an aggressive pediatric cancer with poor prognosis. Cancer stem cells (CSCs) are seeds for tumor relapse and metastasis. However, pathways that maintain stemness genes are not fully understood. Here, we report that the enzyme euchromatic histone lysine methyltransferase 1 (EHMT1) is expressed in primary and relapse ARMS tumors. EHMT1 suppression impaired motility and induced differentiation in ARMS cell lines and reduced tumor progression in a mouse xenograft model in vivo. RNA sequencing of EHMT1-depleted cells revealed downregulation of ALDH1A1 that is associated with CSCs. Consistent with this, inhibition of ALDH1A1 expression and activity mimicked EHMT1 depletion phenotypes and reduced tumorsphere formation. Mechanistically, we demonstrate that EHMT1 does not bind to the ALDH1A1 promoter but activates it by stabilizing C/EBPβ, a known regulator of ALDH1A1 expression. Our findings identify a role for EHMT1 in maintenance of stemness by regulating ALDH1A1 expression and suggest that targeting ALDH+ cells is a promising strategy in ARMS. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Primary cutaneous alveolar rhabdomyosarcoma: Case report in a young adult

Primary cutaneous alveolar rhabdomyosarcoma: Case report in a young adult

Surgical approach and prognosis of primitive chest wall alveolar rhabdomyosarcoma in an adult: A case report and review of the literature

Alveolar rhabdomyosarcomas (ARMS) are rare entities that occur predominantly on the extremities and represent 20% of rhabdomyosarcomas. Other common locations include the peri-rectal and perineal regions, head and neck, and genitourinary system. To our knowledge, this presentation is the first case of alveolar rhabdomyosarcoma of the chest wall reported in the literature. Here, we describe a case of a 64-year-old man with alveolar rhabdomyosarcomas who underwent a chest wall resection. The defect was reconstructed with polypropylene mesh and latissimus dorsi muscle. Our patient did not show recurrence ten months after complete resection. The present paper describes our surgical approach to a case of primary alveolar rhabdomyosarcoma of the chest wall in an adult. The authors discuss the principal judgment criteria for successful surgical resection and prognosis, highlighting the relevance of chest wall reconstruction and their complementary aspects in the multimodal management of this rare entity.

Primary alveolar rhabdomyosarcoma of the thyroid

Abstract Primary thyroid sarcoma is a very rare entity, accounting for less than 1.5% of all malignant thyroid tumors. Primary thyroid rhabdomyosarcoma is extremely rare: Until now, there had been only two child cases and four adult cases diagnosed worldwide. We report herein the case of a 17-year-old female who presented with a large, rapidly growing neck mass. To the best of our knowledge, this is the first reported case of primary alveolar rhabdomyosarcoma in the thyroid. Moreover, this is the only case that shows an outstanding response of RMS in the thyroid to neoadjuvant chemotherapy. It provides an example of a potential new treatment for patients whose tumors cannot be treated surgically.

Primary pulmonary alveolar rhabdomyosarcoma: report of a case

Primary pulmonary alveolar rhabdomyosarcoma: report of a case

Expression and clinical association of programmed cell death-1, programmed death-ligand-1 and CD8+ lymphocytes in primary sarcomas is subtype dependent.

In order to explore the potential of immune checkpoint blockade in sarcoma, we investigated expression and clinical relevance of programmed cell death-1 (PD-1), programmed death ligand-1 (PD-L1) and CD8 in tumors of 208 sarcoma patients. Primary untreated osteosarcoma (n = 46), Ewing sarcoma (n = 32), alveolar rhabdomyosarcoma (n = 20), embryonal rhabdomyosarcoma (n = 77), synovial sarcoma (n = 22) and desmoplastic small round cell tumors (DSRCT) (n = 11) were examined immunohistochemically. PD-L1 expression was predominantly detected in alveolar and embryonal rhabdomyosarcomas (15% and 16%, respectively). In the alveolar subtype PD-L1 expression was associated with better overall, event-free and metastases-free survival. PD-1 expression on lymphocytes was predominantly seen in synovial sarcomas (18%). High levels of CD8+ lymphocytes were predominantly detected in osteosarcomas (35%) and associated with worse event-free survival in synovial sarcomas. Ewing sarcoma and DSRCTs showed PD-1 on tumor cells instead of on tumor infiltrating lymphocytes. Overall, expression and clinical associations were found to be subtype dependent. For the first time PD-1 expression on Ewing sarcoma (19%) and DSRCT (82%) tumor cells was described.

Primary alveolar rhabdomyosarcoma of the bone: two cases and review of the literature

BackgroundRhabdomyosarcoma (RMS) is a malignant tumor of mesenchymal origin and comprises the largest category of soft-tissue sarcomas both in children and adolescents. From a pediatric oncology point of view, RMS has traditionally been classified into alveolar (ARMS) and embryonal (ERMS) subtypes. The anatomical localization of the tumor may vary, but commonly involve the head/neck regions, male and female urogenital tract or the trunk and extremities.Case presentationHere, we report two challenging cases involving 17- and 9-years-olds males where diffuse and multiplex bone lesions suggested either a hematological disease or a primary bone tumor (mesenchymal chondrosarcoma). Biopsies, proved a massive infiltration of the bone marrow cavity with rhabdomyosarcoma. In both cases, the ARMS subtype was confirmed using FOXO1 break-apart probes (FISH). Radiological examination could not identify primary soft tissue component in any localization at the time of diagnosis in either cases.ConclusionsPrimary alveolar rhabdomyosarcoma of the bone as a subtype of ARMS, seems to be a distinct clinico-pathological entity with challenging diagnostic difficulties and different, yet better, biological behavior in comparison to soft tissue ARMS. However, it is difficult to be characterized or predict its prognosis and long-term survival as only sporadic cases (four) were reported so far.

Primary Alveolar Rhabdomyosarcoma of Breast: - A Rare Case Report

Sarcoma is a rare malignant tumour of breast. Primary alveolar rhabdomyoarcoma is extremely rare in breast with limited case reports in literature. We report a case of primary alveolar rhabdomyosarcoma of breast in an adolescent girl who presented with progressively increasing firm to hard swelling in the left breast beneath areola. MRI and FNAC was suggestive of lobular carcinoma of breast. Patient underwent lumpectomy with 2cm margin and latismus dorsi flap reconstruction. After histopathological examination and immunohistochemistry tumour was diagnosed as alveolar rhabdomyosarcoma and patient is in complete remission after one year of treatment.

Inhibiting phosphorylation of the oncogenic PAX3-FOXO1 reduces alveolar rhabdomyosarcoma phenotypes identifying novel therapy options.

Patients with translocation-positive alveolar rhabdomyosarcoma (ARMS), an aggressive childhood tumor primarily characterized by the PAX3-FOXO1 oncogenic fusion protein, have a poor prognosis because of lack of therapies that specifically target ARMS tumors. This fact highlights the need for novel pharmaceutical interventions. Posttranslational modifications such as phosphorylation are becoming attractive biological targets for the development of such interventions. Along these lines, we demonstrated that PAX3-FOXO1 is phosphorylated at three specific sites and that its pattern of phosphorylation is altered relative to wild-type Pax3 throughout early myogenesis and in ARMS tumor cells. However, little work has been performed examining the effect of directly inhibiting phosphorylation at these sites on ARMS development. To address this gap in knowledge, we used small molecule inhibitors or mutational analysis to specifically inhibit phosphorylation of PAX3-FOXO1 to investigate how altering phosphorylation of the oncogenic fusion protein affects ARMS phenotypes. We found that inhibiting the phosphorylation of PAX3-FOXO1 at Ser201 significantly reduced migration, invasion and proliferation in two independent ARMS tumor cell lines. Further, we found that inhibition of phosphorylation at Ser205 also decreased proliferation and anchorage-independent growth. Consistent with these in vitro results, we demonstrate for the first time that PAX3-FOXO1 is phosphorylated at Ser201 and Ser205 in a primary tumor sample and in tumor cells actively invading the surrounding normal tissue. This report is the first to demonstrate that the direct inhibition of PAX3-FOXO1 phosphorylation reduces ARMS tumor phenotypes in vitro and that these phosphorylation events are present in primary human ARMS tumors and invading tumor cells. These results identify phosphorylation of PAX3-FOXO1, especially at Ser201, as a novel biological target that can be explored as a promising avenue for ARMS therapies.

Primary alveolar rhabdomyosarcoma of the brain with long-term survival

Primary alveolar rhabdomyosarcoma of the brain with long-term survival

Primary alveolar rhabdomyosarcoma of breast in a 13 year old female with cardiopulmonary metastases and cyto-histological correlation: A case report

Primary alveolar rhabdomyosarcoma of breast in a 13 year old female with cardiopulmonary metastases and cyto-histological correlation: A case report

Survival following disease recurrence of primary localized alveolar rhabdomyosarcoma

Recurrences in primary localized alveolar rhabdomyosarcoma (RMA) are common. Post-relapse survival is poor. We evaluated prognostic factors including relapse treatment in patients with recurrent RMA. Relapses occurred in 115/235 patients with nonmetastatic RMA treated in four consecutive CWS-trials after achievement of a complete remission. Sufficient information about post-relapse treatment and outcome could be obtained in 99 patients and was retrospectively analyzed. Nine of 99 patients received no salvage therapy and died after a median of 2 months. The remaining 90 patients received multimodal relapse treatment including mandatory chemotherapy. Recurrences were grossly resected in 39 patients; 57 patients received radiation. At a median follow-up from relapse of 8 years, 20 patients were alive and disease-free (5-year post-relapse survival [PROS] 21.3 ± 8). All surviving patients apart from a single individual had an isolated, circumscribed recurrence. Sixteen of 20 survivors were treated with adequate local relapse therapy (ALRT, i.e., either complete resection or gross resection + radiation). Survival in the subgroup of 27 individuals with circumscribed recurrences and ALRT was significantly better (PROS 53.7 ± 19) compared with disseminated recurrences and/or tumors treated without ALRT. Absence of primary lymph node involvement, circumscribed relapses, ALRT, and achievement of a second CR were identified as independent favorable risk factors. Post-relapse survival for primary localized RMA is generally poor. However, certain patient groups differed significantly in their likelihood of survival and 50% of patients with circumscribed relapses treated with ALRT survived. These findings may form the basis for an evidence-based risk-stratification for recurrent disease including relapse treatment.