Transformation of a primitive myxoid mesenchymal tumor of infancy to an undifferentiated sarcoma: a first reported case.

An 8-month-old girl underwent surgical resection of a cervical mass with histologic diagnosis of a primitive myxoid mesenchymal tumor of infancy (PMMTI). More than 5 years after the initial surgical intervention, the tumor recurred locally, with numerous distant metastases. The histologic morphology of this tumor was compatible with a diagnosis of an undifferentiated high-grade sarcoma. PMMTI is a recently described poorly differentiated fibroblastic soft-tissue tumor of infancy, of at least borderline biological behavior, characterized by local recurrence and a potential to metastasize. We present here the first case of a transformation of a PMMTI into an undifferentiated high-grade sarcoma.

Malignant ectomesenchymoma in children and adolescents: report from the Cooperative Weichteilsarkom Studiengruppe (CWS).

BACKGROUND: Malignant ectomesenchymoma (MEM) is a soft tissue tumor with heterologous rhabdomyoblastic components believed to arise from pluripotent migratory neural crest cells. To date merely 50 cases have been published and the knowledge about the course of disease and optimal treatment is limited. METHODS: Six patients with MEM were registered 1996-2009. The diagnosis was confirmed according to current criteria. Their treatment and outcome was analyzed. RESULTS: The median age of the three females and three males was 0.6 years (range, 0.2-13.5). The mesenchymal component in all tumors was rhabdomyosarcoma (RMS), the neural component ganglioneuroblastoma/neuroblastoma (n = 5) and peripheral primitive neuroectodermal tumor in one case. Five patients presented with localized, one with metastatic disease. All but one patient received multiagent chemotherapy during their initial treatment. The tumors of 4/5 patients with localized MEM were at least grossly resected at best surgery; the patient without gross resection was additionally irradiated. Three of four evaluable tumors responded well to induction chemotherapy. All patients achieved a first complete remission (CR), but three recurrences (two local, one systemic) occurred. The individual with metastatic MEM did not survive, but all five patients with localized MEM are currently alive in CR with a median follow-up of 5 years (range: 2.1-13.7). CONCLUSIONS: Risk-factors and outcome of MEM appear to be comparable with other highly malignant pediatric soft tissue sarcoma when a multimodal treatment strategy including chemotherapy and adequate local treatment is pursued. We propose that treatment of patients with MEM be done according to pediatric protocols similar to other rhabdomyosarcoma-like soft tissue sarcoma.

Bleomycin, etoposide and cisplatin (BEP) combination with concurrent imatinib mesylate (GLEEVEC) in chronic myeloid leukemia (CML) patient with mesenchymal tumor.

Imatinib is now indicated as the first line therapy for chronic myeloid leukemia (CML). Treatment of CML with imatinib is generally well tolerated and the risk of severe adverse affects is low. Many new drugs including targeted therapy are combined with antineoplastic agents safely. We here report a patient with CML who developed concurrent mesenchymal tumor while undergoing therapy with imatinib and treated with combination chemotherapy including bleomycin, etoposide, and cisplatin, as well as imatinib without severe toxicity.

[Malignant solid tumors in neonates: a study of 71 cases]. / Tumeurs solides malignes néonatales: à propos de 71 cas.

UNLABELLED: Malignant neonatal tumors are rare and comprise 2% of childhood malignancies. Clinical features, histologic types, prognosis were very different from those seen in older children, facing oncologists with diagnostic, therapeutic and ethical problems. PATIENTS AND METHODS: In a retrospective study from January 1987 to January 2004, we reviewed the management of neonates treated at the Institute Gustave Roussy for a malignant solid tumor for whom symptoms started in the first month of life. RESULTS: Seventy-one neonates were treated, comprising 1,2% of the overall patients treated during the same period of time. Of these 71 patients, 42 (59%) presented with neuroblastomas, 12 (17%) with mesenchymal tumors, 6(8%) with cerebral tumors and 11 with various other types of tumors. Fifty-nine patients underwent surgical resection. Thirty-eight neonates received chemotherapy, administered at a 30 to 50% reduced dose. Hematologic toxicities and infections were the main therapeutic complications. Very small doses of radiotherapy were used in only 5 children. There has been no therapy-related mortality. Twenty-two of the 57 survivors have sequelae, especially patients with intraspinal neuroblastoma. The 5 year overall survival was 79%. CONCLUSIONS: Neonatal malignant solid tumors, except for cerebral tumors, have a good prognosis. The young age of patients resulted in problems of treatment tolerance. The therapeutic regimen should take into account the risk of acute iatrogenic toxicity and long term sequelae. Surgery remains the treatment of choice but chemotherapy, with dose reduction, managed by expert teams, is essential and safer in a lot of case.

Cisplatin therapy for disseminated mixed mesodermal sarcoma of the uterus.

Eighteen patients with metastatic mixed mesodermal sarcoma of the uterus received cisplatin therapy at the University of Texas (UT) M.D. Anderson Hospital and Tumor Institute at Houston. The dose of cisplatin varied from 75 mg/m2 to 100 mg/m2. Previous therapy included surgery in 11 patients, radiotherapy in two patients, and surgery plus radiotherapy in four patients. One patient had no prior therapy. Seven patients had also received prior chemotherapy with doxorubicin. Of 12 patients with measurable disease, one (8%) had a complete response and four (33%) had a partial response for an overall response rate of 42%. The median progression-free survival of patients treated with cisplatin as first- and second-line therapy was 4.5 and 5.5 months, respectively. Cisplatin demonstrated moderate activity with mild toxicity in this group of patients with metastatic mixed mesodermal uterine sarcomas. Further studies including cisplatin-containing combination regimens seem to be warranted.

A randomized clinical trial of adjuvant adriamycin in uterine sarcomas: a Gynecologic Oncology Group Study.

After hysterectomy, 156 evaluable patients with stage I (limited to the corpus) or stage II (limited to the corpus and cervix) uterine sarcomas were randomly assigned to adjuvant chemotherapy with Adriamycin (Adria Laboratories, Columbus, Ohio) for six months or to no further treatment. Pelvic irradiation (external or intracavitary) was optional before randomization. Of 75 patients receiving Adriamycin, 31 have suffered recurrences compared with 43 of 81 receiving no adjuvant chemotherapy. This difference is not statistically significant. Moreover, there is no difference in progression-free interval or survival. The optional radiotherapy did not influence the outcome although there was a suggestion that vaginal recurrence was decreased by pelvic radiotherapy. The recurrence rates in specific cell types (leiomyosarcoma, homologous mixed mesodermal sarcoma, or heterologous mixed mesodermal sarcoma) were not significantly different although the pattern of recurrence differed, with pulmonary metastases being more common in leiomyosarcoma and extrapulmonary recurrence being more common in mixed mesodermal sarcoma. The outcome with respect to chemotherapy was not altered even after adjusting for maldistribution of cases. Thus, we could not show a benefit for this dose schedule of Adriamycin as adjuvant treatment for uterine sarcomas.

Primary chemotherapy in rhabdomyosarcomas and other malignant mesenchymal tumors of the orbit: results of the International Society of Pediatric Oncology MMT 84 Study.

PURPOSE: The MMT 84 multicentric prospective trial of the International Society of Pediatric Oncology (SIOP) was designed to (1) test the effectiveness of ifosfamide 3 g/m2 on days 1 and 2, vincristine 1.5 mg/m2 on days 1 and 14, and dactinomycin 0.9 mg/m2 on days 1 and 2 (IVA) repeated every 21 days; and (2) reduce late effects of treatment by reserving radiation therapy to the primary site for patients not achieving a complete response (CR) to primary chemotherapy. MATERIALS AND METHODS: Between 1984 and 1989, the MMT 84 study registered 34 children with nonmetastatic rhabdomyosarcomas (RMSs) and other malignant mesenchymal tumors (MMTs) of the orbit in this trial. RESULTS: The 4-year event-free survival rate is 62% +/- 9% (SD) and the 4-year survival rate 86% +/- 7% (SD). A total of 11 local recurrences occurred, 10 among 22 patients treated without initial radiation. Salvage of local failure was achieved in nine of 11 patients with the use of radiation and additional chemotherapy, but three later developed distant metastases and two have died. One isolated regional lymph node failure has occurred, while no patient relapsed with isolated distant metastases. Six of 12 patients who failed are alive with no evidence of disease from 16 to 50 months after relapse. The treatment was well tolerated in all patients, except for one with renal tubular acidosis and one who died of cardiotoxicity. Twelve patients remain in first remission without the use of radiation to the primary tumor from 27 to 84 months. CONCLUSION: Despite a higher incidence of local recurrence when treated by primary chemotherapy, early survival rates were not compromised and a significant number of patients avoided the late effects of radiation. However, longer follow-up is required to assess the ultimate outcome of patients treated in this manner.

Treatment of children with nonmetastatic paratesticular rhabdomyosarcoma: results of the Malignant Mesenchymal Tumors studies (MMT 84 and MMT 89) of the International Society of Pediatric Oncology.

PURPOSE: To report the results of the Malignant Mesenchymal Tumors studies (MMT 84 and 89) of the International Society of Pediatric Oncology (SIOP) in males with nonmetastatic paratesticular rhabdomyosarcoma. PATIENTS AND METHODS: From 1984 to 1994, 96 males were treated in SIOP protocols. Radical inguinal orchidectomy was recommended, but initial retroperitoneal lymph node dissection was not performed. Disease was staged according to the SIOP tumor-node-metastasis staging system. Treatment was stratified by stage. In the MMT 89 study, males with completely resected tumors at diagnosis received less chemotherapy (vincristine and dactinomycin) than patients in the MMT 84 study (ifosfamide, vincristine, and dactinomycin). RESULTS: Median age at diagnosis was 65 months. Thirty-one tumors were larger than 5 cm, and 13 males were older than 10 years with a tumor larger than 5 cm. At a median follow-up of 7 years, 87 patients were alive; 79 were in first complete remission and eight were in second complete remission. Relapse occurred in 16 patients (17%). At 5 years, the overall survival (OS) rate was 92%, with an event-free survival (EFS) rate of 82%. OS and EFS were significantly worse for males with tumors greater than 5 cm and for males older than 10 years at diagnosis. CONCLUSION: Males with paratesticular RMS have an excellent prognosis except for a selected group of patients older than 10 years or with tumor greater than 5 cm. Intensified chemotherapy incorporating alkylating agents for this subgroup may be preferred to the use of systematic lymphadenectomy to improve survival while minimizing the burden of therapy.

Effect of incadronate on proliferation of mesenchymal tumor cells with or without activated Ras mutation.

The present investigation examined the effect of bisphosphonates on six mesenchymal tumor cell lines and the mechanisms of inhibition of tumor cell proliferation. HT-1080, a fibrosarcoma cell line that exhibits increased Ras activity due to a mutation of the Ras gene, demonstrated significantly reduced tumor cell proliferation upon treatment with incadronate. The other cell lines, however, which lack mutation of the Ras gene, showed no influence upon treatment with incadronate. Autoradiography demonstrated no difference in the uptake of 3H-labelled incadronate between susceptible and unaffected cells. The anti-proliferation of HT-1080 was reversed by the addition of geranylgeranyl pyrophosphate. Etidronate exhibited no influence on all tested cell lines. On the basis of these data, we hypothesized that incadronate inhibits the mevalonate pathway and blocks oncogenic Ras signaling. In an effort to confirm this hypothesis, the influence of incadronate on an oncogenic Ras transfected BALB/3T3 cell line (Bhas 42) and a parental BALB/3T3 cell line were compared. The parental BALB/3T3 cells showed slight inhibition upon treatment with incadronate, however, the proliferation of Bhas 42 cells was significantly reduced. These results suggest that incadronate suppresses oncogenic Ras-activated mesenchymal tumors through the inhibition of Ras signaling pathways.

Malignant ectomesenchymoma in the wrist of a child: case report and review of the literature.

Malignant ectomesenchymomas, rare and potentially aggressive tumors, occur in children and exhibit mesenchymal and neuroectodermal components. This report describes the first patient diagnosed with a malignant ectomesenchymoma of the hand. The patient was a 17-month-old male who developed a hypothenar mass on his left hand that was surgically excised. Microscopic evaluation revealed ganglioneuroblastic, rhabdomyosarcomatous, and chondrosarcomatous elements. Following excisional biopsy he was treated with cyclophosphamide, doxorubicin, vincristine, ifosfamide, and etoposide. After 3 courses of chemotherapy the patient had a wide reexcision with no residual tumor. The patient is 4 years from diagnosis, without evidence of disease.

A neonate with malignant ectomesenchymoma.

Malignant ectomesenchymoma is a rare tumor reported in head-neck, abdomen and perineal regions. It consists of mesenchymal and neuroectodermal elements. In this tumor group, neoplastic cells are differentiated into neuronal cells. It also has at least one malignant mesenchymal element, generally rhabdomyosarcoma. In this report we present a neonate with ectomesenchymoma.

Primary osteochondrorhabdomyosarcoma (malignant mesenchymoma) of the fibula: a rare tumour in an unusual site -- case report and review of the literature.

Malignant mesenchymoma, defined by Stout as sarcomas comprising two or more unrelated differentiated tissue elements other than a fibrosarcoma component, is rare. We report a case of primary malignant mesenchymoma of the proximal fibula in a 10-year-old female student who presented with pain and swelling of the right knee for 2 months. Initial biopsy showed features of rhabdomyosarcoma only, but the resected specimen revealed additional osteosarcomatous and chondrosarcomatous elements. The patient remained well more than 5 years after initial presentation. Including our present patient, 16 cases of primary malignant mesenchymoma of bone are found in the English literature, affecting mainly adolescents and young adults, with a slight male predominance and predilection for the metaphysis of long bones, especially around the knee. More than 60% of the patients develop metastasis, almost invariably to the lung, but occasionally to the brain. About 60% of the patients, all with metastasis, died mostly within one year of diagnosis. The clinical features of primary malignant mesenchymoma of bone thus resemble those of conventional osteosarcoma. Moreover, our case illustrates that, with combination chemotherapy targeted for individual elements, the prognosis of this rare tumour might be much improved, as in osteosarcoma.

Complete remission of a metastatic gastrointestinal stromal tumour with the tyrosine kinase inhibitor imatinib (STI 571): effect of low dosage in an advanced tumour with exon 11 mutation.

We report a 51-year-old man with an advanced malignant metastatic gastrointestinal stromal tumour, who showed a complete response after 5 months of treatment with imatinib at a dose of 400 mg per day. An early treatment response was demonstrated in an 18fluorodeoxyglucose positron emission tomography scan after 1 month of therapy. Complete remission was documented histologically by negative serial biopsies of residual tumour nodes after 5 months of therapy. No serious side effects were seen with imatinib. A 21 bp, exon 11, in-frame mutation of the c-kit gene was found by DNA sequence analysis of tumour tissue.

Primary malignant mesenchymoma of the heart.

Primary malignant cardiac tumours are uncommon, and cardiac malignant mesenchymoma is extremely rare. A case of primary malignant mesenchymoma in a 41-year-old woman arousing from the left atrial septum, obstructing the mitral orifice by passing through it into the left ventricle is described. The tumour was fully resected, and adjuvant chemotherapy was applied, but the patient had died by tumour recurrence in 8 months.

Malignant mesenchymoma of the liver in children.

Four children, aged 5 to 13 years, were treated for malignant mesenchymoma of the liver. Two survived longer than 5 years with complete resection and adjuvant chemotherapy. Two children who had incomplete resection with microscopic residual mesenchymoma both had tumor recurrence and died of disease progression despite radiation therapy and chemotherapy. Although previous reports emphasize a poor prognosis for children with this tumor, our experience would indicate that long-term survival can be achieved using complete surgical extirpation and adjuvant chemotherapy.

Use of cisplatin for control of metastatic malignant mesenchymoma and hypertrophic osteopathy in a dog.

Cisplatin (cis-diammine-dichloroplatinum) treatment induced partial remission of pulmonary metastatic malignant mesenchymoma and nearly complete radiographic remission of hypertrophic osteopathy in a 14-year-old Beagle. Cisplatin was given once every 3 weeks. Clinical signs of hypertrophic osteopathy resolved one week after initiation of treatment. Partial remission of pulmonary metastases and partial radiographic remission of hypertrophic osteopathy was seen 6 weeks after initiation of treatment. Previous treatment of neoplasia-related hypertrophic osteopathy has consisted of removal of the initiating mass or vagotomy. In this case, appropriate chemotherapy was used to control clinical signs and progression of hypertrophic osteopathy.

High efficacy of imatinib for recurrent gastrointestinal stromal tumor in the jejunum: a case report.

Gastrointestinal stromal tumor is a mesenchymal tumor of the digestive tract. Although there used to be no effective therapy for the tumor, there have been many recent reports on the efficacy of imatinib. We report on a 53-year-old female patient with a primary tumor of the jejunum who underwent 3 operations. As the tumor could not be removed at the 3rd operation, she was given imatinib orally. Results showed significant reduction ratios of the tumor area (83.0%) and volume (92.2%) at 18 months after starting imatinib administration. Also, the mean reduction ratios of the tumor area and volume per month (%/M) after starting imatinib treatment showed remarkable results, especially during the initial 3 weeks: 53.9%/M and 49.5%/M, respectively. Whether imatinib is the first choice of treatment for GIST or not, and what is the appropriate dose and period should be resolved.

[Pelvic malignant ectomesenchymoma: a case report]. / Ectomésenchymome malin pelvien. A propos d'un cas.

We report the case of a 19 month old boy referred to our institution because of a pelvic tumor initially identified as an embryonal rhabdomyosarcoma and treated with surgery and chemotherapy. Eight years after the initial surgery, a local tumor recurrence with bone metastasis was found. Histological examination and immunohistochemistry showed a double differentiation with both muscular and neuronal cells. This double differentiation was retrospectively found in the initial tumor, then allowing the diagnosis of malignant ectomesenchymoma also called gangliorhabdomyosarcoma. This rare tumor, occurring mainly during childhood, is composed of neuroblasts and / or ganglion cells and of malignant mesenchymal cells (usually rhabdomyosarcomatous cells).

[Undifferentiated (embryonal) sarcoma of the liver. Report of a case]. / Sarcoma indiferenciado (embrionario) de hígado. Informe de un caso.

A 15-year-old woman who was studied because an abdominal mass at the Instituto Nacional de la Nutricion Salvador Zubiran (INNSZ) is reported. The history revealed only malaise and mild abdominal pain. At physical exploration, an abdominal mass in the upper right quadrant was found. Liver function tests were normal. Abdominal ultrasound and computerized tomography revealed a large cystic mass of the right hepatic lobe. She underwent exploratory laparotomy. Intraoperative frozen sections of the biopsies demonstrated undifferentiated sarcoma of the liver, and an extended right trisegmentectomy was performed. Postoperative outcome was uneventful. Adjuvant treatment with doxorubicin and dacarbazine was given, and at six months of follow-up, the patient is alive without any evidence of recurrence. Clinical and histopathologic features of this rare malignant tumor are discussed, as well as the therapeutic choices.