Browsing by Subject "GIST"

Now showing 1 - 6 of 6
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    Cystic gastrointestinal stromal tumors of the pancreas simulating cystoadenocarcinoma. Report of three cases and short review of the literature
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Ambrosio, Maria Raffaella; Rocca, B.J.; Mastrogiulio, M.G.; Pesci, A.; De Martino, A.; Mazzei, M.A.; Volterrani, L.; Arcuri, F.; Cintorino, M.; Tripodi, S.A.
    Gastrointestinal stromal tumors (GISTs) represent a distinct subset of mesenchymal tumours of the gastrointestinal tract. They are more common in the stomach and small intestine, and are characterized by the proliferation of spindle or epithelioid cells and by the expression of CD117. Extra-gastrointestinal stromal tumors are rare and only 13 cases of pancreatic GISTs have been reported in the literature, only 1 of which presented as a cystic lesion. Mutational analysis of KIT and Platelet derived growth factor receptor-α genes was performed only in two out of the 13 cases. We report 3 cases of cystic GISTs of the pancreas, radiologically mimicking a cystoadenocarcinoma. Routine histopathology and molecular characterization of the tumours have been performed. In two of them, molecular analysis showed unusual genetic alterations (the internal repeat of codon 502 and 503 in exon 9 of the KIT gene and the KIT exon 9 single nucleotide substitution c.1427G>T). Pancreatic GIST should be included in the differential diagnosis of both cystic and solid masses of the pancreas. The diagnosis should be accomplished by a combination of radiology, histology, immunohistochemistry and molecular biology. The evaluation of CD117 expression and the sequence analysis of KIT and Platelet derived growth factor receptor-α gene is mandatory for therapy.
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    Gastrointestinal stromal tumors: Overview of pathologic features, molecular biology, and therapy with imatinib mesylate
    (Murcia : F. Hernández, 2004) Koh, J.S.; Trent, J.; Chen, L.; El-Naggar, A.; Hunt, K.; Pollock, R.; Zhang, W.
    Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. These tumors develop at any site but are most commonly reported in the stomach. They originate from the neoplastic transformation of the intestinal pacemaker cell, the interstitial cell of Cajal. GISTs strongly express the receptor tyrosine kinase KIT and have mutations in the KIT gene, most frequently in exon 11 encoding the intracellular juxtamembranous region. Expression of KIT is seen in almost all GISTs, regardless of the site of origin, histologic appearance, or biologic behavior, and is therefore regarded as one of the key diagnostic markers. Distinction from smooth muscle tumors, such as leiomyosarcomas, and other mesenchymal tumors is very important because of prognostic differences and therapeutic strategies. Predicting the biologic behavior of GISTs is often difficult by conventional pathologic examination; tumor size and mitotic rate are the most important prognostic indicators. The prognostic significance of KIT mutations is controversial and thus far has not been clearly linked with biologic behavior. KIT mutations are associated with tumor development, and cytogenetic aberrations are associated with tumor progression. The pathogenesis of GISTs involves a gainof- function mutation in the KIT proto-oncogene, leading to ligand-independent constitutive activation of the KIT receptor. KIT-wild-type GISTs have shown mutually exclusive platelet-derived growth factor receptor (PDGFR) mutation and activation. The use of imatinib mesylate (also known as Gleevec or STI-571) has greatly increased the therapeutic efficacy for this otherwise chemotherapy-resistant tumor. GISTs with very low levels of KIT expression may respond to imatinib mesylate therapy if the receptors are activated by specific mechanisms. KIT-activating mutations fall into two groups: the regulatory type and the enzymatic site type. The regulatory type of mutation is conserved at the imatinib binding site, whereas the enzymatic site mutation has a structurally changed drug-binding site, resulting in drug resistance. Resistance to the drug is the major cause of treatment failure in cancer therapy, emphasizing the need for researchers to understand KIT signaling pathways so as to identify new therapeutic targets. This review summarizes the pathologic features of GISTs, recent advances in understanding their molecular and biologic features, and therapy with imatinib mesylate.
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    Incidence trends and main features of Gastro-Intestinal Stromal Tumours in a Mediterranean region: a population-based study
    (MDPI, 2023-05-30) Vaamonde Martín, Ricardo J.; Ballesta Ruiz, Mónica; Sánchez Gil, Antonia; Fernández Hernández, Juan Ángel; Martínez Barba, Enrique; Martínez García, Jerónimo; Gatta, Gemma; Chirlaque López, María Dolores; Ciencias Sociosanitarias; Facultades de la UMU::Facultad de Enfermería
    Gastro-Intestinal Stromal Tumours (GISTs) are a kind of neoplasm whose diagnosis in common clinical practice just started in the current century, implying difficulties for proper registration. Staff from the Cancer Registry of Murcia, in southeastern Spain, were commissioned by the EU Joint Action on Rare Cancers into a pilot study addressing GIST registration that also yielded a population-based depiction of GISTs in the region, including survival figures. We examined reports from 2001 to 2015 from hospitals as well as cases already present in the registry. The variables collected were sex, date of diagnosis, age, vital status, primary location, presence of metastases, and risk level according to Joensuu’s Classification. In total, 171 cases were found, 54.4% occurred in males, and the mean age value was 65.0 years. The most affected organ was the stomach, with 52.6% of cases. Risk level was determined as “High” for 45.0%, with an increment of lower levels in recent years. Incidence for the year 2015 doubled that of 2001. Overall, the 5-year net survival estimation was 77.0%. The rising incidence magnitude is consistent with trends in other European countries. Survival evolution lacked statistical significance. A more interventional approach in clinical management could explain the increase in the proportion of “Low Risk GISTs” and the first occurrence of “Very Low Risk” in recent years.
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    Mast cells or not? - CD117 positive cells in esophageal leiomyoma
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Ye, Ju Xiang; Liu, Yan; Qin, Yun; Ma, Xiao Long; Zhong, Hao Hao; Zhang, Yan; Shi, Xue Ying
    The presence of CD117 positive cells in esophageal leiomyoma may lead to a misdiagnosis of GIST. We reviewed 46 esophageal tumors which were smooth muscle tumors or GIST. Based on morphology, immunohistochemistry and mutation analysis, there were 44 (95.6%) leiomyomas, 1 (2.2%) leiomyosarcoma, and 1 (2.2%) GIST. Variable numbers of CD117 positive cells were seen in all leiomyomas. Tryptase immunostaining identified mast cells in 93.2% (41/44) of leiomyomas, and the number of mast cells per tumor decreased significantly from tumors of the upper esophagus to the esophageal-gastric junction (p<0.01). Immunofluorescence study further confirmed the presence of two types of CD117 positive spindle cells which included spindle-shaped mast cells and DOG-1- positive interstitial cells of Cajal. This is the first study to systemically review mast cells in esophageal leiomyomas and tumors which may be included in the differential diagnosis. We demonstrate that both spindled mast cells and hyperplastic interstitial cells of Cajal are present within esophageal leiomyomas. The immunoreactivity of these cells with CD117 may suggest a diagnosis of GIST, but the presence of mast cells itself supports a diagnosis of esophageal leiomyoma.
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    Synchronous and metachronous multiple gastrointestinal stromal tumors
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2012) Xu, Chen; Liu, Ya-Lan; Yu, Hong-Yu; Hou, Ying-Yong; Lu, Shao-Hua; Zhao, Li-Jun; Zhou, Yang; Shi, Yuan; Tan, Yun-Shan; Zhu, Xiong-Zeng
    Background & Aims: Sporadic multiple gastrointestinal stromal tumors (GISTs) are rare events especially those developed metachronously. This study aimed to investigate the clinico-pathologic and genetic features defining multiple GISTs. Methods: 624 cases of GISTs were retrieved for retrospective review. 15 cases were identified as multiple GISTs including 13 synchronous and 2 metachronous ones. 32 tumors and 15 normal tissues were obtained from these cases each containing 2-3 tumor nodules and the genomic DNA was extracted for mutational analysis of KIT and PDGFRA genes. The associated patients were recruited for clinical follow-up studies, including 5 males and 10 females at 49 to 84 years of age. Results: Multiple GISTs comprised of 2.4% of GIST cases in our consecutive series. Twenty-six tumors showed mutations at KIT gene in exon 11 and one at PDGFRA gene in exon 18. In seven synchronous cases, different tumors from the same patients displayed different genotypes of KIT or PDGFRA, suggesting their polyclonal origin. In the two multiple GISTs occurring metachronously, the tumors from each patient showed different KIT mutations, suggesting that the second tumors were not the relapse or metastasis of the primary GISTs. Conclusions: Based on types of KIT or PDGFRA mutations and other pathological features, multiple primary GISTs can be differentiated from multiple GISTs resulting from recurrence or metastasis of a single primary tumor. Unlike recurrence or metastasis of GISTs that are malignant, most multiple GISTs are mostly benign and do not require aggressive adjuvant therapy. Therefore, correct diagnosis is critical for proper treatment
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    Utility of immunohistochemical investigation of SDHB and molecular genetic analysis of SDH genes in the differential diagnosis of mesenchymal tumors of GIT
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Dubova, M.; Sedivcova, M.; Michal, M.; Kokoskova, B.; Ryska, A.; Smid, D.; Daum, Ondrej
    Loss of expression of beta subunit of succinate dehydrogenase (SDHB) was proved to be present in a subgroup of KIT/PDGFRA wt gastrointestinal stromal tumors (GISTs). To evaluate possible diagnostic utility of SDHB immunohistochemistry in the differential diagnostics of mesenchymal tumors of gastrointestinal tract (GIT), 11 cases of KIT/PDGFRA wt GISTs, 12 gastric schwannomas (GSs), 20 solitary fibrous tumors (SFTs), 4 leiomyomas (LMs), 16 leiomyosarcomas (LMSs), 5 synovial sarcomas (SSs), 3 endometrioid stromal sarcomas (ESSs), and 1 ileal inflammatory myofibroblastic tumor (IMT) were investigated for SDHB immunoexpression together with molecular genetic analysis of genes encoding succinate dehydrogenase (SDH). Three recent cases of KIT/PDGFRA mutant GISTs were used as controls. Among the 11 KIT/PDGFRA wt GISTs, 6 expressed SDHB, 1 of them harboring a sequence change of SDHD. All SDHB-negative cases were SDHB-D wt. In 1 of the control GIST cases molecular genetic analysis revealed an SDHD sequence change in addition to a mutation in KIT exon 11. No SFT was truly SDHBnegative, but in 2 of them the staining was impossible to analyze. Furthermore, 1 SFT carried an SDHB and another 1 SDHD sequence change. All GSs, LMs, LMSs, SSs, ESSs, and IMT were SDHB-positive or nonanalyzable, and SDHB-D wt. Additional factors may play a role in regulating expression of SDHB. Furthermore, SDHB immunohistochemistry alone may be misleading in excluding tumors other than GIST (especially SFT) in the differential diagnosis of KIT/PDGFRA wt mesenchymal tumors of GIT.