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Rhabdomyosarcoma is an often primitive tumor capable of diverse morphologic manifestations. The article describes three cases of childhood rhabdomyosarcoma in which a significant population of lipid-rich tumor cells was present. The lack of specificity and potentially confusing nature of this feature are discussed, and the ultrastructural diagnosis of rhabdomyosarcoma is briefly reviewed.
A 29-year-old man with alveolar rhabdomyosarcoma was considered to be suffering from acute leukemia. A bone marrow aspirate had revealed extensive infiltration by atypical blast-like cells which were interpreted as acute lymphoblastic leukemia. Although there was no confirmation of this diagnosis by immunophenotyping chemotherapy with a protocol suited for the treatment of acute lymphoblastic leukemia was started prior to histological analysis and resulted in a complete temporary remission after the first cycle. Histological analysis of a bone marrow biopsy revealed an alveolar rhabdomyosarcoma, as further confirmed by molecular genetic analysis. Two months after the end of chemotherapy, there was an extensive recurrence and the patient died one year after initial diagnosis with chemotherapy refractory disease. In conclusion, rhabdomyosarcoma should always be included in the differential diagnosis of systemic diseases with extensive bone marrow infiltration by tumor cells which could otherwise be misinterpreted as a haematological malignancy.
The authors report a case of rhabdomyosarcoma originating in the fourth ventricle and review the eight comparable previous reports on true rhabdomyosarcoma, composed solely of mesenchymal elements. Tumors in most adults arose in the cerebral hemisphere, while those in children arose exclusively in the midline structures of the posterior fossa. The tumor in the author's case was initially benign and well circumscribed, but within 2 years had changed into a malignant rhabdomyosarcoma. The histological documentation during the interval is presented and discussed.
In the present work we describe the histology of skin tumours of the black plaice Pleuronectes obscurus from Amursky Bay, the Sea of Japan. The epidermis forms numerous papillary folds protruding above the skin surface and supported by delicate branches of connective tissue. This type of neoplasm is classified as epidermal papilloma. The occurrence of severe epidermal hyperplasia and disturbance of the histoarchitecture in some areas, invasion of the adjacent connective tissues by epithelial cells, dystrophic changes of the epithelial cells, and the occurrence of a large number of mitoses point to an increasing malignancy of the papilloma. Moreover, areas with skeletal-muscle differentiation were found within skin tumours. Among the myogenic cells, features of normal somatic myogenesis were observed along with signs of abnormality of this process, suggesting a disturbance of myogenic differentiation. Cellular polymorphism among myogenic cells and invasion of the skin by neoplastic cells are evidence of the malignant character of this type of tumour and allow us to classify it as rhabdomyosarcoma. Due to the position of tumours in the skin, they are ectopic rhabdomyosarcomas. In the skin tumours, atypical small and large rounded cells were identified, the latter having previously been described in flatfish as X-cells. The origin of these cells is discussed and the assumption is put forward that small and large rounded cells can be regarded as cellular elements of rhabdomyosarcomas.
Four rhabdomyosarcoma and three neuroblastoma cell lines were characterised for the presence of P-glycoprotein and MDR-1 expression using immunohistochemistry, northern analysis, RT-PCR and in situ mRNA hybridisation. None of the rhabdomyosarcoma lines were unequivocally positive in contrast to all three neuroblastoma lines. Chemosensitivity to cytotoxic agents was determined using the MTT assay and chemosensitisation by cyclosporin and verapamil was evaluated. In a single rhabdomyosarcoma line (HX 170) there was sensitisation to etoposide using verapamil but not to other drugs or using cyclosporin A. In contrast, in all three neuroblastoma lines both cyclosporin and verapamil sensitised to vincristine and doxorubicin. No evidence of sensitisation to etoposide was apparent. The sensitisation was most marked for vincristine, using either modulator and therefore the influence of modulator scheduling was evaluated with this drug in the neuroblastoma line SK N BE. Prolonged pre-exposure to modulator did not appear necessary and maximum sensitisation was apparent where either cyclosporin or verapamil was added 1-3 h prior to and post vincristine. Continuity of exposure was important and even a break of 30 min appeared to reduce sensitisation. These data confirm the potential for chemosensitisation in MDR-1 positive neuroblastoma cell lines and provide some basis for rational schedule design in clinical practice. Because of the probability that vincristine resistance is predominantly related to MDR-1 and less multifactorial than for other drugs such as doxorubicin or etoposide, this agent should be considered for inclusion in any clinical evaluation of MDR reversal strategies.
Differentiation of a tumor plays an important role in terms of biological aggressiveness. The question arises as to whether this is reflected in differences in the metabolic and energetic status of solid tumors. The aim of this study was to analyze the influence of clonal tumor cell differentiation on the microenvironment of rat rhabdomyosarcomas. Two distinct lines of a rhabdomyosarcoma (BA-HAN-1) with different histomorphological properties were used (line F1, co-existence of mononuclear stellate cells and multinuclear myotube-like giant tumor cells; G8, polygonal, mononuclear tumor cells). Solid tumors were grown s.c. on the hind food dorsum of Lewis rats. Tumor oxygenation was measured using O2-sensitive needle electrodes. For determining tumor blood flow, the 133Xe clearance method was used. Global glucose and lactate concentrations were measured enzymatically, global ATP, ADP, and AMP were analyzed by HPLC. The regional distribution of metabolic and energetic parameters within the tumors was analyzed using quantitative bioluminescence and image analysis. Tumor growth rate was significantly different between the two lines. The volume doubling time was 2.5 days for the F1 and 3.0 days for G8 tumors. No differences in blood flow were seen between the two lines investigated, oxygenation was slightly poorer, glucose and ATP levels slightly higher, and lactate concentration somewhat lower in the F1 line as compared to the G8 line. From these differences - although marginal - it is concluded that the G8 line presumably relies on glycolysis whereas the F1 line seems to prefer oxidative glucose turnover. Despite these different metabolic profiles between the two tumor lines, the histopathology of the rhabdomyosarcomas seems to be only of limited significance for the tissue oxygenation status as already postulated for various tumors in the clinical setting.
The survival rate of children with localized orbital rhabdomyosarcoma is now greater than 90% 3 years after diagnosis as a result of advances in radiation and chemotherapy. Ninety percent of these children develop cataracts within 1 to 4 years after the completion of radiotherapy. The correction of aphakia in these children is complicated by the concurrent keratoconjunctivitis and dryness associated with radiotherapy. Three patients with a diagnosis of orbital rhabdomyosarcoma underwent treatment for uniocular cataract. Two of the patients were unable to use extended wear contact lenses. Both underwent epikeratophakia with poor results. One patient who had clinically significant ocular drying prior to cataract extraction underwent successful implantation of an intraocular lens as a primary procedure, with excellent visual results. Clinicians should be aware of the difficulties associated with contact lens wear and epikeratophakia tissue lenses in children who have had high doses of radiation for orbital rhabdomyosarcoma. Such patients are probably best served by primary intraocular lens implantation or by preservation of the posterior capsule at the time of cataract extraction to allow secondary lens implantation if contact lens wear is unsuccessful.
OBJECTIVE: To describe a case of metastatic rhabdomyosarcoma originating from the sphenoid sinus in a patient previously treated with conventional irradiation for a prolactinoma, presenting as hypercalcemia in the setting of a normal level of serum parathyroid hormone-related protein (PTHrP). METHODS: We report the case of a patient who underwent remote pituitary irradiation for a prolactinoma and then presented decades later with hypercalcemia of unknown cause. His clinical course, the initial biochemical and radiologic investigations, and the results of examination of pathology specimens are reviewed. RESULTS: The patient was found to have a mass in the sphenoid sinus. The pathologic features were consistent with alveolar rhabdomyosarcoma. Although he had a normal serum PTHrP level, staining of his tumor with an antibody against PTHrP revealed local production of PTHrP at the tumor margins. His bone marrow biopsy specimen showed 100% involvement with rhabdomyosarcoma. CONCLUSION: PTHrP staining of pathology specimens might explain hypercalcemia of undetermined cause in patients with a known malignant lesion, in whom elevated serum PTHrP levels cannot be demonstrated.
A 19-year-old man presented with left aggressive painless scrotal swelling. On the diagnosis of left intrascrotal tumor, left high orchiectomy with partial scrotal skin resection was performed. Pathological examination of the specimen and systemic metastasis survey revealed embryonal rhabdomyosarcoma of left spermatic cord with multiple lung metastasis (Intergroup Rhabdomyosarcoma Study Group IV). Systemic chemotherapy with etoposide (VP-16), cisplatin (CDDP), and ifosfamide (IFO) (VIP therapy) was started. Although epilepsy-like symptoms occurred at the first course of VIP therapy, these symptoms immediately improved by diazepam administration. These symptoms were thought to be due to the adverse effects of IFO. To our knowledge, there were little reports on epilepsy-like symptoms caused by IFO in Japan. On the other hand, his multiple lung metastasis disappeared after the second course of VIP therapy. Although IFO may be effective in rhabdomyosarcoma, the toxicity of various nervous systems may be discovered.
Since 1979, 15 children with rhabdomyosarcoma have been treated at our institution. Included in this group are six children who presented with rhabdomyosarcoma of an extremity or trunk, requiring the use of combined multimodality therapy. The patients were clinically grouped and treated in accordance with the Intergroup Rhabdomyosarcoma Study protocol. All patients received combination chemotherapy based on their respective stage of disease at diagnosis. When feasible, the primary tumor was resected en bloc before chemotherapy was begun. After surgery, patients with unclear postoperative surgical margins and an initial good response to chemotherapy received radiotherapy to the primary site and at the regional lymphatics. Three of six patients developed or maintained a complete tumor response to induction chemotherapy. Radiotherapy maintained control of local disease in both groups. Overall, four patients, including one with disseminated disease at diagnosis, are alive, with a median survival time from diagnosis of 39 months. In children, treatment must be individualized, but complete local excision of the tumor with a tumor-free margin should be the goal. Major ablative amputation surgery was not performed.
Rhabdomyosarcomas are the most common sarcomas of the soft tissues found in children under 15 years. The reported observation is of a vaginal tumour having developed in an eleven-month-year-old little girl. It was a typical botryoid rhabdomyosarcoma, usually found in the hollow organs surrounded on the edges by mucus. Rhabdomyosarcomas have many characteristics which vary greatly according to the degree of their cellular differenciation. The majority of these tumours can be classified into four histological categories: embryonic, botryoid, alveolar or plemorphous. The treatment is exeresis surgery with radio- and chemotherapy. Prognosis, however, remains dim despite the therapeutic advances of the last few years.
Rhabdomyosarcomas are the most common soft-tissue sarcoma found in children. The alveolar subtype is clinically more aggressive than the embryonal subtype. In addition to the presence of specific chromosome translocations and associated fusion gene products in a high proportion of the alveolar subtype, we previously showed that tumors with this histology frequently show evidence of genomic amplification. Here, we substantially extended the number of alveolar rhabdomyosarcoma samples examined by comparative genomic hybridization analysis. Regions of loss were noted, including the smallest overlapping regions corresponding to 16q, 17/17p, and 9q32-34, in 16%, 10%, and 10% of cases, respectively (44 primary samples/6 cell lines). Amplification or gain at 12q13-15 in the region of the MDM2/GLI1/SAS/CDK4 loci and 2p24 at the MYCN locus was found in 28% and 32% of cases, respectively. Single amplicons were found at locations that in other samples showed consistent gain, including the regions 5q15-23, 7q21-31, 11p11-14, 17q23-24, and 20q13, and amplification was found in two cases at 15q24-26. However, most striking was a novel region of amplification or gain at 13q31 in 19% of cases (51 primary samples/6 cell lines). This indicates that a gene or genes at 13q31 are significant in the development or progression of alveolar rhabdomyosarcoma.
Rhabdomyosarcoma accounts for almost 20% of all primary malignant neoplasms of the heart. These tumors usually arise from the ventricular walls. In adult patients, they sometimes arise from the atrial walls and mimic atrioventricular valve stenosis. We describe a case of left atrial rhabdomyosarcoma that presented as severe mitral stenosis and required emergency surgery. The atrial mass was detected by transthoracic and transesophageal echocardiography, but only histopathology confirmed the nature of the lesion. Although rhabdomyosarcomas of the heart are highly lethal, operation is indicated for emergency cases, in order to clarify the diagnosis, relieve symptoms, and improve short-term survival.
The authors report a case of paratesticular thabdomyosarcoma in a young adult. This tumour is more frequent in children than in adults. Rhabdomyosarcoma is the commonest variety of soft tissue sarcoma in children and young adults. It represents 6.5% of all malignant tumours in paediatrics with an annual incidence of 4 to 7 cases/million children. The primary paratesticular site is considered to have a good prognosis in comparison with other rhabdomyosarcomas, despite the frequency of retroperitoneal lymph node invasion. This superficial site allows rapid diagnosis and consequently often complete resection of the tumour. The multidisciplinary treatment of paratesticular rhabdomyosarcoma has improved control of the disease with a 2-year survival of 80%.
The lack of new highly efficacious drugs for cancer treatment promotes the search for innovative therapeutic modalities. The authors reported the results leading to the definition of parameters needed to demonstrate a possible radiopotentiation by topotecan (TPT) on two representative human rhabdomyosarcomas (RMSs) xenografted into nude mice. Experimental studies of radiopotentiation with different doses of topotecan showed that concomitant association of topotecan and RT for 5 consecutive days provided a synergistic therapeutic effect. Response rates were statistically higher with the radiochemotherapeutic combination (P < 0.001). Efficacy enhancement factors of this combination compared with the sum of the antitumoral activity of these treatments separately administrated were 1.54 and 1.60, respectively, on both rhabdomyosarcomas. Moreover, the efficiency of the combination of radiotherapy at the dose of 20 Gy with topotecan (12.5 mg/kg) was not statistically different from that of radiotherapy at the dose of 40 Gy. According to microscopy results, the analyses performed at different periods after topotecan treatment alone, radiotherapy alone, and their combination seemed to show that tumoral repopulation by malignant cells is as fast as the dose of radiotherapy and/or topotecan is low. Furthermore, lesions observed with the dose of 40 Gy were similar to those obtained with the association of topotecan at the dose of 12.5 mg/kg and radiotherapy at the dose of 20 Gy. In conclusion, all clinical and pathological results are consistent with a radiopotentiation effect of topotecan on the two xenografted human rhabdomyosarcomas and are currently leading to the design of clinical studies.
Brachytherapy has been widely used at the Institut Gustave-Roussy since 1972 in pediatric oncology. In genitourinary rhabdomyosarcoma, because of its ballistic and physical characteristics, it represents the optimal treatment whenever irradiation is required and brachytherapy feasible. Between 1976 and 1998, 23 children with bladder or prostate rhabdomyosarcoma were treated with a protocol including brachytherapy, with five of them treated with a salvage brachytherapy. All but one brachytherapy was performed during the surgery. Among the 18 brachytherapies performed as a first-line treatment, eight presented a tumoral evolution: five presented a local evolution, one a local and nodal evolution and two a nodal evolution. Brachytherapy allowed a conservative treatment among ten out of 11 children alive with no evidence of disease. Among the five patients with salvage brachytherapy, two presented a second recurrence. Sequelae were minimal, consisting of one grade I rectitis and one asymptomatic vesical and ureteral reflux. These results are consistent with the published data using more radical treatment. Brachytherapy can represent an alternative to radical surgery, when indications are clearly defined in bladder or prostate rhabdomyosarcoma. This type of treatment can be performed only integrated with other treatments, more particularly with surgery. This approach requires a close cooperation between the different specialists: pediatricians, surgeons and brachytherapists.
Cells of nickel sulfide-induced rhabdomyosarcomas were studied with the electron microscope. Cells in the proliferative compartment were mononucleate and exhibited neither myofilaments nor other features of normal muscle cell differentiation. Cells in the nonproliferative compartment had myofilaments and differentiated similarly to the normal fetal and early postnatal muscle cells. The tumor cells did not differentiate beyond the initial stage of formation of triads and of the smooth endoplasmic reticulum. Transitional forms between undifferentiated and differentiated tumor cells were observed. Only a fraction of the progeny of the dividing cells seemed to differentiate; the remaining fraction did not and remained in the proliferative cell compartment as stem cells. The ratio between these cells and the descendants of the dividing cells that, by differentiation, became part of the nonproliferative cell compartment was a factor in the growth of the rhabdomyosarcomas. The pattern of fetal differentiation of the rhabdomyosarcomas was analogous to that of diethylnitrosamine-induced hepatomas studied previously in this laboratory.
Primary embryonal rhabdomyosarcoma of the orbit is an extremely rare tumor in adults. A 38 year old female patient with immunohistochemically proved embryonal rhabdomyosarcoma of the right orbit is reported. The histologic types, diagnosis, management and out come of rhabdomyosarcoma is discussed.