Malignant ectomesenchymoma

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Malignant ectomesenchymoma(MEM) is a rare, fast-growing tumor of the nervous system or soft tissue that occurs in children and young adults. MEM is part of a group of small round blue cell tumors which includes neuroblastoma, rhabdomyosarcoma, non-Hodgkin's lymphoma, and the Ewing's family of tumors. [1]

Contents

Typical Pathology

Small Blue Round Cell Tumor under a microscope Dsrct1.jpg
Small Blue Round Cell Tumor under a microscope

Malignant ectomesenchymomas may form in the head and neck, abdomen, perineum, scrotum, or limbs. The tumor is defined by its heterologous rhabdomyoblastic components. [2] MEM histology is that of an elongated cell with an embryonic morphology. [3] Onset time is relatively rapid and occurs early in life with the average age of onset is 0.6 years of age. [2] However, children have been known to develop MEM up until they reach 5 years old. [4] The neuroectodermal component has the potential to display any neuroblastic tumor including neuroblastoma, ganglioneuroblastoma, and ganglion cells with or without schwannian stroma. [4] The rhabdomyoblastic component is derived from pluripotent migratory neural crest cells. [2] The nature and wide migration patterns of neural crest cells allow them to give rise to both neural and non-nervous tissue including neurons, glia, smooth muscle, and melanocytes. [5] Patients have the potential to display primary tumors in various locations prior to metastasis making this cancer particularly complicated.

Differing Representations Across Patients

Unfortunately, heterogenous tumors have the potential to represent further heterogeneity between patients. Because of the rarity of cases, in 2014 there were only 64 cases reported in the literature, [6] most studies of ectomesenchymoma are limited by very small cohort sizes. In an investigation of six cases, researchers attempted to create a profile for the different presentations in ectomesenchymomal tumors. Mesenchymal elements, represented by rhabdomyosarcoma, were the dominant component in the majority of cases (5/6) while embryonal and alveolar morphology had equal distribution (3/6). [7] Patients with the alveolar subtype harbored the characteristic translocations including translocation of the FOXO1 gene fusing with the PAX3 or PAX7 gene [7] . In the neuroectodermal component of the tumors, neuroblastic neoplasm was the most common presentation (4/6) and the other two cases represented a primitive neuroectodermal tumor-like morphology. [8]

Genetic Factors

Several translocations and genetic markers have been identified as possible oncogenic transformations in ectomesenchymoma:

Treatment with chemotherapy led to a reduction in amplification of 6p21.32-p21.2 and 6p11.2 leading to rescue of HMGA1 and HMGA2 protein expression. [9]

History

The first records of ectomesenchymoma are from 1971 in an investigation into neoplasms of mixed mesenchymal and neuroepithelial origin. [10] In the same year another research group identified gangliorhabdomyosarcoma originating from the ectomesenchyme. [11] The term ectomesenchymoma was first termed in 1977 to refer to a facial tumor found in a 6 month old female. This tumor persisted with evidence of regrowth 8 months after extensive debulking, triple chemotherapy, and radiation treatment. Biopsical investigation identified four different phenotypes present in the tumor and all were originally derived from the neural crest cell lineage. [12] The varied nature of these tumors sparked questions about the transformational factors which lead to cancerous expression across multiple mature cell types. A publication in 2017 was the first to identify FOX01 gene rearrangements in ectomesemchymoma. [8]

Treatment & Complications

Current treatment options for ectomesenchymomas are limited to traditional therapies as reported in the literature. Typical treatment options include chemotherapy, radiotherapy and surgical debulking when possible. [13] Lack of specific therapies has the potential to cause discomfort and damage to the patient. Because most of the effected population of ectomesenchymoma are juveniles, the long term carcinogenic and developmental risk of radiation therapy is fairly high. Risk of development of leukemia and thyroid cancers also increases significantly with cancer treatment. [14] Another major concern for chemotherapy and radiotherapy, particularly in the central nervous system and brain, is the potential developmental impacts. [15]

Related Research Articles

<span class="mw-page-title-main">Sarcoma</span> Medical condition

A sarcoma is a malignant tumor, a type of cancer that arises from transformed cells of mesenchymal origin. Connective tissue is a broad term that includes bone, cartilage, fat, vascular, or hematopoietic tissues, and sarcomas can arise in any of these types of tissues. As a result, there are many subtypes of sarcoma, which are classified based on the specific tissue and type of cell from which the tumor originates. Sarcomas are primary connective tissue tumors, meaning that they arise in connective tissues. This is in contrast to secondary connective tissue tumors, which occur when a cancer from elsewhere in the body spreads to the connective tissue. The word sarcoma is derived from the Greek σάρκωμα sarkōma "fleshy excrescence or substance", itself from σάρξsarx meaning "flesh".

<span class="mw-page-title-main">Rhabdomyosarcoma</span> Medical condition

Rhabdomyosarcoma (RMS) is a highly aggressive form of cancer that develops from mesenchymal cells that have failed to fully differentiate into myocytes of skeletal muscle. Cells of the tumor are identified as rhabdomyoblasts.

<span class="mw-page-title-main">Desmoplastic small-round-cell tumor</span> Aggressive and rare cancer

Desmoplastic small-round-cell tumor (DSRCT) is an aggressive and rare cancer that primarily occurs as masses in the abdomen. Other areas affected may include the lymph nodes, the lining of the abdomen, diaphragm, spleen, liver, chest wall, skull, spinal cord, large intestine, small intestine, bladder, brain, lungs, testicles, ovaries, and the pelvis. Reported sites of metastatic spread include the liver, lungs, lymph nodes, brain, skull, and bones. It is characterized by the EWS-WT1 fusion protein.

A blastoma is a type of cancer, more common in children, that is caused by malignancies in precursor cells, often called blasts. Examples are nephroblastoma, medulloblastoma, and retinoblastoma. The suffix -blastoma is used to imply a tumor of primitive, incompletely differentiated cells, e.g., chondroblastoma is composed of cells resembling the precursor of chondrocytes.

<span class="mw-page-title-main">PAX3</span> Paired box gene 3

The PAX3 gene encodes a member of the paired box or PAX family of transcription factors. The PAX family consists of nine human (PAX1-PAX9) and nine mouse (Pax1-Pax9) members arranged into four subfamilies. Human PAX3 and mouse Pax3 are present in a subfamily along with the highly homologous human PAX7 and mouse Pax7 genes. The human PAX3 gene is located in the 2q36.1 chromosomal region, and contains 10 exons within a 100 kb region.

<span class="mw-page-title-main">Primitive neuroectodermal tumor</span> Medical condition

Primitive neuroectodermal tumor is a malignant (cancerous) neural crest tumor. It is a rare tumor, usually occurring in children and young adults under 25 years of age. The overall 5 year survival rate is about 53%.

Sarcoma botryoides or botryoid sarcoma is a subtype of embryonal rhabdomyosarcoma, that can be observed in the walls of hollow, mucosa lined structures such as the nasopharynx, common bile duct, urinary bladder of infants and young children or the vagina in females, typically younger than age 8. The name comes from the gross appearance of "grape bunches".

<span class="mw-page-title-main">Fibroblast growth factor receptor 1</span> Protein-coding gene in the species Homo sapiens

Fibroblast growth factor receptor 1 (FGFR1), also known as basic fibroblast growth factor receptor 1, fms-related tyrosine kinase-2 / Pfeiffer syndrome, and CD331, is a receptor tyrosine kinase whose ligands are specific members of the fibroblast growth factor family. FGFR1 has been shown to be associated with Pfeiffer syndrome, and clonal eosinophilias.

Alveolar rhabdomyosarcoma (ARMS) is a subtype of the rhabdomyosarcoma soft tissue cancer family whose lineage is from mesenchymal cells and are related to skeletal muscle cells. ARMS tumors resemble the alveolar tissue in the lungs. Tumor location varies from patient to patient, but is commonly found in the head and neck region, male and female urogenital tracts, the torso, and extremities. Two fusion proteins can be associated with ARMS, but are not necessary, PAX3-FKHR. and PAX7-FKHR. In children and adolescents ARMS accounts for about 1 percent of all malignancies, has an incidence rate of 1 per million, and most cases occur sporadically with no genetic predisposition. PAX3-FOXO1 is now known to drive cancer-promoting gene expression programs through creation of distant genetic elements called super enhancers.

Ectomesenchymoma is a rare, fast-growing tumor of the nervous system or soft tissue that occurs mainly in children, although cases have been reported in patients up to age 60. Ectomesenchymomas may form in the head and neck, abdomen, perineum, scrotum, or limbs. Also called malignant ectomesenchymoma.

<span class="mw-page-title-main">PAX7</span> Paired box transcription factor protein

Paired box protein Pax-7 is a protein that in humans is encoded by the PAX7 gene.

<span class="mw-page-title-main">Follicular thyroid cancer</span> Medical condition

Follicular thyroid cancer accounts for 15% of thyroid cancer and occurs more commonly in women over 50 years of age. Thyroglobulin (Tg) can be used as a tumor marker for well-differentiated follicular thyroid cancer. Thyroid follicular cells are the thyroid cells responsible for the production and secretion of thyroid hormones.

<span class="mw-page-title-main">Small-blue-round-cell tumor</span>

In histopathology, a small-blue-round-cell tumour, also known as a small-round-blue-cell tumor (SRBCT) or a small-round-cell tumour (SRCT), is any one of a group of malignant neoplasms that have a characteristic appearance under the microscope, i.e. consisting of small round cells that stain blue on routine H&E stained sections.

<span class="mw-page-title-main">Aggressive angiomyxoma</span> Medical condition

Angiomyxoma is a myxoid tumor involving the blood vessels.

<span class="mw-page-title-main">Melanotic neuroectodermal tumor of infancy</span> Medical condition

Melanotic neuroectodermal tumor of infancy is a very rare oral cavity tumor that is seen in patients usually at or around birth. It must be removed to be cured. Definitions: A rare, biphasic, neuroblastic, and pigmented epithelial neoplasm of craniofacial sites, usually involving the oral cavity or gums.

Embryonal rhabdomyosarcoma (EMRS) is a rare histological form of cancer in the connective tissue wherein the mesenchymally-derived malignant cells resemble the primitive developing skeletal muscle of the embryo. It is the most common soft tissue sarcoma occurring in children. Embryonal rhabdomyosarcoma is also known as PAX-fusion negative or Fusion-Negative rhabdomyosarcoma, as tumors of this subtype are unified by their lack of a PAX3-FOXO1 fusion oncogene. Fusion status refers to the presence or absence of a fusion gene, which is a gene formed from joining two different genes together through DNA rearrangements. These types of tumors are classified as embryonal rhabdomyosarcoma "because of their remarkable resemblance to developing embryonic and fetal skeletal muscle."

A rhabdomyoblast is a cell type which is found in some rhabdomyosarcomas. When found histologically, a rhabdomyoblast aids the diagnosis of embryonal, alveolar, spindle cell/sclerosing, and pleomorphic rhabdomyosarcomas; however, in a tumor, expression of the rhabdomyoblast phenotype is not the only factor in diagnosing a rhabdomyosarcoma. Mesenchymal malignancies can exhibit this phenotype as well. Immunohistochemistry techniques allow for the sensitive detection of desmin, vimentin, muscle specific actin, and MyoD1. Similarly the rhabdomyoblast phenotype can be detected morphologically. Rhabdomyoblasts are early stage mesenchymal cells, having the potential to differentiate into a wide range of skeletal cells. Each stage of differentiation exhibits unique and distinguishable histological characteristics. In its initial from, stellate cells with amphiphilic cytoplasm and ovular central nuclei are observed. Commonly referred to as rhabdoid features, the maturing rhabdomyoblast will likely exhibit low levels of eosinophilic cytoplasm in proximal distances to the nucleus. As maturation and differentiation progress, the cell's cytoplasmic levels of white blood cells increase; additionally, elongated shapes, commonly depicted as “tadpole”, “strap” and "spider cells", are observed. In the concluding phase of differentiation, the white blood cell rich cytoplasm appears bright and exhibits cross-striation. The highly regulated organization of actin and myosin microfilaments in contractile proteins results in this appearance.

Vulvar tumors are those neoplasms of the vulva. Vulvar and vaginal neoplasms make up a small percentage (3%) of female genital cancers. They can be benign or malignant. Vulvar neoplasms are divided into cystic or solid lesions and other mixed types. Vulvar cancers are those malignant neoplasms that originate from vulvar epithelium, while vulvar sarcomas develop from non-epithelial cells such as bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Epithelial and mesenchymal tissue are the origin of vulvar tumors.

Askin's tumor is a rare, primitive neuroectodermal tumor which arises from the soft tissues of the chest wall, particularly of the paravertebral region. It was first described by Askin et al. in 1979. Askin's tumor is now recognized as part of the Ewing's sarcoma family of tumors. This neoplasm tended to recur locally, but did not seem to disseminate as widely as some of the other small cell tumors of childhood such as rhabdomyosarcoma or neuroblastoma.

References

  1. ↑ "Small round blue cell tumor Medical Definition". MedicineNet. Retrieved 2020-04-12.
  2. 1 2 3 Dantonello, Tobias M.; Leuschner, Ivo; Vokuhl, Christian; Gfroerer, Stefan; Schuck, Andreas; Kube, Stefanie; Nathrath, Michaela; Bernbeck, Benedikt; Kaatsch, Peter; Pal, Niklas; Ljungman, Gustaf (2013). "Malignant ectomesenchymoma in children and adolescents: Report from the Cooperative Weichteilsarkom Studiengruppe (CWS)". Pediatric Blood & Cancer. 60 (2): 224–229. doi:10.1002/pbc.24174. ISSN   1545-5017. PMID   22535600. S2CID   21224318.
  3. ↑ Holland, James F.; Frei III, Emil; Weichselbaum, Ralph R.; Bast, Robert C.; Gansler, Ted S.; Kufe, Donald W.; Pollock, Raphael E., eds. (2003), "Resemblance to embryonal tissue", Holland-Frei Cancer Medicine (6th ed.), Hamilton, Ontario, Canada: BC Decker, ISBN   1-55009-213-8, OCLC 53895425, retrieved 3 Dec 2011
  4. 1 2 Boudjemaa, Sabah; Petit, Arnaud (2019). "Malignant Ectomesenchymoma: A Potential Pitfall of Diagnosis in the Spectrum of Pediatric Small Blue Round Cell Tumors". Applied Immunohistochemistry & Molecular Morphology. 27 (6): e63–e64. doi:10.1097/PAI.0000000000000584. ISSN   1541-2016. PMID   28968263.
  5. ↑ Shakhova, Olga; Sommer, Lukas (2008), "Neural crest-derived stem cells", StemBook, Harvard Stem Cell Institute, doi:10.3824/stembook.1.51.1, PMID   20614636 , retrieved 2020-04-12
  6. ↑ Nael, A.; Siaghani, P.; Wu, W. W.; Nael, K.; Shane, Lisa; Romansky, S. G. (2014). "Metastatic Malignant Ectomesenchymoma Initially Presenting as a Pelvic Mass: Report of a Case and Review of Literature". Case Reports in Pediatrics. 2014: 792925. doi: 10.1155/2014/792925 . PMC   4227373 . PMID   25405050.
  7. 1 2 3 Sumegi, Janos; Streblow, Renae; Frayer, Robert W.; Cin, Paola Dal; Rosenberg, Andrew; Meloni-Ehrig, Aurelia; Bridge, Julia A. (2010). "Recurrent (2;2) and (2;8) Translocations in Rhabdomyosarcoma without the Canonical PAX-FOXO1 fuse PAX3 to Members of the Nuclear Receptor Transcriptional Coactivator (NCOA) Family". Genes, Chromosomes & Cancer. 49 (3): 224–236. doi:10.1002/gcc.20731. ISSN   1045-2257. PMC   2808450 . PMID   19953635.
  8. 1 2 Griffin, Brannan B.; Chou, Pauline M.; George, David; Jennings, Lawrence J.; Arva, Nicoleta C. (2018). "Malignant Ectomesenchymoma: Series Analysis of a Histologically and Genetically Heterogeneous Tumor". International Journal of Surgical Pathology. 26 (3): 200–212. doi:10.1177/1066896917734915. ISSN   1940-2465. PMID   28994342. S2CID   4875773.
  9. 1 2 Griffin, Brannan B.; Chou, Pauline M.; George, David; Jennings, Lawrence J.; Arva, Nicoleta C. (2018-05-01). "Malignant Ectomesenchymoma: Series Analysis of a Histologically and Genetically Heterogeneous Tumor". International Journal of Surgical Pathology. 26 (3): 200–212. doi:10.1177/1066896917734915. ISSN   1066-8969. PMID   28994342. S2CID   4875773.
  10. ↑ Shuangshoti, Samruay; Netsky, Martin G. (1971-04-01). "Neoplasms of Mixed Mesenchymal and Neuroepithelial OriginRelation to "Monstrocellular Sarcoma" or "Giant-Celled Glioblastoma"". Journal of Neuropathology & Experimental Neurology. 30 (2): 290–309. doi:10.1097/00005072-197104000-00010. ISSN   0022-3069. PMID   4947980. S2CID   26687724.
  11. ↑ Holimon, J. L.; Rosenblum, W. I. (1971). ""Gangliorhabdomyosarcoma": a tumor of ectomesenchyme. Case report". Journal of Neurosurgery. 34 (3): 417–422. doi:10.3171/jns.1971.34.3.0417. ISSN   0022-3085. PMID   5313338.
  12. ↑ Karcioglu, Zeynel; Someren, Ayten; Mathes, Stephen J. (1977). "Ectomesenchymoma: A malignant tumor of migratory neural crest (ectomesenchyme) remnants showing ganglionic, schwannian, melanocytic and rhabdomyoblastic differentiation". Cancer. 39 (6): 2486–2496. doi: 10.1002/1097-0142(197706)39:6<2486::aid-cncr2820390627>3.0.co;2-e . ISSN   1097-0142. PMID   872048.
  13. ↑ Nael, A.; Siaghani, P.; Wu, W. W.; Nael, K.; Shane, Lisa; Romansky, S. G. (2014). "Metastatic Malignant Ectomesenchymoma Initially Presenting as a Pelvic Mass: Report of a Case and Review of Literature". Case Reports in Pediatrics. 2014: 792925. doi: 10.1155/2014/792925 . ISSN   2090-6803. PMC   4227373 . PMID   25405050.
  14. ↑ Kutanzi, Kristy R.; Lumen, Annie; Koturbash, Igor; Miousse, Isabelle R. (2016). "Pediatric Exposures to Ionizing Radiation: Carcinogenic Considerations". International Journal of Environmental Research and Public Health. 13 (11): 1057. doi: 10.3390/ijerph13111057 . ISSN   1661-7827. PMC   5129267 . PMID   27801855.
  15. ↑ Schatz, Jeffrey; Kramer, Joel H.; Ablin, Arthur; Matthay, Katherine K. (2000). "Processing speed, working memory, and IQ: A developmental model of cognitive deficits following cranial radiation therapy". Neuropsychology. 14 (2): 189–200. doi:10.1037/0894-4105.14.2.189. ISSN   1931-1559. PMID   10791859.

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