Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Breast angiosarcoma following surgery and radiotherapy for breast cancer is a rare but important clinical entity. This article reviews all published cases and includes data on incidence, etiology, presentation, diagnosis, management and prognosis. Breast angiosarcoma remains challenging clinically, radiologically and histologically, and thus a high index of suspicion is required in susceptible patients. Surgery is the primary treatment option and there are an increasing number of studies on the use of radiotherapy and chemotherapy, each with variable success. There have been recent reports of patients with metastatic disease responding to taxane chemotherapy, and there might be a future role for targeted agents given the expression of c-KIT in a subset of angiosarcomas. Overall survival, however, remains poor.
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PMID:Angiosarcoma of the breast following surgery and radiotherapy for breast cancer. 1893 92

Gastrointestinal stromal tumors (GISTs) comprise a great majority of small intestinal mesenchymal tumors previously designated as smooth muscle tumors (SMTs), but true SMTs occur with a low-frequency encompassing both leiomyomas and leiomyosarcomas (LMSs). In this study, we analyzed 25 tumors in the spectrum of primary SMTs of the small intestine. Metastatic tumors and those with external attachment only were excluded. These tumors occurred in 15 men and 10 women of median age of 62 years (range: 18 to 80 y). There were 9 well-differentiated SMTs with no atypia and low mitotic activity [< or = 5/50 high-power fields (HPFs)] and these were considered leiomyomas. All 6 tumors examined were positive for SMA and desmin, and negative for KIT; all 3 tumors in female patients that were tested were negative for estrogen receptor. Two leiomyomas, a 5 mm, and another, 2 cm tumor, were examples of a muscularis mucosae leiomyomas. The other 7 were considered intramural leiomyomas; their median diameter was 4.5 cm (range: 0.8 to 9 cm). No patient with these tumors experienced recurrences or metastases, and 6 patients were alive with a median follow-up of 16 years (range: 9 to 28 y). Sixteen tumors had atypia and mitotic activity warranting the designation of LMS. One of these tumors, a 16 cm diverticular tumor, had mitotic activity of only 1/50 HPFs, and this tumor recurred 4 times. All other LMSs had > or =35 mitoses/50 HPFs. Four of 5 such LMSs with follow-up recurred or metastasized, and at least 3 patients died of disease; several others had a short survival but cause of death could not be determined. One patient, an 18-year-old woman, who died of LMS, was a survivor of a Wilms tumor radiated in infancy. All 6 LMSs studied for GIST-specific KIT and platelet-derived growth factor receptor alpha mutations showed wild-type sequences. This series demonstrates that primary small intestinal SMTs are rare (estimated frequency 1 SMT for 36 GISTs). A majority of these are mitotically active tumors with atypia warranting the diagnosis of LMS, and have a high malignant potential. The number of LMS cases is too small for stratification for risk assessment. True SMTs of small intestine should be separated from GISTs because of different pathogenesis and treatment.
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PMID:True smooth muscle tumors of the small intestine: a clinicopathologic, immunhistochemical, and molecular genetic study of 25 cases. 1897 81

Recent studies showed KIT gene aberrations in a substantial number of melanomas on acral skin and mucosa, suggesting the therapeutic benefit of tyrosine kinase inhibitors, such as imatinib. We therefore examined the expression and mutations of KIT in 4 primary and 24 metastatic acral and mucosal melanomas. Immunohistochemistry revealed moderate or strong KIT protein expression in 13 (48%) tumors. Sequence analysis revealed K642E and D820Y mutations in two metastases. Amplification of KIT was identified by real-time PCR in 4 tumors, including one that had K642E. Western blot analysis showed phosphorylation of the KIT receptor in 8 (62%) of 13 cryopreserved samples, indicating the frequent pathological activation of the receptor in vivo. Phosphorylation of KIT protein was detected in 2 tumors harboring KIT mutations, as well as in one tumor with KIT gene amplification. Furthermore, 5 tumors without detectable KIT gene aberrations showed phosphorylation of the KIT receptor. Expression of stem cell factor (SCF) in melanoma cells as well as stromal cells suggests SCF/KIT autocrine and paracrine activation in these tumors. Finally, we found significant growth suppressive effects of sunitinib in two acral melanoma cell lines; one harboring the D820Y mutation and one showing SCF-dependent KIT activation. These results show pathological activation of KIT in a substantial number of metastatic tumors of acral and mucosal melanomas, and suggest a potential therapeutic benefit of sunitinib for these melanomas.
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PMID:Pathological activation of KIT in metastatic tumors of acral and mucosal melanomas. 1903 43

Gastrointestinal stromal tumors (GIST) are the most frequent mesenchymal tumours of the digestive tract. They can arise anywhere in the gastrointestinal tract, from oesophagus to anus, and rarely from peritoneal cavity or mesentery. GIST usually remain asymptomatic for a long time. Therefore 10 to 20% are found incidentally at endoscopy or at time of surgery for others reasons and metastases are found in 15 to 50% of cases at diagnonis. Histologicaly, they are characterized by a cellular proliferation constituted of either spindle or epithelioid cells. Diagnosis has to be confirmed by immunohistochemistry, with positivity of KIT in 95% of cases, or by molecular biology, with "gain of function" mutations of KIT or PDGFRA in 85% of cases. Primary localization, mitotic activity and tumor size are the main prognostic factors. Metastases occur in 30 to 50% of patients with GIST. GIST are highly resistant to conventional chemotherapy and results obtained with new targeted therapies like Imatinib constitute one of the major progress in oncology during the decade.
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PMID:[GIST: definition, physiopathology]. 1906 Aug 40

Gastrointestinal stromal tumors (GISTs) are a rare and heterogeneous group of spindle cell neoplasms that have also been reported outside of gastrointestinal (GI) tract. These tumors are characterized by somatic mutations of c-KIT (CD117), a proto-oncogene that encodes a receptor tyrosine kinase normally expressed in the interstitial cell of Cajal that control the GI smooth muscle peristalsis, and an exquisite sensitivity to the action of the tyrokinase inhibitor imatinib mesylate (STI571; Gleevec). We report two cases of gastrointestinal stromal tumor identified on prostatic biopsies, where a primary prostatic sarcoma was considered in the differential diagnosis. In one of the cases, there was extensive local disease involving prostate, rectum, and pelvic wall, as well as metastatic disease that quickly lead to the patient's death despite aggressive treatment with imatinib mesylate and conventional chemotherapy. In the other case, the tumor was mostly confined to the rectum but also focally extended into the prostate capsule. The patient underwent resection and was alive without disease 18 months after surgery. In both cases, tissue samples from prostate and the rectum showed a malignant spindle cell neoplasm, which was positive for CD117 (c-kit). Given their unique clinical management, gastrointestinal stromal tumors should be considered in the differential diagnosis of spindle cell lesions on prostatic needle biopsies and CD117 should be added to the immunohistochemical panel in the work-up of such lesions to avoid misinterpreting them as primary prostatic neoplasms.
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PMID:Gastrointestinal stromal tumors presenting as a prostatic mass. 1922 92

The response of gastrointestinal stromal tumors (GISTs) to tyrosine kinase receptor inhibitors (TKR-I) has been a breakthrough for small molecular therapy. We report here on the very different long-term outcome of a synchronous metastatic GIST with complete remission of the primary tumor and progressive liver metastases under TKR-I therapy. In 2003, a 52-year-old patient was diagnosed with gastric GIST and synchronous multiple liver metastases. Therapy with imatinib, 400 mg daily, was started immediately. Fifteen months later, the primary was no longer detectable by endoscopy. In 2006, progression of the liver metastases was observed. Mutation analysis of the initial biopsy specimen from the primary, as well as the biopsy from the three main liver metastases after 3 years of imatinib treatment, revealed the common KIT exon 11 deletion (W557_K558del) in all tumor samples. Two of the metastases had a separate secondary mutation in KIT exon 14 and 17, respectively, while the largest cystic metastatic lesion had no other mutation. Imatinib was then increased to a daily dose of 800 mg, and in April 2007 the treatment was changed to sunitinib. Fifty-two months after initial diagnosis, the patient died of liver failure. At no time point, relapse of the gastric primary tumor was observed. Whilst TKR-Is are commonly very effective in treating GISTs, the present case illustrates their varying effects regarding the clinical behavior and genetic variations within different tumors of the same patient after long-term treatment.
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PMID:Analysis of a case with disappearance of the primary gastrointestinal stromal tumor and progressive liver metastases under long-term treatment with tyrosine kinase inhibitors. 1929 38

Gastrointestinal stromal tumors (GISTs) rarely metastasize to the skin. We describe 5 patients with GIST with subcutaneous and cutaneous metastases. The mean age at metastasis was 54 years (range 30-68 years) with a male predominance (4:1). Primary tumors occurred in the stomach (n = 3), small bowel (n = 1), and abdomen, not otherwise specified (n = 1). The average time from primary tumor resection to the resection of skin metastases was 59 months (range 11-155 months). The metastases occurred in the scalp (n = 2), cheek (n = 1), and abdomen (n = 2) with 3 patients presenting with solitary nodules and 2 patients with multiple nodules. The average size was 2 cm (range 0.6-4 cm). Histologically, 2 cases were spindled and 3 cases demonstrated mixed epithelioid and spindle cell morphology. All were confirmed to have CD117 reactivity. KIT genotyping was performed in 4 of 5 cases. Two cases harbored a mutation in exon 11, and the remaining 2 cases were wild type in exons 9, 11, 13, and 17. All 5 patients had multiple concurrent or subsequent abdominal and/or hepatic metastases. In 4 patients with an average follow-up of 32 months (range 6-75 months), after the resection of the metastases, 2 were alive with disease and 2 died of disease. Cutaneous metastases seem to be a late complication of GIST, but their presence does not necessarily herald a rapid demise of the patient.
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PMID:Cutaneous and subcutaneous metastases of gastrointestinal stromal tumors: a series of 5 cases with molecular analysis. 1938 74

Gastrointestinal stromal tumors (GISTs) metastasize primarily within the peritoneal cavity and to the liver. Superficial soft tissue metastases occur in about 1% of advanced GIST and are mostly associated with abdominal laparotomy scars and advanced disease. Extra-abdominal subcutaneous metastases of GIST have not been previously reported. Subcutaneous spindle cell tumors constitute a diagnostic challenge of which the differential diagnostic list can be limited by recognition of morphological, immunohistochemical en molecular genetic patterns. A 69-year-old woman presented with a fast growing subcutaneous nodule on her right upper arm. She was known with an imatinib-resistant advanced GIST, treated with sunitinib. The nodule was excised. Histopathological examination revealed a sharply demarcated tumor nodule in the subcutaneous fat with slightly spindled tumor cells, with pleomorphic nuclei and multiple mitoses. There was a hemangiopericytomatous vascular pattern. The cells stained positive for CD117 (KIT) and CD34. No KIT or platelet-derived growth factor receptor-alpha mutations were detected. We report the first case of an extra-abdominal subcutaneous metastasis of GIST. Although rare, metastatic GIST should therefore be included in the differential diagnosis of subcutaneous spindle cell tumors. A comparative survey of the histological, immunohistochemical and molecular genetic features of spindle cell tumors of the subcutis and a review of the literature is presented.
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PMID:Extra-abdominal subcutaneous metastasis of a gastrointestinal stromal tumor: report of a case and a review of the literature. 1947 25

Gastrointestinal stromal tumors (GISTs) typically occur late in life; however, there also are reports of pediatric and young adult patients. This rare subset of GISTs has clinicopathologic and molecular features distinct from their adult counterparts. Most pediatric GIST patients are female and often present with multifocal tumors that are epithelioid in nature. Although these young patients often have metastatic disease, it progresses slowly. Most pediatric GISTs lack the gain-of-function mutation in KIT or PDGFRA commonly found in adult cases. Expression profiling and genomic studies of pediatric GISTs show distinct molecular signatures, suggesting a unique origin as compared with adult GISTs. We and others have shown that the insulin-like growth factor 1 receptor may have a prominent role in driving KIT/PDGFRA mutation-negative adult and pediatric GISTs, and clinical trials are currently being designed to exploit these types of discoveries.
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PMID:Clinical and molecular characteristics of gastrointestinal stromal tumors in the pediatric and young adult population. 1950 37

Multifocal sporadic gastrointestinal stromal tumours (GISTs) may be misinterpreted as recurrent or metastatic disease, leading to inappropriate treatment. As molecular analysis is generally not available in routine practise, histological criteria that would facilitate diagnosis of multiple primary GISTs in routine slides are needed. We studied 14 GISTs (mean size, 2.7 cm) from six men and one woman (mean age, 70 years) applying morphological features and direct sequencing of KIT, PDGFRA, BRAF, and KRAS. Diagnosis was synchronous in five and metachronous in two patients. Paired tumours originated in stomach/small bowel (n = 5), duodenum/jejunum (n = 1), and stomach/oesophagus (n = 1) and revealed spindle (n = 10) and mixed spindle and epithelioid (n = 4) phenotype. Tumours were well circumscribed and have involved the muscularis propria in a pattern typical of primary GISTs. Different somatic KIT mutations were found in tumours from four patients. One patient had a KIT-mutated and a BRAF-mutated (V600E) tumour. Two patients had wild-type tumours. No PDGFRA or KRAS mutations were detected. Our results underscore the molecular heterogeneity of sporadic multifocal GISTs. The characteristic involvement of the muscularis propria and the site-typical morphology and immunophenotype facilitated the diagnosis of primary GISTs in all cases and correlated with molecular findings, emphasising the value of conventional histology in recognising independent primary GISTs.
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PMID:Multiple sporadic gastrointestinal stromal tumours arising at different gastrointestinal sites: pattern of involvement of the muscularis propria as a clue to independent primary GISTs. 1957 46


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