Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0000737 (abdominal pain)
 31,184 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Schwannomas of the colon and rectum are uncommon and incompletely characterized tumors, and only a small number of cases have been reported. This study was undertaken to determine the clinicopathologic profile of such tumors. A total of 20 colorectal schwannomas were identified and analyzed in a review of 600 mesenchymal tumors of the colon and rectum from the files of the Armed Forces Institute of Pathology. The schwannomas occurred equally in men (n = 9) and women (n = 11) in a wide age range (18-87 years; median age 65 years). The most common location was cecum (n = 7), followed by sigmoid and rectosigmoid (n = 6), transverse colon (n = 3), descending colon (n = 2), and rectum (n = 1); the location of one tumor had not been specified. The tumors commonly presented as polypoid intraluminal lesions, often with mucosal ulceration. Rectal bleeding, colonic obstruction, and abdominal pain were the most common presenting symptoms. The most common histologic variant (n = 15) was a spindle cell schwannoma with a trabecular pattern and vague or no Verocay bodies. These tumors ranged from 0.5 to 5.5 cm in diameter. A lymphoid cuff with germinal centers typically surrounded these tumors and focal nuclear atypia was often present, but mitotic activity never exceeded 5 per 50 HPF. All four epithelioid schwannomas occurred in the descending colon or sigmoid, three of them as small submucosal tumors. There was one plexiform schwannoma in the sigmoid composed of multiple nodules of prominently palisading schwann cells similar to those seen in conventional soft tissue schwannomas. All tumors studied were strongly positive for S-100 protein and also for low affinity nerve growth factor receptor (p75), collagen IV, and GFAP. Three tumors had CD34-positive cells, but all were negative for CD117 (KIT), neurofilament proteins, smooth muscle actin, and desmin. The percentage of MIB-1-positive cells was usually less than 1% and never higher than 3%. Colorectal schwannomas behaved in a benign fashion with no evidence of aggressive behavior or connection with neurofibromatosis 1 or 2, based on follow-up information on 18 patients.
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PMID:Schwannomas in the colon and rectum: a clinicopathologic and immunohistochemical study of 20 cases. 1142 Apr 55

Imatinib mesylate (imatinib) is an orally administered competitive inhibitor of the tyrosine kinases associated with the KIT protein (stem cell factor receptor), ABL protein and platelet-derived growth factor receptors. The KIT tyrosine kinase is abnormally expressed in gastrointestinal stromal tumour (GIST), a rare neoplasm for which there has been no effective systemic therapy. In a randomised, nonblind, multicentre study that evaluated imatinib 400 or 600mg once daily in 147 patients with advanced GIST, confirmed partial responses were achieved in 54% of patients overall (median duration of follow-up was 288 days). Stable disease was experienced by 28% of patients and the estimated 1-year survival rate was 88%. Similar response rates were reported in a smaller, dose-escalation study, in which objective tumour response was a secondary endpoint. Although nearly all patients with GIST treated with imatinib experienced adverse events, most events were mild or moderate in nature. Severe or serious adverse events occurred in 21% of patients in the larger study, and included gastrointestinal or tumour haemorrhage. The control of cellular processes, such as cell growth, division and death, involves signal transduction, which commonly involves the transfer of phosphate from adenosine triphosphate (ATP) to tyrosine residues on substrate proteins, by tyrosine kinase enzymes. Activation of oncogenes coding for kinase proteins can lead to the production of kinases that are continually active in the absence of a normal stimulus,leading to increased cell proliferation and/or decreased apoptosis. A major focus of cancer research in recent years has been to identify oncogenic molecules and the signal transduction pathways in which they are involved, in order to develop specifically targeted drugs. One such drug is imatinib mesylate (imatinib, Glivic/Gleevec), an orally administered 2-phenylaminopyrimidine derivative that is a competitive inhibitor of the tyrosine kinases associated with platelet-derived growth factor (PDGF) receptors, the Abelson (ABL) protein and the KIT protein (also known as stem cell factor [SCF] receptor). Imatinib was initially evaluated for the treatment of chronic myeloid leukaemia (CML) [reviewed previously in Drugs]. More recently, imatinib has been approved for the treatment of patients with advanced gastrointestinal stromal tumour (GIST), in which KIT, a tyrosine kinase receptor, is abnormally expressed. GISTs are soft tissue gastrointestinal sarcomas probably arising from mesenchymal cells. They are rare neoplasms, with between 5000 and 10 000 new cases being diagnosed each year in the US. GISTs occur throughout the gastrointestinal tract but the stomach and small intestine are the most common sites. Symptoms depend on the site and size of the tumour, and may include abdominal pain, gastrointestinal bleeding or signs of obstruction; small tumours may be asymptomatic. The diagnosis of GIST is made by immunohistochemical staining for CD117, a cell surface antigen on the extracellular domain of KIT, in conjunction with pathological examination of tissue with light microscopy. All GISTs may have some degree of malignant potential. They are unresponsive to standard chemotherapy and to radiotherapy, and the mainstay of treatment in the past has been surgery. However, recurrence rates are high, and there has been no effective systemic treatment for unresectable GIST or metastatic disease. For patients in whom complete resection is not possible, or in patients with metastatic or recurrent disease, the median duration of survival is 9-12 months, and 10-19 months, respectively. Gain-of-function mutations of the KIT proto-oncogene occur in up to 90% of GISTs, allowing constitutive activation of tyrosine kinase (i.e. auto-phosphorylation of tyrosine residues independent of ligand-receptor binding), leading to aberrant cell division and tumour growth. Imatinib selectively inhibits the tyrosine kinase activity associated with KIT, which forms the rationale for evaluating its effects in GIST. Subsequent to initial evidence of the clinical efficacy of imatinib in a single patient with progressive, metastatic, CD117-positive GIST, formal studies of imatinib in this new indication were initiated. This article summarises the pharmacology, efficacy and tolerability profile of imatinib in the treatment of patients with advanced GIST.
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PMID:Imatinib mesylate: in the treatment of gastrointestinal stromal tumours. 1260 Feb 28

Three cases of gastrointestinal stromal tumors (GIST) are reported as typical examples of the broad clinical spectrum in which these rare tumors can be detected. The first case describes an 82-year-old patient with a hemorrhagic shock due to upper gastrointestinal bleeding from a GIST of the stomach. GIST most frequently present with either gastrointestinal bleeding, abdominal pain or a detectable mass on physical examination or by ultrasound imaging. Clinically asymptomatic tumor growth also occurs as demonstrated by the second case of a 44-year-old -woman with an incidental finding of GIST during surgery of the esophagus. The cases are used to discuss the consequences for therapy and prognosis resulting from the heterogeneity of this tumor entity; the relevant immunohistochemical markers used to distinguish between various tumor subtypes of gastrointestinal mesenchymal tumors (GIMT) are listed. Since gastrointestinal stromal tumors (GIST) represent the most common subgroup of GIMT, we focus on the clinicopathological prognostic factors of GIST. The third case of a 40-year-old patient with a malignant GIST recurrence after surgery and exhibiting secondary resistance after one year of successful therapy with the receptor tyrosine kinase inhibitor imatinib (Gleevec), antagonizing pathogenetically relevant constitutive c-KIT activation, illustrates the potential and limitations of the only effective drug treatment for advanced GIST.
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PMID:[Gastrointestinal stromal tumors: a broad clinical spectrum from incidental -discovery to acute gastrointestinal bleeding]. 1502 11

The frequent association of stromal tumors with neurofobromatosis raises high suspicion of a possible correlation between the two entities. The aim of this study was to analyze clinicopathologic features of patients with concomitant neurofibromatosis and gastrointestinal stromal tumors and to discuss the molecular basis for their possible pathogenesis. Detailed information about clinical presentation, histology, immunostains, polymerase chain reaction amplification, and sequencing in three of our own cases was obtained. Stromal tumors presented with abdominal pain in one case and hemorrhage in another. One patient underwent surgery for malignant transformation of neurofibroma and stromal tumors were found incidentally. Stromal tumors were consistently positive for CD117, while the malignant peripheral sheath tumor was not. Mutation in the KIT juxtamembrane domain was found in one case. In this respect, some stromal tumors lack demonstrable KIT mutations but KIT remains activated. We reasoned that other mechanisms, like the Ras pathway involved in neurofibromatosis type 1, might play a role in KIT activation.
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PMID:Neurofibromatosis with gastrointestinal stromal tumors: insights into the association. 1538 40

Gastrointestinal stromal tumors are the most common mesenchymal tumors of the gastrointestinal tract. These tumors are present in almost all case mutations of KIT-CD117. When located in different places other than the gastrointestinal tract they are called extragastrointestinal stromal tumors (EGISTs). We present the case of a 70-year old patient with abdominal pain. Computed tomography (C/T) and ultrasound (U/S) indicated the existence of a hypoechoic enlarged 9.6 x 10 cm uterus due to leiomyoma. The clinical condition of the patient deteriorated and obtained the characteristics of an acute abdomen. The patient underwent urgent exploratory laparotomy, which revealed the incidental existence of a large tumorous formation in the pouch of Douglas. A total abdominal hysterectomy, bilateral ovarectomy, omentectomy, and tumor resection from the rectouterine pouch were performed. Histology analysis confirmed the diagnosis of a malignant EGIST. EGISTs are infrequent in pelvis. In our case, pelvic EGIST led to an acute pain symptomatology obtaining characteristics of invasive uterine leiomyosarcoma. Pelvic imaging with classical methods of U/S and C/T may lead to confusion and false diagnosis. To the best of our knowledge, this is the first case report about an EGIST located in the rectouterine pouch of Douglas leading to acute abdomen symptomatology.
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PMID:Extragastrointestinal stromal tumor mimicking a uterine tumor. A rare clinical entity. 1798 44

Systemic mastocytosis is an uncommon condition characterized by abnormal proliferation of mast cells in one or more organ. The specific D816V KIT mutation is present in most cases. Gastrointestinal symptoms occur commonly but histologic characterization of gastrointestinal involvement is incomplete. The purpose of this study was (1) to describe the clinicopathologic features in five patients with systemic mastocytosis involving the gastrointestinal tract and (2) to determine whether gastrointestinal involvement is associated with the usual D816V mutation or a different mutation. Clinical details were obtained from the hospital of origin or referring pathologist. Histologic features were documented in slides stained with hematoxylin and eosin, mast cell tryptase and CD117. Molecular analysis for the D816V KIT mutation was performed on formalin-fixed paraffin-embedded sections. Symptoms included diarrhea/loose stools (n=5), abdominal pain (n=4), vomiting (n=3) and weight loss (n=3). Other findings included cutaneous lesions of mastocytosis (n=4), malabsorption (n=2), hypoalbuminemia (n=2) and constitutional growth delay (n=1). Sites of gastrointestinal involvement included the colon (n=5), duodenum (n=3) and terminal ileum (n=3). Endoscopic/gross findings included mucosal nodularity (n=4), erosions (n=2) and loss of mucosal folds (n=2). In three patients the endoscopic appearance was considered consistent with inflammatory bowel disease. All cases showed increased mast cell infiltration of the lamina propria, confirmed by immunohistochemistry for mast cell tryptase and CD117. In two cases, mast cells had abundant clear cytoplasmic resembling histiocytes. Marked eosinophil infiltrates were present in four patients, in one patient leading to confusion with eosinophilic colitis. Architectural distortion was noted in three cases. The D816V KIT mutation was present in all four cases tested. In conclusion, gastrointestinal involvement by systemic mastocytosis is characterized by a spectrum of morphologic features that can be mistaken for inflammatory bowel disease, eosinophilic colitis or histiocytic infiltrates. Systemic mastocytosis involving the gastrointestinal tract is associated with the usual D816V KIT mutation.
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PMID:Systemic mastocytosis involving the gastrointestinal tract: clinicopathologic and molecular study of five cases. 1893 52

Gastrointestinal stromal tumours (GISTs) are sarcomas arising in the gastrointestinal tract. They are characterised by a gain in function mutation of the KIT oncogene and the majority express the receptor tyrosine kinase KIT, which can be detected by the immunohistochemical stain CD117. Patients with a GIST present with symptoms such as abdominal pain or gastrointestinal bleeding, or may be asymptomatic. We describe the clinical history and pathological features of a patient with a GIST who presented with a paratesticular mass which, to our knowledge, has never previously been reported. With the development of new drugs to treat GISTs, the knowledge of the type of mutations may in the future prove helpful in determining optimal treatment strategies and prognosis.
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PMID:Gastrointestinal stromal tumour with a KIT exon 11 mutation presenting as a paratesticular mass. 1938 57

Spontaneous rupture of gastrointestinal stromal tumor (GIST) with hemoperitoneum is an extremely rare clinical presentation of this mesenchymal tumor. We report the unusual case of a 68-year-old man who was admitted to the hospital with abdominal pain. While waiting for the results of his laboratory tests the patient became pale and tachycardic and his abdomen distended with generalized rebound tenderness. A CT scan suggested rupture of a cavernous angioma of the liver and the patient was brought to the operating room for an explorative laparoscopy, which revealed hemoperitoneum from a ruptured giant gastric GIST. After conversion to laparotomy, the tumor was excised: it was 11 x 10 x 5 cm in size, with massive necrosis and clotted blood inside. Immunohistochemical examination revealed reactivity to c-KIT and CD34, consistent with the diagnostic criteria for GIST, with low mitotic activity (< 5/50 HPF). The postoperative course was uneventful, and the clinical and radiological follow-up at 6 months is negative for recurrence.
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PMID:Spontaneous rupture of giant gastric GIST presenting as hemoperitoneum and mimicking cavernous liver angioma. 1957 71

The author herein reports histopathologic features of 31 surgical cases of gastrointestinal stromal tumor (GIST) of the digestive organs. The 31 cases of GIST were diagnosed in our pathology laboratory. They consisted of 24 cases of gastric GIST, 1 case of hepatic GIST, 1 case of small intestinal GIST, 4 cases of colon GIST, and 1 case of rectal GIST. The age of the patients ranged from 56 year to 84 years with a mean of 71 years. Male to female ratio was 21:10. The presenting symptoms were gastrointestinal bleeding in 13 cases, abdominal pain and discomfort in 13 cases, and asymptomatic in 5 cases. Endoscopy and imaging modalities including US, CT and MRI were useful to detect the tumors in all cases, and biopsies confirmed the GIST diagnosis in 21 cases. The size of GIST ranged from 1 cm to 12 cm with a mean of 4.3 cm. Grossly, 23 cases were submucosal tumors, 6 serosa-side tumors, 1 solid tumor in the liver, and 1 rectal polyp. Histologically, 28 cases were of spindle cell type and 3 of epithelioid type. According to mitotic counts and tumor size, the malignant risk was very low in 4 cases, low in 14 cases, intermediate in 9 cases, and high in 4 cases. Immunohistochemically, all cases were positive for KIT and vimentin, 30 cases for CD34, and 4 cases for alpha-smooth muscle actin. None were positive for desmin and S100 protein. Ki-67 labeling ranged from 2% to 18%. P53 protein was negative in all cases. PDGFRA was positive in 20 cases among 24 cases examined. Genetic analysis using PCR-direct sequencing method was performed in 5 GISTs; all the 5 GISTs showed point mutations or deletions in KIT gene, but did not in PDGFRA gene. The 5 cases of GIST were positive for PDGFRA protein, suggesting that PDGFRA overexpression is not associated with PDGFRA gene mutations. Four of the 31 cases showed metastases. The chemotherapy was imatinib mesylate in 6 cases, and none in 25 cases. Four cases of high risk died of GIST, and 27 cases are alive now without tumors.
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PMID:Gastrointestinal stromal tumor of the digestive organs: a histopathologic study of 31 cases in a single Japanese institute. 2012 84

Familial gastrointestinal stromal tumor (GIST) is an extremely rare autosomal dominant disorder, and approximately 20 families have been reported to date. In this article, we present one additional family. A 25-year-old Japanese woman presented with abdominal pain, and subsequent image analyses disclosed multiple tumors measuring 12 cm in maximum diameter in the lower digestive tract. The postoperative histologic examination showed multiple GISTs and diffuse hyperplasia of interstitial cells of Cajal. Her mother had a history of GIST in the digestive tract. Three members of this family including her younger sister and mother had cutaneous hyperpigmentation of external genitalia and axilla. Their DNA samples showed identical missense mutation at exon 11 in the juxtamembrane domain of the KIT gene, and this mutation site was considered to be a hot spot in familial GIST. One year after, her younger sister suffered from multiple GISTs in the digestive tract at the age of 25 years. To correctly diagnose familial GIST, mutual information should be exchanged among clinicians, pathologists, and molecular scientists.
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PMID:Familial gastrointestinal stromal tumor with germ line mutation of the juxtamembrane domain of the KIT gene observed in relatively young women. 2095 81


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