Treatment strategies and outcomes for spinal rhabdomyosarcoma: A series of 11 cases in a single center and review of the literature.

OBJECTIVES: Rhabdomyosarcoma (RMS) involving the spine is rare. The aim of the present study is to explore the clinicopathological features, surgical treatments and outcomes of this rare disease. PATIENTS AND METHODS: Eleven patients with spinal RMS who received surgery in our institution between 2012 and 2018 were retrospectively investigated. The literature on spinal RMS was also reviewed. RESULTS: Our study consisted of 7 cases of primary RMS and 4 cases of metastatic RMS. Seven primary and one metastatic spinal RMS received radical resection, the remaining three metastatic patients received palliative resection. Eight patients died with a median survival time of 8 months. The mean value of Ki-67 positivity was 48.2 %. Literature review revealed a total of 22 previously reported cases. 54.5 % of the pooled cases of the 33 patients were under the age of 18. Of the 20 patients with primary spinal RMS, 9 cases were diagnosed as embryonal, while 6 of the 13 metastatic patients were diagnosed as alveolar. Multiple modalities, including surgery and concurrent adjuvant therapy were performed in 19 patients. The median overall survival (OS) for 28 patients with detailed follow-up information was 10 months. Radical resection offered a significant longer median OS than non-radical resection (18 vs. 6 months, p = 0.027). CONCLUSION: Spinal RMS mainly affects young patients. The embryonal form and alveolar form is the most frequent subtype for primary and metastatic spinal RMS respectively. Spinal RMS is highly aggressive with dismal prognosis. Multimodality therapies are the mainstay of treatment. Radical resection is strongly recommended in eligible patients.

Nasal embryonal rhabdomyosarcoma with bone marrow metastasis simulating acute leukemia: A case report and review of the literature.

We present a case of a nasal rhabdomyosarcoma (RMS) in a 27-year-old male with epistaxis and nasal obstruction due to a mass, which was subjected to prophylactic tumor embolization. However, histopathological study on the nasal biopsy was impossible due to necrotic changes. As blast cells were present in peripheral blood samples, a bone marrow biopsy was recommended in order to reach a definitive diagnosis. The possibility of an RMS in cases of bone marrow infiltration by a diffuse tumor constituted by small, round, blast-like cells mimicking acute leukemia should be assessed. Immunohistochemical staining in bone marrow biopsy and flow cytometry in aspirate samples may help to establish the diagnosis (CD45 negativity and CD56 positivity) and cytogenetic studies can be useful in identifying a RMS subtype. When clinically possible, it is desirable to await the results of the tumor immunophenotype and those of the primary mass or bone marrow biopsy to avoid possible errors of diagnosis and treatment.

Embryonal rhabdomyosarcoma of urinary bladder in an adult patient: an unusual manifestation.

An adult man presented with off and on painless haematuria, which was diagnosed as bladder mass on contrast-enhanced CT. He underwent transurethral resection of bladder tumour with complete resection. A diagnosis of embryonal rhabdomyosarcoma was made following histopathology and immunohistochemistry report. The patient was planned for radical cystectomy but was found to have large recurrent infiltrating bladder mass with liver and bone metastasis. Hence, the plan for radical cystectomy was deferred and the patient was counselled regarding chemotherapy (vincristine, cisplatin and doxorubicin regime). The patient tolerated the first cycle of chemotherapy, but his condition deteriorated prior to the second cycle and the patient expired.

Rabdomyosarcoma of the Mandible: An Uncommon Clinical Presentation.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and adolescents. Most patients present with a mass in the head and neck region, urogenital region, or with distal extremity involvement. The authors describe a challenging case of a 6-year-old male patient presenting with mandibular RMS. The clinical/radiographic/tomographic evaluations classified the tumor as an advanced stage (stage IV), with a mass of 6.0 cm involving the left side of the mandible and parotid region. The biopsy revealed round, spindled, and pleomorphic cells with hyperchromatic nuclei and rare larger rhabdomyoblasts with eosinophilic cytoplasm. The diagnosis was of embryonal RMS. The patient was referred for treatment with cycles of chemotherapy; however, pulmonary and bone marrow metastasis were identified. Radiotherapy and local surgery with microvascular reconstruction were performed later; however, the patient died after a few months. Early diagnosis is critical for a good prognosis and cure of patients with RMS. Correct diagnosis considering also the histological subtype is important for adequate treatment, which according to the literature is not uniform probably because of the rarity of this neoplasm.

Metastatic Embryonal Conjunctival Rhabdomyosarcoma in a 4-Year-Old Boy.

The authors report the case of a 4-year-old boy who presented with unilateral ptosis and a mass lesion of palpebral conjunctiva of the left upper eyelid, that had been present for 2 weeks, and had rapidly enlarged. The lesion was salmon colored and was easily distinguished from the conjunctiva. There was no obvious orbital extension in the MRI studies. Excisional biopsy was performed through a conjunctival approach. The histopathology was consistent with embryonal rhabdomyosarcoma. Thoracoabdominal CT scans revealed nodules in both lungs, indicating stage 4 disease. The patient received chemotheraphy and intensity-modulated radiation therapy. Rhabdomyosarcoma confined to the conjunctiva and distant metastasis without orbital involvement is rare. It should be included in the differential diagnosis of any atypical conjunctival mass lesions in children, and histopathology is necessary to establish proper treatment. As the case indicates, detailed systemic evaluation and careful systemic follow up of these patients are mandatory.

Spindle cell embryonal rhabdomyosarcoma of the prostate in an adult patient - case report and review of clinicopathological features.

BACKGROUND: Embryonal rhabdomyosarcoma of the prostate in an adult is a very rare event with only a few cases published. Diagnosis usually occurs with advanced disease frequently already with metastatic spread. In adults prognosis is very poor, therefore early diagnosis is crucial. To date, only three cases of spindle cell subtype of embryonal rhabdomyosarcoma of the prostate in an adult have been published. CASE PRESENTATION: We report an additional case of prostatic spindle cell embryonal rhabdomyosarcoma subtype in an adult. CONCLUSIONS: We discuss relevant clinicopathological features of spindle cell embryonal rhabdomyosarcoma of the prostate in adult patients in the context of the literature.

Neoadjuvant Intraarterial Chemotherapy for Treatment of Malignant Vaginal Tumors in Children: A Single-Center Experience.

Six patients (aged 3-36 mo) with vaginal tumors (rhabdomyosarcoma and endodermal sinus tumor [EST]; n = 3 each) received intraarterial chemotherapy (IAC) and intravenous chemotherapy. Patients underwent internal iliac artery infusion with cisplatin, pirarubicin, and vindesine. Intravenous chemotherapy with vindesine, ifosfamide, and etoposide was administered after 3 weeks. Vaginal tumors disappeared in all patients after 2 or 3 cycles of alternating therapy. Two patients underwent resection of pelvic metastases. Intravenous consolidation chemotherapy was applied. Four patients were disease-free at a median follow-up of 5.8 years. One patient had pelvic recurrence treated with "salvage" therapy with IAC and surgery and was disease-free for 2.5 years.

Radiation therapy may increase metastatic potential in alveolar rhabdomyosarcoma.

BACKGROUND: We previously determined that radiation could be safely administered using a mouse-flank in vivo model to both alveolar (Rh30) and embryonal (Rh18) rhabdomyosarcoma xenografts. Mice from both tumor lines in this experiment developed metastases, an event not previously described with these models. We sought to determine if radiation-induced changes in gene expression underlie an increase in the metastatic behavior of these tumor models. PROCEDURE: Parental Rh18 and Rh30 xenografts, as well as tumor that recurred locally after radiotherapy (Rh18RT and Rh30RT), were grown subcutaneously in the flanks of SCID mice and then subjected to either fractionated radiotherapy or survival surgery alone. Metastasis formation was monitored and recorded. Gene expression profiling was also performed on RNA extracted from parental, recurrent, and metastatic tissue of both tumor lines. RESULTS: Rh30 and Rh30RT xenografts demonstrated metastases only if they were exposed to fractionated radiotherapy, whereas Rh18 and Rh18RT xenografts experienced significantly fewer metastatic events when treated with fractionated radiotherapy compared to survival surgery alone. Mean time to metastasis formation was 40 days in the recurrent tumors and 73 days in the parental xenografts. Gene expression profiling noted clustering of Rh30 recurrent and metastatic tissue that was independent of the parental Rh30 tissue. Rh18RT xenografts lost radiosensitivity compared to parental Rh18. CONCLUSION: Radiation therapy can significantly decrease the formation of metastases in radio-sensitive tumors (Rh18) and may induce a more pro-metastatic phenotype in radio-resistant lines (Rh30).

Orbital rhabdomyosarcoma with skin metastasis: a case report.

BACKGROUND: Rhabdomyosarcoma is a soft tissue neoplasm that usually arises in the head and neck region and genitourinary tract. Skin metastasis of rhabdomyosarcoma is extremely rare; of thirteen cases reported in the literature, most were children younger than 10 years and only three cases have been reported in adults. CASE PRESENTATION: A 20-year-old Moroccan man was admitted with a right orbital tumor. The tumor was excised and histopathology examination confirmed a diagnosis of rhabdomyosarcoma. The patient was treated with chemotherapy, but local recurrence occurred one year later. The patient underwent right orbital exenteration followed by chemotherapy and radiotherapy. After 6 months, the patient developed a cutaneous mass in the right lumbar region, which was resected. Immunohistochemical examination of the tumor showed this to be a cutaneous metastasis of rhabdomyosarcoma. The patient was treated by chemotherapy and there appeared to be no recurrence after 9 months of follow up. CONCLUSIONS: Skin metastasis from rhabdomyosarcoma is extremely rare, particularly in adults. The purpose of presenting this case report is to raise awareness among clinicians--skin biopsy and immunohistochemistry are needed to distinguish this neoplasm from other cutaneous tumors so that appropriate treatment can be initiated.

The impact of age on outcome of embryonal and alveolar rhabdomyosarcoma patients. A multicenter study.

BACKGROUND: The prognosis of rhabdomyosarcoma (RMS) in children and adolescents has improved since the introduction of multi-agent chemotherapy. However, outcome data of adults with RMS are scarce. This multicenter retrospective study investigated the effect of age on outcome of RMS. PATIENTS AND METHODS: Data were collected from three Dutch University Medical Centers between 1977-2009. The effect of age and clinical prognostic factors on relapse-free and disease-specific survival (DSS) were analyzed. RESULTS: Age as a continuous variable predicted poor survival in multivariate analysis. Five-year DSS was highest for non-metastatic embryonal RMS, followed by non-metastatic alveolar RMS and was poor in metastatic disease. Higher age correlated with unfavorable histological subtype (alveolar RMS) and with metastatic disease at presentation in embryonal RMS. In non-metastatic embryonal RMS and in all alveolar RMS, higher age was an adverse prognostic factor of outcome. CONCLUSION: This study indicates that age is a negative predictor of survival in patients with embryonal and alveolar RMS.

The over-expression of cell migratory genes in alveolar rhabdomyosarcoma could contribute to metastatic spread.

Alveolar (ARMS) and Embryonal (ERMS) rhabdomyosarcoma differ in their response to current treatments. The ARMS subtype has a less favourable prognosis and often presents with widespread metastases, while the less metastatic ERMS has a 5 year survival rate of more than 80 %. In this study we investigate gene expression differences that could contribute to the high frequency of metastasis in ARMS. Microarray analysis identified significant differences in DNA repair, cell cycle and cell migration between the two RMS subtypes. Two genes up regulated in ARMS and involved in cell migration; the engulfment and cell motility gene 1 (ELMO1) and NEL-like 1 gene (NELL1) were selected for further investigation. Over-expression of ELMO1 significantly increased cell invasion from 24.70 ± 7% to 93 ± 5.4% in primary myoblasts and from 29.43 ± 2.1% to 87.33 ± 4.1% in the ERMS cell line RD. siRNA knockout of ELMO1 in the ARMS cell line RH30 significantly reduced cell invasion from 88.2 ± 3.8% to 35.2 ± 2.5%. Over-expression of NELL1 significantly increased myoblast invasion from 23.6 ± 6.9% to 100 ± 0.1%, but had no effect on invasion of the ERMS cell line RD. These findings suggest that ELMO1 may play a key role in ARMS metastasis. NELL1 increased invasion in primary myoblasts, but other factors required for it to enhance motility were not present in the RD ERMS cell line. Impairing ELMO1 function by pharmacological or siRNA knockdown could be a highly effective approach to reduce the metastatic spread of RMS.

Orbital embryonal rhabdomyosarcoma with metastasis in a young dog.

A 2-year-old male Welsh corgi dog was brought to an animal hospital because of left upper eyelid enlargement with lachrymal gland protrusion. The lachrymal and orbital cavity mass was removed surgically. Microscopically, the orbital mass consisted of a mixture of large rhabdomyoblastic and small round tumour cells. Immunohistochemically, the rhabdomyoblastic cells expressed desmin and myoglobin and the small round cells expressed desmin, myogenin and MyoD1. A diagnosis of embryonal rhabdomyosarcoma (ERS) was made. One month later, multiple masses throughout the body were identified, in particular around the cervical region. One of these lesions was sampled and diagnosed as metastatic ERS. The dog died 84 days after the time of first admission.

Local control with reduced-dose radiotherapy for low-risk rhabdomyosarcoma: a report from the Children's Oncology Group D9602 study.

PURPOSE: To analyze the effect of reduced-dose radiotherapy on local control in children with low-risk rhabdomyosarcoma (RMS) treated in the Children's Oncology Group D9602 study. METHODS AND MATERIALS: Patients with low-risk RMS were nonrandomly assigned to receive radiotherapy doses dependent on the completeness of surgical resection of the primary tumor (clinical group) and the presence of involved regional lymph nodes. After resection, most patients with microscopic residual and uninvolved nodes received 36 Gy, those with involved nodes received 41.4 to 50.4 Gy, and those with orbital primary tumors received 45 Gy. All patients received vincristine and dactinomycin, with cyclophosphamide added for patient subsets with a higher risk of relapse in Intergroup Rhabdomyosarcoma Study Group III and IV studies. RESULTS: Three hundred forty-two patients were eligible for analysis; 172 received radiotherapy as part of their treatment. The cumulative incidence of local/regional failure was 15% in patients with microscopic involved margins when cyclophosphamide was not part of the treatment regimen and 0% when cyclophosphamide was included. The cumulative incidence of local/regional failure was 14% in patients with orbital tumors. Protocol-specified omission of radiotherapy in girls with Group IIA vaginal tumors (n = 5) resulted in three failures for this group. CONCLUSIONS: In comparison with Intergroup Rhabdomyosarcoma Study Group III and IV results, reduced-dose radiotherapy does not compromise local control for patients with microscopic tumor after surgical resection or with orbital primary tumors when cyclophosphamide is added to the treatment program. Girls with unresected nonbladder genitourinary tumors require radiotherapy for postsurgical residual tumor for optimal local control to be achieved.

Teratoma with naturally occurring malignant transformation in a child.

We present a 12-year-old girl with a teratoma with malignant transformation (TMT) of the mediastinum. Computed tomography showed a cystic mass (5.0 cm × 4.0 cm) with a thick solid portion, in the anterior mediastinum. Six months later, the solid portion of the mass had enlarged, and surgical resection was performed. The resected tumor was 7.0 × 5.0 × 4.0 cm in size. The cystic portion was a mature teratoma, and the solid portion predominantly comprised a viable embryonal rhabdomyosarcoma. There were no immature teratomatous elements or other germ-cell components. The histopathologic diagnosis was a mature teratoma with embryonal rhabdomyosarcoma, a so-called TMT. The tumor recurred, despite adjuvant chemotherapy. The patient died of progressive disease 16 months postoperatively. To the best of our knowledge, no naturally occurring TMT of the mediastinum has previously been reported in a child. Surgical resection at an early stage is necessary.

Embryonal rhabdomyosarcoma with metastases confined to the lungs: report from the CWS Study Group.

BACKGROUND: Embryonal rhabdomyosarcoma [RME] is the most common pediatric soft tissue sarcoma. Whereas the prognosis of localized rhabdomyosarcoma has improved, it remains poor for metastatic disease. METHODS: We analyzed RME-patients with isolated pulmonary metastases [PRME] treated in four consecutive CWS-trials. Treatment included multiagent chemotherapy and local treatment of the primary tumor. Therapy of lung metastases after induction chemotherapy depended on response and individual decisions. RESULTS: Twenty-nine patients <21 years had PRME. Their median age was six years, the median follow-up nine years. Twenty-eight children had their primary tumor located in an unfavorable site and 22 of the primaries were >5 cm. In addition to conventional chemotherapy, seven patients received high-dose treatment and eight patients oral metronomic chemotherapy. The lung metastases were in remission after induction chemotherapy in 22 individuals. 19 patients received no local treatment of metastases; 3 patients had pulmonary metastasectomy and lung radiation was administered to 9 individuals. In total, 24/29 patients achieved a complete remission [CR]. Actuarial 5-year event-free and overall survival for all patients was 37.9 ± 18% and 48.7 ± 18%, respectively; it was 45.8 ± 20% and 58.3 ± 20% for the 24 patients who achieved a CR. Local treatment of metastases had no impact on the failure pattern. Younger age, good response, achievement of CR and maintenance-treatment were favorable prognostic factors in univariate analysis. CONCLUSIONS: Children with PRME have a fair prognosis. Local treatment of metastases did not improve outcome in our sample. Metronomic treatment may be an attractive option for PREM-patients.

Results of the Intergroup Rhabdomyosarcoma Study Group D9602 protocol, using vincristine and dactinomycin with or without cyclophosphamide and radiation therapy, for newly diagnosed patients with low-risk embryonal rhabdomyosarcoma: a report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group.

PURPOSE: Patients with localized, grossly resected, or gross residual (orbital only) embryonal rhabdomyosarcoma (ERMS) had 5-year failure-free survival (FFS) rates of 83% and overall survival rates of 95% on Intergroup Rhabdomyosarcoma Study Group (IRSG) protocols III/IV. IRSG D9602 protocol (1997 to 2004) objectives were to decrease toxicity in similar patients by reducing radiotherapy (RT) doses and eliminating cyclophosphamide for the lowest-risk patients. PATIENTS AND METHODS: Subgroup A patients (lowest risk, with ERMS, stage 1 group I/IIA, stage 1 group III orbit, stage 2 group I) received vincristine plus dactinomycin (VA). Subgroup B patients (ERMS, stage 1 group IIB/C, stage I group III nonorbit, stage 2 group II, stage 3 group I/II) received VA plus cyclophosphamide. Patients in group II/III received RT. Compared with IRS-IV, doses were reduced from 41.4 to 36 Gy for stage 1 group IIA patients and from 50 or 59 to 45 Gy for group III orbit patients. RESULTS: Estimated 5-year FFS rates were 89% (95% CI, 84% to 92%) for subgroup A patients (n = 264) and 85% (95% CI, 74%, 91%) for subgroup B patients (n = 78); median follow-up: 5.1 years. Estimated 5-year FFS rates were 81% (95% CI, 68% to 90%) for patients with stage 1 group IIA tumors (n = 62) and 86% (95% CI, 76% to 92%) for patients with group III orbit tumors (n = 77). CONCLUSION: Five-year FFS and OS rates were similar to those observed in comparable IRS-III patients, including patients receiving reduced RT doses, but were lower than in comparable IRS-IV patients receiving VA plus cyclophosphamide. Five-year FFS rates were similar among subgroups A and B patients.

Prognostic significance and tumor biology of regional lymph node disease in patients with rhabdomyosarcoma: a report from the Children's Oncology Group.

PURPOSE: Regional lymph node disease (RLND) is a component of the risk-based treatment stratification in rhabdomyosarcoma (RMS). The purpose of this study was to determine the contribution of RLND to prognosis for patients with RMS. PATIENTS AND METHODS: Patient characteristics and survival outcomes for patients enrolled onto Intergroup Rhabdomyosarcoma Study IV (N = 898, 1991 to 1997) were evaluated among the following three patient groups: nonmetastatic patients with clinical or pathologic negative nodes (N0, 696 patients); patients with clinical or pathologic positive nodes (N1, 125 patients); and patients with a single site of metastatic disease (77 patients). RESULTS: Outcomes for patients with nonmetastatic alveolar N0 RMS were significantly better than for patients with N1 RMS (5-year failure-free survival [FFS], 73% v 43%, respectively; 5-year overall survival [OS], 80% v 46%, respectively; P < .001). Patients with a single site of alveolar metastasis had even worse FFS and OS (23% FFS and OS, P = .01) when compared with patients with N1 RMS; however, the differences was not as large as the differences between patients with N0 RMS and N1 RMS. For embryonal RMS, there was no statistically significant difference in FFS or OS (P = .41 and P = .77, respectively) for patients with N1 versus N0 RMS. Gene array analysis of primary tumor specimens identified that genes associated with the immune system and antigen presentation were significantly increased in N1 versus N0 alveolar RMS. CONCLUSION: RLND alters prognosis for alveolar but not embryonal RMS. For patients with N1 disease and alveolar histology, outcomes were more similar to distant metastatic disease rather than local disease. Current data suggest that more aggressive therapy for patients with alveolar N1 RMS may be warranted.

Testicular fusocellular rhabdomyosarcoma as a metastasis of elbow sclerosing rhabdomyosarcoma: A clinicopathologic, immunohistochemical and molecular study of one case.

Sclerosing rhabdomyosarcoma (SRMS) is an infrequent variant of rhabdomyosarcoma characterized by extensive intercellular hyaline fibrosis. We report the case of a 37 year-old male with a 9 x 6 cm SRMS on the right elbow. Histologically, the tumor showed an abundant extracellular hyaline matrix with extratumoral vascular emboli and microscopic foci of fusocellular embryonal rhabdomyosarcoma (FRMS) separated by a fibrotic band from the sclerosing areas. One year later the patient presented with a right intratesticular tumor of 1.2 x 0.8 cm, which was reported as pure FRMS. Immunohistochemically, SRMS was positive only for MyoD1 and Vimentin and negative for Myogenin and Desmin. Both the elbow emboli with the extratumoral foci of FRMS and the intratesticular tumor were positive for Myogenin, MyoD1, Vimentin and Desmin. Using fluorescent in situ hybridization (FISH), the SRMS and the FRMS tumor cells of the elbow and the FRMS tumor cells of the testis were found to be negative for FOXO1A translocation in chromosome 13. PCR chimeric transcriptional products PAX3-FKHR and PAX7-FKHR were not found. Six months following testicular resection, the patient died of multiple metastases in the mediastinum, lung and right thigh.