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PubMed1995

Second malignant neoplasms in long-term survivors of childhood rhabdomyosarcoma.

BACKGROUND: The occurrence of second malignant neoplasms (SMNs) in successfully treated pediatric patients with cancer has been an area of increasing concern because survival of these patients has improved with intensification of therapy. Therefore, the incidence of SMNs in long term survivors of childhood rhabdomyosarcoma (RMS) was studied. METHODS: From 1970 to 1989, 210 newly diagnosed patients (median age, 9.7 years; range, 1 month to 27 years) with RMS were treated at Memorial Sloan-Kettering Cancer Center (New York, NY). Multimodality treatment included chemotherapy, surgery, and radiotherapy, when indicated. There were 130 long term survivors (> 2 years off therapy) with a median follow-up of 9 years (range, 2-20 years). The cumulative dose of each chemotherapeutic agent and the radiation doses each patient received were reviewed. Statistical analysis was performed by comparison with the Connecticut Tumor Registry data. RESULTS: Seven patients developed a SMN, including three with acute nonlymphoblastic leukemia (ANLL) and four with solid tumors. Acute nonlymphoblastic leukemia developed a median of 4.5 years after diagnosis. Of the solid tumors, 3 developed within the radiation field at a median of 10 years after diagnosis, whereas the fourth occurred 9.3 years after initial diagnosis in a patient who did not receive radiotherapy. All seven patients with SMNs received total dactinomycin doses higher than the median (9.6 mg/M2) for the group. All three patients with ANLL received total cyclophosphamide doses higher than the median (16.8 g/M2). Moreover, six of the seven patients received a dose of radiotherapy greater than 4000 cGy. The standardized incidence ratio was: 17.07 (95% confidence interval, 6.68-35.18; P < 0.0001). CONCLUSIONS: Multimodality therapy has improved long term survival for patients with childhood RMS. The combination of high dose radiotherapy and chemotherapy appears to increase the risk for developing a second malignancy.

Adolescent↗
PubMed2001

Neonatal alveolar rhabdomyosarcoma with skin and brain metastases.

BACKGROUND: Approximately 5-10% of patients with rhabdomyosarcomas (RMS) are diagnosed during the first year of life, and their clinical characteristics have been well documented. However, because RMS rarely occurs during the neonatal period, little is known about neonatal RMS. METHODS: Four patients with neonatal RMS were treated at St. Jude Children's Research Hospital between 1962 and 1999. The authors report the results of a review of these patients and of cases described in the literature. Clinical, radiologic, and pathologic features of these patients and their outcomes were evaluated. RESULTS: One patient with embryonal RMS was treated successfully with a combination of systemic chemotherapy and local control measures. The other three patients had alveolar RMS. Two of them had multiple skin and subcutaneous metastatic nodules at the time of diagnosis and developed brain metastases early in their course. In one of these patients, the PAX3-FKHR fusion transcript was detected. Three other similar cases of neonatal alveolar RMS with metastases to the skin and brain have been reported in the literature. CONCLUSIONS: A distinct syndrome of neonatal RMS is described. This syndrome is characterized by alveolar histology, multiple skin and subcutaneous metastases, and fatal outcome as the result of early brain metastasis.

Brain Neoplasms↗
PubMed2003

Hypereosinophilia associated with cardiac rhabdomyosarcoma.

Hypereosinophilia, defined as an absolute eosinophil count exceeding 1,500/mm(3), is caused by a limited number of disorders. Its association with malignancy is a rare occurrence that typically denotes extensive metastasis and a poor prognosis. Several theories have been proposed to explain the hypereosinophilia associated with malignancy, focusing on the production of eosinophilopoietic cytokines by tumors. We describe a patient with hypereosinophilia associated with a cardiac rhabdomyosarcoma, review the etiologies of hypereosinophilia, and discuss the possible mechanisms.

Adult↗
PubMed2001

Hematologic masquerade of rhabdomyosarcoma.

We present the case of a 12-year-old boy admitted with the diagnosis of acute leukemia, but found to have an infiltration of the marrow by an alveolar rhabdomyosarcoma (RMS) as determined by the cytogenetic demonstration of a t(2;13)(q25;q14). A primary tumor could not be found. With this case as a basis, we have tabulated features of all similar cases in the literature and discuss the possible optimal approaches to establishing the correct diagnosis in such patients.

Acute Disease↗
PubMed2002

Five additional Costello syndrome patients with rhabdomyosarcoma: proposal for a tumor screening protocol.

We report five new cases of rhabdomyosarcoma (RMS) in Costello syndrome. These cases, combined with those previously reported, increase the number of solid tumors to 17 (10 RMSs, 3 neuroblastomas, 2 bladder carcinomas, 1 vestibular schwannoma, 1 epithelioma), in at least 100 known Costello syndrome patients. Despite possible ascertainment bias, and the incomplete identification of all Costello syndrome patients, the tumor frequency could be as high as 17%. This is comparable to the 7-21% frequency of solid tumors in Beckwith-Wiedemann syndrome (BWS), and may justify tumor screening. Based on the recommendations for screening BWS patients, we propose a screening protocol consisting of ultrasound examination of the abdomen and pelvis every 3-6 months until age 8-10 years for RMS and abdominal neuroblastoma; urine catecholamine metabolite analysis every 6-12 months until age 5 years for neuroblastoma; and urinalysis for hematuria annually for bladder carcinoma after age 10 years. These recommendations may need to be modified, as new information becomes available. Potential criticism of the tumor screening protocol concerns the lack of evidence for improved outcome, and possible overestimation of the tumor risk. The ability of RMSs to occur at various sites complicates tumor screening, but 8 of the 10 RMSs in Costello syndrome patients originated from the abdomen, pelvis and urogenital area. Prior diagnosis of Costello syndrome is a prerequisite for the implementation of any screening protocol. The diagnosis of Costello syndrome should also be considered in individuals with RMS and physical findings suggestive of Costello syndrome.

Abnormalities, Multiple↗
PubMed1991

Two forms of ring 13 in a child with rhabdomyosarcoma.

Mosaicism for two forms of ring 13 was found in a child with embryonal rhabdomyosarcoma of the bladder, minor anomalies, and developmental delay. Her chromosome constitution was 46,XX,r(13)(p11q34)/46,XX,r del(13)(p11q14). Both cell lines were present in lymphocytes and fibroblasts. The cell line with the smaller ring chromosome predominated in both tissues. The child's manifestations reflect the presence of both cell lines.

Abnormalities, Multiple↗
PubMed2002

Adult rhabdomyosarcoma: outcome following multimodality treatment.

BACKGROUND: Childhood rhabdomyosarcoma (RMS) has a relatively good prognosis. Outcome for adults with this disease is poorly documented due to its rarity. METHODS: The clinicopathologic features, treatment methods, and disease outcome were reviewed retrospectively for 82 adults with locoregional RMS treated between 1960 and 1998. Patients with distant metastasis at diagnosis were excluded. Actuarial univariate and multivariate statistical methods were used to evaluate outcome. RESULTS: Patient ages ranged from 17 to 84 years (median, 27 years). Histologic subtypes were embryonal (34%), pleomorphic (43%), and alveolar (23%). Anatomic sites of origin were head and neck (52%), trunk (26%), and extremity (7%). Tumor size was 5 cm or smaller in 51% of patients. Regional lymph node metastasis was present in 33% of patients at presentation. Treatment consisted of radiation alone in 11%, radiation and surgery in 18%, radiation and chemotherapy in 34%, and all three modalities in 37%. With a median follow-up of 10.5 years, the 10-year actuarial disease-free and overall survival rates were 41% and 40%, respectively. The 10-year actuarial local, lymph node, and metastatic control rates were 75%, 82%, and 53%, respectively. The major determinant of metastatic control and survival was primary tumor size (< or = 5 vs. > 5 cm). Local control was satisfactory (10-year rate of 87%) for sites other than parameningeal (50% at 10 years). Patients whose disease responded to chemotherapy had a significantly better metastasis free period (72% at 10 years) than those whose disease failed to respond (19% at 10 years). CONCLUSIONS: Adult RMS is a highly malignant tumor with a significant incidence of metastatic recurrence. Continuing investigation of new and potentially more effective chemotherapy is crucial. Local control is satisfactory for sites other than parameningeal where new radiation technologies such as intensity-modulated therapy may be necessary to safely deliver adequate doses.

Adolescent↗
PubMed2003

Long-term results of three-dimensional conformal radiation therapy for patients with rhabdomyosarcoma.

BACKGROUND: The authors evaluated the outcome of patients with rhabdomyosarcoma (RMS) who were treated with three-dimensional (3D) conformal radiation therapy (RT) at a single institution. METHODS: The records of all 69 patients with RMS who received 3D RT from 1989 to 2001 were reviewed. All patients received multiagent chemotherapy with or without surgical resection. Follow-up of surviving patients ranged from 1.0 year to 12.8 years (median, 4.3 years). RESULTS: The median patient age was 6 years (range, 1-29 years), and there was a male:female ratio of 1.5:1. Forty-eight patients had embryonal sarcomas, 14 patients had alveolar sarcomas, and 7 patients had undifferentiated sarcomas. The parameningeal area (n = 22 patients) and the trunk (n = 21 patients) were the most common sites. Twelve percent of patients had Stage I disease, 10% of patients had Stage II disease, 51% of patients had Stage III disease, and 27% of patients had Stage V disease. Nine percent of patients were in clinical Group II, 64% of patients were in Group III, and 27% of patients were in Group IV. Regional lymph nodes were involved in 33% of patients, and 77% of tumors measured > or = 5 cm in greatest dimension. The actuarial 5-year local and regional control rates were 90% and 91%, respectively. No predictive factors for local failure were identified; however, alveolar histology was correlated with regional recurrence (29% compared with 4%; P = 0.02). The disease free and overall survival rates were 60% and 63% at 5 years, respectively. Disease stage was most predictive of 5-year survival (76% of patients with Stage I-III disease compared with 24% of patients with Stage IV disease; P < 0.001). CONCLUSIONS: High rates of local control were achieved in patients with RMS using 3D RT. Regional lymph node failure was increased significantly among patients with alveolar histology. Control of metastatic disease remains a formidable problem for patients with Stage IV RMS.

Adolescent↗
PubMed2003

Multidrug resistance proteins in rhabdomyosarcomas: comparison between children and adults.

BACKGROUND: Pediatric rhabdomyosarcomas (RMS) have a more advantageous prognosis after multimodality treatment compared with adult RMS, which might be related to a decreased sensitivity to chemotherapy in adults. Resistance to chemotherapy might be conveyed by the multidrug resistance (MDR)-associated proteins P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1), and lung resistance-related protein (LRP). It was therefore suggested that these proteins were expressed differently in pediatric and adult patients. METHODS: The expression of P-gp, MRP1, and LRP was assessed immunohistochemically in 45 specimens of untreated RMS: 29 were obtained from children younger than 16 years old and 16 were obtained from adults. All children had an embryonal or botryoid RMS. Among the adults, there were 10 embryonal, 3 alveolar, and 3 pleomorphic RMS. Samples were scored as negative or positive according to the percentage of immunoreactive tumor cells: 0.5 (1-5%), 1 (5-25%), 2 (26-50%), 3 (51-75%), or 4 (> 75%). RESULTS: Expression of LRP was more pronounced in embryonal and pleomorphic RMS in adults compared with RMS in children. In addition, LRP expression correlated with age at diagnosis. Alveolar RMS had remarkably low LRP expression. Expression of P-gp and MRP1 did not differ significantly between children and adults. CONCLUSIONS: In this series of embryonal and pleomorphic RMS, an increased LRP expression was observed in adults, which may explain their worse response to chemotherapy reported in other studies. In alveolar RMS, a low LRP expression was observed, suggesting that other mechanisms are responsible for the resistant phenotype in most of these tumors.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2003

Primary transcrotal excision for paratesticular rhabdomyosarcoma: is hemiscrotectomy really mandatory?

BACKGROUND: To evaluate the role of primary reexcision (PRE) with scrotal resection in patients with paratesticular rhabdomyosarcoma enrolled in the German-Italian Cooperative Studies. The authors compared patients who underwent this procedure, according to the protocol guidelines, with those who did not. METHODS: In 32 of 198 patients with localized disease, the primary surgery was performed through a noncorrect scrotal approach. Twenty-four patients underwent PRE as recommended by the protocol guidelines (Group A) and 8 did not receive this treatment (Group B). The Group B patients were treated with the same chemotherapeutic regimens as the Group A patients and no radiotherapy was given to either group. RESULTS: After PRE, residual tumor was not detected in 21 of the 24 Group A patients. Twenty patients are alive in first complete remission 26-250 months after diagnosis (median, 40 months), 2 are alive in second complete remission at 3 and 9 months from diagnosis of lymph node and lung recurrence, and 2 died of disease after lymph node and distant metastases at 16 and 13 months from diagnosis. Three-fourths of these patients were older than 10 years old and the tumor was larger than 5 cm. The eight Group B patients are all alive in first complete remission 24-250 months since diagnosis. CONCLUSIONS: The data on the eight patients who obtained local control without PRE or radiotherapy warrant further investigation. Because of the supposed high risk of contamination with subsequent microscopic residual tumor after a transcrotal approach, we emphasize the utility of PRE with hemiscrotectomy.

Child↗
PubMed2003

Rhabdomyosarcoma in infants younger than one year old: a report from the Italian Cooperative Group.

BACKGROUND: The management of rhabdomyosarcoma (RMS) in patients age < 1 year is particularly problematic and requires a tailored therapeutic approach. We report on the Italian Cooperative Group's 20-year study of 50 children with RMS who were age < 1 year at diagnosis. METHODS: Patients were treated using multimodality therapeutic approaches that were based on three consecutive protocols. Chemotherapy was administered to all patients, with dosages calculated according to body weight; calculated doses subsequently were reduced by 33-50%. Radiotherapy was administered to 10 patients. RESULTS: With a median follow-up of 76 months, 5-year event-free survival and overall survival rates were 42.3% and 61.7%, respectively. Local recurrence was the major reason for treatment failure. In particular, the local recurrence rate was high in patients who warranted radiotherapy but received none due to their age. Completeness of surgery and nodal involvement were the most significant prognostic factors. After a suitable reduction in dosage was made, acute toxicity was no different from what has been observed in older children. The most relevant toxic event was cardiotoxic death in a newborn (n = 1). CONCLUSIONS: The current study confirmed that the outcome for infants with RMS is less satisfactory than for older children and that infants with RMS require more careful monitoring and specific treatment guidelines. The absence of local control is the major cause of treatment failure; aggressive conservative surgery should be encouraged, but more radiotherapy may be advisable in selected cases. Intensive chemotherapy is essential; a 33% dose reduction may ensure adequate tolerance. In addition, patients age < 3 months should not receive anthracyclines.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Long-term survival probabilities for childhood rhabdomyosarcoma. A population-based evaluation.

BACKGROUND: Evidence from clinical trials has documented improvements in event-free survival from childhood rhabdomyosarcoma (RMS) since the 1970s; however, the survival experience of children enrolled on cancer clinical trials may not reflect the full range of patients treated in community settings. The current study evaluated 5-year survival and 10-year conditional survival for RMS from U.S. population-based cancer registry data. METHODS: Public-use data from the Surveillance, Epidemiology, and End Results (SEER) program were used in life table and Cox regression analyses to evaluate RMS survival by patient age at diagnosis, gender, tumor histology, tumor site and stage, and major treatment eras among 848 children who were age < 20 years at the time of diagnosis, were a resident of 1 of 9 geographic reporting regions, and were diagnosed between 1973 and 2000. RESULTS: The 5-year survival probabilities were found to be highest for younger-age children (ages 1-4 years: 77%), patients with localized disease (83%), those whose tumors had an embryonal histology (67%), and patients with orbital (86%) and genitourinary (80%) tumor sites. Poor prognosis was associated with diagnosis during infancy (47%) and adolescence (48%); metastatic disease at the time of presentation (31%); alveolar histology (49%); and tumors of the extremities (50%), retroperitoneum (52%), and trunk (52%). Conditional 10-year survival probabilities among those who survived > or = 5 years were 85% or higher. The probability of survival by stage at the time of diagnosis increased with each successive treatment era, suggesting a stage shift phenomenon over time. CONCLUSIONS: Large variations in 5-year survival were evident depending on patient age and tumor characteristics. However, children who survived the first 5 years after diagnosis were found to have an excellent long-term prognosis. The patterns in RMS survival noted from the current population-based evaluation did not appear to differ substantially from those previously reported by major clinical trials.

Adolescent↗
PubMed2005

Outcomes and prognostic factors after recurrence in children and adolescents with nonmetastatic rhabdomyosarcoma.

BACKGROUND: Although > 90% of children with nonmetastatic rhabdomyosarcoma (RMS) achieve complete remission with current treatment, up to one-third of them experience a recurrence. Survival rates are not always poor in patients who develop recurrences; thus, prognostic factors are needed to tailor salvage treatment. METHODS: The current analysis included 125 children who were affected by localized RMS and were enrolled in 3 consecutive Italian protocols (RMS79, RMS88, and RMS96) who developed recurrences after complete remission. Patient, tumor, and treatment characteristics were studied in univariate and multivariate analyses to determine the independent significance of different factors. RESULTS: The median time from diagnosis to recurrence was 17.8 months. Most patients had local recurrences (72%). The 5-year overall survival (OS) rate was 28.3% +/- 8.7%. Multivariate analysis identified 4 factors that were associated with poor survival: 1) alveolar subtype (relative risk [RR], 2.0), 2) parameningeal or "other" sites (RR, 2.6), 3) systemic recurrence (RR, 3.1), and 4) recurrence on therapy (RR, 2.3). The absence of any of these risk factors identified a "favorable risk" group (12% of patients) with a 5-year OS rate of 71.8% +/- 23.5%. Patients with a single risk factor (32%) had an OS rate of 37.5% +/- 17.2%. Combining patients with 0 or 1 risk factor, the OS rate was 66.5% in the subgroup who had not received radiotherapy compared with an OS rate of 30.3% in the subgroup who had received radiotherapy; this difference was significant (P = 0.03). CONCLUSIONS: The results of the current analysis demonstrated that groups with a different prognosis can be identified among patients with recurrent RMS. Patients with a nonalveolar histology, a primary site other than the parameningeal or "other" sites, local recurrence, and recurrence off therapy had a better prognosis. First-line treatment may have an impact on prognostic variables. In fact, patients who had no or only one risk factor and patients who had tumors with a nonalveolar histology benefited more from salvage therapy if they had not received radiotherapy for their initial treatment. These data may be useful in planning risk-adapted salvage protocols.

Adolescent↗
PubMed1985

Cell cycle kinetic measurements in an irradiated rat rhabdomyosarcoma using a monoclonal antibody to bromodeoxyuridine.

Cell cycle kinetics after X-irradiation were studied in a solid rat rhabdomyosarcoma using a monoclonal antibody to bromodeoxyuridine (BrdUrd) in cells in which the DNA was labeled by BrdUrd. It could be shown that this tumor was composed of about 80% diploid host cells, and only 20% of the cells in the dissociated tumor were actually tetraploid tumor cells. When rats were injected intraperitoneally with BrdUrd to label S-phase cells in the tumor, only a fraction of both types of cells became labeled with BrdUrd during S-phase, even 24 h after injection. The diploid BrdUrd-labeled cells progressed rapidly into cycle; 4 h after injection of BrdUrd, labeled diploid G1-phase cells could be observed. Only 25% of the tetraploid S-phase cells could be labeled by a single injection of BrdUrd (160 mg/kg body weight). These labeled tetraploid cells progressed through the cell cycle with similar velocities as did labeled diploid cells. Using a "Mini Osmotic Pump" containing bromodeoxycytidine (BrdCyd) at high concentration (0.3 mol/L) that released BrdCyd continuously into the organism where it was converted to BrdUrd, it could be shown that after 2 days about 60% of cells in S-phase and 70% of cells in G2-phase were labeled. The fraction of labeled G2-phase cells in irradiated tumors (D = 10 and 20 Gy) was enhanced between 10 and 50 h after irradiation due to a radiation-induced G2 block in cycling tetraploid tumor cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2004

Paint-assisted microdissection-FISH: Rapid and simple mapping of translocation breakpoints in the embryonal rhabdomyosarcoma cell line RD.

BACKGROUND: Spectral karyotyping and multiple fluorophore fluorescence in situ hybridisation (M-FISH) facilitate identification of inter-chromosomal rearrangements, but are of low cytogenetic resolution in mapping translocation breakpoints. Reverse chromosome painting yields increased cytogenetic information but isolation of aberrant chromosomes is technically difficult. We have developed the technique of paint-assisted microdissection FISH (PAM-FISH), which enables microdissection of aberrant chromosomes to be carried out easily and rapidly using relatively simple apparatus. METHODS: A selected chromosome paint is hybridised to abnormal metaphases to label a chromosome of interest, which is then microdissected, amplified, labelled by polymerase chain reaction (PCR), and reverse painted onto extended normal metaphases. RESULTS: PAM-FISH was used to reassess structural chromosomal abnormalities identified by molecular cytogenetics in the rhabdomyosarcoma cell line RD. PAM-FISH improved the analysis of virtually all structural abnormalities, identifying six novel translocations and indicating that seven previously described rearrangements were in fact not present in RD. Accuracy of the breakpoint mapping obtained was confirmed by bacterial artificial chromosome-FISH. CONCLUSIONS: PAM-FISH is ideally suited to analysis of tumour metaphases as it is not affected by poor chromosome morphology. Reagents generated by PAM-FISH are also suitable for other investigations, such as mapping using sequence tagged-site PCR or genomic microarrays. PAM-FISH is technically straightforward and could readily be adopted in a routine cytogenetics laboratory for accurate high-throughput analysis of chromosome breakpoints.

Cell Line, Tumor↗
PubMed2002

Application of adjunct techniques in cytologic material in the diagnosis of rhabdomyosarcoma: case report and review of the literature.

A 4(1/2)-yr-old female presented with right-sided pleural effusion and a retroperitoneal mass. Cytologic analysis of the pleural fluid yielded malignant small round blue cells, which were noncohesive, 3-4 times the size of lymphocytes. The malignant cells had hyperchromatic, pleomorphic nuclei with moderate amounts of vacuolated cytoplasm. A few fiber-shaped cells were also seen. Immunostains for desmin, muscle-specific actin were positive; ultrastructural findings of thick and thin actin-myosin filaments confirmed the diagnosis of embryonal rhabdomyosarcoma. This case illustrates the importance of performing appropriate immunohistochemical stains and ultrastructural studies on cytological material to arrive at a definitive diagnosis.

Abdominal Neoplasms↗
PubMed2001

Fine-needle aspiration biopsy of alveolar rhabdomyosarcoma of the parotid: a case report and review of the literature.

The cytologic features of an alveolar rhabdomyosarcoma arising within the parotid gland are described. The occurrence of this neoplasm as a primary malignancy in the parotid gland is very rare, and the tumor is usually not included in the cytologic differential diagnosis of parotid tumors. The diagnosis of the current case was achieved by a combination of fine-needle aspiration biopsy and frozen sections. Realizing the difficulty of recognizing this tumor both histologically and cytologically, we present this case to increase the awareness of this tumor's occurrence within the parotid gland and other salivary glands, and to highlight cytomorphologic features that will aid the pathologist in making the correct diagnosis.

Adult↗
PubMed2005

Rhabdomyosarcoma in an adult presenting with nodal metastasis: a pitfall in fine-needle aspiration cytology of lymph nodes.

A 40-yr-old woman with an asymptomatic sinonasal rhabdomyosarcoma (RMS) initially presented with submental nodal metastasis. The fine-needle aspiration (FNA) and the subsequent biopsy of the nodal metastasis were misinterpreted as metastatic carcinoma because the primary tumor was occult, the tumor cells were exclusively round cells with a nested arrangement, and rhabdomyoblasts were absent. The correct diagnosis of metastatic RMS became apparent when the primary sinonasal tumor, detected in a CT, was biopsy proven to be an alveolar RMS. Retrospectively, there were helpful clues to the correct diagnosis in the nodal FNA and biopsy. When FNA cytology or biopsy histology of a lymph node suggests metastatic carcinoma but the tumor cells are nonimmunoreactive to carcinoma markers, the differential diagnosis should be expanded to include not only metastatic melanoma but also metastatic sarcoma and lymphoma. Cytologically, the presence of multinucleated giant tumor cells, including the rosette forms, in the FNA smears should alert the cytopathologist to the possibilities of sarcoma and anaplastic large cell lymphoma.

Adult↗