Carcinoid tumors can be encountered in all age groups. They are accompanied by a polymorphic clinical presentation and can originate from the gut wall, lungs, kidneys, thymus, ovaries, prostate, testis, pancreas, liver, bronchus or mediastinum. Localized disease implicates a good prognosis, but they have a high potential for metastasis and metastatic cases are more difficult to treat.
The tumor in itself, as well as metastatic disease cause symptoms, ranging up to the carcinoid syndrome. Most pediatric cases of carcinoid tumor originate in the gut. Appendicular tumors can be asymptomatic (especially when they are non-functioning) and discovered incidentally or can cause acute appendicitis. Pediatric intestinal carcinoid tumors cause abdominal pain due to intestinal obstruction or kinking or mesentery fibrosis. Abdominal pain can also be caused by appendicular perforation .
Clinical signs can also be caused by the hormones and other substances that the tumor secretes, such as bradykinin, serotonin, vasoactive intestinal peptide, 5-hydroxytryptophan and histamine or adrenocorticotropic hormone. Frank carcinoid syndrome, the most severe presentation of a carcinoid tumor is very infrequent in children . It occurs more often in children with functioning tumors that have metastasized to the liver and it consists of a constellation of signs and symptoms, such as cutaneous flushing of the head and neck, tachycardia, and palpitations, lacrimation, diaphoresis, hypersalivation, blood pressure disturbances (hypertension or hypotension), abdominal pain, diarrhea and decreased mental state. Flushing can be accompanied by edema and itching and the erythema can progress to cyanosis. The duration of these episodes is initially short (minutes) but as the disease progresses, they may last up to several hours.
The stools may range from watery diarrhea to steatorrhea and patients may suffer from malabsorption. Bronchial carcinoid tumors may cause asthma-like symptoms, such as wheezing, dyspnea, cough or shortness of breath  and may be accompanied by signs of Cushing syndrome .
The heart may also be affected by the disease. Carcinoid tumors may cause endocardial fibrosis often involving the right cavities and the tricuspid valvular apparatus. Other valves, such as the pulmonary may also be involved, resulting in stenosis or regurgitation. Disease progression may cause heart failure.
Patients sometimes also complain about joint pain secondary to arthritis, sexual dysfunction or visual abnormalities caused by vascular occlusion. Skin hyperkeratosis can occur, but it is considered to be an uncommon finding, as is laryngeal involvement .
Patients affected by Peutz-Jeghers syndrome or multiple endocrine neoplasia type 1 can develop a carcinoid tumor. Also, secondary malignancies such as hepatocellular carcinoma can be encountered in carcinoid tumor patients .
Childhood carcinoid tumor workup includes blood and urine tests, as well as several imaging methods. Certain tests such as 5-hydroxyindoleacetic acid , histamine, catecholamines, serotonin, chromogranin, neuropeptide K and 5-5-hydroxytryptamine have been proved useful, but the diagnosis remains difficult because the level of these substances is not always elevated. False positive results can be eliminated by avoiding serotonin rich foods for two days before urine collection.
Imaging methods that can be used consist of simple radiography, contrast radiography, angiography, computed tomography (CT), magnetic resonance imaging, scintigraphy , positron emission tomography (PET) and radionuclide imaging (using yttrium and indium-111 diethylenetriamine pentaacetic acid (111 In-DTPA) as radiotracers), depending on the location of the suspected tumor. PET-CT is considered to have poor sensitivity but good specificity, while scintigraphy combined with computed tomography is optimum for chest tumors discovery. Hepatic lesions can be diagnosed via computed tomography, while this method is relatively unreliable for small bowel tumors. The large bowel can be explored via colonoscopy and the diagnosis is relatively easy to establish. This technique, as well as the upper digestive endoscopy, offers the advantage of being able to obtain biopsies. Bone metastasis is not infrequent and can be diagnosed by technetium-99m bone scanning. Extra-abdominal disease can be diagnosed by scintiscan with Octreotide .
The first treatment choice of carcinoid tumors is represented by surgical excision. This is more or less feasible, depending on the location of the pathological process. Appendicular tumors are easy to extract by appendectomy, while block resection is needed in intestinal carcinoids. When the margins of the resection piece are not tumor free, a larger portion of the organ should be excised. Adjacent lymph nodes must also be averted in this instance and the need for reoperation cannot be excluded. Large tumors are infrequent in the pediatric age groups. Bronchial carcinoids should be resected by classic surgery, not by bronchoscope interventional procedures . Endoscopic procedures may be used in adults with rectal tumors, when facing a small tumor located in the mucosa, but even in this age group classical surgical procedures are preferred due to improved survival .
Patients with hepatic tumors that cannot be evacuated may benefit for a short period of time from hepatic artery surgical ligation or hepatic artery chemoembolization or cryotherapy. In cases where surgery or interventional procedures are not an option, chemotherapy remains the only alternative. Several chemotherapeutic agents, such as 5-Fluorouracil, Cisplatin, Streptozotocin, Doxorubicin, Etoposide, Dacarbazine and Actinomycin D are widely used, at least for palliative purposes. Octreotide provides symptom decrease, but more studies are needed regarding stunted linear growth and survival improvement. When associated with everolimus, octreotide shows superior results . Experimental data regarding treatment with octreotide attached to a radioactive load like yttrium or indium is currently available and showing positive results.
Exact data regarding the prognosis of childhood carcinoid tumors is unavailable, but the outcome of properly treated appendix located tumor cases seems to be favorable. Tumors that are found in other locations tend to be larger and to have already spread at the time of diagnosis, therefore their prognosis is grimmer. Also, the probability of recurrence is higher in these cases. Metastases are more frequent in patients with periappendiceal or mesoappendix fat invasion , but all neuroendocrine tumors are considered to have a high risk for metastases in general .
Childhood carcinoid tumors derive from stem cells located mainly in the intestinal wall, but the disease may also originate in the respiratory, reproductive or urinary systems, in the mediastinum or in other parts of the digestive tract. The tumors may be argentaffin positive or negative. The cause of tumor development remains unknown, but chromosomal abnormalities are suspected. Reported cases describe chromosomal abnormalities like allelic losses or numerical imbalances. Metastatic cells may lose chromosomal arms 16q, 11q or 18q and gain 4p or losses may be more discrete, involving only certain bands: 16q21-qter, 18q22-qter or 11q22-q23. Homeobox gene Hoxc6 may also be involved in carcinoid etiology .
Carcinoid tumors are more frequent in adults than children and adolescents. Still, in the pediatric age group, carcinoid tumors represent the most frequent type of gastrointestinal epithelial tumor . Their incidence is reported to be around 0.08% of pediatric cancers. 2 to 5 in 100 pediatric appendectomies incidentally discover the presence of a carcinoid , but the disease can also be found during a laparotomy . In adults, the incidence is thought to be steadily increasing , and this has been speculated to be due to more extensive proton pump inhibitors use.
Carcinoid tumors may have a secretory activity and/or other, mechanical consequences. They may bulge into the intestinal lumen appearing as nodules or polyps that may be ulcerated or not. They may cause vascular sclerosis, leading to intestinal or appendicular ischemia. The secretory activity consists of multiple substance excretion: somatostatin, gastrin, glucagon, alpha-1-antitrypsin, atrial natriuretic polypeptide, catecholamines, dopamine, histamine, insulin, pancreastatin, neuropeptides, serotonin, vasoactive intestinal polypeptide, and so on.
Pediatric carcinoid tumor patients may be entirely asymptomatic or they may present with various symptoms and clinical signs. Their complaints may be due to the tumor itself, to the substances secreted by the tumor or to its metastases. Patients may experience periodic abdominal pain, diarrhea, cutaneous flushing affecting the head and the neck, accompanied by an itching sensation, sweating, diaphoresis, lacrimation and salivation; palpitations, tachycardia and hypertension; signs of heart failure caused by endocardial fibrosis or valvular lesions; respiratory symptoms may include cough, dyspnea and wheezing. More infrequent signs: mental disturbances and pellagra with scale-like skin lesions.
Useful laboratory tests include the determination of histamine, catecholamines, serotonin, chromogranin-A and 5-hydroxyindoleacetic acid. The location of the tumor can be determined using one or more imaging methods: plain radiographs, ultrasound, endoscopic ultrasound, computed tomography, magnetic resonance imaging, contrast digestive radiography, angiography, scintigraphy, positron emission tomography or radionuclide imaging. Upper and lower digestive endoscopy, as well as bronchoscopy may be necessary in some cases.
Surgical excision is the best therapeutic measure in childhood carcinoid tumor. Metastasis is treated by chemotherapy using etoposide, doxorubicin, dacarbazine, 5-fluorouracil, cisplatin or streptozocin. Interferon alfa, radioactive somatostatin analogs and other experimental agents show promising results.
Childhood carcinoid tumor is a very rare disease, much more rare than the carcinoid tumor found in adults. The tumor is usually located in the appendix or in the intestines, but cases of liver, lungs or pancreas tumors have also been described. The carcinoid grows slowly and may cause no symptoms. Some children, however, do experience fast heartbeats and palpitations, episodes of face and neck redness and warm feeling or itching (flushing), impaired breathing, abdominal pain, diarrhea, restlessness, dizziness, confusion, or blood pressure variations. The physician will conduct a clinical examination and may order several blood tests, to look for substances that may be produced by the tumor and eliminated in the bloodstream. He or she can also ask that a 24 hour urine probe is collected and analyzed. If suspicion persists, the location of the tumor must be established and this is accomplished using imaging methods and procedures. An upper or lower digestive endoscopy or a bronchoscopy may be needed, or the doctor will ask for a computer tomography, a magnetic resonance imaging exam, a radiography, an echography or other, more sophisticated tests: radionuclide imaging, scintigraphy, angiography or positron emission tomography.
The tumor is best removed from the body by a surgeon. However, by the time of diagnosis it may have already spread to other locations. These secondary tumors, called metastases, may not be resectable and, in this case, the patient must undergo chemotherapy. Even if properly treated, the tumor can reappear after some time.