Gastrointestinal stromal tumor of the duodenum: a case report.

The report describes a malignant gastrointestinal stromal tumor occurring in the duodenum in a 71-year-old woman. The neoplasm showed both epithelioid and spindle cell patterns by light microscopy. The ultrastructural features were diagnostic of nerve sheath origin. The tumor had numerous wrapping processes joined by junctions and surrounded by axons. No features of smooth muscle differentiation were identified. Immunocytochemistry was inconclusive. The differential diagnosis of such neoplasms is discussed.     

Gastrointestinal stromal tumor of the prostate: a case report and literature review

We report a case of gastrointestinal stromal tumor (GIST) of the prostate in a 75-year-old man with dysuria and urinary retention. Digital rectal examination revealed a markedly enlarged prostate. The serum level of prostate-specific antigen was 0.2 ng/dL. Imaging studies showed an expanded prostate, measuring 6.7 x 5.6 x 5.5 cm, with heterogeneity in contrast enhancement. No metastatic disease was found. The pathologic diagnosis of prostatic GIST was made based on characteristic morphological features, immunoprofiles, and molecular analysis. The possibility of secondary involvement by a rectal GIST was excluded by radiological and intraoperative findings. To our knowledge, this is the second case of a primary GIST of the prostate reported in the literature.     

Gastrointestinal stromal tumours: from KIT to succinate dehydrogenase

The discovery of activating mutations in the tyrosine kinase receptor genes KIT and PDGFRA has led to the development of effective targeted therapies for gastrointestinal stromal tumours (GISTs). Specific genotypes, in part, predict the response to treatment with tyrosine kinase inhibitors. However, ~10% of GISTs lack such mutations (often referred to as ‘wild‐type’ GISTs). Recent insights into the biology of ‘wild‐type’ GISTs have resulted in clinically significant subclassification of this heterogeneous group of tumours, a large subset of which are now known to represent succinate dehydrogenase‐deficient GISTs. Recognition of this distinctive class of tumours has critical implications for prognosis, therapy, clinical follow‐up, and genetic counselling. Other uncommon genetic groups include neurofibromatosis type I‐associated and BRAF‐mutant GISTs. This review provides an update on the diagnosis and pathogenesis of these less common classes of GISTs, summarizes the clinical and pathological features associated with particular genotypes, and discusses mechanisms of resistance to targeted therapies.     

Epithelioid variant of gastrointestinal stromal tumor harboring PDGFRA mutation and MLH1 gene alteration: A case report

Gastrointestinal stromal tumors (GISTs) are the most important and common mesenchymal tumors of the gastrointestinal tract, especially in the stomach. GISTs are usually driven by activating mutations in either KIT or PDGFRA genes. It is known that activating gene mutations predicts, to a certain extent, not only the morphology of the tumor cells but also a response to treatment with tyrosine kinase inhibitors. Here, we present a case of an epithelioid variant of GIST harboring PDGFRA and MLH1 gene alterations in the stomach of a 55‐year‐old Japanese woman. The tumor of 98 mm with multiple cysts showed exophytic growth from the gastric fundus. Histopathologically, it consisted of scattered medium‐sized epithelioid tumor cells in a loose myxoid background. Based on c‐kit and DOG‐1 immunoreactivity and a PDGFRA mutation (p.Trp559_Arg560del), the tumor was diagnosed as an epithelioid variant GIST. Interestingly, it had a gene alteration (p.Met524Ile) in the MLH1 gene of unknown pathogenicity. It was assigned to Group 3a (low risk for malignant behavior). After surgery, the patient has been on imatinib therapy and disease‐free for 10 months.     

Familial gastrointestinal stromal tumor with germ line mutation of the juxtamembrane domain of the KIT gene observed in relatively young women

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.     

后肾间质肿瘤一例

患者女,4岁.洗澡时无意发现腹部包块3 d,未伴随其他症状,于2009年8月18日入院.体检:腹软,左侧稍膨隆,可触及约10 cm×10 cm大小肿块,活动度差,边界清,压痛阴性,肝脾肋缘下未触及,移动性浊音阴性.彩超显示:左肾区探及11.8 cm×7.1cm不均匀略低回声,边界清,形态欠规则.肿物内血供丰富.     

Germline-activating mutation in the kinase domain of KIT gene in familial gastrointestinal stromal tumors

The proto-oncogene KIT encodes the receptor tyrosine kinase KIT. Gain-of-function mutations in the juxtamembrane domain of KIT have been reported in human gastrointestinal stromal tumors. In a family with multiple gastrointestinal stromal tumors and diffuse hyperplasia of myenteric plexus layer, we have identified another mutation of KIT, a single base mutation, resulting in the substitution of Glu for Lys(642) in the kinase I domain, and studied its biological effect in a cellular system. The mouse homologue of the human KIT mutant was generated by site-directed mutagenesis and stably transfected into the interleukin-3-dependent Ba/F3 murine cell line. The oncogenic potential of the mutated KIT was assessed in vitro by a proliferation assay and in vivo by transplantation into nude mice. Transfected Ba/F3 cells grew autonomously in absence of growth factors and formed tumors in nude mice. Substitution of Glu for Lys(642) is an oncogenic mutation in the tyrosine kinase domain of KIT. As germline heterozygous mutation, it causes a diffuse hyperplasia of myenteric interstitial cells of Cajal during embryonic development and occurrence of multiple gastrointestinal stromal tumors at adulthood.     

Gastrointestinal stromal tumor colliding with angiosarcoma

The collision of gastric tumors is rare, and those involving gastrointestinal stromal tumor and angiosarcoma have not been previously reported. This article reports a gastric tumor involving collision of gastrointestinal stromal tumor and angiosarcoma. The patient was an 81-year-old man who presented with dyspepsia and large gastric mass. The mass showed a proliferation of spindle cells expanding the muscularis propria. Most of the tumor consisted of spindle cells with low-grade cytology that were positive for CD117 (c-kit), indicating gastrointestinal stromal tumor. Occasional prominent foci showed dissecting and anastomosing channels of ectatic vascular spaces lined by cytologically malignant cells that were positive focally for CD117 and diffusely positive for multiple vascular markers, indicating angiosarcoma.     

Extra-gastrointestinal stromal tumor of the pelvic cavity: case report

Extra-gastrointestinal stromal tumors (E-GISTs) not associated with the alimentary tract in the pelvic cavity are extremely rare. We treated a 49-year-old Japanese man with such an E-GIST in the pelvic cavity who underwent an intrapelvic tumorectomy with a total prostatectomy and partial rectum resection. Gross examination of the specimen revealed an 8.1 × 5 × 4 cm white-grayish mass. Histological findings showed uniform spindle cells with scant atypia that formed interlacing bundles or whorl patterns. These neoplastic cells did not invade adjacent organs, including the gut. Immunohistochemical findings revealed that the neoplastic cells were positive for c-kit, CD34, and vimentin. Molecular analysis showed a c-kit mutation at exon 9 with duplication of Ala and Tyr. Our diagnosis was E-GIST, which belongs to the intermediate group of GIST. Following the operation, we administered imatinib mesylate for 6 months. After stopping for 5 months, it was administered again for local recurrence. We are planning our future strategy for this case including surgical resection as necessary.     

Solitary fibrous tumor of the pancreas: a case report

Solitary fibrous tumor (SFT) is an unusual mesenchymal neoplasm that most often arises in the pleura; however, it has recently been described in a number of extrapleural sites. This report describes an extremely rare case of a benign SFT arising in the pancreas. A 41-year-old woman presented in the clinic with right upper abdominal pain. Subsequent ultrasonographic studies revealed a 1.5x1.5x1.4 cm hypoechoic mass within the pancreatic body, which was later confirmed on both helical computerized tomography and magnetic resonance imaging studies. An endocrine tumor was clinically suspected. Laparoscopic enucleation of the mass was performed. Microscopically, the tumor was composed of bland uniform spindle cells arranged between collagen bundles. On immunohistochemical studies, these spindle cells were positive for CD34 and bcl-2 but negative for cytokeratin (AE1+AE3 and Cam5.2), smooth muscle actin, desmin, S-100, and c-kit. Based on the light microscopic morphology and immunohistochemical staining profile, the diagnosis of SFT was rendered.     

卵巢微囊性间质肿瘤一例

患者女,69岁.体检时发现盆腔左侧肿块,无腹痛、腹胀、阴道出血等症状,无腹水,于2009年6月在外院行全子宫双附件切除术.术中见肿瘤位于左侧卵巢,表面光滑,无盆腹腔播散灶.原病理诊断:颗粒细胞瘤.后因寻求进一步治疗来本院会诊.     

Synchronous poorly-differentiated neuroendocrine carcinoma and gastrointestinal stromal tumor of the stomach: a case report with immunohistochemical and molecular genetic analyses of KIT and PDGFRA

Although the stomach is the most common location for gastrointestinal stromal tumor (GIST) with co-primary tumors, the synchronous appearance of a poorly differentiated neuroendocrine carcinoma (NEC) and GIST in the stomach is extremely rare. To the best of our knowledge, this is the first case of gastric GIST coexisting with gastric NEC to be reported in the literature. The current study reports the case of a 71-year-old male with gastric poorly differentiated NEC and GIST discovered incidentally during surgical treatment of the NEC. Immunohistochemistry analysis showed that the NEC tumor cells were positive for CK (cytokeratin), CD57, synaptophysin, chromogranin, CD117 (KIT protein), Dog-1 (discovered on GIST-1 protein) and CD34. The synchronous GIST immunophenotype showed positivity for CD117, Dog-1 and CD34 (100%), whereas staining for CK, SMA, desmin and S100 was negative. Ki-67 labeling of proliferating cells was 90% in NEC and 1% in GIST. An accurate diagnosis was confirmed by immunohistochemical findings. Furthermore, genetic analysis using PCR direct sequencing identified no mutations in the KIT (exons 9, 11, 13 and 17) and PDGFRA (exons 12 and 18) genes. The patient developed lymph node metastases and underwent cisplatin-based chemotherapy after the operation. This is the first documented case of synchronous gastric GIST and NEC with the examination of protein expression and gene mutations in KIT and PDGFRA, which will help to further understand the etiology and pathogenesis of NEC coexisting with GIST in a gastric location.     

Gastrointestinal stromal tumor with skeinoid fibers of the ileum

Gastrointestinal stromal tumor (GIST) is not uncommon among gastrointestinal nonepithelial tumors, but there are few reports describing the cytologic findings. We report a case of GIST with skeinoid fibers in scrape cytology preparation. The patient was a 53-year-old man with a tumor in the small intestine. Scrape preparations from the cut surface of the resected tumor revealed cellular material composed of spindle cells showing loose clusters or single cells. The nuclei were spindled, elongated or cigar-shaped, and relatively uniform. The cytoplasm was fragile and demonstrated a finely fibrillar material. Dense hyaline materials with irregular outline were observed within the loose clusters composed of the tumor cells. The hyaline materials were also observed in the background. Histologic preparation showed spindle cells arranged in a fascicular or storiform pattern. Most eosinophilic globules were distributed between the tumor cells. The globules were positive in periodic acid-Schiff reaction, and were stained blue with Masson's trichrome stain. Immunohistochemically, the tumor cells were strongly and diffusely positive for c-kit, focally and weakly positive for alpha-smooth muscle actin, and negative for CD34 and S-100 protein. We emphasize that skeinoid fibers are characteristic of GIST arising in the small intestine, and their presence predicts a good prognosis, even in malignant GIST.     

前列腺恶性胃肠道间质瘤一例

患者男,49岁。因无明显诱因感会阴部酸痛不适10d。无尿急、尿频及尿痛,无血尿,在当地医院就诊,B超检查发现盆腔前列腺部位实性占位性病变,CT检查发现前列腺增大约8·03cm×6·58cm,提示前列腺肿瘤。实验室检查:前列腺特异性抗原1·11ng/ml,血清游离前列腺特异性抗原0·2ng/ml,为进一步诊治于2005年3月入本院治疗。直肠指诊:前列腺增大约6cm×8cm,质坚硬,无压痛,中央沟消失,表面不平。X线和ECT检查未发现转移病灶。临床初步诊断为:前列腺肿瘤,肉瘤可能。患者入院1周后行前列腺肿瘤根治术,手术顺利,术中未发现盆腔肿大淋巴结。病理检查:带…     

Malignant gastrointestinal stromal tumor of intestine: a case report

Smooth muscle tumors of the alimentary tract are uncommon.Cancer of small intestine comprises less than 20% of all malignant tumors. A 65-year-old male patient was admitted with complain of pain in abdomen since 7 days. He was diagnosed as a case of acute intestinal obstruction and on laparotomy an extraluminal mass was found at jejunoileal junction. Histopathology revealed a malignant gastrointestinal stromal tumor (GIST) which was confirmed by immunohistochemistry. The case is reported with review of literature and criteria for differentiation between benign and malignant tumors are enumerated.