Desmoplastic small-round-cell tumor

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Desmoplastic small-round-cell tumor
Other namesDSRCT [1]
Desmoplastic small round cell tumour - intermed mag.jpg
Micrograph of a desmoplastic small round cell tumor, showing the characteristic desmoplastic stroma and angulated nests of small round cells. H&E stain.
Specialty Oncology
Prognosis Five-year survival rate 15% [2]
Frequency~200 cases reported [2] [3]

Desmoplastic small-round-cell tumor (DSRCT) is an aggressive and rare cancer that primarily occurs as masses in the abdomen. [4] 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.

Contents

The tumor is classified as a soft tissue sarcoma and a small round blue cell tumor. It most often occurs in male children. The disease rarely occurs in females, but when it does the tumors can be mistaken for ovarian cancer. [5]

Signs and symptoms

Display of small round blue cells characteristic of desmoplastic small-round-cell tumor. Dsrct1.jpg
Display of small round blue cells characteristic of desmoplastic small-round-cell tumor.
Cell exhibiting blue oval and round shapes of desmoplastic small-round blue cell tumor Dsrct2.jpg
Cell exhibiting blue oval and round shapes of desmoplastic small-round blue cell tumor

There are few early warning signs that a patient has a DSRCT. Patients are often young and healthy as the tumors grow and spread uninhibited within the abdominal cavity. These are rare tumors and symptoms are often misdiagnosed by physicians. The abdominal masses can grow to enormous size before being noticed by the patient. The tumors can be felt as hard, round masses by palpating the abdomen.[ citation needed ]

First symptoms of the disease often include abdominal distention, abdominal mass, abdominal or back pain, gastrointestinal obstruction, lack of appetite, ascites, anemia, and cachexia.[ citation needed ]

Other reported symptoms include unknown lumps, thyroid conditions, hormonal conditions, blood clotting, kidney and urological problems, testicle, breast, uterine, vaginal, and ovarian masses.[ citation needed ]

Genetics

There are no known risk factors that have been identified specific to the disease. The tumor appears to arise from the primitive cells of childhood, and is considered a childhood cancer.[ citation needed ]

Research has indicated that there is a chimeric relationship between DSRCT and Wilms' tumor and Ewing sarcoma. Together with neuroblastoma and non-Hodgkin's lymphoma, they form the small-cell tumors.[ citation needed ]

DSRCT is associated with a unique chromosomal translocation (notated as t(11;22)(p13:q12)) [6] that merges the EWSR1 FET family gene normally located on band 12 of the long (or "q") arm of chromosome 22 with part of the WT1 transcription factor gene normally located on band 13 of the short arm of chromosome 11. [7] The resulting EWSR1-WT1 fusion gene is converted to a fusion transcript [8] that directs the formation of an EWSR1-WT1 chimeric protein. [9] The EWSR1-WT1 chimeric protein contains the N-terminal transactivation domain of EWSR1 and the DNA-binding domain of WT1. This translocation is seen in virtually all cases of DSRCT. [10]

The EWS/WT1 translocation product targets ENT4. [11] ENT4 is also known as PMAT.

Pathology

The entity was first described by pathologists William L. Gerald and Juan Rosai in 1989. [12] Pathology reveals well circumscribed solid tumor nodules within a dense desmoplastic stroma. Often areas of central necrosis are present. Tumor cells have hyperchromatic nuclei with increased nuclear/cytoplasmic ratio.[ citation needed ]

On immunohistochemistry, these cells have trilinear coexpression including the epithelial marker cytokeratin, the mesenchymal markers desmin and vimentin, and the neuronal marker neuron-specific enolase. Thus, although initially thought to be of mesothelial origin due to sites of presentation, it is now hypothesized to arise from a progenitor cell with multiphenotypic differentiation.[ citation needed ]

Diagnosis

Differential diagnosis

Because this is a rare tumor, not many family physicians or oncologists are familiar with this disease. DSRCT in young patients can be mistaken for other abdominal tumors including rhabdomyosarcoma, neuroblastoma, and mesenteric carcinoid. In older patients DSRCT can resemble lymphoma, peritoneal mesothelioma, and peritoneal carcinomatosis. In males DSRCT may be mistaken for germ cell or testicular cancer while in females DSRCT can be mistaken for ovarian cancer. DSRCT shares characteristics with other small-round blue cell cancers including Ewing's sarcoma, acute leukemia, small cell mesothelioma, neuroblastoma, primitive neuroectodermal tumor, rhabdomyosarcoma, and Wilms' tumor.[ citation needed ]

Treatment

DSRCT is frequently misdiagnosed. Adult patients should always be referred to a sarcoma specialist. This is an aggressive, rare, fast spreading tumor and both pediatric and adult patients should be treated at a sarcoma center.[ citation needed ]

There is no standard protocol for the disease; [13] however, recent journals and studies have reported that some patients respond to high-dose (P6 Protocol) chemotherapy, maintenance chemotherapy, debulking operation, cytoreductive surgery, and radiation therapy. Other treatment options include: hematopoietic stem cell transplantation, intensity-modulated radiation therapy, radiofrequency ablation, stereotactic body radiation therapy, intraperitoneal hyperthermic chemoperfusion, and clinical trials.

Prognosis

The prognosis for DSRCT remains poor. [14] Prognosis depends upon the stage of the cancer. Because the disease can be misdiagnosed or remain undetected, tumors frequently grow large within the abdomen and metastasize or seed to other parts of the body.

There is no known organ or area of origin. DSRCT can metastasize through lymph nodes or the blood stream. Sites of metastasis include the spleen, diaphragm, liver, large and small intestine, lungs, central nervous system, bones, uterus, bladder, genitals, abdominal cavity, and the brain.

A multi-modality approach of high-dose chemotherapy, aggressive surgical resection, [15] radiation, and stem cell rescue improves survival for some patients. Reports have indicated that patients will initially respond to first line chemotherapy and treatment but that relapse is common.

Some patients in remission or with inoperable tumor seem to benefit from long term low dose chemotherapy, turning DSRCT into a chronic disease.

Research

The Stehlin Foundation [16] currently offers DSRCT patients the opportunity to send samples of their tumors free of charge for testing. Research scientists are growing the samples on nude mice and testing various chemical agents to find which are most effective against the individual's tumor.

Patients with advanced DSRCT may qualify to participate in clinical trials that are researching new drugs to treat the disease.

The Cory Monzingo Foundation is a 501(c)(3) organization that supports the research for treatments and a cure for DSRCT. The Cory Monzingo Foundation provides funding to MD Anderson Cancer Center and may also provide funding to other nonprofit cancer research organizations.

In 2002, Nishio and al, [17] established a novel human tumor cell line derived from the pleural effusion of a patient with a typical intra-abdominal DSRCT, called JN-DSRCT-1 [18] that can now be used in research.

St. Jude Children’s Research Hospital has, in 2018, make available resources from the Childhood Solid Tumor Network, that upon request gives access to patient-derived orthotopic xenografts. [19]

Alternative names

This disease is also known as: desmoplastic small round blue cell tumor; intra-abdominal desmoplastic small round blue cell tumor; desmoplastic small cell tumor; desmoplastic cancer; desmoplastic sarcoma; DSRCT.

There is no connection to peritoneal mesothelioma which is another disease sometimes described as desmoplastic.

See also

Related Research Articles

<span class="mw-page-title-main">Soft-tissue sarcoma</span> Medical condition

A soft-tissue sarcoma (STS) is a malignant tumor, a type of cancer, that develops in soft tissue. A soft-tissue sarcoma is often a painless mass that grows slowly over months or years. They may be superficial or deep-seated. Any such unexplained mass must be diagnosed by biopsy. Treatment may include surgery, radiotherapy, chemotherapy, and targeted drug therapy. Bone sarcomas are the other class of sarcomas.

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

A sarcoma is a malignant tumor, a type of cancer that arises from cells of mesenchymal origin. Connective tissue is a broad term that includes bone, cartilage, fat, vascular, or other structural 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. Sarcomas are one of five different types of cancer, classified by the cell type from which they originate. 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">Mesothelioma</span> Cancer associated with asbestos

Mesothelioma is a type of cancer that develops from the thin layer of tissue that covers many of the internal organs. The area most commonly affected is the lining of the lungs and chest wall. Less commonly the lining of the abdomen and rarely the sac surrounding the heart, or the sac surrounding the testis may be affected. Signs and symptoms of mesothelioma may include shortness of breath due to fluid around the lung, a swollen abdomen, chest wall pain, cough, feeling tired, and weight loss. These symptoms typically come on slowly.

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

Liposarcomas are the most common subtype of soft tissue sarcomas, accounting for at least 20% of all sarcomas in adults. Soft tissue sarcomas are rare neoplasms with over 150 different histological subtypes or forms. Liposarcomas arise from the precursor lipoblasts of the adipocytes in adipose tissues. Adipose tissues are distributed throughout the body, including such sites as the deep and more superficial layers of subcutaneous tissues as well as in less surgically accessible sites like the retroperitoneum and visceral fat inside the abdominal cavity.

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

Pseudomyxoma peritonei (PMP) is a clinical condition caused by cancerous cells that produce abundant mucin or gelatinous ascites. The tumors cause fibrosis of tissues and impede digestion or organ function, and if left untreated, the tumors and mucin they produce will fill the abdominal cavity. This will result in compression of organs and will destroy the function of the colon, small intestine, stomach, or other organs. Prognosis with treatment in many cases is optimistic, but the disease is lethal if untreated, with death occurring via cachexia, bowel obstruction, or other types of complications.

<span class="mw-page-title-main">Blastoma</span>

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">Aggressive fibromatosis</span> Medical condition

Aggressive fibromatosis or desmoid tumor is a rare condition. Desmoid tumors are a type of fibromatosis and related to sarcoma, though without the ability to spread throughout the body (metastasize). The tumors arise from cells called fibroblasts, which are found throughout the body and provide structural support, protection to the vital organs, and play a critical role in wound healing. These tumors tend to occur in women in their thirties, but can occur in anyone at any age. They can be either relatively slow-growing or malignant. However, aggressive fibromatosis is locally aggressive and can cause life-threatening problems or even death when the tumors compress vital organs such as intestines, kidneys, lungs, blood vessels, or nerves. The condition is rarely fatal. Most cases are sporadic, but some are associated with familial adenomatous polyposis (FAP). Approximately 10% of individuals with Gardner's syndrome, a type of FAP with extracolonic features, have desmoid tumors.

<span class="mw-page-title-main">Ewing sarcoma</span> Type of cancer

Ewing sarcoma is a type of pediatric cancer that forms in bone or soft tissue. Symptoms may include swelling and pain at the site of the tumor, fever, and a bone fracture. The most common areas where it begins are the legs, pelvis, and chest wall. In about 25% of cases, the cancer has already spread to other parts of the body at the time of diagnosis. Complications may include a pleural effusion or paraplegia.

Carcinosis, or carcinomatosis, is disseminated cancer, forms of metastasis, whether used generally or in specific patterns of spread.

<span class="mw-page-title-main">RNA-binding protein EWS</span> Human protein and coding gene

RNA-binding protein EWS is a protein that in humans is encoded by the EWSR1 gene on human chromosome 22, specifically 22q12.2. It is one of 3 proteins in the FET protein family.

<i>ERG</i> (gene) Protein-coding gene in the species Homo sapiens

ERG is an oncogene. ERG is a member of the ETS family of transcription factors. The ERG gene encodes for a protein, also called ERG, that functions as a transcriptional regulator. Genes in the ETS family regulate embryonic development, cell proliferation, differentiation, angiogenesis, inflammation, and apoptosis.

The Ewing family of tumors (EFTs) is a group of small cell sarcomas including Ewing sarcoma of the bone, extra osseous Ewing tumors, and primitive neuroectodermal tumors. They are rare cancers, usually diagnosed in peoples' twenties. The sarcoma of bone is the most common of the variants. All forms are predisposed to metastasis and have had historically high rates of mortality. The family of tumors shares a common translocation mutation of the EWS gene on chromosome 22 to an ETS-type gene, most commonly the FLI1 gene. EFTs are highly malignant, with 5-year survival for patients with metastatic disease at 20%. The current standard of care includes resection, radiation, and chemotherapy.

<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.

Extraskeletal myxoid chondrosarcoma (EMC) is a rare low-grade malignant mesenchymal neoplasm of the soft tissues, that differs from other sarcomas by unique histology and characteristic chromosomal translocations. There is an uncertain differentiation and neuroendocrine differentiation is even possible.

<span class="mw-page-title-main">Hyperthermic intraperitoneal chemotherapy</span>

Intraperitoneal hyperthermic chemoperfusion is a type of hyperthermia therapy used in combination with surgery in the treatment of advanced abdominal cancers. In this procedure, warmed anti-cancer medications are infused and circulated in the peritoneal cavity (abdomen) for a short period of time. The chemotherapeutic agents generally infused during IPHC are mitomycin-C and cisplatin.

Hyperthermic intrathoracic chemotherapy (HITOC) is part of a surgical strategy employed in the treatment of various pleural malignancies. The pleura in this situation could be considered to include the surface linings of the chest wall, lungs, mediastinum, and diaphragm. HITOC is the chest counterpart of HIPEC. Traditionally used in the treatment of malignant mesothelioma, a primary malignancy of the pleura, this modality has recently been evaluated in the treatment of secondary pleural malignancies.

EWS/FLI1 is an oncogenic protein that is pathognomonic for Ewing sarcoma. It is found in approximately 90% of all Ewing sarcoma tumors with the remaining 10% of fusions substituting one fusion partner with a closely related family member.

Andrea A. Hayes Dixon is an American surgeon. She was the first pediatric surgeon to perform a high-risk, life-saving procedure in children with a rare form of cancer and developed the first orthotropic xenograft model of metastatic Ewing's sarcoma. In 2002, she became the first African American female pediatric surgeon board-certified in the United States.

Sclerosing epithelioid fibrosarcoma (SEF) is a very rare malignant tumor of soft tissues that on microscopic examination consists of small round or ovoid neoplastic epithelioid fibroblast-like cells, i.e. cells that have features resembling both epithelioid cells and fibroblasts. In 2020, the World Health Organization classified SEF as a distinct tumor type in the category of malignant fibroblastic and myofibroblastic tumors. However, current studies have reported that low-grade fibromyxoid sarcoma (LGFMS) has many clinically and pathologically important features characteristic of SEF; these studies suggest that LGSFMS may be an early form of, and over time progress to become, a SEF. Since the World Health Organization has classified LGFMS as one of the malignant fibroblastic and myofibroblastic tumors that is distinctly different than SEF, SEF and LGFMS are here regarded as different tumor forms.

The FET protein family consists of three similarly structured and functioning proteins. They and the genes in the FET gene family which encode them are: 1) the EWSR1 protein encoded by the EWSR1 gene located at band 12.2 of the long arm of chromosome 22; 2) the FUS protein encoded by the FUS gene located at band 16 on the short arm of chromosome 16; and 3) the TAF15 protein encoded by the TAF15 gene located at band 12 on the long arm of chromosome 7 The FET in this protein family's name derives from the first letters of FUS, EWSR1, and TAF15.

References

  1. ↑ RESERVED, INSERM US14-- ALL RIGHTS. "Orphanet: Desmoplastic small round cell tumor". www.orpha.net. Retrieved 17 November 2019.{{cite web}}: CS1 maint: numeric names: authors list (link)
  2. 1 2 "Desmoplastic Small Round Cell Tumor". St. Jude Children's Research Hospital . Retrieved March 22, 2023.
  3. ↑ "Desmoplastic Small Round Cell Tumors (DSRCT)". National Cancer Institute . Retrieved March 22, 2023.
  4. ↑ Lee YS, Hsiao CH: Desmoplastic small round cell tumor: a clinicopathologic, immunohistochemical and molecular study of four patients. J Formos Med Assoc 2007; 106: 854–860.
  5. ↑ Bland AE, Shah AA, Piscitelli JT, Bentley RC, Secord AA (2007). "Desmoplastic small round cell tumor masquerading as advanced ovarian cancer". International Journal of Gynecological Cancer. 18 (4): 847–50. doi:10.1111/j.1525-1438.2007.01110.x. PMID   18081791.
  6. ↑ Murphy AJ, Bishop K, Pereira C, et al. (December 2008). "A new molecular variant of desmoplastic small round cell tumor: significance of WT1 immunostaining in this entity". Hum. Pathol. 39 (12): 1763–70. doi:10.1016/j.humpath.2008.04.019. PMID   18703217.
  7. ↑ Flucke U, van Noesel MM, Siozopoulou V, Creytens D, Tops BB, van Gorp JM, Hiemcke-Jiwa LS (June 2021). "EWSR1-The Most Common Rearranged Gene in Soft Tissue Lesions, Which Also Occurs in Different Bone Lesions: An Updated Review". Diagnostics (Basel, Switzerland). 11 (6): 1093. doi: 10.3390/diagnostics11061093 . PMC   8232650 . PMID   34203801.
  8. ↑ Gerald WL, Haber DA (June 2005). "The EWS-WT1 gene fusion in desmoplastic small round cell tumor". Semin. Cancer Biol. 15 (3): 197–205. doi:10.1016/j.semcancer.2005.01.005. PMID   15826834.
  9. ↑ Lee YS, Hsiao CH (2007). "Desmoplastic small round cell tumor: a clinicopathologic, immunohistochemical and molecular study of four patients". J. Formos. Med. Assoc. 106 (10): 854–60. doi: 10.1016/S0929-6646(08)60051-0 . PMID   17964965.
  10. ↑ Martínez-Trufero J, Cruz Jurado J, Hernández-León CN, Correa R, Asencio JM, Bernabeu D, Alvarez R, Hindi N, Mata C, Marquina G, Martínez V, Redondo A, Floría LJ, Gómez-Mateo MC, Lavernia J, Sebio A, Garcia Del Muro X, Martin-Broto J, Valverde-Morales C (September 2021). "Uncommon and peculiar soft tissue sarcomas: Multidisciplinary review and practical recommendations. Spanish Group for Sarcoma research (GEIS -GROUP). Part II". Cancer Treatment Reviews. 99: 102260. doi:10.1016/j.ctrv.2021.102260. PMID   34340159.
  11. ↑ Li H, Smolen GA, Beers LF, et al. (2008). "Adenosine transporter ENT4 is a direct target of EWS/WT1 translocation product and is highly expressed in desmoplastic small round cell tumor". PLOS ONE. 3 (6): e2353. Bibcode:2008PLoSO...3.2353L. doi: 10.1371/journal.pone.0002353 . PMC   2394657 . PMID   18523561. Open Access logo PLoS transparent.svg
  12. ↑ Gerald, W. L.; Rosai, J. (1989). "Case 2. Desmoplastic small cell tumor with divergent differentiation". Pediatr. Pathol. 9 (2): 177–83. doi:10.3109/15513818909022347. PMID   2473463.
  13. ↑ Talarico F, Iusco D, Negri L, Belinelli D: Combined resection and multi-agent adjuvant chemotherapy for intra-abdominal desmoplastic small round cell tumour: case report and review of the literature. G Chir 2007; 28: 367–370.
  14. ↑ Lal DR, Su WT, Wolden SL, Loh KC, Modak S, La Quaglia MP (January 2005). "Results of multimodal treatment for desmoplastic small round cell tumors". J. Pediatr. Surg. 40 (1): 251–5. doi:10.1016/j.jpedsurg.2004.09.046. PMID   15868593.
  15. ↑ Talarico F, Iusco D, Negri L, Belinelli D (October 2007). "Combined resection and multi-agent adjuvant chemotherapy for intra-abdominal desmoplastic small round cell tumour: case report and review of the literature". G Chir. 28 (10): 367–70. PMID   17915050.
  16. ↑ "Official website for Stehlin Foundation". Archived from the original on 2021-04-12. Retrieved 2006-10-08.
  17. ↑ Nishio, Jun; Iwasaki, Hiroshi; Ishiguro, Masako; Ohjimi, Yuko; Fujita, Chikako; Yanai, Fumio; Nibu, Keiko; Mitsudome, Akihisa; Kaneko, Yasuhiko (September 2002). "Establishment and characterization of a novel human desmoplastic small round cell tumor cell line, JN-DSRCT-1". Laboratory Investigation; A Journal of Technical Methods and Pathology. 82 (9): 1175–1182. doi: 10.1097/01.LAB.0000028059.92642.03 . ISSN   0023-6837. PMID   12218078.
  18. ↑ "Jn-Dsrct-1".
  19. ↑ "St Jude Children's Research Hospital".
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