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.

Pharmacokinetics of cyclophosphamide and its metabolites in paediatric patients receiving high-dose myeloablative therapy.

INTRODUCTION: In order to better understand the impact of high-dose on the pharmacokinetics and metabolism of cyclophosphamide, a pharmacological study was performed in children with malignant mesenchymal tumours with metastatic disease. METHODS: Patients received four courses of chemotherapy including two courses of cyclophosphamide. Plasma concentrations of cyclophosphamide and the metabolites 4-ketocyclophosphamide, dechloroethylcyclophosphamide and carboxyphosphamide were determined on days 1, 2 and 3 of each course. A population pharmacokinetic model for cyclophosphamide was developed using non-linear mixed effects modelling and metabolite AUC values were compared between days and courses. RESULTS: Data were available on 21 cyclophosphamide courses from 15 patients. A one compartment model, incorporating a term in surface area for both CL and V, best described cyclophosphamide pharmacokinetics. Typical CL and V on day 1 of treatment for a patient with a SA of 1.4m(2) were 4.3 L/h and 28.5L, respectively. On days 2 and 3 CL increased by 88% (95% CI, 72-105%) and 125% (95% CI, 108-145%) over day 1 levels; V increased by 14% (95% CI, 5-23%) on days 2 and 3. V tended to be larger for males than similarly sized females but no effect of age was found upon CL or V. Significant increases in metabolite AUCs were observed on days 2 and 3 compared to day 1 and a significant increase in CXCP AUC from course 1 to course 3. CONCLUSION: Administration of high-dose cyclophosphamide over several days results in an increase in metabolism, possibly by induction of the activation pathway. This induction is effectively reversed following a four week period between cyclophosphamide doses. The degree of intersubject variation in cyclophosphamide elimination is largely accounted for by body surface area and is less than previously reported.

Tumores mesenquimales diagnosticados en la unidad de gastroenterología del HMPC entre los años 2007 aL 2009 / Mesenchymal tumors diagnosed in the gastroenterology unit of HPMC from 2007 to 2009

Se evaluaron las historias médicas con diagnóstico de tumores mesenquimales confirmados por análisis inmunohistoquímico entre los años 2007 y 2009. El objetivo fue describir a la población según características clínicas, epidemiológicas, diagnósticos por imágenes y análisis anatomopatológico. Se obtuvieron 11 pacientes con diagnósticos de GIST(7), Leiomiomas(2), GANT(1) y Leiomiosarcoma(1). Del género femenino (82%) y masculino (18%). Con un promedio de 55 años de edad. Clínicamente presentaron dolor abdominal (45%), mareos (27%), pirosis (9%) y disfagia (1%). El 18% permaneció asintomático. Entre los signos encontrados figuran: melena (36%), pérdida de peso (27%), palidez cutánea (9%) y vómitos (9%). El 36% de los pacientes no presentaron hallazgos al examen físico. Se realizó ultrasonido abdominal en el 100% de los pacientes, con hallazgos patológicos relacionados con el tumor en el 27 % de los casos. Al 90% de los pacientes se les realizó una Endoscopia Digestiva Superior, el 82% de los hallazgos se describieron como Tumores Submucosos y 9% se reportó como normal. Las lesiones se ubicaron en el estómago (60%), 27% en el intestino delgado ( duodeno y yeyuno); 9% en esófago y 9% en retroperitoneo. El ultrasonido endoscópico fue practicado al 82% de los pacientes, con un porcentaje de aciertos diagnósticos en el 90% de los tumores localizados en esófago, estómago e intestino delgado, y de 87,5% si se incluye el tumor retroperitoneal. La Tomografía Computada (TC) de abdomen fue practicada en 45% de los pacientes, con hallazgos patológicos en el 100% de los casos, descritos como Lesiones Ocupantes de Espacio (LOE), en estómago, intestino, esófago y retroperitoneo; y en el 20% de los pacientes se encontró enfermedad metastásica hepática Recibieron tratamiento quirúrgico el 82%, el 18% restante no se realizó por contraindicación médica o se encuentran en espera del procedimiento. Y un 18% de los pacientes recibieron tratamiento médico con Imatinib...

We evaluated the clinical records with a diagnosis of mesenchymal tumors confirmed by immunohistochemical analysis, from 2007 to 2009. The objective was to describe the population according to clinical and epidemiological features, diagnostic imaging and histopathological analysis. We found 11 patients with diagnoses of GIST(7), leiomyoma(2), leiomyosarcoma(1) and GANT(1); (82%) female and (18%) male, with a mean age of 55 years. They clinically presented abdominal pain (45%), dizziness (27%), heartburn (9%) and dysphagia (1%). 18% remained asymptomatic. Among the symptoms were: melena (36%), weight loss (27%), paleness (9%) and vomiting (9%). 36% of the patients had no findings at physical examination. Abdominal ultrasound was performed in 100% of the patients, with pathological findings related to the tumor in 27% of cases. In 90% of patients an upper digestive endoscopy was performed. 82% of findings were described as submucosal tumors and 9% was reported as normal. Lesions were located in stomach (60%); 27% in small bowel (duodenum and jejunum), 9% in esophagus and 9% in retroperitoneum. Endoscopic ultrasound was performed to 82% of patients, with a diagnostic accuracy of 90% for the tumors located in esophagus, stomach and small bowel; and 87,5% if the retroperitoneal tumor is included. The abdomen Computed Tomography (CT) was performed in 45% of patients with pathological findings in 100% of the cases, described as Space occupying lesion (SOL) in stomach, intestine, esophagus and retroperitoneum; and, in 20% of patients metastatic liver cancer was found. 82% received surgical treatment, the remaining 18% was not performed due to contraindication or are waiting for the procedure. And 18% of patients received medical therapy with Imatinib...

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.

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.

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.

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.

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.

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.

Osteosarcoma with rhabdomyosarcomatous component or so-called malignant mesenchymoma of bone.

BACKGROUND: Primary malignant mesenchymoma of the bone is a rare neoplasm consisting of two or more unrelated malignant mesenchymal components. The literature reports fewer than 20 cases, most of which were composed of osteosarcoma and liposarcoma. OBSERVATION: We report an exceedingly rare case of primary malignant mesenchymoma of bone composed of rhabdomyosarcoma, osteosarcoma, and a minor chondrosarcoma component, arising in the right proximal humerus of a 15-year-old girl. The rhabdomyosarcomatous component was present in the initial biopsy and persisted in surgical specimen following chemotherapy. CONCLUSION: Effect of chemotherapy is enigmatic since rhabdomyosarcomatous component could appear, persist or disappear after chemotherapy according to literature.

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.

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.