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The first symptoms of neuroblastoma are often vague making diagnosis difficult. Fatigue, loss of appetite, fever, and joint pain are common. Symptoms depend on primary tumor locations and metastases if present:
- In the abdomen, a tumor may cause a swollen belly and constipation.
- A tumor in the chest may cause breathing problems.
- A tumor pressing on the spinal cord may cause weakness and thus an inability to stand, crawl, or walk.
- Bone lesions in the legs and hips may cause pain and limping.
- A tumor in the bones around the eyes or orbits may cause distinct bruising and swelling.
- Infiltration of the bone marrow may cause pallor from anemia.
Neuroblastoma often spreads to other parts of the body before any symptoms are apparent and 50 to 60% of all neuroblastoma cases present with metastases.
The most common location for neuroblastoma to originate (i.e., the primary tumor) is in the adrenal glands. This occurs in 40% of localized tumors and in 60% of cases of widespread disease. Neuroblastoma can also develop anywhere along the sympathetic nervous system chain from the neck to the pelvis. Frequencies in different locations include: neck (1%), chest (19%), abdomen (30% non-adrenal), or pelvis (1%). In rare cases, no primary tumor can be discerned.
Rare but characteristic presentations include transverse myelopathy (tumor spinal cord compression, 5% of cases), treatment-resistant diarrhea (tumor vasoactive intestinal peptide secretion, 4% of cases), Horner's syndrome (cervical tumor, 2.4% of cases), opsoclonus myoclonus syndrome and ataxia (suspected paraneoplastic cause, 1.3% of cases), and hypertension (catecholamine secretion or renal artery compression, 1.3% of cases).
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 neck, chest, abdomen, or spine. Symptoms may include bone pain, a lump in the abdomen, neck, or chest, or a painless bluish lump under the skin.
Occasionally neuroblastoma may be due to a mutation inherited from a person's parents. Environmental factors have not been found to be involved. Diagnosis is based on a tissue biopsy. Occasionally it may be found in a baby by ultrasound during pregnancy. At diagnosis the cancer has usually already spread. The cancer is divided into low, intermediate, and high risk groups based on a child's age, cancer stage, and what the cancer looks like.
Treatment and outcomes depends on the risk group a person is in. Treatments may include observation, surgery, radiation, chemotherapy, or stem cell transplantation. Low-risk disease in babies typically has a good outcome with surgery or simply observation. In high-risk disease chances of long term survival, however, are less than 40% despite aggressive treatment.
Neuroblastoma is the most common cancer in babies and the third most common cancer in children after leukemia and brain cancer. About 1 in every 7,000 children is affected at some point in time. About 90% of cases occur in children less than 5 years old and it is rare in adults. Of cancer deaths in children about 15% are due to neuroblastoma. The disease was first described in the 1800s.
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, anemia, and/or cachexia.
Other reported symptoms include unknown lumps, thyroid conditions, hormonal conditions, blood clotting, kidney or urological problems, testicle, breast, uterine, vaginal, or ovarian masses.
Ganglioneuroblastoma is a variant of neuroblastoma that is surrounded by ganglion cells.
It can be difficult to diagnose.
Nodular ganglioneuroblastoma can be divided by prognosis.
It is contained within the "neuroblastic tumors" group, which includes:
- Ganglioneuroma (benign)
- Ganglioneuroblastoma (intermediate).
- Neuroblastoma (aggressive)
Esthesioneuroblastoma will first frequently present as a nasal mass. The most common signs and symptoms of esthesioneuroblastoma are nasal obstruction (70%) and epistaxis (50%). Less common symptoms include hyposmia (loss of smell), headache, rhinorrhea, vision loss, proptosis, facial pain, diplopia (double vision), masses in the neck and changes in mental status. Esthesioneuroblastoma occurs in the upper nasal cavity, near the optic nerves and optic chiasm. Thus, tumor growth can impinge nerve function and result in vision loss and diplopia. As the tumor metastasizes to the oral cavity, there can be tooth pain and tooth mobility.
Desmoplastic small-round-cell tumor 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.
The tumor is classified as a soft tissue sarcoma. It is considered a childhood cancer that predominantly strikes boys and young adults. The disease rarely occurs in females, but when it does the tumors can be mistaken for ovarian cancer.
In dogs, mast cell tumors are the most frequent round cell tumor.
Esthesioneuroblastoma, also called "olfactory neuroblastoma", is a rare cancer of the nasal cavity. Arising from the upper nasal tract, esthesioneuroblastoma is believed to originate from sensory neuroepithelial cells, also known as neuroectodermal olfactory cells. Fewer than 700 cases have been documented in the United States. Due to the location of the tumor and its proximity to the cranial cavity, esthesioneuroblastoma can be highly invasive and challenging to treat. There is no consensus on appropriate treatment approach of esthesioneuroblastoma because of the rarity of the disease. Most studies reported cranial surgical resection with radiotherapy or chemotherapy to target the tumor.
Esthesioneuroblastoma was first characterized in 1924.
Because different parts of the brain are responsible for different functions, symptoms vary depending on the site of metastasis within the brain. However, brain metastases should be considered in any cancer patient who presents with neurological or behavioral changes.
Brain metastases can cause a wide variety of symptoms which can also be present in minor, more common conditions. Neurological symptoms are often caused by increased intracranial pressure, with severe cases resulting in coma. The most common neurological symptoms include:
- New onset headaches: headaches occur in roughly half of brain metastasis patients, especially in those with many tumors.
- Paresthesias: patients often present with (hemiparesis), or weakness on only one side of the body, which is often a result of damage to neighboring brain tissue.
- Ataxia: when metastasis occurs to the cerebellum, patients will experience various difficulties with spatial awareness and coordination.
- Seizures: when present, often indicates disease involvement of the cerebral cortex.
A ganglioneuroma is typically asymptomatic, and is typically only discovered when being examined or treated for another condition. Any symptoms will depend upon the tumor's location and the nearby organs affected.
For example, a tumor in the chest area may cause breathing difficulty, chest pain, and trachea compression. If the tumor is located lower in the abdomen, it may cause abdominal pain and bloating. A tumor near the spinal cord may cause spinal deformity or spinal compression, leading to pain and loss of muscle control or sensation in the legs and/or arms.
These tumors may produce certain hormones, which can cause diarrhea, an enlarged clitoris (in females), high blood pressure, increased body hair, and sweating.
The tumor largely affects children under 15 years of age and about 20% only are found in adults with nearly 60% involving males and 40% females (1). The most frequent locations are head and neck (orbit and nasopharynx), central nervous system, abdomen and retroperitoneum, pelvis, perineum, scrotum and prostate(1). Clinical symptoms are not specific and usually caused by local tumor compression and infiltration.
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.
Malignant ectomesenchymoma (MEM) is a rare tumor of soft tissues or the CNS, which is composed of both neuroectodermal elements [represented by ganglion cells and/or well-differentiated or poorly differentiated neuroblastic cells such as ganglioneuroma, ganglioneuroblastoma, neuroblastoma, peripheral primitive neuroectodermal tumors – PNET] and one or more mesenchymal neoplastic elements, usually rhabdomyosarcoma . The most accepted theory suggests that this tumor arises from remnants of migratory neural crest cells and thus from the ectomesenchyme.
Ganglioneuroma is a rare and benign tumor of the autonomic nerve fibers arising from neural crest sympathogonia, which are completely undifferentiated cells of the sympathetic nervous system. However, ganglioneuromas themselves are fully differentiated neuronal tumors that do "not" contain immature elements.
Ganglioneuromas most frequently occur in the abdomen, however these tumors can grow anywhere sympathetic nervous tissue is found. Other common locations include the adrenal gland, paraspinal retroperitoneum, posterior mediastinum, head, and neck.
The most common sources of brain metastases in a case series of 2,700 patients undergoing treatment at the Memorial Sloan–Kettering Cancer Center were:
- Lung cancer, 48%
- Breast cancer, 15%
- Genitourinary tract cancers, 11%
- Osteosarcoma, 10%
- Melanoma, 9%
- Head and neck cancer, 6%
- Neuroblastoma, 5%
- Gastrointestinal cancers, especially colorectal and pancreatic carcinoma, 3%
- Lymphoma, 1%
Lung cancer and melanoma are most likely to present with multiple metastasis, whereas breast, colon, and renal cancers are more likely to present with a single metastasis.
The most common cancers in children are (childhood) leukemia (32%), brain tumors (18%), and lymphomas (11%). In 2005, 4.1 of every 100,000 young people under 20 years of age in the U.S. were diagnosed with leukemia, and 0.8 per 100,000 died from it. The number of new cases was highest among the 1–4 age group, but the number of deaths was highest among the 10–14 age group.
In 2005, 2.9 of every 100,000 people 0–19 years of age were found to have cancer of the brain or central nervous system, and 0.7 per 100,000 died from it. These cancers were found most often in children between 1 and 4 years of age, but the most deaths occurred among those aged 5–9. The main subtypes of brain and central nervous system tumors in children are: astrocytoma, brain stem glioma, craniopharyngioma, desmoplastic infantile ganglioglioma, ependymoma, high-grade glioma, medulloblastoma and atypical teratoid rhabdoid tumor.
Other, less common childhood cancer types are:
- Neuroblastoma (6%, nervous system)
- Wilms tumor (5%, kidney)
- Non-Hodgkin lymphoma (4%, blood)
- Childhood rhabdomyosarcoma (3%, many sites)
- Retinoblastoma (3%, eye)
- Osteosarcoma (3%, bone cancer)
- Ewing sarcoma (1%, many sites)
- Germ cell tumors (5%, many sites)
- Pleuropulmonary blastoma (lung or pleural cavity)
- Hepatoblastoma and hepatocellular carcinoma (liver cancer)
Lewis lung carcinoma is a tumor discovered by Dr. Margaret R. Lewis of the Wistar Institute in 1951. This tumor originated spontaneously as a carcinoma of the lung of a C57BL mouse. The tumor does not appear to be grossly hemorrhagic and the majority of the tumor tissue is a semifirm homogeneous mass. It is also called 3LL and LLC and is used as a transplantable malignancy. It has been used in many studies.
In 1975, Munson discovered that cannabinoids suppress Lewis lung carcinoma cell growth. The mechanism of this action was shown to be inhibition of DNA synthesis Cannabinoids increase the life span of mice carrying Lewis lung tumors and decrease primary tumor size. There are multiple modes of action.
Childhood cancer (also known as pediatric cancer) is cancer in a child. In the United States, an arbitrarily adopted standard of the ages used are 0–14 years inclusive, that is, up to 14 years 11.9 months of age. However, the definition of childhood cancer sometimes includes adolescents between 15–19 years old. Pediatric oncology is the branch of medicine concerned with the diagnosis and treatment of cancer in children.
Worldwide, it is estimated that childhood cancer has an incidence of more than 175,000 per year, and a mortality rate of approximately 96,000 per year. In developed countries, childhood cancer has a mortality of approximately 20% of cases. In low resource settings, on the other hand, mortality is approximately 80%, or even 90% in the world's poorest countries. In many developed countries the incidence is slowly increasing, as rates of childhood cancer increased by 0.6% per year between 1975 and 2002 in the United States and by 1.1% per year between 1978 and 1997 in Europe.
The exact causes for the development of canine mammary tumors are not fully understood. However, hormones of the estrous cycle seem to be involved. Female dogs who are not spayed or who are spayed later than the first heat cycle are more likely to develop mammary tumors. Dogs have an overall reported incidence of mammary tumors of 3.4 percent. Dogs spayed before their first heat have 0.5 percent of this risk, and dogs spayed after just one heat cycle have 8 percent of this risk. The tumors are often multiple. The average age of dogs with mammary tumors is ten to eleven years old. Obesity at one year of age and eating red meat have also been associated with an increased risk for these tumors, as has the feeding of high fat homemade diets.
There are several hypotheses on the molecular mechanisms involved in the development of canine mammary tumors but a specific genetic mutation has not been identified.
Historically, about 50 percent of mammary tumors in dogs were found to be malignant, although taking into account tumor behavior, one study has estimated true malignancy in mammary tumors to be 21 to 22 percent. Adenomas and fibroadenomas make up the benign types. Malignant mammary tumors are divided into sarcomas, carcinosarcomas, inflammatory carcinomas (usually anaplastic carcinomas), and carcinomas (including adenocarcinomas), which are the most common. Inflammatory carcinomas describe tumors that are fast growing and have bruising, edema, and pain, and can also cause disseminated intravascular coagulation. They are the most malignant type of canine mammary tumor.
Malignant tumors are also subdivided histopathologically into those showing blood vessel wall invasion and those that do not. Without blood vessel wall invasion there is a better prognosis. Dogs with noninvasive adenocarcinomas have an average survival time of two years, while dogs with invasive adenocarcinomas have an average survival time of one year. Tumor size also affects the prognosis, in that dogs with tumors greater than five centimeters have a greater chance of lymph node metastasis. Tumor type is also important. Sarcomas and carcinosarcomas carry an average survival time of nine to twelve months. Inflammatory carcinomas have a very poor prognosis, and have usually metastasized by the time of diagnosis. Metastasis for any malignant mammary tumor is usually to the regional lymph nodes and lungs.
The molecular carcinogenesis of canine mammary tumors are not completely understand. However, the increasing information on molecular pathways involved in the carcinogenesis of this canine tumor has potential to complement and refine the current diagnostic and therapeutic approach to this tumor type. Furthermore, current data show that significant similarities and differences exist between canine and human mammary tumors at the molecular level.
Recognised symptoms up till now are:
- Autism or autistic behaviors
- ADHD
- Learning disability
- Large head
- Dysmorphic facial appearance - mild
- Prominent forehead
- Wide-set eyes (hypertelorism)
- Schizophrenia
- Loose joints
- GERD
- Sleep disturbances
- Sleep Apnea
- Underdeveloped parts of brain - corpus callosum and cerebellar vermis
- Neuroblastoma
- Speech & developmental delays
- Chiari malformation of the brain
- Congenital heart defects
- Hypotonia
It is not clear whether the list of symptoms is complete. Very little information is known about the syndrome. The symptomology may be different among individuals, even in the same family.
1q21.1 duplication syndrome or 1q21.1 (recurrent) microduplication is a rare aberration of chromosome 1.
In a common situation a human cell has one pair of identical chromosomes on chromosome 1. With the 1q21.1 duplication syndrome one chromosome of the pair is over complete, because a part of the sequence of the chromosome is duplicated twice or more. In 1q21.1, the '1' stands for chromosome 1, the 'q' stands for the long arm of the chromosome and '21.1' stands for the part of the long arm in which the duplication is situated.
Next to the duplication syndrome, there is also a 1q21.1 deletion syndrome. While there are two or three copies of a similar part of the DNA on a particular spot with the duplication syndrome, there is a part of the DNA missing with the deletion syndrome on the same spot. Literature refers to both the deletion and the duplication as the 1q21.1 copy-number variations (CNV).
The CNV leads to a very variable phenotype and the manifestations in individuals are quite variable. Some people who have the syndrome can function in a normal way, while others have symptoms of mental retardation and various physical anomalies.
Costello syndrome, also called faciocutaneoskeletal syndrome or FCS syndrome, is a rare genetic disorder that affects many parts of the body. It is characterized by delayed development and delayed mental progression, distinctive facial features, unusually flexible joints, and loose folds of extra skin, especially on the hands and feet. Heart abnormalities are common, including a very fast heartbeat (tachycardia), structural heart defects, and overgrowth of the heart muscle (hypertrophic cardiomyopathy). Infants with Costello syndrome may be large at birth, but grow more slowly than other children and have difficulty feeding. Later in life, people with this condition have relatively short stature and many have reduced levels of growth hormones. It is a RASopathy.
Beginning in early childhood, people with Costello syndrome have an increased risk of developing certain cancerous and noncancerous tumors. Small growths called papillomas are the most common noncancerous tumors seen with this condition. They usually develop around the nose and mouth or near the anus. The most frequent cancerous tumor associated with Costello syndrome is a soft tissue tumor called a rhabdomyosarcoma. Other cancers also have been reported in children and adolescents with this disorder, including a tumor that arises in developing nerve cells (neuroblastoma) and a form of bladder cancer (transitional cell carcinoma).
Costello Syndrome was discovered by Dr Jack Costello, a New Zealand Paediatrician in 1977. He is credited with first reporting the syndrome in the Australian Paediatric Journal, Volume 13, No.2 in 1977.
1q21.1 deletion syndrome or 1q21.1 (recurrent) microdeletion is a rare aberration of chromosome 1.
A human cell has one pair of identical chromosomes on chromosome 1. With the 1q21.1 deletion syndrome, one chromosome of the pair is not complete, because a part of the sequence of the chromosome is missing. One chromosome has the normal length and the other is too short.
In 1q21.1, the '1' stands for chromosome 1, the 'q' stands for the long arm of the chromosome and '21.1' stands for the part of the long arm in which the deletion is situated.
The syndrome is a form of the 1q21.1 copy number variations and it is a deletion in the distal area of the 1q21.1 part. The CNV leads to a very variable phenotype and the manifestations in individuals are quite variable. Some people who have the syndrome can function in a normal way, while others have symptoms of mental retardation and various physical anomalies.
1q21.1 microdeletion is a very rare chromosomal condition. Only 46 individuals with this deletion have been reported in medical literature as of August 2011.
There are two types of SGBS, each found on a different gene:
SGBS is also considered to be an overgrowth syndrome (OGS). OGS is characterized by a 2-3 standard deviation increase in weight, height, or head circumference above the average for sex and age. One of the most noted features of OGS is the increased risk of neoplasms in certain OGSs. SGBS in particular has been found to have a 10% tumor predisposition frequency with 94% of cases occurring in the abdominal region, most being malignant. It is common for tumors to be embryonal in type and appear before the age of 10.
There are five different types of tumors that patients with SGBS might develop, all intra-abdominal: Wilms tumor, Hepatoblastoma, Hepatocarcinoma, Gonadoblastoma, and Neuroblastoma.
The most common types of tumors developed in patients are the Wilms tumor and hepatoblastoma.
Recognised symptoms are:
- Only one set of genes on the two chromosomes function (Haploinsufficiency)
- Thrombocytopenia-absent radius (TAR syndrome), in case of a class II-deletion
- Neurological-psychiatric problems: Autism; schizophrenia; epilepsy; learning problems; cognitive disabilities — mild to moderate; developmental delay — mild to moderate (milestones like sitting, standing and walking; come at a later period in childhood); children show an ataxic gait and fall down a lot
- Dysmorphism: Slightly unusual facial appearance; disturbed growth; skeletal malformations; small head (microcephaly); prominent forehead; bulbous nose; deep-set eyes; broad thumbs; broad toes; squint; very flexible joints; clavicular pseudoarthrosis (the collarbone doesn't develop normally) (Class II-deletion); An extra transverse crease of the fifth finger (Class II-deletion)); Problems with the development of the vagina (Müllerian aplasia)
- Eyes: Cataracts
- Heart abnormalities and cardiovascular anomalies (30% of the cases): Anomalous origin of the coronary artery (Class II-deletion)
- Kidneys: Missing kidney or floating kidneys
- Cancer: Neuroblastoma
- Sleep disturbances
It is not clear whether the list of symptoms is complete. Very little information is known about the syndrome. The syndrome can have completely different effects on members of the same family.
A common deletion is between 1.0–1.9Mb. Mefford states that the standard for a deletion is 1.35Mb. The largest deletion seen on a living human is over 5 Mb.