Malignant Ectomesenchymoma Research Articles

Primary Intracranial Malignant Ectomesenchymoma in an Infant: Case Report and Review of Literature

Primary Intracranial Malignant Ectomesenchymoma in an Infant: Case Report and Review of Literature

An integrative morpho-molecular approach in malignant ectomesenchymoma diagnosis: report of a new paediatric case and a review of the literature.

Malignant ectomesenchymoma (MEM) is a soft tissue tumour, consisting of both malignant neuroectodermal elements and one or more mesenchymal elements. Here we describe the case of a 6-months-old male, previously treated in another hospital for abdominal rhabdomyosarcoma (RMS). Histological re-examination demonstrated that the tumour had mesenchymal and neuroectodermal elements components, with a new diagnosis of abdominal-pelvic MEM. A Next-Generation Sequencing (NGS) analysis was performed on a surgical tumour specimen and revealed the presence of a somatic mutation, already reported in MEM cases. We carried out a review of the literature and we found 33 new cases of MEM since the last review. We reported the clinic-pathologic features of new cases of MEM, highlighting the role of molecular studies in supporting the diagnosis of this ambiguous tumours. We promote the importance of a diagnosis based on an integrative morpho-molecular approach, that routinely include molecular analysis and the use of bioinformatic mutation detection tools, to support diagnostic and therapeutical queries and to highlight tumour biology and behaviour.

Malignant ectomesenchymoma in children: The European pediatric Soft tissue sarcoma Study Group experience.

Malignant ectomesenchymoma (MEM) is an extremely rare soft tissue tumor typical of young children, currently included in the category of skeletal muscle malignancies and characterized by a neuroblastic component. This study describes a series of 10 patients prospectively registered in the European paediatric Soft tissue sarcoma Study Group (EpSSG) database Of the 10 cases, seven had an initial local diagnosis of rhabdomyosarcoma. All patients received chemotherapy according to rhabdomyosarcoma strategy, four had radiotherapy. Overall, six patients were alive in first remission, two in second remission and one after second tumor. Only the patient with initially metastatic tumor died of disease.

Clinicopathological analysis of malignant ectomesenchymoma in children

目的： 探讨恶性外胚层间叶瘤（malignant ectomesenchymoma，MEM）的临床病理学特征及分子生物学特点。 方法： 回顾性分析4例儿童MEM的临床和病理资料，并复习相关文献。 结果： 4例MEM中男女各2例，年龄11个月至12岁，中位年龄1岁10个月。肿瘤由横纹肌肉瘤以及节细胞神经母细胞瘤或分化的节细胞2类成分构成。免疫组织化学显示胚胎性及腺泡状横纹肌肉瘤细胞结蛋白、MyoD1和Myogenin阳性，节细胞神经母细胞瘤及节细胞突触素和嗜铬粒素A阳性。荧光原位杂交检测1例（含腺泡状横纹肌肉瘤成分）FOXO1（13q14）基因重排，其伙伴基因为PAX3（2q36）。另1例测序发现BCOR-CCNB3基因融合。 结论： MEM是由间叶组织和神经外胚层组织构成的多表型肉瘤，因神经源性成分容易被忽略，应多取材及免疫组织化学排查避免误诊。.

Malignant Ectomesenchymoma of Pelvis in an Infant

Malignant ectomesenchymoma is a rare pediatric soft tissue tumor that contains both neuroectodermal and mesenchymal components. It is frequently found in the pelvis, paratesticular soft tissue, external genitalia and the head-neck region. We present a 12-month-old boy with a recurrent pelvic tumor excised 5 months ago and diagnosed as neuroblastoma. Histological consultation of the initial tumor tissue revealed a biphasic pattern with rhabdomyosarcomatous and neural components. The mesenchymal component was embryonal rhabdomyosarcoma showing desmin, myogenin, and Myo-D1 positivity. The neuroectodermal component was mainly Schwannian stroma stained with S100 antibody and scattered synaptophysin and chromogranin positive ganglion cells were also present. The patient was diagnosed with malignant ectomesenchymoma. A chemotherapy regime was started and surgical approach to the recurrent tumor was planned. We present here a pediatric case of malignant ectomesenchymoma because of its rarity and it is important that this entity should be considered in the differential diagnosis for appropriate clinical management.

Infant malignant ectomesenchymoma masquerading as inguinal hernia in two patients

Infant malignant ectomesenchymoma masquerading as inguinal hernia in two patients

Malignant Ectomesenchymoma of the Scalp

Malignant Ectomesenchymoma of the Scalp

Malignant Ectomesenchymoma: Series Analysis of a Histologically and Genetically Heterogeneous Tumor.

Malignant ectomesenchymoma is a rare pediatric neoplasm with dual mesenchymal and neuroectodermal elements. Mesenchymal component is usually rhabdomyosarcoma, particularly embryonal subtype, whereas neuroectodermal derivatives are frequently a neuroblastic tumor. Ectomesenchymoma manifests in various sites given the wide migration of neural crest cells during development, though the pelvis/perineum is most often involved. Moreover, no unique unifying molecular abnormality has been determined. We conducted a retrospective study to analyze the spectrum of ectomesenchymal tumors encountered in our pediatric population. Six patients were identified and data pertaining to patients' demographic, tumor size and site, histologic components with immunophenotypic profile, molecular alterations, treatment, and outcome were collected. Mesenchymal elements, represented by rhabdomyosarcoma in all instances, were the dominant component in the majority of cases (5/6). Embryonal and alveolar morphology had similar distribution (3/6) and all patients with alveolar subtype harbored the characteristic translocations of this entity. The neuroectodermal component was most often a neuroblastic-like neoplasm (4/6); however, 2/6 cases demonstrated primitive neuroectodermal tumor-like morphology. No unifying alterations were found on molecular studies. Our analysis extends the histologic and molecular spectrum of these tumors and highlights their heterogeneity. The percentage of cases with alveolar rhabdomyosarcoma or primitive neuroectodermal-like tumor components suggests that these types of elements might be underreported. This study is also the first to demonstrate FOXO1 gene rearrangements in malignant ectomesenchymoma with alveolar rhabdomyosarcoma subtype.

Frequent HRAS Mutations in Malignant Ectomesenchymoma: Overlapping Genetic Abnormalities With Embryonal Rhabdomyosarcoma.

Malignant ectomesenchymoma (MEM) is an exceedingly rare pediatric sarcoma with a predilection for infants and young children and is composed of dual malignant mesenchymal and neuroectodermal components. Microscopically, MEM displays areas of rhabdomyosarcoma (RMS) with intermixed neuronal/neuroblastic foci. The molecular alterations associated with MEM and its relationship with embryonal RMS (ERMS) and malignant peripheral nerve sheath tumor (MPNST) have not yet been elucidated. In this study we used whole-transcriptome sequencing in 2 MEM index cases with available frozen tissue, followed by screening of the identified genetic abnormalities in 5 additional cases. No candidate fusion genes were detected by FusionSeq analysis; however, the mutation detection algorithms revealed HRAS and PTPRD hotspot mutations in both index cases, with 1 case harboring an additional FBXW7 mutation. As these mutation profiles have been previously described in ERMS we have tested their incidence in a control group of 7 age-matched ERMS. In addition, the gene signature of MEM was compared with that of RMS, MPNST, and neuronal lineage. All 7 MEM patients were male, with a mean age of 7.5 months (range, 0.6 to 17 mo). All except 1 occurred in the pelvic/urogenital region. Most cases showed ERMS elements, with occasional spindle or undifferentiated/round cell areas. The intermixed neuroectodermal components were mostly scattered ganglion cells, ganglioneuroma, or ganglioneuroblastoma. By Sanger sequencing, 6 of 7 (86%) MEMs had HRAS mutations, with no additional case harboring PTPRD or FBXW7 mutations. The only case lacking HRAS mutation showed neuroblastic micronodules without ganglion cells. The trimethylation at lysine 27 of histone H3 (H3K27me3) expression, typically lost in MPNST, was retained in all cases. In the control ERMS group, 5 of 7 (71%) showed RAS mutations, equally distributed among NRAS, KRAS, and HRAS genes. The expression profiling of MEM showed upregulation of skeletal muscle and neuronal genes, with no significant overlap with MPNST. Our results of common HRAS mutations and composite gene signature with RMS and neuronal/neuroblastic elements suggest a closer genetic link of MEM to RMS rather than to MPNST.

Metastatic malignant ectomesenchymoma initially presenting as a pelvic mass: report of a case and review of literature.

Pediatric soft tissue sarcomas account for approximately 10% of all pediatric malignancies. Malignant ectomesenchymoma is rare biphasic sarcomas consisting of both mesenchymal and neuroectodermal elements. Approximately 64 cases have been reported in the literature and are believed to arise from pluripotent embryologic migratory neural crest cells. We report a 4-year-old boy who initially presented with a pelvic mass and inguinal lymphadenopathy at 6 months of age. Inguinal lymph node biopsy revealed a distinct biphasic tumor with microscopic and immunophenotypic characteristics diagnostic for both alveolar rhabdomyosarcoma and poorly differentiated neuroblastoma. The patient received national protocol chemotherapy against rhabdomyosarcoma with good response and presented with a cerebellar mass 21 months later. The metastatic tumor revealed sheets of primitive tumor cells and diagnostic areas of rhabdomyosarcoma and neuroblastoma were identified only by immunohistochemistry. Cytogenetic analysis of metastatic tumor demonstrated complex karyotype with multiple chromosomal deletions and duplications. The patient received national protocol chemotherapy against neuroblastoma and adjuvant radiotherapy after surgical resection of the cerebellar tumor with good response. He is currently off from any treatment for 18 months with no evidence of tumor recurrence or metastasis.

A novel case of pediatric thoracic malignant ectomesenchymoma in an infant

This case describes a 5-month-old male who presented with respiratory distress and superior vena cava syndrome due to malignant ectomesenchymoma (MEM). Surgical treatment was limited to biopsy because of the extensive tumor involvement of the heart and great vessels. The patient was treated with sarcoma-directed chemotherapy. This is the first reported case of a primary MEM in the chest as well as the first case of MEM with cardiac invasion. The work up, differential diagnosis, and treatment of this extremely rare entity are presented.

Malignant pediatric brain tumor of primitive small round cell proliferation with bland-looking mesenchymal spindle cell elements

It is often difficult to classify rare malignant pediatric mixed brain tumors composed of mesenchymal elements. A 6-year-old boy presented to our hospital with a left frontal massive tumor manifesting as complaints of rapidly progressive right hemiparesis and motor aphasia over 2weeks. Computed tomography showed a left frontal mass with thick calcification. Magnetic resonance imaging revealed an enhanced lesion with perifocal edema and mass effect. Total removal of the tumor was performed. Histological examination of the resected tumor revealed an anaplastic malignant small round cell component with a bland-looking mesenchymal spindle cell component. The patient was treated with irradiation to the whole craniospinal axis and a boost to the tumor bed, followed by chemotherapy consisting of ifosfamide, cisplatin, and etoposide, resulting in good control without local recurrence or metastasis at 2years. A combined malignant tumor composed of ectodermal and mesenchymal components is generally named malignant ectomesenchymoma (MEM). The more malignant part of MEM is the mesenchymal component in most cases. In the present case, the more malignant component was not the mesenchymal component, but the small round cells.

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

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. Six patients with MEM were registered 1996-2009. The diagnosis was confirmed according to current criteria. Their treatment and outcome was analyzed. 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). 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.

Malignant ectomesenchymoma of paranasal sinuses with proptosis and nodal involvement

Malignant ectomesenchymoma of paranasal sinuses with proptosis and nodal involvement

Malignant ectomesenchymoma of the nasal cavity

Malignant ectomesenchymomas are rare tumors. This tumor affects predominantly young children. Most common site is head and neck. A multi modality approach should be appropriate for this soft-tissue tumor. We present a 43 year old female with malignant ectomesenchymoma of the nasal cavity.

A rare case of malignant pediatric ectomesenchymoma arising from the falx cerebri

Malignant ectomesenchymoma is a rare tumor arising from mature ganglion cells with immature myogenous elements, with only 4 pediatric intracranial cases having been previously reported. The authors report a rare case of intracranial malignant ectomesenchymoma originating from the falx cerebri in a 10-year-old boy. The patient presented with a 2-week history of headache, nausea, and blurry vision, with mild lateral gaze diplopia. A CT scan revealed a solitary 7.2 × 3.8-cm dural-based mass that extended along the falx. No metastatic disease was identified, and the lesion was grossly resected without complication. Pathological investigation identified single and small groups of cells in a myxoid background, with polygonal or spindle-shaped cells containing eccentric nuclei and prominent nucleoli. Immunohistochemical staining of some cells was positive for smooth-muscle actin, CD99, and vimentin, whereas other cells (often process forming) were positive for S100 protein, synaptophysin, and neurofilament protein. Staining was negative for CD138, CD45, α-fetoprotein, CK AE1/3, glial fibrillary acidic protein, CK7, CK20, CD31, CD34, myoD, and desmin. Normal immunopositivity was seen for INI-1. The Ki 67 immunostaining had < 25% reactivity. The patient was treated with a sarcoma-based chemotherapy regimen and radiation to the craniospinal axis, and was found to be without recurrence or metastatic disease at 20 months.

Malignant Ectomesenchymoma: Genetic Profile Reflects Rhabdomyosarcomatous Differentiation

Malignant ectomesenchymoma (MEM) represents a heterogeneous group of tumors, most likely originating from pluripotent primitive neural crest cells. In this report, we present an 8-month-old infant boy with an MEM on the left scrotum. Retrospective review of the incision biopsy showed the presence of a few ganglion cells in an otherwise classic embryonal rhabdomyosarcoma (RMS), whereas in the resection specimen after chemotherapy the combined RMS and ganglioneuroma components were very obvious. Cytogenetic analysis of the residual lesion showed an abnormal karyotype, 49, XY, +2, -6, +11, +20, +mar, with a hyperploidy in a subset of cells. By fluorescence in situ hybridization analysis, the marker chromosome was identified as originating from chromosome 6, and the tumor cells were negative for PAX3/PAX7 disrupting translocations specific for alveolar RMS. Gains of chromosomes 2, 11, and 20, found in the current case, are a common finding in embryonal RMS. These gains probably reflect the myogenic differentiation of MEM and support the genetic link between these 2 neoplasms. In addition to the conventional cytogenetics, array comparative genomic hybridization analysis was performed on the primary and residual tumors. The genomic profiles of both specimens were basically the same including the presence of 2 distinctive chromosome 6p21.32-p21.2 and 6p11.2 amplification regions in the primary tumor, which vanished in the postchemotherapy specimen. The pretreatment biopsy exhibited strong expression of HMGA1 and HMGA2 proteins in immunohistochemistry, with the shift toward the loss of expression of both genes in the posttreatment tumoral tissue. This finding supports the oncogenic properties of the HMGA family of proteins and their role in the process of malignant transformation.

Molecular and gene array analyses of rare pediatric mesenchymal tumors: malignant intracranial ectomesenchymoma compared to rhabdomyosarcoma, malignant peripheral nerve sheath tumor, and Ewing sarcoma

Molecular and gene array analyses of rare pediatric mesenchymal tumors: malignant intracranial ectomesenchymoma compared to rhabdomyosarcoma, malignant peripheral nerve sheath tumor, and Ewing sarcoma

Malignant ectomesenchymoma of the nasal cavity

In April, 2004, a 62-year-old man with epistaxis, rhinorrhea, and sensation of nasal obstruction attended an appointment at the ear, nose, and throat department that found a solid mass of the right nasal cavity with no clinical evidence of lymph-node or distant metastases as confi rmed by CT and MRI (fi gure 1A). Biopsy of the mass revealed a proliferation of undiff erentiated cells with scant cytoplasm, hyper chromatic nuclei, and high mitotic rate, which formed infi ltrating nests in the stroma of the nasal mucosa (fi gure 2A). Tumour cells showed immuno reactivity for cytokeratin AE1/AE3, synaptophysin, neuron-specifi c enolase (fi gure 2B), CD56, and p53, but not for CD45. The histological features and the immunophenotype were suggestive of a poorly diff erentiated neuroendocrine small-cell carcinoma of the nasal cavity. The patient underwent somatostatin-receptor scintigraphy, which showed tracer uptake in the nasal region only. Blood concentrations of neuron-specifi c enolase, chromogranin A, carcinoembryonic antigen, and Cyfra 21-1 were unremarkable. The patient was treated with carboplatin (area under curve=6) on day 1 and etoposide (100 mg/m) on days 1–3 for seven cycles from May to October, 2004. In October, 2004, CT and MRI showed partial reduction of the mass (fi gure 1B). The patient sub sequently underwent transcranial-endoscopic endo nasal resection of the neoplasm with partial removal of the ethmoid and inferior conchae, the nasal septum, the fl oor and the lateral walls of the right nasal cavity, and the right maxillary sinus. Histologically, the tumour showed two main components. The predominant component was represented by clusters of mature synaptophysin and CD56-positive ganglion cells dispersed in a schwannianlike glial fi brillary acidic protein (GFAP)-positive background (fi gure 2C). Ganglion cells also stained positively for somatostain-receptor 2A (fi gure 2D). The second component was characterised by a proliferation of malignant cells, with abundant eosinophilic cytoplasm strongly positive for actin and desmin (fi gures 2E and 2F). This component was consistent with a rhabdomyosarcoma. The proliferation of undiff erentiated cells seen in the nasal biopsy done during the fi rst clinical investigation was not clearly identifi ed. Only scattered malignant cells that were immunoreactive for cytokeratin AE1/AE3 were seen in the surgically resected tumour tissue. The occurrence of a rhabdomyosarcoma associated with ganglio neuromatous and undiff erentiated components led us to diagnose a malignant ectomesenchymoma. Postsurgical adjuvant treatment with concurrent chemotherapy (weekly cisplatin [45 mg total] and radiotherapy [50 Gy total]) to the right nasal cavity was given from March to April, 2005. The patient was still alive at last follow-up in September, 2006, and had complete remission of the tumour, which was confi rmed both radiologically (fi gure 1C) and histologically. Malignant ectomesenchymoma is a rare multiphenotypic soft-tissue tumour with both mesenchymal and neuroectodermal components. It is believed to arise from pluripotential migratory neural crest cells (ectomesenchym) that can diff erentiate into neuroectodermal and mesenchymal tissues. The mesenchymal component usually consists of rhabdomyoblastic elements, although other malignant mesenchymal components have also been described. Neuroectodermal elements are mainly represented by ganglion cells and neuroma-like structures. About 50 cases have been reported in studies published in English. This neoplasm most frequently aff ects children, although a few cases in Lancet Oncol 2007; 8: 358–60

Molecular and gene array analyses of rare pediatric mesenchymal tumors: malignant intracranial ectomesenchymoma compared to rhabdomyosarcoma, malignant peripheral nerve sheath tumor, and Ewing sarcoma

Molecular and gene array analyses of rare pediatric mesenchymal tumors: malignant intracranial ectomesenchymoma compared to rhabdomyosarcoma, malignant peripheral nerve sheath tumor, and Ewing sarcoma