[Serotonin producing tumors (carcinoid tumors and carcinoid syndrome)].
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Heart neoplasms are of increasing interest among clinicians and surgeons. A review of primary malignant cardiac tumors, secondary cardiac tumors and carcinoid heart tumors is presented, with special reference to their pathological and surgical aspects. Primary malignant heart tumors represent about 25% of all cardiac tumors, the great majority are sarcomas and the whole family of this group is described including angiosarcoma, rhabdomyosarcoma, fibrosarcoma, leiomyosarcoma, liposarcoma, neurogenic sarcoma, synovial sarcoma and osteosarcoma; mesothelioma, lymphoma, malignant teratoma and thymoma are also included. Metastatic heart tumors are 20-40 times more common than primary malignancies, their behavior and more relevant aspects in diagnostic and surgical therapy are mentioned. Carcinoid heart tumors represent a distinctive entity and are discussed individually.
A review of the current state of carcinoid tumors is presented, with special attention to the diagnostic, pronostic and new therapeutic aspects. In spite of being a well known entity the diagnosis is difficult being confirmed only by pathologic findings. The current medical therapy and surgical options are described. New surgical alternatives--organ cluster transplantation--seems to be the definitive solution in metastatic disease.
One hundred and four consecutive cases of carcinoid among 194 APUD-omas (cerebral and gynecological tumours expected) are presented. Localization is as follows: bronchopulmonary (21%), duodenum (5,5%), small intestine (19%), Meckel's diverticulum (5,5%), appendix (39%), colorectal (5,5%), other (4,5%). Average age at diagnosis is very different for each localization of carcinoid tumour, as is prognosis: in our material, 33% of cases had an infiltrative tumour, 17% had lymph nodes metastases and 16% hepatic metastases. All 15 patients with carcinoidosis died but their survival varied considerably in length (from a few weeks to 21 years after the beginning of carcinoidosis). In addition, 3 patients presented with the Zollinger-Ellison syndrome, 2 of them having an atypical or probable form of the MEN I syndrome.
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Carcinoid tumors of the trachea and bronchi account for approximately 2% of all lung tumors. Carcinoid tumors, especially those in the bronchi, often produce obstruction that can mimic foreign body aspiration or asthma and may lead to post-obstruction atelectasis and pneumonia. Management of carcinoid tumors of the bronchi has been by endoscopic resection, sleeve lobectomy with parenchymal sparing, and pneumonectomy. We present a case in which an obstructing bronchial carcinoid tumor was successfully managed by long-segment mainstem-bronchial resection with total lung preservation by re-implantation.
Carcinoid tumors of the midgut type are slowly growing neoplasms which often present clinically and histologically pronounced fibrosis around the tumors. Cryosections from 41 neuroendocrine tumors (31 midgut carcinoid tumors, 8 endocrine pancreatic carcinomas, 1 parathyroid carcinoma, and 1 pheochromocytoma) and 22 nonneuroendocrine carcinomas were examined for the presence of platelet-derived growth factor (PDGF) beta-receptor by immunohistochemistry using the monoclonal antibody PDGFR-B2. Twenty midgut carcinoid tumor tissues (66%) and 4 endocrine pancreatic carcinomas (50%) and the parathyroid carcinoma stained positively with the antibody. In contrast, only 2 nonneuroendocrine tumor tissues (10%) were stained, and the staining in these cases was weak. The immunoreaction in the carcinoid tumors was observed in connective tissue cells adjacent to tumor cell clusters but not in the tumor cells themselves. The degree of positive PDGF beta-receptor expression in the carcinoid tissues seems to correlate positively with the presence of macrophages as determined by the monoclonal antibody anti-Leu-M5, but not with other infiltrated lymphocytes identified with the monoclonal antibody anti-Leu-4, or with anti-HLA-DR antibodies. Stromal cells adjacent to tumor cells, including small capillaries, stained more strongly than the stromal cells which were distant from tumor cell clusters. Furthermore, carcinoid tumor metastases from lymph nodes as well as from liver showed stronger immunoreactivity in the stromal cells with the PDGF beta-receptor antibody than the corresponding primary tumors. Our data suggest that carcinoid tumor cells may directly or indirectly induce expression of PDGF beta-receptor on adjacent stromal cells in the tumor tissue, which may contribute to the fibrosis that is often seen around carcinoid tumors.
Carcinoid tumors are potentially malignant neoplasms that arise in various body sites, including the lung and gastrointestinal tract. Those that appear cytologically atypical are more likely to behave aggressively than more typical carcinoid tumors. However, in the absence of cytological atypia or large tumor size, it is difficult to predict the biology of an individual tumor, because some lesions metastasize, whereas others do not. This study had four aims: (1) To study the expression pattern of p53, Ki-67, NCAM, and S-100 in carcinoid tumors and to relate these expression patterns to classical histopathologic features and to tumor location. (2) To identify nonhistological markers that might more accurately predict the early behavior of carcinoid tumors. (3) To determine whether sustentacular cells are present in carcinoid tumors arising in tissues derived from different embryological derivatives. (4) To determine the synaptophysin and chromogranin immunoreactivity in neuroendocrine tumors arising in various locations. The immunostaining reactions were quantitatively scored by three observers. Only 3 of the 39 tumors (all histologically atypical) were strongly positive for Ki-67; two of these were also strongly p53 immunoreactive. NCAM immunostaining differed according to the site of origin: 76.5% of foregut lesions, 58% of the midgut lesions, and 20% of hindgut lesions were positive. S-100 immunostaining ranged from 41% in foregut lesions to 50% in both the hindgut- and midgut-derived tumors. S-100-positive sustentacular cells were present in 20.5% of carcinoid tumors. All tumors stained with antibodies against synaptophysin. In contrast, 100% of midgut, 60% of hindgut, and 88% of foregut tumors were chromogranin positive. Carcinoid tumors tend to have low proliferative rates. p53 immunostaining tends to be strongly positive in tumors that are histologically atypical, but it is negative in typical carcinoid tumors arising in the gastrointestinal tract and lungs. Immunostaining reactions with antibodies to NCAM, S-100, and chromogranin differ depending on the site of origin. Synaptophysin stains 100% of carcinoid tumors regardless of their site of origin. In contrast, antibodies to chromogranin fail to stain 40% of hindgut tumors and 12% of foregut carcinoid tumors. S-100-positive sustentacular cells are present in foregut and midgut tumors but not in hindgut tumors.
Carcinoid tumor associated with carcinoid syndrome is a very difficult condition to treat. Many different drugs have been used in order to control symptoms and different antineoplastic agents were experimentated to reduce the often large neoplastic lesions. Recently the description of the existence of estrogen receptors in carcinoid tumor tissue arose great enthusiasm on the possibility of using the antiestrogen tamoxifen as a direct antitumor agent. Few experiences appeared in the international literature and contrastant results were reported. In this paper we describe one case of long term treatment with tamoxifen for a metastatic carcinoid tumor. The patient experienced the regression of carcinoid syndrome symptoms with tamoxifen therapy. Unfortunately after one year symptoms reappeared in spite of tamoxifen therapy. We conclude that tamoxifen is at the moment the best therapy in patient affected by carcinoid tumor associated with carcinoid syndrome. Data on other drugs as the oral analogues of Somatostatin or Calcitonin need to be confirmed by additional studies.
Carcinoid tumors are rare, slow-growing neuroendocrine neoplasms that often are indolent and may not become clinically apparent until there has been metastatic spread or evidence of carcinoid syndrome. Recent evidence has revealed that the overall incidence of carcinoid tumors has been steadily increasing, and although the disease was thought to be relatively benign, it is now considered one of increasing malignancy. Carcinoid tumors derive from different embryonic divisions of the gut: foregut carcinoid tumors commonly originate in the lungs, bronchi, or stomach; midgut carcinoid tumors in the small intestine, appendix, or proximal large bowel; and hindgut carcinoid tumors in the distal colon or rectum. Carcinoid syndrome, although rare, is most associated with midgut carcinoid tumors. The diagnosis of a carcinoid tumor often is coincidental with surgery performed for another reason. Treatment and prognosis are dependent on the location of the primary tumor and the degree and extent of metastasis at the time of diagnosis.
Carcinoid tumors are diminutive growths found along the gastrointestinal tract, in the lungs and, occasionally, within the confines of teratomas. Carcinoid tumors of the intestinal tract are found in decreasing order of frequency in the rectum, the appendix, the ileum, the jejunum, the lung, the stomach and the duodenum. Arising from argentaffin elements in the crypts of Lieberkuehn, and secreting serotonin, carcinoid tumors belong to the order of functioning neoplasms. Their indolent growth seems to place them between benign neoplasms and carcinomas. However, they possess propensities for metastasis that correlate with increase in size. The symptoms that are produced are almost always due to the presence of metastatic lesions. In ileal and gastric carcinoid tumors, the tendency to metastasis is augmented and the metastatic masses are sometimes of sufficient bulk to cause the carcinoid syndrome or to interfere with the supply of blood to the affected segment. More often they produce the clinical picture of intestinal obstruction. The unusually long interval from onset to death associated with carcinoid tumors makes palliative subtotal resections and short-circuiting operations in symptomatic patients with advanced disease worthwhile, for by such unorthodox procedures the patients may be afforded many additional years of useful life.
Carcinoid tumors arise from enterochromaffin or enterochromaffin-like cells that are present in the gastrointestinal tract, ovaries, and lungs. Over 90% of carcinoids originate in the gastrointestinal tract with the most common sites in order of frequency being the appendix, terminal ileum, rectum, and the remainder of the colon. Gastroduodenal and pancreatic carcinoids are infrequent. Carcinoid syndrome is associated with small intestine carcinoids in about 40%. Common symptoms include intermittent intestinal obstruction with crampy abdominal pain and vomiting, and weight loss. Upper gastrointestinal bleeding with melaena or hematochezia is a relatively rare early symptom of patients with small intestine carcinoid tumors. We report on a 69-year-old man, treated with acenocoumarol for previous thromboembolic complications of hereditary protein S deficiency. He was admitted to hospital because of an acute episode of hematochezia followed by melaena. Endoscopic evaluation of esophagus, stomach, duodenum and colonoscopy revealed no apparent source of bleeding. Selective angiographic evaluation of mesenterial arteries showed pathologic vasculature approximately in mid jejunum. Laparotomy revealed bleeding from a small submucosal malignant carcinoid tumor in small intestine and multiple large metastases within mesenteric tissue. Segmental resection of small intestine and exstirpation of the metastatic masses was performed. Postoperative period was uneventful. Cytotoxic chemotherapy in this adjuvant setting has not been recommended. Small intestinal carcinoid tumor has to be considered as a rare cause of gastrointestinal bleeding with melaena or hematochezia. Nevertheless, bleeding is a relatively rare early symptom of patients with small intestine carcinoid tumor.
Carcinoid tumors are one among the most uncommon source of metastatic lesion to the brain. Four cases of single brain metastases from carcinoid tumors operated upon and verified by both histology and immunohistochemical staining are reported. The site of the primary carcinoid tumor was the lung in two cases, ileum in one and the left colon in another. The location of the brain metastasis was supratentorial in two cases and cerebellar in two. A high vascular tumor with large blood channels was found at surgery. Immunohistochemical studies showed in all four cases positive staining for synaptophysin, neuron-specific enolase, chromogranine and cytocheratine and negative staining for S-100 and HMB-45. The postoperative survival time ranged from 5 to 18 months. The epidemiological, surgical and pathological features of brain metastases from carcinoid tumors are also discussed from the analysis of 44 well-documented cases reported in the literature.
Carcinoid tumors are rare forms of gastrointestinal tumors, although lately they have been found with increasing frequency. We report here the combined diagnosis of an intestinal metastasized carcinoid tumor. A 67-year-old patient was followed up during a nine-year period. In 1990 the patient was diagnosed with carcinoid tumor of intestinal origin with multiple liver metastases. Initial treatment consisted of partial resection of the intestine and resection of the liver. Since multiple liver metastases were found, chemoembolization was also performed. After this therapy the patient was free of complaints until 1996. That year the patient reported upper abdominal pain with occasional diarrhea. Given his past medical history and multiple hepatic metastases proven by three-dimensional ultrasonography, combined octreotide and interferon therapy was started following octreoscan scintigraphy. During a three-year period the patient was without complaints and the tumor marker value decreased to almost normal. In 1998 the patient at a regular follow-up visit complained about colic abdominal pain around the umbilical region. Abdominal ultrasonography showed a local wall thickening in the intestinal region. The computed tomography and selective enterography were positive as well. The surgical treatment and histology demonstrated intestinal recurrence of the tumor in the ileal region. After the operation we started a long-acting sandostatin and interferon treatment. We conclude that an ultrasound with a high index of clinical suspicion is a useful test for the diagnosis of carcinoid tumor in detection and in follow-up examinations.
Carcinoid tumors belong to the family of neuroendocrine tumors, which are usually slow growing with distinct biological and clinical characteristics. The incidence of these tumors is approximately 2.5 in 100,000 people per year. The former classification system of foregut, midgut and hindgut tumors is still used in clinical routine, although there is a new World Health Organization classification. Determination of the histopathology of carcinoid tumors is of utmost importance and involves specific immunohistochemical staining for chromogranin A, synaptophysin, serotonin and gastrin. Proliferation capacity measured by Ki67 is used to guide forthcoming medical treatment. Localization procedures include computerized tomography, ultrasound, magnetic resonance imaging, somatostatin receptor scintigraphy and positron emission tomography. Surgery remains the cornerstone of treatment and provides the only chance of a cure. Other cytoreductive procedures include radiofrequency ablation, laser treatment and chemoembolization. Biological treatment includes cytotoxic agents, such as somatostatin analogs and interferon-alpha, which should be applied in slow-growing neoplasms. Combination regimens including cisplatin, etoposide, streptozotocin and 5-fluorouracil should be reserved for treatment of highly proliferating tumors. Future therapy of carcinoid tumors will be based on the specific tumor biology and treatment will be customized for each individual patient. New therapies, such as antiangiogenic agents and new, long-acting somatostatin analogs, together with further development of tumor-targeted treatments, will come into clinical use in the near future.
Carcinoid tumors are rare and mainly found in the G.I. tractus but also in the tracheobronchial tree and ovaries. The testicular localization, primary or metastatic, is rare. The authors report a primary carcinoid tumor of the testis in a 35 years old male. The tumor characteristics are well enough known from the literature. Primary carcinoid tumors of the testis appear to be of a low grade malignancy. Local therapy suffices for care of the patient as long as, on microscopic examination, it is not an expression of a teratocarcinoma. The diagnosis is made by the discovery of a tumor since the carcinoid syndrome is seldom in the clinical picture (only 2 cases in the literature, one of whom with generalized metastasis).
Carcinoid tumors of the thymus are very rare, and their cytologic findings have not been reported previously in English. Retrospective study of fine needle aspiration (FNA) cytologic features in four histopathologically verified thymic carcinoid tumors are described here in detail. The FNA cytology of thymic carcinoids is characterized by predominantly single and some loose clusters of small, round to oval cells with scanty cytoplasm, interspersed with some larger cells with moderate to abundant, granular cytoplasm. The differential diagnosis of the cytologic features between carcinoid tumor and other mediastinal tumors is also discussed.
Carcinoid tumors most commonly occur in the gastrointestinal tract and are known best for the bizarre manifestations of the carcinoid syndrome caused by the release of tumor products. However, many carcinoid tumors do not present with or cause the carcinoid syndrome, and this has led to the development of new diagnostic markers for these tumors. New treatments have emerged recently and are being developed, because although these tumors are relatively indolent, they can metastasize. The biology of carcinoid tumors of the gastrointestinal tract can be classified in large part by the embryologic regions of the gut in which they occur. More carcinoid tumors will be discovered as the indications and use of gastrointestinal endoscopies increase, so the diagnosis and initial management of carcinoid tumors will fall largely on the gastroenterologist.