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[Update on rhabdomyosarcomas in children].

Rhabdomyosarcoma is a rare tumour corresponding to 60-70% of soft tissue sarcomas in children. Significant advances in treatment have been made possible, and will be further obtained, by multicentric treatment protocols conducted in paediatric oncology centres. Overall survival and disease-free survival have been significantly improved over the past 30 years. In the meantime, diagnosis improvements have made the classification of rhabdomyosarcomas more complex. A review of European and American studies has evidenced a number of criteria that should be taken into account for selecting treatment strategy: histological examination (refined with the use of molecular biology) had proved very informative, suggesting a worse prognosis for alveolar rhabdomyosarcomas. Other criteria of interest are the tumour site (favourable or unfavourable), patient age (under or above 10), tumour size ( 5 cm), and disease stage. The number of sub-groups of patients requiring different, more adapted treatment strategies increases with the number of prognostic parameters to be considered. For convenient clinical management, patients will therefore be classified into 4 risk groups for systemic therapy (low, standard, high and very high risk), whereas local treatment strategies will take into account the whole set of prognostic criteria defined above.

Age Factors↗

[Update of orbital rhabdomyosarcoma therapy in children].

INTRODUCTION: Rhabdomyosarcoma is the most frequent primitive orbital malignant tumor in children. If the treatment is started as soon as possible after discovery of the disease, the vital prognosis is considerably better than otherwise. The goal of this paper is to present the new therapeutic protocol and to report our experience in this field. MATERIAL AND METHOD: During the past 35 years, 102 cases of orbital tumors were collected in children under 15 years of age: 5 cases of rhabdomyosarcoma were cared for in our department. At the time of tumor diagnosis, the age of our patients ranged from 3 weeks to 13 years. After a biopsy or excision biopsy, all our cases were treated by chemotherapy with or without radiotherapy. Medication was mostly vincristine, ifosfamide and actinomycine D. When the result of the treatment was not satisfactory, carboplatine and epirubicine, vincristine as well as ifosfamide were given. Radiotherapy was performed only in particular cases or in recurrences. CONCLUSION: Rhabdomyosarcoma is a highly malignant tumor. Although rare, it is the most frequent of malignant tumors in children. It is important to keep it in mind in order to perform a biopsy enabling quick diagnosis and treatment following the modern protocol giving the highest chances of survival to these patients: about 98% in 3 years.

Adolescent↗

Reactivation of a silenced H19 gene in human rhabdomyosarcoma by demethylation of DNA but not by histone hyperacetylation.

BACKGROUND: The active copy of the imprinted gene H19 is turned off by inappropriate methylation in several pediatric tumors including Wilms' Tumour and embryonal rhabdomyosarcoma. H19 controls in cis the linked Insulin-like Growth Factor 2 (IGF2) gene, encoding an important growth factor. Recent work has suggested that methylation of a gene may lead to deacetylation of its associated histones and that silenced genes can be reactivated by increasing histone acetylation levels. RESULTS: Treatment of a rhabdomyosarcoma cell line which has a silent, methylated H19 gene with histone deacetylase (HDAC) inhibitors under conditions which gave maximal hyperacetylation of histone 4, both globally and at the H19 gene itself could not reactivate H19 or affect the active Insulin-like Growth Factor 2 (IGF2) gene, but caused clear up-regulation of the Tissue-type Plasminogen Activator (TPA) gene, a non-imprinted gene known to respond to changes in histone acetylation. In contrast, mild treatment of the cells with the methylation inhibitor 5-AzaC-2'-deoxycytidine (AzaC) on its own was able to reactivate H19. Combining AzaC treatment with HDAC inhibitors gave a reduced rather than enhanced reactivation. These findings were confirmed in mouse primary liver and kidney explants which maintain normal imprinting, where we also found that the silent Igf2 gene could not be reactivated by HDAC inhibitors. CONCLUSION: These results suggest that DNA methylation rather than histone acetylation is the primary determinant of silencing of H19 in rhabdomyosarcoma.

Acetylation↗

[Pediatric rhabdomyosarcoma of the infratemporal fossa].

OBJECTIVE: Prognosis of rhabdomyosarcoma of the infratemporal fossa is generally poor. We report our experience. MATERIAL AND METHODS: Twenty-three children with rhabdomyosarcoma of the infratemporal fossa were treated at the Gustave Roussy and Curie Institutes between 1984 and 1999. Seventeen children received radiotherapy (group 1), four children were treated surgically with or without postoperative radiotherapy (group 2), and two children received no further treatment after chemotherapy (group 3). RESULTS: In group 1, there were 10 local recurrences and one metastatic failure; all 11 children died from their disease. Nodal recurrence was salvaged successfully in one other with chemotherapy and surgery. In group 2, three children were disease free at 3 years and one died of local recurrence. In group 3, one child experienced a local recurrence successfully salvaged with radiotherapy. This child was disease free at 3 years. The other child developed local recurrence and died. DISCUSSION: Overall survival rate in our patients was 50%. Local control remained the main prognostic factor for survival. Surgery has already been shown to improve local control in other localizations of rhabdomyosarcoma. If residual tumor tissue remains after neo-adjuvant chemotherapy, surgery should be considered in a multidisciplinary discussion of therapeutic options. Indications for postoperative radiotherapy depend on age and histological features of the surgical specimen.

Adolescent↗

[Endobronchial pulmonary rhabdomyosarcoma. A case report].

We report a case of pleiomorphous pulmonary rhabdomyosarcoma observed in a 64-year-old patient with no history of soft tissue tumor. The tumor was found extending into the right lower and middle lobes. The intra-parenchymatous extension protruded into the middle lobular bronchus and was prolonged by a 4 cm polyp. The polyp extended up to the carina and reached the contralateral common bronchus. Outcome was fatal after surgery performed in an emergency setting due to asphyxia. Explorations could not be continued to determine the primary or secondary nature of the tumor. An intraparenchymatous endobronchial localization is uncommon. Primary rhabdomyosarcoma is generally a purely intra-parenchymatous tumor. The endobronchial localization has been described before but is very exceptional. This localization would also be exceptional for secondary rhabdomyosarcoma mimicking a primary malignant tumor. The histology study revealed an undifferentiated pleiomorphous tumor. Immunohistochemistry provided the final diagnosis.

Bronchial Neoplasms↗

[Clinical analysis of 17 cases rhabdomyosarcoma in ear nose and throat].

OBJECTIVE: To better understand the rhabdomyosarcoma in ear nose and throat and make correct diagnosis. METHOD: 17 patients with rhabdomyosarcoma in ear nose and throat were investigated. Diagnosis, treatment and prognosis were analyzed retrospectively. RESULT: Among 17 patients with rhabdomyosarcoma, three patients were in stage I, four patients were in stage II, eight patients were in stage III and two patients were in stage IV. It is the commonest in nose and predisposed to male. The clinic presentations were related to the size and location of tumor. Comprehensive therapy was need in most of patients. Poor prognosis was noted in this disease. CONCLUSION: This disease is easy to misdiagnose. Early diagnosis and comprehensive therapy will make contribution to better prognosis.

Adolescent↗

[Primary cardiac rhabdomyosarcoma involving the mitral valve].

Primary cardiac rhabdomyosarcoma is rare and its extension to the mitral valve even rarer. We report a case of left atrial rhabdomyosarcoma involving the mitral valve. The patient was a 62-year-old man who complained of recurrent pre-syncopal episodes, dyspnoea often sudden in onset, asthenia and major weight loss (10 kg in one month). 2-D echocardiography revealed a 4.9 cm2 wide mass attached to the atrial side of the anterior mitral leaflet and to the adjacent inferior interatrial septum, where it seemed to have origin. CT scan and scintigraphy revealed bone, kidney and spleen metastases. The patient underwent emergency cardiac surgery because of increasing pre-syncopal and dyspnoeic episodes due to obstruction by the intracardiac mass. At surgery a tumor was found infiltrating the left atrial wall, the interatrial septum, the mitral anulus and the anterior mitral leaflet up to its tip. Invasion of mitral anulus did not allow mitral valve replacement, so that an excision of the intracardiac mass was performed as extensively as possible. Histology revealed a rhabdomyosarcoma. A post-operative chemotherapy cycle had to be stopped due to onset of atrial fibrillation and dyspnoea. 2-D echo monitoring revealed rapid new growth of the tumor across the basal portion of mitral valve leaflet to the atrioventricular orifice. After several episodes of increasing dyspnoea, the patient had a pulmonary oedema and died.

Dyspnea↗

[Detection of PAX3/PAX7-FKHR fusion transcript in rhabdomyosarcoma by one-step RT-PCR].

OBJECTIVE: To detect the PAX3-FKHR and PAX7-FKHR fusion transcripts in formalin-fixed, paraffin-embedded rhabdomyosarcoma tissues by one-step RT-PCR and discuss its diagnostic potential. METHODS: One-step RT-PCR were used to detect the expression of the PAX3-FKHR and PAX7-FKHR fusion transcripts in 15 cases of rhabdomyosarcoma (6 cases of ARMS, 9 cases of ERMS and 1 case of PRMS) and 15 cases of non-rhabdomyosarcomous small round cell tumor. RESULTS: PAX3-FKHR and PAX7-FKHR fusion transcripts were positive in 3/6 and 1/6 of ARMS patients, respectively, and were all negative in ERMS, PRMS and Control tumors including 4 cases of synovial sarcoma,4 cases of Ewing's sarcoma,4 cases of lymphoma and 3 cases of neuroblastoma. CONCLUSION: Expression of PAX3-FKHR and PAX7-FKHR fusion transcripts detected by one-step RT-PCR is useful in diagnosis and classification of rhabdomyosarcoma.

DNA-Binding Proteins↗

Pure rhabdomyosarcoma of the corpus uteri in a postpartum patient: report of a case and review of the literature.

Pure rhabdomyosarcomas originate in the female genital tract. They are uncommon and most often occur in infancy or childhood as sarcoma botryoides (embryonal rhabdomyosarcoma) which involve the vagina and cervix. Such tumors rarely occur in adults. A pure rhabdomyosarcoma of the uterus that arose in a postpartum patient is described. The pertinent literature is discussed.

Adult↗

[Leiomyosarcoma of the breast 16 years following successful treatment of a rhabdomyosarcoma of the orbit in childhood].

A case of a mammary leiomyosarcoma in a 23-year-old woman is presented. The tumor appeared 16 years after successful treatment of an embryonal rhabdomyosarcoma of the orbit. Rhabdomyosarcomas are the most frequent soft tissue tumors of childhood, the orbit and the paratesticular region being the most common primary site for this tumor. In contrast, leiomyosarcomas other than those evolving from the viscera or the urogenital organs are rare neoplasms at any age. With the improvement of cancer treatment and survival rates, the risk of late effects after successful treatment for malignant tumors during childhood is increasing. Growth, development and fertility may be impaired and cosmetically disturbing facial and dental complications are common. Development of novel primary tumors is a known further consequence of successful treatment of brain tumors, retinoblastoma and acute leukemias. This is the case when high dose local radiation therapy and/or chemotherapy, especially alkylating agents, were used. Development of novel primary tumors is also known after treatment of childhood rhabdomyosarcomas. This report is intended to show that a second primary tumor may occur many years after a first successfully treated malignant neoplasm, and that young people are at risk for development of tumors at sites that are uncommon to this age group.

Adult↗

Adult parameningeal rhabdomyosarcoma--a case report and literature review.

Although rhabdomyosarcoma is predominantly a malignant disease of children, it is also seen in adults. Since adults account for only 15% of rhabdomyosarcomas, the experience gathered for the treatment of the malignancy has been derived from treating children. The treatment of a case of adult extensive parameningeal rhabdomyosarcoma with CyVADlC chemotherapy and radiotherapy is described, together with a review of the literature.

Adult↗

[A case report of primary rhabdomyosarcoma of the heart treated with mitral valve replacement].

We report a case of rhabdomyosarcoma involving the mitral valve of a 57-year-old female. She was referred to our hospital for progressive orthopnea and edema. Chest X-ray showed marked cardiomegaly and pulmonary congestion. Echocardiogram revealed solid mass in left atrium involving the mitral valve. Emergency operation was required because of acute heart failure. At the operation, the mitral orifice was obstructed by the tumor arising from the left atrium. After partial resection of the left atrium, mitral valve replacement with a Carpentier-Edward prosthesis was performed. Subsequently microscopic examination diagnosed as rhabdomyosarcoma. She died three months after the operation of heart failure probably due to progression of the remnant of the tumor. This, to our knowledge, is the first case of mitral valve replacement for a primary rhabdomyosarcoma of the heart in Japan.

Female↗

[Rhabdomyosarcoma of the epididymis].

A 5-year-old boy with intrascrotal rhabdomyosarcoma arising from the epididymis is described. The patient was submitted to radical orchidectomy via the inguinal approach and high ligation of the spermatic cord. The anatomopathological examination revealed germ cell rhabdomyosarcoma of the epididymis with no testicular or spermatic cord involvement, which corresponded to stage I of the IRS classification (Intergroup Rhabdomyosarcoma Study). Its clinical and histological features and treatment are discussed.

Child, Preschool↗

Metastatic rhabdomyosarcoma to the breast.

Secondary malignancy metastatic to the breast is uncommon, with an incidence of 0.5% to 3% of patients with extramammary malignancy. Although rhabdomyosarcoma is a common aggressive primary malignancy in the pediatric age group, metastatic deposits to the breast rarely occur and are mainly seen in adolescent girls. Here, we report an intriguing, rare adult case with metastasis to the breast from nasal rhabdomyosarcoma. A 31-year-old woman with the complaint of right neck mass noted recently came to this hospital for help. She had a history of nasal malignancy treated with radiotherapy in another hospital three months previously. Physical examination revealed multiple neck masses at bilateral neck areas. Bilateral neck dissection was performed and rhabdomyosarcoma, metastatic to lymph node, was the final diagnosis. One year after operation, the patient felt a large lump in her left breast. Surgical excision was performed and histological analysis was consistent with rhabdomyoblastic origin. Secondary malignancy metastatic to the breast is uncommon, yet this entity does exist. In view of the therapeutic implication, a metastatic breast lesion should not be mistaken as the primary breast carcinoma. Only with the awareness of such a possibility can prompt diagnosis and optimal treatment be achieved.

Actins↗

Botryoid rhabdomyosarcoma of vagina--two case reports.

Botryoid rhabdomyosarcoma, previously considered a type of embryonal rhabdomyosarcoma, has clinicopathological features distinctive enough to warrant its classification as a separate entity. It almost always occurs in children under 5 years of age. Two cases of botryoid rhabdomyosarcoma are reported here because of their relative rarity.

Biopsy↗

Adult rhabdomyosarcoma in the nasal and paranasal sinuses showing complete local response to a combination of chemotherapy and radiotherapy using 3D-CRT and IMRT.

We report on a 69-year-old woman with rhabdomyosarcoma arising from the nasal and paranasal sinuses. She was referred to our hospital with a reduced ability to smell and impaired bilateral vision, narrowing of the visual field, and left facial pain. Computed tomography (CT) revealed a large tumor in the nasal and left paranasal sinuses invading the left orbital cavity and anterior skull base, and lymph node swellings in the submental and left accessory nerve areas. A biopsy specimen from the nasal tumor was diagnosed histologically as a rhabdomyosarcoma, alveolar type. Because the intracranial direct invasion and distant metastases to the thoracic spine were suspected by pretreatment examination, our case was determined to be inoperable by a head and neck surgeon. Radiotherapy with a total dose of 60 Gy was carried out to control the primary disease. The three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) techniques were used in order to reduce the doses to risk organs. Combined with radiotherapy, chemotherapy was also performed for the treatment of lymph-node metastases and distant diseases. After the treatment was completed, the primary tumor and lymph-node metastases disappeared completely; there was no sign of re-growth during the follow-up period. Chemoradiotherapy may be an effective treatment also for inoperable adult rhabdomyosarcoma in the head and neck region. Furthermore, the 3D-CRT and IMRT techniques are both useful methods of radiotherapy for this disease.

Aged↗

[Pleomorphic rhabdomyosarcoma of the larynx--a case report and literature review].

Rhabdomyosarcoma is a very rare malignant tumor of the larynx which can present in a number of histologic variants. The pleomorphic variant of the tumor has been described in 16 patients to date. Being a rarity, rhabdomyosarcoma is as a rule managed according to the principle of treatment for malignant mesenchymal tumors of the head and neck, and includes radical surgery with postoperative radiotherapy and/or chemotherapy. A case is presented of a pleomorphic rhabdomyosarcoma of the vocal cord. Successfully treated by endoscopic CO2 laser cordectomy with adjuvant chemotherapy and 6-year uneventful follow up.

Humans↗

[Primary rhabdomyosarcoma of the cerebellum. Histopathological and immunohistochemical study of an autopsy case].

Primary rhabdomyosarcoma of the cerebellum. Histopathological and immunohistochemical study: a necropsy case. A necropsy case of primary cerebellar rhabdomyosarcoma occurred in a 38-year-old man has been investigated by histological and immunohistochemical techniques. In the most differentiated rhabdomyoblasts microscopic analysis showed obvious cross-striations and immunohistochemical reactivity for myoglobin (PAP method). Many tumor cells were positive for vimentin and muscle-specific intermediate filament protein desmin, but neither for glial fibrillary acidic protein nor neuron-specific enolase. The diagnostic role of the immunohistochemistry in this tumor is pointed out. The clinicopathological features of 30 cases of primary rhabdomyosarcoma of the central nervous system previously reported in the literature are briefly reviewed, and the histogenesis is discussed.

Adult↗