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Rhabdomyosarcoma is the most common type of soft tissue sarcoma in children. The tumor spreads by local extension, to regional lymph nodes, or by distant metastases. Metastatic spread to the testicle has been rarely described. The authors describe 2 boys who were found to have intratesticular metastases after presenting with primary tumors in their extremities. The first patient, an 11-year-old boy presented with primary disease in his left foot and an enlarged testicle. Rhabdomyosarcoma was found histologically in both the foot and the testicle. A second boy 17 years of age had a primary tumor involving the left upper extremity treated with amputation, chemotherapy, and radiotherapy. A relapse was noted 2 years later in the left testicle and was treated with orchiectomy. The authors discuss the implications and the management of this rare presentation of metastatic rhabdomyosarcoma.

Cardiac tumors in infants and children are extremely rare. Their clinical manifestations vary widely from asymptomatic presentations to life-threatening cardiac events. Improvements in diagnostic techniques, such as those offered by echocardiography, have made early detection of cardiac masses possible, with or without the presence of clinical symptoms. Fifteen pediatric cases of cardiac tumor were diagnosed at our institution between July 1989 and July 2002 (male-female ratio, 10:5; age range, one day to nine years). Eleven of the cases involved primary cardiac tumors [rhabdomyoma (n = 10) and fibroma (n = 1)]. Ninety percent of the rhabdomyomas (9/10) were associated with tuberous sclerosis. Four of the fifteen cases were secondary metastatic tumors [hepatoblastoma (n = 2), hepatoma (n = 1) and rhabdomyosarcoma (n = 1)]. Clinical manifestations of the cardiac tumors included shortness of breath (n = 5), seizure (n = 4), cardiac murmur (n = 6), and cyanosis (n = 3). Surgery was performed for three of 11 patients with primary cardiac tumor (27%) due to severe obstruction of flow (n = 2) and other cardiac defects (n = 1). The primary cardiac tumor spontaneously regressed in five of the tuberous sclerosis patients. All four of the patients with secondary cardiac tumors continued to receive chemotherapy, and only one of them subsequently experienced regression. Based on our experiences, we conclude that: 1) rhabdomyoma is the most common primary cardiac tumor in children; 2) most pediatric tumors are associated with tuberous sclerosis; 3) clinical presentation is determined by the tumor size and number of tumors, and whether expansion of the malignancy has resulted in cardiac blood-flow obstruction; 4) there is a strong possibility of regression of the primary cardiac tumor, with surgery recommended only when cardiac symptoms are severe; and, 5) unless there is a significant obstruction of blood flow, chemotherapy is still the treatment of choice for secondary cardiac tumors.

We report a case of intrascrotal rhabdomyosarcoma in a 59-year-old-male. The patient with a mass in the right scrotum was at first diagnosed with epididymitis and treated with antibiotics. The mass however, grew gradually and right orchiectomy revealed intrascrotal alveolar rhabdomyosarcoma. Para-aortic lymph node metastasis was pointed out by abdominal computed tomography. He received multidrug chemotherapy consisting of vincristine, actinomycin-D, cyclophosphamide, adriamycin, and cisplatin (IRS-III regimen 35). A complete response was obtained 3 months after the start of the chemotherapy. The patient is alive without recurrence 2 years after the surgery.

Right posterior thigh malignant peripheral nerve sheath tumor with malignant glandular and rhabdomyoblastic components was diagnosed in a 24-year-old African American man. Malignant glands and rhabdomyoblastic cells were admixed with the spindle cells. Immunohistochemistry demonstrated spindle cells positive for S100 and vimentin; the glandular component was positive for chromogranin, and rare cells were positive for CK20 but negative for CK7. Rhabdomyoblastic cells were positive for muscle-specific actin and desmin. A single pulmonary metastasis occurred 5 months after surgical resection of the tumor. Death occurred 1 month later and was probably due to a pulmonary embolus.

Purpose: To identify risk factors associated with outcomes in children with metastatic rhabdomyosarcoma (RMS) treated on the fourth Intergroup Rhabdomyosarcoma Study (IRS-IV)., Patients and Methods: Patients with metastatic RMS were treated with one of two regimens that incorporated a window of either ifosfamide and etoposide (IE) with vincristine, dactinomycin, and cyclophosphamide (VAC) or vincristine, melphalan (VM) and VAC. Study end points were failure-free survival (FFS) and overall survival (OS). Clinical factors including age, histology, sites of primary and metastatic disease, and number of sites of metastatic disease were correlated with those end points., Results: One hundred twenty-seven patients were eligible for analysis. The estimated 3-year OS and FFS for all patients were 39% and 25%, respectively. By univariate analysis, 3-year OS was significantly influenced by histology (47% for embryonal v 34% for all others, P =.026) and increasing number of metastatic sites (P =.028). By multivariate analysis, the presence of two or fewer metastatic sites was the only significant predictor (P =.007 and.006, respectively). The combination of embryonal histology with two or fewer metastatic sites identified a subgroup with 3-year FFS of 40% and OS of 47%., Conclusion: Children with group IV RMS treated on the IRS-IV study had improved OS and FFS if they had two or fewer metastatic sites and embryonal histology. This favorable subset of patients has outcomes approaching those observed in selected patients with localized, nonmetastatic disease. Thus, these patients might not be appropriate candidates for regimens that include experimental agents with substantial toxicities or unproven antitumor activity.

Primary breast carcinoma is the commonest neoplasm in women. Although rare, metastases of solid tumors from elsewhere to the breast may occur. Apart from cross-lymphatic metastasis from contralateral primary breast carcinoma, hematopoietic neoplasms occasionally involve the breast. As far as we know, less than 500 patients with secondary extramammary solid neoplasms involving the breasts have been reported in the English literature, of which malignant melanoma and lung tumors constitute the leading cause. Herein, five additional adult cases are reported and literature is reviewed. Two of the patients had primary rhabdomyosarcomas, two ovarian carcinomas, and one colon carcinoma. In one case with ovarian carcinoma, breast mass was the only manifestations of the disease relapse. All, except one with disseminated disease, had pathological diagnosis. Two of the patients died soon after the detection of breast metastasis. As a result, breast mass can be the first manifestation of relapse or part of a disseminated disease, and usually predicts poor survival.

Background: We describe a unique case of Merkel cell (primary neuroendocrine) carcinoma of the skin with a lymph node metastasis showing rhabdomyosarcomatous differentiation. Skeletal muscle differentiation has occasionally been described in primary small cell neuroendocrine carcinomas and considered a form of dual differentiation rather than a collision tumor. In the present case, capacity for divergent differentiation appeared late in the course of the tumor, which suggests a clonal origin for both components of the neoplasm., Conclusions: The coexistence of neural and rhabdomyoblastic types of differentiation, best epitomized by the Triton tumor, has been construed as the product of dual differentiation of cells originated from neural crest-derived ectomesenchyme. Since Merkel cells seem to originate from a pluripotential primitive keratinocyte and not from the neural crest, rhabdomyoblastic differentiation in a metastasis of primary neuroendocrine carcinoma of the skin probably reflects the close proximity between the programs of neural and skeletal muscle differentiation, which would have been sequentially activated in the case we are reporting.

Rhabdomyosarcomas (RMSs) are classified into embryonal (ERMS), alveolar (ARMS), and pleomorphic (PRMS) subtypes. ERMS, including botryoid variants, typically occurs in young children, ARMS typically occurs in older children and young adults, and PRMS occurs in older adults. Although ARMSs show thin fibrous bands separating nests of cells, abundant extracellular matrix production is rare in RMS. In the course of reviewing hyalinizing sarcomas we discovered a distinctive RMS in adults that closely mimicked osteosarcoma or chondrosarcoma because of the extensive matrix production. Four RMSs with hyalinized matrix were retrieved from our files. These cases were evaluated with respect to patient age and sex, tumor site and size, growth pattern, nuclear grade, cellularity, mitotic figures/20 high power fields, vascular invasion, necrosis, the presence of rhabdomyoblasts, multinucleated cells, and alveolar growth pattern. Immunohistochemistry for desmin, myogenin, MyoD1, actin, cytokeratin, S-100 protein, collagen II, and CD99 was performed. Reverse transcriptase polymerase chain reaction for the ARMS-associated PAX3/FKHR and PAX7/PKHF was also performed on three cases. The cases involved the forearm, hand, orbit, and nasopharynx of a 40-year-old woman, a 50-year-old man, an 18-year-old man, and a 21-year-old man, respectively. The tumors ranged from 3.7 to 8 cm and consisted of lobules and infiltrating cords of small round malignant cells embedded in a densely hyalinized matrix having both a chondroid and osteoid-like appearance. No definite lacunae or matrix calcification was present. An alveolar pattern was only present focally, and tumor giant cells were not present. One case had a single focus of rhabdomyoblastic differentiation with strap cells. Mitotic activity was >20 mitotic figures/20 high power fields in three of four cases. Immunohistochemically, one case strongly expressed desmin, whereas three cases expressed it focally, with a dot-like pattern. Myogenin was only focally positive, but MyoD1 was present in nearly every cell of each case. Two cases expressed actin and one expressed CD99. No case expressed cytokeratin, S-100 protein, or collagen II. Only one case contained adequate RNA for reverse transcriptase polymerase chain reaction, and this case was negative for the ARMS-associated gene fusions. Follow-up showed one patient to be dead of metastatic disease at 60 months despite intensive therapy, another patient to be disease free at 26 months, and the third patient to be disease free at 5 months. The fourth case is recent. These cases are a distinctive-appearing rhabdomyosarcoma easily mistaken for variants of chondrosarcoma, osteosarcoma, or even sclerosing epithelioid fibrosarcoma because of their hyalinizing appearance compounded by their typically focal and dot-like desmin expression. These four cases are essentially identical to the three unusual RMSs recently reported by Mentzel and Katenkamp as "sclerosing, pseudovascular rhabdomyosarcoma in adults." Although the focal alveolar architecture and the primitive cytologic appearance of these hyalinizing RMS suggest a relationship with ARMS, the presence of abundant strap cells in one case, the predominant expression of MyoD1 rather than myogenin, and the absence of ARMS-associated fusions genes point more strongly toward a variant of ERMS. However, the late adult age in two cases is unusual for both EMRS and ARMS, suggesting that sclerosing RMS may prove to be a distinct subtype of RMS. Study of additional cases will be necessary to more fully elucidate its place among RMS and its prognostic significance.

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., (Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10669)

Background: Chemotherapy (Cht) for rhabdomyosarcoma (RMS) given before local treatment can prevent mutilating surgery and high-dose irradiation (RT). Fine needle aspiration biopsy (FNAB) can confirm the diagnosis and neoadjuvant treatment can start without delay. The purpose of our study was to assess the role of FNAB in the management of childhood RMS in Slovenia., Procedure: A total of 78 children and young adults were included. FNAB provided the pre-treatment diagnosis in 37 and surgical biopsy in 41 patients. In 61 cases recurrent/metastatic disease was aspirated. Cytological diagnoses were compared to the original histological diagnoses. All case histories, cytological and histological material were reviewed and immunocytochemical staining performed when necessary., Results: FNAB provided a correct diagnosis of malignancy in all 37 primary tumours, a specific diagnosis of RMS was given in 29 (78%). With the use of immunocytochemistry during the last 15 years, the accuracy has risen to 87%. FNAB provided the diagnosis of recurrence/metastasis in 57/61 cases. No complications of FNAB were noted. Review of histology reclassified five original diagnoses of RMS into one malignant rhabdoid tumour and four sarcomas NOS. In review of cytology we were able to sub classify 80% of RMS., Conclusions: FNAB is a safe method, which enables us to establish the pre-treatment diagnosis of RMS, and to some extent even its type, without delay. In our study, FNAB successfully replaced surgical biopsy in 87% of RMS patients during the last 15 years. Neoadjuvant Cht was started immediately, surgery was delayed and more conservative. Consequently, the risk for treatment sequelae was considerably reduced., (Copyright 2002 Wiley-Liss, Inc.)

Background: Brain metastases from soft tissue sarcoma (STS) are uncommon. To the authors' knowledge limited information is available regarding the influence of the initial STS site, the significance of parenchymal versus leptomeningeal metastases, and the role of surgical resection., Methods: STS patients evaluated between July 1982 and March 1999 who presented with or developed brain metastases were identified from a prospective database. Association between factors was determined using the Fisher exact test. Survival was estimated using the Kaplan-Meier method. The influence of factors on the endpoint (disease specific survival [DSS]) was analyzed using the log-rank test. Significance was defined at P < or = 0.05., Results: A total of 3829 STS patients were evaluated during the study interval; 21 patients presented with and 19 patients subsequently developed brain metastases, accounting for < 1% (40 of 3829 patients) of the total patient group. The STS presentation status for this group of patients (n = 40) included 15 patients with primary STS, 1 patient with local recurrence, and 24 patients with metastatic disease. The most frequent types of STS metastasizing to the brain were leiomyosarcoma (eight patients), liposarcoma (five patients), rhabdomyosarcoma (four patients), and malignant fibrous histiocytoma (MFH) (four patients). Fourteen other sarcoma types were determined in the remaining 19 patients. Of the 19 patients who developed subsequent brain metastases, 18 had lung metastases as the immediate prior site of disease. The median overall follow-up for the 40 patients was 14 months (range, 1-128 months); for survivors (n = 5), the median overall follow-up was 18 months. During follow-up, 34 patients died of disease and 1 patient died of other causes. Brain metastasectomy was performed in 27 of the 40 patients and was highly associated with the initial site of STS; 20 of the 27 patients who underwent resection versus 2 of the 13 patients who did not undergo resection initially had extremity or trunk STS (P < 0.001). No association was observed between parenchymal versus leptomeningeal site of metastases and any outcome factor. The 1-year and 2-year overall DSS for the 40 patients was 55% and 25%, respectively, with a median survival of 15 months. The 1-year and 2-year postmetastasis survival rates were 34% and 20%, respectively, with a median survival of 7 months. Metastasectomy (n = 27) was associated with an improved median postmetastasis survival (9.6 months vs. 2.7 months for unresected patients; P < 0.01). The 2-year postmetastasis survival was 27% for those patients who underwent resection and 0% for the unresected patients., Conclusions: Although brain metastases from STS are rare, vigilance is warranted. Symptomatic patients should be examined neurologically and investigated thoroughly for metastases. Surgical resection may be an appropriate treatment for selected patients; however, survival is dismal.

Objective: The objective was to study the clinicopathologic features of rhabdomyosarcoma (RMS) of the oral and maxillofacial region in Jordanians., Study Design: Data were collected from records of patients treated between 1989 and 2000 at the Maxillofacial Unit of Jordan University of Science and Technology. The main outcome measures were age, gender, location, stage of disease, histopathologic type, treatment received, follow-up period, and eventual outcome., Results: Nine patients with RMS aged 4 to 17 years were found, with a male to female ratio of 2:1. Six (67%) bony sites and 7 (78%) soft tissue sites were involved. The extent of disease was locoregional in 8 (89%) cases, nodal in 3 (33%) cases, and distant metastatic in 2 (22%) cases. The Intergroup Rhabdomyosarcoma Study classification of clinical groups was as follows: 2 (22%) cases in stage II, 5 (56%) cases in stage III, and 2 (22%) cases in stage IV. The histopathologic types found were 6 (67%) embryonal, 2 (22%) alveolar, and 1 (11%) undifferentiated. Triple agent chemotherapy was used in the treatment of 8 cases, singly or in combination with surgery or radiotherapy. Two patients are still alive, and 5 patients have died of disease., Conclusions: The clinicopathologic features of maxillofacial RMS in this group of Jordanians are different from those of people from other countries. Further studies are needed to have a better understanding of the behavior of RMS in the oral and maxillofacial area.

Objective: To report a rare presentation of metastatic orbital rhabdomyosarcoma and the corresponding findings on magnetic resonance imaging (MRI)., Design: Interventional case report., Results: A 29-year-old white man was diagnosed with rhabdomyosarcoma of the left sinus and orbit for which he was treated with chemotherapy and radiation. Eighteen months after diagnosis, he returned with subacute right eye pain and dysmotility of his extraocular muscles. MRI revealed solitary enlargement of the right medial rectus muscle, and thyroidopathy was suspected. Over the next 2 months, symptoms progressed, and proptosis developed. MRI showed infiltration of seven extraocular muscles. A biopsy of right orbital tissues and the right medial rectus muscle was performed. Special tissue typing confirmed metastatic alveolar rhabdomyosarcoma. The patient underwent palliative radiation therapy and chemotherapy, but he ultimately died of disseminated disease., Conclusions: Rhabdomyosarcoma can rarely metastasize to the extraocular muscles. Earlier recognition of orbital metastasis through radiographic and biopsy findings, along with prompt and aggressive treatment, may prevent fulminant spread of rhabdomyosarcoma.

The author described the case of parotid gland rhabdomyosarcoma in 4 years old boy. As there was no parents agreement to initial, radical surgical treatment, the patient underwent chemo- and radiotherapy, after which temporary remission of the disease was observed. The surgical treatment was performed for local recurrence, but despite radical parotidectomy, which was done, the progression of disease was occurred (with local recurrence and bone metastases). The patient died 3 years after initial diagnosis.

A case of ovarian immature teratoma with rhabdomyosarcomatous recurrence in a 6-year-old girl is described. The primary tumor consisted of a dermoid cyst and a solid nodule composed of mature and immature mesenchymal tissue. The most immature mesenchymal cells showed no distinctive differentiation except for focal rhabdomyoblastic differentiation. The primary tumor was diagnosed as immature teratoma, grade 2, stage IIa. Despite left oophorectomy and excision of uterine serosal implants, chemotherapy, and radiation, four intrapelvic recurrences developed within 3 years. Although the primary tumor contained only a few rhabdomyoblasts, the recurrent tumors became increasingly rhabdomyosarcomatous. The patient died of systemic disease 3 years after presentation. This case and previous reports indicate that the prognosis of patients with ovarian immature teratoma with rhabdomyosarcomatous recurrence is poor and similar to that of primary ovarian rhabdomyosarcoma.

Intraperitoneal neoplastic involvement in rhabdomyosarcoma is rare and its incidence and imaging characteristics need to be further described. We present the computerized tomography (CT) findings of a case with pelvic rhabdomyosarcoma and intraperitoneal neoplastic involvement. Enhanced peritoneal and retroperitoneal masses were seen around the liver, spleen, in the paracolic gutters, and in the lesser sac without evidence of ascites, mesenteric nodules or omental caking. Our case also showed that absence of ascites does not preclude the presence of peritoneal involvement. Progression in the peritoneal disease was also well demonstrated by CT.

Treatment and prognosis have not been well characterized in germ cell tumors (GCT) with a malignant nongerm cell component. Patients with a mediastinal tumor, neural or rhabdomyosarcomatous differentiation and distant metastases have the poorest prognosis. We report a rare case of mixed GCT composed of seminoma, teratoma and rhabdomyosarcoma with the rhabdomyosarcomatous component metastasized into the liver and bone marrow (BM) causing hypercalcemia. The patient was treated with differentiation-tailored chemotherapy (CHT) including a disease-adapted high-dose (HD) CHT regimen with purified autologous PBSCT (APBSCT) and pamidronate. To date, remission has lasted for 4 years. Tumor-adapted CHT including HD-CHT with APBSCT can induce long term remissions in high-risk patients with transformed GCT. A review of the literature is given.

Background: To the authors' knowledge, the incidence of brain metastases at the time of diagnosis in children with metastatic rhabdomyosarcoma (RMS) arising outside the head and neck region is unknown, and routine imaging to identify metastatic brain involvement is costly., Methods: The authors retrospectively reviewed the results of computed tomography (CT) or magnetic resonance imaging (MRI) scans of the head, which was mandated by protocol, in patients with metastatic RMS arising outside the head and neck region who were enrolled on the fourth Intergroup Rhabdomyosarcoma Study (IRS-IV; 1991--1997)., Results: Of 100 eligible patients with metastatic RMS arising outside the head and neck region, 56 (56%) underwent head CT (n = 51) and/or MRI (n = 11) scans. Seven of these 56 patients (12.5%) had abnormal scans. Three patients with physical findings suggesting head or neck pathology underwent imaging that confirmed the presence of metastases in bone (one patient), orbit (one patient), or lymph nodes (one patient). One patient who presented with seizures had imaging findings consistent with cerebral embolic infarctions. Of three asymptomatic patients, one had bone metastases that also were identified on skeletal survey and one had bone metastases in the base of the skull that were not identified on bone scan. The remaining asymptomatic patient had a retroperitoneal paraspinal tumor with spinal canal extension and subsequently developed leptomeningeal disease dissemination., Conclusions: Brain metastases are uncommon at the time of initial diagnosis of metastatic RMS arising outside the head and neck region, and the majority of abnormalities detected on head CT or MRI scans are evident clinically or on other imaging studies. Patients with clinical findings suggesting intracranial pathology and those with paraspinal tumors may benefit from brain imaging, but cost savings may be realized by foregoing imaging in patients without these features., (Copyright 2001 American Cancer Society.)

PSA is an oncodevelopmental antigen usually expressed in human tumors with high metastatic potential. Here we set up a metastatic model in nude mice by using TE671 cells, which strongly express PSA-NCAM. We observed the formation of lung metastases when TE671 cells were injected intravenously, intramuscularly, and intraperitoneally, but not subcutaneously. Intraperitoneal injections also induced peritoneal carcinosis, ascites, and liver metastases. To evaluate the putative role of PSA in the metastatic process we used a specific cleavage of PSA on NCAM by endoneuraminidase-N on intraperitoneal primary tumors. Mice with primary intramuscular tumors were taken as control. Repeated injections of endoneuraminidase-N led to a decrease in PSA expression in primary intraperitoneal nodules and ascites but not in intramuscular primary tumors. Endoneuraminidase-N also increased the delay in ascitic formation and decreased the number of lung or liver metastases in the case of intraperitoneal tumors but not in the case of intramuscular tumors. When metastases occurred in endoneuraminidase-N injected animals, they strongly expressed PSA-NCAM. Therefore, we established a relationship between PSA expression on the surface of primary tumor cells and the metastatic process.

The rhabdomyosarcoma (RMS) is a tumour derived from the mesenchymal cells that give origin to striate muscle. It appears most frequently at the pediatric age, although some appear in adolescence and in young adulthood. It is a high grade malignancy that metastatisis frequently (most importantly to the lung). There are two principal types: alveolar RMS and embrionary RMS. It can appear in any localization, being the most frequent the periorbitary area and the paranasal sinuses, and the second in frequency the genitourinary system (bladder, prostate and vagina). The therapeutic management is multidisciplinary and local therapies must always be accompanied with polychemotherapy. With combined treatments a curation rate of almost 90% can be reached in good prognosis cases, although it drops to 20% in those with disfavourable prognostic factors. The protocols with higher chemotherapy doses and subsequent rescue with blood-borne progenitor cells have not yet proved their efficiency. We present the case of a fifteen-year old patient with an embrionary rhabdomyosarcoma of the prostate, we analyze the clinical evolution and we revise the present therapeutic management of these neoplasies.

We report appearance of two cases of metastases to the breast on MR mammography. Metastasis from cervical cancer displayed a hypointense tumor with a central area of high signal intensity on T2-weighted images and rapid annular enhancement with persistent central contrast enhancement. The metastases from rhabdomyosarcoma were characterized by multiple tumors with high signal intensity on T2-weighted images and fast annular contrast enhancement. We show unusual malignant breast lesions for possible identification in dynamic MR mammography.

Purpose: To investigate the antitumor activity and toxicity of topotecan, used alone and in combination with conventional therapy, in patients with metastatic rhabdomyosarcoma (RMS)., Patients and Methods: Forty-eight patients younger than 21 years of age with newly diagnosed metastatic RMS received 2.0 to 2.4 mg/m(2) of topotecan intravenously daily for 5 days every 21 days before standard therapy. Two courses were given in the absence of progressive disease or excessive toxicity and response was assessed. Patients with at least a partial response (PR) to topotecan proceeded to therapy with alternating courses of vincristine 1.5 mg/m(2), dactinomycin 1.5 mg/m(2), and cyclophosphamide 2.2 g/m(2) (VAC) and vincristine 1.5 mg/m(2), topotecan 0.75 mg/m(2) daily x 5, and cyclophosphamide 250 mg/m(2) daily x 5. Patients who did not respond to topotecan received continuation therapy with VAC alone., Results: The overall response rate to topotecan was 46% (complete response, 4%; partial response 42%). Unexpectedly, patients with alveolar RMS had a higher rate of response (65%) than those with embryonal RMS (28%; P: = .08). The most common grade 3 or 4 toxicities were neutropenia (67%), anemia (33%), thrombocytopenia (25%), and infection (21%). Two-year failure-free survival and survival estimates were 24% and 46%, respectively. Response to window therapy did not correlate with survival., Conclusion: The high response rate and acceptable toxicity profile of topotecan in children with advanced RMS support further evaluation of this agent in phase III trials. The superior responses in alveolar RMS are of interest.

Small bowel perforation is rarely caused by metastasis from an extra-abdominal malignancy. This report describes three cases of small bowel perforation that occurred secondary to a metastatic tumor. The first case involved a 72-year-old man with malignant lymphoma of the larynx that had been treated with chemo- and radiation therapy; the second involved a 70-year-old man with rhabdomyosarcoma of the mediastinum that had been treated with radiation therapy; and the third involved a 41-year-old man with lung carcinoma that had been treated with surgery 10 months prior to perforation. Each patient presented with acute abdominal pain, had X-ray findings of free air in the abdomen, and underwent limited emergency surgery. Wedge resection and closure of the ileum was performed for the first patient and partial bowel resection with the creation of an intestinal stoma was performed for the second and third patients. In each case, the histologic findings of the resected specimens were consistent with the extra-abdominal primary tumors. Although the patients recovered sufficiently to begin eating and moving about, all three died of cancer or cancer-related complications within 45 days of surgery. We conclude that surgeons should be aware of the poor prognosis of such patients and perform only the minimal surgery required.

Background: The incidence of bone metastases in soft tissue sarcoma (STS) patients seems to be low but has not been studied separately. In this study, the authors aimed to determine the value of routine radionuclide bone scanning in preoperative staging of STS patients., Methods: Preoperative bone scans were evaluated retrospectively in 109 consecutive patients (median age, 44 years; range, 1-86) with intermediate or high grade STS. Scans were scored in 3 categories: 1, metastases very likely; 2, equivocal; and 3, normal or benign lesions., Results: Category 1 scans were found in 8 of 109 patients (7%); in all 8 patients, bone metastases were confirmed. Six of these eight patients reported pain, and all had additional lung, bone marrow, or lymph node metastases. The highest rate (17%) was found in the rhabdomyosarcoma subgroup (n = 18). Category 2 (equivocal) scans were present in 12 of 109 patients (11%), in all of which bone metastases were excluded through additional investigations. Category 3 (normal) scans were found in 81%. Bone metastases were at least as frequent as lung metastases (4%) and were the single site of systemic disease in 4%. The rate of bone metastases was 55% in patients with bone pain versus 2% in patients without pain., Conclusions: Bone metastases in primary STS patients are rare (7%) yet in this study at least as frequent as lung metastases. The low rate in asymptomatic patients versus the high rate in symptomatic patients supports the use of bone scanning in symptomatic patients only. The yield of routine bone scanning is low., (Copyright 2000 American Cancer Society.)

Background: Among nonepithelial second neoplasms which are known to be induced by irradiation, rhabdomyosarcomas are extremely rare, and melanomas are infrequent. We report a high-grade sarcoma with rhabdomyoblastic differentiation, which appeared 30 years after megavoltage irradiation for an endometrial adenocarcinoma, and a malignant melanoma which arose after 6 years in the irradiation field of a fibrosarcoma., Methods: Histology and immunohistochemistry were performed in both cases. In the first case, electron microscopy was also performed. In the second, the previous tumor was re-evaluated., Results: The first case showed histological, immunohistochemical and ultrastructural features of a rhabdomyosarcoma. In the second case, a lentigoid malignant melanoma was histologically and immunohistochemically demonstrated, whereas the previously resected tumor was a fibrosarcoma negative to melanoma markers., Conclusions: Rare cases of rhabdomyosarcomas and melanomas are induced by irradiation, although in some cases other factors (i.e., genetic risk, chemotherapy) may have a prominent etiopathogenetic role in their development. A close follow-up and a careful examination of the irradiated area should facilitate an early diagnosis of these aggressive postradiation second neoplasms.

We retrospectively analyzed the MRI findings of rhabdomyosarcoma (RMSA) in 23 patients to evaluate its role in staging and management. Heterogeneous signal abnormalities were noted in the sarcoma lesions with significant contrast enhancement. Seven head and neck cases showed direct bone invasion and destruction; only one had distant bony metastasis. Metastasis was noted in the lymph nodes, lung, bone, abdominoperitoneum, and head and neck soft tissue. MRI findings of RMSA are most helpful in staging and assessing therapeutic response.

Background and Purpose: Macroscopic subcutaneously growing R1H-tumours have been shown to respond almost independently of the dose per fraction when treated under ambient conditions. In addition decelerated repopulation during fractionated irradiation has been shown for this experimental tumour. The aim of the present study was to investigate whether this is also the case for pulmonary micrometastases which are assumed to be fully oxygenated or whether differences in the oxygenation status of the tumour possibly alters its response to fractionation. The influence of the dose per fraction and overall treatment time on the response of micrometastases to fractionated irradiation was studied., Materials and Methods: Pulmonary metastases were induced by i.v. injection of viable tumour cells. Treatment was started 14 days later, when metastases reached an average size of four cells. Total doses of 16 to 28 Gy were administered within an overall treatment time of 11 or 25 days, using doses per fraction of 1, 2, or 4 Gy. Tumour response was quantified by metastatic control (MCD(37%))., Results: Fractionation had a significant influence on local control (P=0.009). After application of 1, 2, or 4 Gy and an overall treatment time of 11 days the MCD(37%) was 25.4 (95% C.I.: 21.5-32.0) Gy, 20.7 (17. 0-24.0) Gy, and 18.5 (14.9-21.6) Gy, respectively. When overall treatment time was prolonged to 25 days the MCD(37%) increased to 25. 5 (21.3-33.5) Gy when fractions of 2 Gy where applied, but this difference was not significant (P=0.13). The doubling time of 12.8 days determined for the metastatic clonogenic tumour cells during fractionated irradiation was significantly longer than the 4.1 days observed for untreated metastases (P=0.006)., Conclusions: The results show a strong influence of fractionation on treatment outcome and a decelerated repopulation during fractionated irradiation treatment for well oxygenated pulmonary metastases of the R1H-tumour.

According to data available at the Institute (1985-1999, approx. 1,200 patients), the lung is the most frequent site of cancer dissemination (up to 75%). Such most frequent pediatric children tumors as Wilms' tumor, neuroblastoma, rhabdosarcoma, osteogenic sarcoma and that of Ewing disseminate to lung in 85%, particularly, at advanced stages.

Purpose: Although brain metastases rarely occur in children with solid tumors, pediatric Ewing sarcoma (ES) and rhabdomyosarcoma (RMS) are among those most likely to metastasize to the brain. The authors review their institution's experience of brain metastases of ES and RMS., Patients and Methods: The clinical characteristics, therapy, and outcome of all patients treated at St. Jude Children's Research Hospital over a 36-year period who had ES or RMS with brain metastases were reviewed., Results: Of 419 patients with RMS, 10 (2.4%) had brain metastases. Of 335 patients with ES, 11 (3.3%) had brain metastases. The median age of the 21 patients was 10.4 years (range, 0.4-18.0 years) at the time of primary diagnosis. All had clinical signs of central nervous system (CNS) involvement. Outcome was dismal: The median duration of survival after diagnosis of brain metastasis was 2.7 months. The estimated survival 1 year after detection of brain involvement was 23.8%+/-8.5% (mean +/- standard error). One patient, who underwent chemotherapy, surgical resection, and radiotherapy, at the time of this writing is a long-term survivor., Conclusions: Brain metastases are rare in children with ES and RMS, but carry a grave prognosis. Because most brain metastases are accompanied by signs of neurologic involvement, routine imaging studies of asymptomatic children are not necessary. Combined-modality treatment offers the best chance of long-term survival.

Rhabdomyosarcoma is a common childhood malignancy that may occasionally occur as a component of a mixed mesenchymal tumor, e.g., a triton tumor or malignant ectomesenchymoma. A case is reported of a 13-year-old boy who had resection of a paratesticular embryonal rhabdomyosarcoma with subsequent radiation and chemotherapy. Two years later, a retroperitoneal metastasis was resected. Histology showed a mixture of rhabdomyoblasts, ganglion cells, and a third population of cells with combined features of these two distinct cell types. Electron microscopy confirmed the presence of rhabdomyoblasts with characteristic bundles of myofilaments and Z-band material, and ganglion cells with prominent nuclei and nucleoli, rough endoplasmic reticulum, dense core granules, filaments, and tubules. Notably, the third cell population showed features of both rhabdomyoblasts and ganglion cells. Immunohistochemistry confirmed the mixed population of rhabdomyoblasts (positive for vimentin, desmin, negative for S-100, NSE), ganglion cells (positive for S-100 and NSE, negative for vimentin and desmin), and the third population expressing all test antigens. The features of this metastatic lesion are those of a malignant ectomesenchymoma with combined rhabdomyosarcoma and ganglioneuroma components. It is postulated that this lesion results from biphenotypic expression of tumor cells that previously expressed only rhabdomyoblastic differentiation. The role of prior chemotherapy and radiotherapy in this particular case is unclear.

Background: In musculoskeletal sarcomas, brain metastases are rare, but severely affect quality of life., Methods: All patients with musculoskeletal sarcomas who were treated at our institutions from 1975 to 1997 were reviewed for examples of brain metastasis., Results: Of 480 sarcoma patients, 179 had distant metastases, including 20 patients with brain metastases (4.2%). Alveolar soft part sarcoma (3/4), extraskeletal Ewing's sarcoma (2/8), rhabdomyosarcoma (2/13) and bone Ewing's sarcoma (2/18) tended to metastasize to the brain. All 20 patients had distant or local relapses and 16 of the 20 patients had pulmonary metastases. Three patients underwent surgical treatment and two of them survived over 1 year. Mean survival after diagnosis of brain metastasis was 5.1 months., Conclusions: Patients with alveolar soft part sarcoma, Ewing's sarcoma, rhabdomyosarcoma and pulmonary metastases have a high risk of brain metastasis.

Background: Fine needle aspiration (FNA) is a valuable technique in the diagnosis of soft tissue tumors or their metastases., Case Report: A rhabdomyosarcoma of the left atrium with metastasis to the pancreas was diagnosed by FNA in a 74-year-old female. The patient presented with dyspnea, weight loss and generalized weakness and was found to have a cardiac arrhythmia. Magnetic resonance imaging showed a 9-cm mass in the left atrium and anterior mediastinum. Computed tomography (CT) of the abdomen revealed a 2.8-cm nodule within the head of the pancreas. The patient underwent CT-guided percutaneous aspiration biopsy of the pancreatic mass on the first hospital day and, on the second day, transvenous FNA biopsy of the intracardiac mass. The cytologic morphology and immunocytochemistry of the aspirated material from both sites established a diagnosis of cardiac rhabdomysarcoma with metastasis to the pancreas., Conclusion: This is the fifth reported case of rhabdomysarcoma metastatic to the pancreas and the first in which the diagnosis was made by FNA, thereby eliminating the need for open biopsy.

Background: Only anecdotal reports about the results of combined resection of T4 lung tumors infiltrating the thoracic aorta exist., Methods: Seven patients (mean age, 57.5 years; range, 43 to 78 years) underwent a resection of the infiltrated segment of the thoracic aorta together with a left pneumonectomy (n = 6) or left upper lobectomy (n = 1). Five tumors were primary non-small cell lung carcinomas (T4N2 in 3 patients, T4N1 in 2), one was a metastasis of breast cancer, and one was rhabdomyosarcoma., Results: No patient died perioperatively. The 2 patients with rhabdomyosarcoma and metastasis of breast cancer died 2 and 7 months postoperatively. Of the 5 patients with bronchial carcinoma, 3 died after 17, 26, and 27 months as a result of distant metastasis. Two patients are alive after 14 and 50 months without evidence of disease recurrence. One-year, 2-year, and 4-year survival rates for patients with bronchial carcinoma were 100%, 75%, and 25%, respectively., Conclusions: Combined resection of the lung and thoracic aorta can be performed with low morbidity and mortality when offered to highly selected patients. Adequate local control of tumor can be achieved for N1 and single-level N2 non-small cell lung carcinomas, but not for tumors with other histologies.

A 15-year-old patient is described who presented with cervical lymphadenopathy. A lymph node biopsy confirmed a metastatic neoplasm composed of islands and aggregates of round to polygonal-shaped cells with surrounding hyalinised fibrous stroma. The tumour cells contained a clear glycogen-rich cytoplasm and stained for desmin, muscle-specific actin and sarcomeric actin. Electron microscopy revealed paranuclear thick and thin filaments. These findings confirm striated muscle differentiation and a diagnosis of glycogen-rich clear cell rhabdomyosarcoma. The tumour recurred in a cervical lymph node after 2 years. This is yet another tumour that must be considered in the differential diagnosis of clear cell tumours of the head and neck region.

Uterine rhabdomyosarcoma is rare, with only 60 reported cases. We describe an asymptomatic patient with metastatic uterine rhabdomyosarcoma manifested as extensive mediastinal lymphadenopathy. This 73-year-old woman had been previously treated for endometrial rhabdomyosarcoma and was referred to us when a right hilar density was seen on a chest radiograph; computed tomography showed a nodule in the right upper lobe and extensive right hilar and subcarinal lymphadenopathy. The diagnosis of metastatic rhabdomyosarcoma was made by fiberoptic bronchoscopy using transbronchial needle aspiration (TBNA). The patient is well 11 months after completing five cycles of chemotherapy. This is the first reported case of uterine rhabdomyosarcoma with metastasis to the mediastinum and the first case diagnosed with TBNA, which avoided the need for an invasive diagnostic procedure.

Aim: Influenced by the incorrect diagnosis of a bone metastasis caused by bone necrosis we evaluated reasons and frequency of bone necrosis in patients referred for bone scanning in follow-up of tumors., Methods: Bone scans performed within two years on patients with primary bone tumors or tumors metastatic to bone were reviewed in respect to the final diagnosis bone necrosis., Results: We found the cases of three young patients who presented the appearance of hot spots on bone scintigrams which were finally diagnosed as bone necrosis. In two cases the diagnosis was based on histological findings, in one case the diagnosis was made evident by follow-up. All the three patients had been treated by chemotherapy and presented no other reason for the development of bone necrosis. Enhanced tracer uptake in all sites decreased within eight weeks up to two years without therapy., Conclusion: Single and multiple hot spots after chemotherapy may be originated by bone necrosis but mimicry metastases.

Tumor growth and proliferative activity of tumor cells were suppressed and the number of pulmonary metastases in C57B16 mice decreased 3.3-fold following seven injections of cycloferon (100 mg/kg body) to induce interferon production. Injections were carried out 1-16 days after subcutaneous transplantation of Lewis lung carcinoma. After mice were immunized with ovine red blood cells, cycloferon administration raised thymus-dependent humoral immune response. After eight injections of cycloferon (50 mg/kg body) into rats, from day of intravenous transplantation of rhabdomyosarcoma RA-23 until day 20, no significant effect on metastasizing into the lung was recorded. However, single injection of cyclophosphamide 50 mg/kg inhibited metastasis formation. The highest suppressor effect was registered with combination cycloferon-cyclophophamide treatment: mean weight of metastasis decreased by half, as compared with treatment with cyclophosphamide alone. Both drugs caused karyotypical abnormalities to occur in metastatic cells. Tumor growth and spreading suppression after cycloferon should be attributed to cytotoxic antitumor action, cell proliferation inhibition and immunomodulating effect.

Previous studies have demonstrated that IL-15 administration after cyclophosphamide (CY) injection of C57BL/6J mice bearing the i.m. 76-9 rhabdomyosarcoma resulted in a significant prolongation of life. In the present study, we investigated the immune response against the 76-9 experimental lung metastases after CY + IL-15 therapy. Administration of CY + IL-15, but not IL-15 alone, induced prolongation of life and cures in 32% of mice bearing established experimental pulmonary metastases of 76-9 tumor. The CY + IL-15 therapy resulted in increased levels of NK1.1+/LGL-1+ cells, and CD8+/CD44+ T cells in PBL. In vitro cytotoxic assay of PBL indicated the induction of lymphokine-activated killer cell activity, but no evident tumor-specific class I-restricted lytic activity. Survival studies showed that the presence of NK and T lymphocytes is necessary for successful CY + IL-15 therapy. Experiments using knockout mice implied that either alphabeta or gammadelta T cells were required for an antitumor effect induced by CY + IL-15 therapy. However, mice lacking in both alphabeta and gammadelta T cells failed to respond to combination therapy. Cured B6 and alphabeta or gammadelta T cell-deficient mice were immune to rechallenge with 76-9, but not B16LM tumor. B cell-deficient mice showed a significant improvement in the survival rate both after CY and combination CY + IL-15 therapy compared with normal B6 mice. Overall, the data suggest that the interaction of NK cells with tumor-specific alphabeta or gammadelta T lymphocytes is necessary for successful therapy, while B cells appear to suppress the antitumor effects of CY + IL-15 therapy.

Purpose: We assess the benefit of retroperitoneal lymph node dissection for adult paratesticular rhabdomyosarcoma., Materials and Methods: A total of 19 adults with paratesticular rhabdomyosarcoma who underwent retroperitoneal lymph node dissection between 1980 and 1997 comprise our study population. Postoperative chemotherapy was administered in all patients, including cyclophosphamide, doxorubicin and vincristine with or without consolidation with ifosfamide and etoposide in 17, and vincristine, actinomycin D and cyclophosphamide in 2. Radiation therapy also was administered in 2 patients. Patients were classified into pathological and clinical groups according to the Intergroup Rhabdomyosarcoma Studies. Mean followup was 6.4 years (range 0.5 to 17.6)., Results: A total of 17 patients (89%) were disease-free and 2 (1 in pathological group I and 1 in pathological group II) died of disease that recurred outside of the retroperitoneum. Of 16 clinical group I patients 9 were in pathological group II. There were negative nodes in 2 of 3 clinical group II patients. Thus, abdominal computerized tomography correctly staged only 8 of 19 patients (42%)., Conclusions: Retroperitoneal lymph node dissection accurately stages paratesticular rhabdomyosarcoma and eliminates the need for abdominal radiotherapy in patients in pathological group II. Combined modality therapy with retroperitoneal lymph node dissection and postoperative chemotherapy achieves a high cure rate.

Objective: To evaluate the relationship between alteration of p16 gene, its protein expression and the pathogenesis and development of rhabdomyosarcoma (RMS)., Methods: 44 cases of RMS were examined for alteration of p16 gene with PCR-SSCP and 47 cases of RMS were examined for p16 protein expression with immunohistochemical method., Results: The homozygous deletion of p16 gene was observed in 2 cases and mutations in 6 cases. Of these 8 cases with altered p16 gene, 6 had extensive invasion, recurrence or metastasis. The total negative rate of p16 protein expression in RMS was 38.3% (18/47 cases). Of these 8 cases with alterations of p16 gene, negative expression for p16 protein was observed in 7 cases and positive in only 1 cases. In contrast, no structural abnormalities of the p16 gene were detected in another 11 cases with negative expression of p16 protein. Higher rates of p16 gene abnormality and loss of p16 protein were observed in ARMS than in ERMS. Higher rate of extensive invasion, recurrence or metastasis was also found in the group negative for p16 protein., Conclusion: The abnormalities of p16 gene and loss of p16 protein expression may be related to the pathogenesis and development of some RMS.

Objective: The purpose of this study was to determine the incidence and CT imaging features of intraperitoneal rhabdomyosarcoma in children., Conclusion: Approximately 10% of children with rhabdomyosarcoma may have intraperitoneal neoplastic involvement either at the time of diagnosis or subsequently. On CT, intraperitoneal rhabdomyosarcomas are associated with ascites, enhancing nodules, masses, a pseudomyxoma peritonei-like appearance, and omental caking.

Chromosome 11p15 has attracted considerable attention because of the biological importance of this region to human disease. Apart from being an important tumor suppressor locus showing loss of heterozygosity (LOH) in several adult and childhood cancers, 11p15 has been shown by linkage analysis to harbor the gene(s) for the Beckwith-Wiedemann syndrome. Furthermore, the clustering of known imprinted genes in the 11p15.5 region suggests that the target gene may also be imprinted. However, positional cloning efforts to identify the target genes have been complicated by the large size (approximately 10 Mb) and complexity of LOH at 11p15. Here, we have analyzed 94 matched normal and breast tumor samples using 17 polymorphic markers that map to 11p15.5-15.4. We have defined precisely the location of a breast tumor suppressor gene between the markers D11S1318 and D11S4088 (approximately 500 kb) within 11p15.5. LOH at this region occurred in approximately 35-45% of breast tumors analyzed. In addition, we have fine-mapped a second, critical region of LOH, that spans the markers D11S1338-D11S1323 (approximately 336 kb) at 11p15.5-p15.4, that is lost in approximately 55-60% of breast tumors. There is a striking correlation between the loss of the two 11p loci and the clinical and histopathological features of breast tumors. LOH at region 1 correlated significantly (P = 0.016) with early events in malignancy and invasiveness. In contrast, the loss of the more proximal region 2, is highly predictive (P = 0.012) of aggressive metastatic disease. Thus, two distinct tumor suppressor loci on chromosome 11p15 may contribute to tumor progression and metastasis in breast cancer. The fine mapping of this intriguing chromosomal region should facilitate the cloning of the target genes and provide critical clues to understanding the mechanisms that contribute to the evolution of adult and childhood cancers.

Objective: To observe the correlation between MDM2, p53 genes and the pathogenesis, clinical pathology and prognosis in rhabdomyosarcoma (RMS)., Methods: Thirty one cases of MRS with follow-up history were covered for this study. MDM2 and p53 genes were detected by digoxigenin labeling in situ hybridization-technique., Results: The positive rates for MDM2 and p53 genes were 77.4% (24/31) and 66.7% (21/31) respectively, regardless of age, sex and the histological typing of RMS, but there was remarkable difference in the positive rates and intensity between the well and poorly differentiated cases, metastatic and non-metastatic cases as well as one year and three years survival period (P < 0.05)., Conclusions: The detection of MDM2 and p53 gene is considered valuable in evaluating the malignant degree, predictable metastasis and prognosis of RMS.

Reconstruction techniques for pathological fractures caused by bone metastases often include acrylic cement to stabilise defects. The aim of this study was to test in a rodent model, whether outcome could be improved by local chemotherapy from an anticancer drug added to the acrylic cement. Tumour excision 17 days after transplantation into the femur was followed by fractionated irradiation. Supplementation of acrylic cement with daunorubicin led to a considerable reduction of TCD37% from 72.9 Gy (62.2-82.8) to 29.3 Gy (21.8-37.5) (P = 0.0007). Local chemotherapy diffusing from bone cement combined with postoperative radiotherapy was highly effective in the experimental system studied.