Desmoplastic Small Round Cell Tumor
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Desmoplastic small-round-cell tumor (DSRCT) is an aggressive and rare
cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...
that primarily occurs as masses in the
abdomen The abdomen (colloquially called the gut, belly, tummy, midriff, tucky, or stomach) is the front part of the torso between the thorax (chest) and pelvis in humans and in other vertebrates. The area occupied by the abdomen is called the abdominal ...
. Other areas affected may include the
lymph nodes A lymph node, or lymph gland, is a kidney-shaped Organ (anatomy), organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphoc ...
, the lining of the
abdomen The abdomen (colloquially called the gut, belly, tummy, midriff, tucky, or stomach) is the front part of the torso between the thorax (chest) and pelvis in humans and in other vertebrates. The area occupied by the abdomen is called the abdominal ...
, diaphragm, spleen, liver, chest wall, skull, spinal cord, large intestine, small intestine, bladder, brain, lungs, testicles, ovaries, and the
pelvis The pelvis (: pelves or pelvises) is the lower part of an Anatomy, anatomical Trunk (anatomy), trunk, between the human abdomen, abdomen and the thighs (sometimes also called pelvic region), together with its embedded skeleton (sometimes also c ...
. Reported sites of metastatic spread include the
liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...
,
lung The lungs are the primary Organ (biology), organs of the respiratory system in many animals, including humans. In mammals and most other tetrapods, two lungs are located near the Vertebral column, backbone on either side of the heart. Their ...
s,
lymph nodes A lymph node, or lymph gland, is a kidney-shaped Organ (anatomy), organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphoc ...
,
brain The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...
, skull, and
bone A bone is a rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, ...
s. It is characterized by the EWS-WT1 fusion protein. The
tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
is classified as a
soft tissue sarcoma 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 ...
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 Ovarian cancer is a cancerous tumor of an ovary. It may originate from the ovary itself or more commonly from communicating nearby structures such as fallopian tubes or the inner lining of the abdomen. The ovary is made up of three different ...
.


Signs and symptoms

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. First symptoms of the disease often include abdominal distention, abdominal mass, abdominal or back pain, gastrointestinal obstruction, lack of appetite,
ascites Ascites (; , meaning "bag" or "sac") is the abnormal build-up of fluid in the abdomen. Technically, it is more than 25 ml of fluid in the peritoneal cavity, although volumes greater than one liter may occur. Symptoms may include increased abdo ...
, anemia, and
cachexia Cachexia () is a syndrome that happens when people have certain illnesses, causing muscle loss that cannot be fully reversed with improved nutrition. It is most common in diseases like cancer, Heart failure, congestive heart failure, chronic o ...
. Other reported symptoms include unknown lumps, thyroid conditions, hormonal conditions, blood clotting, kidney and urological problems, testicle, breast, uterine, vaginal, and ovarian masses.


Genetics

There are no known risk factors that have been identified specific to the disease (but see below). The tumor appears to arise from the primitive cells of childhood, and is considered a childhood cancer. Research has indicated that there is a chimeric relationship between DSRCT and
Wilms' tumor Wilms' tumor or Wilms tumor, also known as nephroblastoma, is a cancer of the kidneys that typically occurs in children (rarely in adults), and occurs most commonly as a renal tumor in child patients. It is named after Max Wilms, the German sur ...
and Ewing sarcoma. Together with neuroblastoma and non-Hodgkin's lymphoma, they form the small-cell tumors. DSRCT is associated with a unique
chromosomal translocation In genetics, chromosome translocation is a phenomenon that results in unusual rearrangement of chromosomes. This includes "balanced" and "unbalanced" translocation, with three main types: "reciprocal", "nonreciprocal" and "Robertsonian" transloc ...
(notated as t(11;22)(p13:q12)) that merges the ''
EWSR1 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. Clinical significance The q22.2 region of chromosome 22 encod ...
'' FET family gene normally located on
band Band or BAND may refer to: Places *Bánd, a village in Hungary * Band, Iran, a village in Urmia County, West Azerbaijan Province, Iran * Band, Mureș, a commune in Romania * Band-e Majid Khan, a village in Bukan County, West Azerbaijan Province, ...
12 of the long (or "q") arm of
chromosome 22 Chromosome 22 is one of the 23 pairs of chromosomes in human cells. Humans normally have two copies of chromosome 22 in each cell. Chromosome 22 is the second smallest human chromosome, spanning about 51 million DNA base pairs and representing b ...
with part of the ''
WT1 Wilms tumor protein (WT33) is a protein that in humans is encoded by the ''WT1'' gene on chromosome 11p. Function This gene encodes a transcription factor that contains four zinc finger motifs at the C-terminus and a proline / glutamine-rich ...
''
transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription (genetics), transcription of genetics, genetic information from DNA to messenger RNA, by binding t ...
gene normally located on band 13 of the short arm of
chromosome 11 Chromosome 11 is one of the 23 pairs of chromosomes in humans. Humans normally have two copies of this chromosome. Chromosome 11 spans about 135 million base pairs (the building material of DNA) and represents between 4 and 4.5 percent of the tota ...
. The resulting ''EWSR1-WT1'' fusion gene is converted to a
fusion transcript Fusion transcript is a chimeric RNA encoded by a fusion gene or by two different genes by subsequent trans-splicing. Certain fusion transcripts are commonly produced by cancer cells, and detection of fusion transcripts is part of routine diagnostics ...
that directs the formation of an EWSR1-WT1
chimeric protein Fusion proteins or chimeric (kī-ˈmir-ik) proteins (literally, made of parts from different sources) are proteins created through the joining of two or more genes that originally coded for separate proteins. Translation of this ''fusion gene'' r ...
. The EWSR1-WT1 chimeric protein contains the N-terminal
transactivation domain The transactivation domain or trans-activating domain (TAD) is a transcription factor scaffold domain which contains binding sites for other proteins such as transcription coregulators. These binding sites are frequently referred to as activatio ...
of
EWSR1 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. Clinical significance The q22.2 region of chromosome 22 encod ...
and the
DNA-binding domain A DNA-binding domain (DBD) is an independently folded protein domain that contains at least one structural motif that recognizes double- or single-stranded DNA. A DBD can recognize a specific DNA sequence (a recognition sequence) or have a gener ...
of
WT1 Wilms tumor protein (WT33) is a protein that in humans is encoded by the ''WT1'' gene on chromosome 11p. Function This gene encodes a transcription factor that contains four zinc finger motifs at the C-terminus and a proline / glutamine-rich ...
. This translocation is seen in virtually all cases of DSRCT. The EWS/WT1 translocation product targets ENT4. ENT4 is also known as PMAT.


Pathology

The entity was first described by pathologists William L. Gerald and
Juan Rosai Juan Rosai (August 20, 1940 – July 7, 2020) was an Italian-born American physician who contributed to clinical research and education in the specialty of surgical pathology. He was the principal author and editor of a major textbook in that fi ...
in 1989. 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. 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.


Diagnosis


Differential diagnosis

Because this is a rare tumor, not many family physicians or even oncologists are familiar with this disease. DSRCT in young patients can be mistaken for other abdominal tumors including
rhabdomyosarcoma 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 neoplasm, tumor are identified as rhabdomyoblasts. The four ...
,
neuroblastoma Neuroblastoma (NB) is a type of cancer that forms in certain types of nerve tissue. It most frequently starts from one of the adrenal glands but can also develop in the head, neck, chest, abdomen, or Vertebral column, spine. Symptoms may include ...
, and mesenteric
carcinoid A carcinoid (also carcinoid tumor) is a slow-growing type of neuroendocrine tumor originating in the cells of the neuroendocrine system. In some cases, metastasis may occur. Carcinoid tumors of the midgut (jejunum, ileum, appendix, and cecum) ...
. In older patients DSRCT can resemble
lymphoma Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). The name typically refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlarged lymph node ...
,
peritoneal mesothelioma Peritoneal mesothelioma is the name given to the cancer that attacks the lining of the abdomen. This type of cancer affects the lining that protects the contents of the abdomen and provides a lubricating fluid to enable the organs to move and work ...
, and peritoneal carcinomatosis. In males DSRCT may be mistaken for
germ cell A germ cell is any cell that gives rise to the gametes of an organism that reproduces sexually. In many animals, the germ cells originate in the primitive streak and migrate via the gut of an embryo to the developing gonads. There, they unde ...
or
testicular cancer Testicular cancer is cancer that develops in the testicles, a part of the male reproductive system. Symptoms may include a lump in the testicle or swelling or pain in the scrotum. Treatment may result in infertility. Risk factors include an c ...
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 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%. It gets its name because the ...
,
rhabdomyosarcoma 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 neoplasm, tumor are identified as rhabdomyoblasts. The four ...
, and Wilms' tumor.


Treatment

DSRCT is frequently
misdiagnosed A medical error is a preventable adverse effect of care ("iatrogenesis"), whether or not it is evident or harmful to the patient. This might include an inaccurate or incomplete diagnosis or treatment of a disease, injury, syndrome, behavior, i ...
. 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. There is no standard protocol for the disease. However, recent research has reported that some patients respond to high-dose (P6 Protocol)
chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...
,
maintenance chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) in a standard regimen. Chemotherapy may be given with a curat ...
, debulking operation,
cytoreductive surgery Cytoreductive surgery (CRS) is a surgical procedure that aims to reduce the amount of cancer cells in the abdominal cavity for patients with tumors that have spread intraabdominally ( peritoneal carcinomatosis). It is often used to treat ovarian c ...
, and
radiation therapy Radiation therapy or radiotherapy (RT, RTx, or XRT) is a therapy, treatment using ionizing radiation, generally provided as part of treatment of cancer, cancer therapy to either kill or control the growth of malignancy, malignant cell (biology), ...
. Other treatment options include:
hematopoietic stem cell transplantation Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood, in order to replicate inside a patient and produce ...
, intensity-modulated radiation therapy,
radiofrequency ablation Radiofrequency ablation (RFA), also called fulguration, is a medical procedure in which part of the electrical conduction system of the heart, tumor, sensory nerves or a dysfunctional tissue is ablated using the heat generated from medium fre ...
, stereotactic body radiation therapy,
intraperitoneal hyperthermic chemoperfusion The peritoneum is the serous membrane forming the lining of the abdominal cavity or coelom in amniotes and some invertebrates, such as annelids. It covers most of the intra-abdominal (or coelomic) organs, and is composed of a layer of mesotheli ...
, and
clinical trial Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...
s.


Prognosis

The prognosis for DSRCT remains poor. 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 Metastasis is a pathogenic agent's spreading from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, ...
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, 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 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 Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...
that are researching new drugs to treat the disease. Th
Cory Monzingo Foundation
is a
501(c)(3) organization A 501(c)(3) organization is a United States corporation, Trust (business), trust, unincorporated association or other type of organization exempt from federal income tax under section 501(c)(3) of Title 26 of the United States Code. It is one of ...
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, 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 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.


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 Peritoneal mesothelioma is the name given to the cancer that attacks the lining of the abdomen. This type of cancer affects the lining that protects the contents of the abdomen and provides a lubricating fluid to enable the organs to move and work ...
which is another disease sometimes described as desmoplastic.


See also

*
Desmoplasia In medicine, desmoplasia is the growth of fibrous connective tissue. It is also called a desmoplastic reaction to emphasize that it is secondary to an insult (medical), insult. Desmoplasia may occur around a neoplasm, causing dense fibrosis arou ...
* Kate Granger (1981–2016), an English physician, whose diagnosis with DSRCT led to her campaigning for better patient care, and fund-raising for cancer research.


References


External links

{{DEFAULTSORT:Desmoplastic Small Round Cell Tumor Hepatology Small-blue-round-cell tumors Rare cancers Sarcoma