Gastrointestinal stromal tumors of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of 1765 cases with long-term follow-up

Gastrointestinal (GI) stromal tumors (GISTs), the specific KIT- or PDFGRA-signaling driven mesenchymal tumors, are the most common mesenchymal tumors of the GI tract. In this study, we analyzed 1869 cases originally classified as smooth muscle tumors of the stomach and found that 1765 (94%) of these were GISTs. The GISTs had a slight male predominance (55%) with a median age of 63 years. Only 2.7% of tumors occurred before the age of 21 years and 9.1% before the age of 40 years. The tumors varied from 0.5 to 44 cm (median, 6.0 cm) and most commonly presented with GI bleeding; 12% were incidentally detected. Several histologic variants were recognized among the spindle cell tumors (sclerosing, palisaded-vacuolated, hypercellular, and sarcomatous) and of epithelioid tumors (sclerosing, dyscohesive, hypercellular, and sarcomatous). Outcome was strongly dependent on tumor size and mitotic activity. Only 2% to 3% of tumors <10 cm and <5 mitoses/50 HPFs metastasized, whereas 86% of tumors >10 cm and >5 mitoses/50 HPFs metastasized. However, tumors >10 cm with mitotic activity <5/50 HPFs and those <5 cm with mitoses >5/50 HPFs had a relatively low metastatic rate (11% and 15%). A small number of patients survived intra-abdominal metastasis up to over 20 years. Tumor location in fundus or gastroesophageal junction, coagulative necrosis, ulceration, and mucosal invasion were unfavorable factors (P <0.001), whereas tumor location in antrum was favorable (P <0.001). KIT expression was detected in 91% of the cases, CD34 in 82%, smooth muscle actin in 18%, and desmin in 5%; the latter two were favorable (P <0.001). KIT exon 11 mutations were detected in 119 cases; patients with point mutations fared better than those with deletions (P <0.01). PDGFRA exon 18 mutations (total 86 cases) were common in epithelioid GISTs and most commonly represented a D842V point mutation; none of these was prognostically significant. The above results may be helpful for setting the criteria for adjuvant treatment such as Gleevec.     

True smooth muscle tumors of the small intestine: a clinicopathologic, immunhistochemical, and molecular genetic study of 25 cases

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.     

Gastrointestinal stromal tumors of the jejunum and ileum: a clinicopathologic, immunohistochemical, and molecular genetic study of 906 cases before imatinib with long-term follow-up

Gastrointestinal (GI) stromal tumors (GISTs), the specific KIT- or PDFGRA-signaling driven mesenchymal tumors, are the most common mesenchymal tumors of the GI tract. This study analyzed 1091 tumors originally classified as smooth muscle tumors of the small intestine (including jejunum or ileum and excluding duodenum), and found that 906 (83%) of these were GISTs. The GIST patients had 55:45 male-to-female ratio with a median age of 59 years (range, 13-94 years). Only 0.6% of tumors occurred before the age of 21 years and 13.6% before the age of 40 years. The tumors varied from 0.3 to 40 cm (median, 7.0 cm) and most commonly presented with GI bleeding or acute abdomen; 18% were incidentally detected. Histologically, the tumors were relatively monotypic with spindle cell (86%), epithelioid (5%), or mixed patterns (9%). Skeinoid fibers were present in 44% of cases, and their presence was associated with a favorable course. Most epithelioid tumors were malignant, and this morphology sometimes emerged from less cellular and less mitotically active spindle cell tumors, suggesting that it represented a transformation. KIT was immunohistochemically detected in 98%, CD34 in 40%, smooth muscle actin in 34%, desmin in 0.2%, and S-100 protein in 14% of the tumors tested. Outcome was strongly dependent on tumor size and mitotic activity, with an overall 39% tumor-related mortality, twice that for gastric GISTs. Only <3% of tumors <5 cm and < or = 5 mitoses/50 HPF metastasized, whereas 86% of tumors >10 cm and >5 mitoses/50 HPF metastasized. In stark contrast to corresponding gastric tumors, tumors >10 cm with mitotic activity < or = 5/50 HPF and those < or = 5 cm with mitoses >5/50 HPF had a high metastatic rate (>50%); tumors >5 cm < or = 10 cm with low mitotic rate had a 24% metastatic rate. The median survival times of patients with low mitotic rate tumors who died of disease decreased by increasing tumor size. KIT exon 11 mutations were detected in 90 cases, exon 9 mutation in 17 cases, and exon 17 mutation in 1 case; the presence of mutation or mutation type was not prognostically significant. There were no PDGFRA exon 12 or 8 mutations. Systematic data on prognosis of small intestinal GISTs of various size and mitotic activity categories can be helpful in management and surveillance of patients with these tumors.     

Gastrointestinal stromal tumors and leiomyosarcomas in the colon: a clinicopathologic, immunohistochemical, and molecular genetic study of 44 cases

Gastrointestinal stromal tumors (GISTs), mesenchymal tumors largely specific for the gastrointestinal tract, have been well defined in the stomach and small intestine, but have not been extensively documented or contrasted with true smooth muscle tumors in the colon. This study was undertaken to determine the clinicopathologic features of GISTs of the colon, excluding the rectum, and to compare them with leiomyosarcomas (LMSs) of the same location. A total of 37 colonic GISTs and seven LMSs from the files of the Armed Forces Institute of Pathology and the Haartman Institute of the University of Helsinki were analyzed. The GISTs occurred predominantly in adults older than 50 years of age (median, 67 yrs), and most were histologically malignant; four small benign tumors (< or = 1 cm) were incidentally detected, and 10 others had minimal mitotic activity (five or fewer mitoses per 50 high-power fields). The colonic GISTs were typically transmural tumors with frequent intraluminal and outward bulging components. Histologically, they usually showed a spindle cell pattern (92%), whereas 8% were epithelioid. Most tumors (19 of 25) were positive for CD117 (KIT) and for CD34 (16 of 27); six tumors coexpressed alpha-smooth muscle actin and CD117; none showed desmin or S-100 protein. C-kit mutations in exon 11 were seen in 5 (36%) of 14 colonic GISTs. None of the patients with incidental small tumors had a recurrence, whereas 2 of 10 patients with tumors larger than 1 cm but minimal mitotic activity died of the disease with liver metastasis. Nearly all patients whose tumor was larger than 1 cm and showed more than five mitoses per 50 high-power fields died of disease; half had evidence of metastasis. LMSs were typically intraluminally bulging, polypoid masses that showed a histologic likeness to differentiated smooth muscle cells. They occurred in five men and two women with a median age of 61 years. Most LMSs were high-grade histologically and showed smooth muscle actin, desmin, or both. All were negative for CD34 and CD117 and lacked c-kit mutations. Five of the seven patients died of disease, and two had a long-term survival, despite high mitotic activity. These results show that KIT-positive GISTs are more common than LMSs of the colon, and these tumor groups have clinicopathologic differences that warrant their separation.     

Gastrointestinal stromal tumors in patients with neurofibromatosis 1: a clinicopathologic and molecular genetic study of 45 cases

Gastrointestinal stromal tumors (GISTs), the specific KIT- or PDFGRA-signaling driven mesenchymal tumors, most commonly occur sporadically, but there seems to be some increased tendency for these tumors to develop in patients with neurofibromatosis 1 (NF1). The clinicopathologic profile, KIT, and PDGFRA mutation status and long-term prognosis of patients with GIST in NF1 are incompletely characterized. In this study, we analyzed 45 patients who had NF1 and GIST. There were 26 females and 19 males with a median age of 49 years (10 years lower than the median age of GIST patients in general). A great majority of tumors occurred in the jejunum or ileum, with multiple tumors occurring in 28 cases. Ten patients had a duodenal and one had a gastric GIST. The most common presentations were gastrointestinal bleeding and anemia, and many patients had intermittent bleeding over several years. The majority of the tumors were small and mitotically inactive; only 7 had mitotic activity >5/50 HPFs and 15 tumors were >5 cm. Associated Cajal cell hyperplasia was common. One patient had an intraabdominal peri-intestinal neurofibroma. Five of 35 patients with follow-up died of metastatic disease; all of these had a tumor >5 cm, mitotic rate >5/50 HPFs, or both; three of these tumors were located in the duodenum. The presence of multiple small tumors was not associated with progressive disease. Most patients with long-term follow-up enjoyed a good prognosis; 2 died of other NF1-associated tumors (malignant peripheral nerve sheath tumors, brain tumor). None of the 16 tumors from 15 patients had a KIT exon 9, 11, 13, or 17 or PDGFRA exon 12 or 18 mutation as is typically seen in sporadic GISTs, indicating that GISTs in NF1 patients have a different pathogenesis than sporadic GISTs.     

影响胃肠道间质瘤患者预后的因素分析

目的探讨影响胃肠道间质瘤预后的临床病理因素。方法 收集临床病理资料,单因素及多因素分析各变量与患者预后的关系。结果患者1、3、5 a生存率分别是89.7%、79.3%和70.7%。单因素分析和多因素分析均显示肿瘤大小、核分裂像数目、肿瘤原发部位是影响预后的重要因素（P〈0.05）。结论肿瘤直径〉10 cm、核分裂数〉10个/50 HPF常提示胃肠道间质瘤恶性度较高,预后不良。     

A modification of NIH consensus criteria to better distinguish the highly lethal subset of primary localized gastrointestinal stromal tumors: a subdivision of the original high-risk group on the basis of outcome

BACKGROUND: By reappraising the National Institutes of Health (NIH) consensus criteria, we worked on establishing a modified scheme to identify highly lethal gastrointestinal stromal tumors (GISTs), which have an imperative demand for sequencing analysis to assess the suitability of an adjuvant imatinib trial. METHODS: Clinicopathologic features, including NIH and modified schemes, were retrospectively analyzed for 289 patients with localized GISTs. We combined the very low/low-risk GISTs into a single "risk level I" group (5 cm and >10/50 HPF, with the rest of high-risk GISTs defined as "risk level III." RESULTS: The cumulative 5-year rate of disease-specific survival (DSS) for all 289 patients was 82%, and the DSS rates for patients with GISTs classified as risk levels I to IV were 100%, 96%, 67%, and 25% at 5 years, respectively. The prognostic differences were striking between the risk level II and III groups (P < .0001) and between the risk level III and IV groups (P = .0002). The higher risk level of our scheme represented the strongest independent adverse factor (risk ratio [RR] = 11.299 for risk level III; RR = 33.815 for risk level IV; P < .0001), followed by mixed/epithelioid histology (RR = 2.837, P = .003) and older age (>or=70 years, RR = 1.955, P = .044). CONCLUSIONS: Remarkable prognostic heterogeneity exists in the high-risk category of the NIH scheme, which is not as effective as the modified criteria in identifying highly lethal GISTs that we classified as risk level IV.     

Adjuvant systemic therapy for intermediate and large gastric gastrointestinal stromal tumors (GISTs): Is there a survival benefit following margin negative surgical resection?

BackgroundThe value of adjuvant systemic therapy after margin-negative resection for gastric gastrointestinal stromal tumors (GISTs) remains unclear.MethodsThe National Cancer Data Base was queried to identify patients undergoing margin negative resections for gastric GISTs >2 cm between 2010 and 2015. Patients were stratified by tumor size (small: 2.1–5 cm, intermediate: 5.1–10 cm, large: >10 cm), histologic grade (low: ≤5 mitoses/50 HPF and high: >5 mitoses/50 HPF), and use of adjuvant therapy. Multivariable cox proportional hazard methods were used to compare overall survival (OS).Results3520 patients met inclusion criteria. Adjuvant therapy was associated with a statistical improvement in OS (86% vs. 76%, p = 0.014) for those with large tumors but had no measurable effect in patients with small or intermediate sized tumors. On multivariable analysis, this association was independent of grade.ConclusionsAdjuvant therapy is associated with improved OS for patients with gastric GISTs >10 cm but provides no statistically significant benefit in OS for those with GISTs 2–10 cm     

Gastrointestinal stromal tumors,intramural leiomyomas,and leiomyosarcomas in the duodenum: a clinicopathologic,immunohistochemical, and molecular genetic study of 167 cases

In this study we analyzed the clinicopathologic features of duodenal smooth muscle or stromal tumors, including 156 GISTs, 6 leiomyomas (LMs), and 5 leiomyosarcomas (LMSs) from the files of the Armed Forces Institute of Pathology and the Haartman Institute of the University of Helsinki. GISTs were documented as KIT positive (n = 109); 47 tumors were also included because of their histologic identity to KIT-positive cases. GIST-specific c-kit gene mutations were documented in exon 11 in 9 of 30 cases (30%) and exon 9 in 4 of 30 cases (13%). The GISTs occurred in patients with an age range of 10-88 years (median 56 years); 54% were male. Ten patients had neurofibromatosis type I; six of them had multiple GISTs. The GISTs ranged from small asymptomatic intramural or external nodules to large masses that extended into the retroperitoneum (median size 4.5 cm). They were mostly spindle cell tumors; three malignant GISTs had an epithelioid morphology, and 81 cases had skeinoid fibers. The tumors often coexpressed CD34 and KIT (54%) and were variably positive for smooth muscle actin (39%) and S-100 protein (20%) but never for desmin. A total of 86% of patients with tumors >5 cm with >5 mitoses/50 high power fields (HPF) (n = 21) died of disease, whereas no tumor <2 cm with <5 mitoses/50 HPF (n = 12) recurred or caused death. Long latency was common between primary operation and recurrences or metastases; either one occurred in 49 of 140 patients with follow-up (35%). No formula could accurately predict metastases, which occasionally developed even if mitotic activity was <5/50 HPF and size <5 cm. Metastases were in the abdominal cavity, liver, and rarely in bones and lungs but never in lymph nodes. Four actin- and desmin-positive and KIT-negative benign intramural LMs were similar to those more often seen in the esophagus. There were five LMSs, one of which formed a polypoid intraluminal mass; all were actin positive and KIT negative. The great majority of duodenal mesenchymal tumors are GISTs, which have a spectrum from small indolent tumors to overt sarcomas. LMs and LMSs are rare.     

Gastrointestinal stromal tumors, intramural leiomyomas, and leiomyosarcomas in the rectum and anus: a clinicopathologic, immunohistochemical, and molecular genetic study of 144 cases.

Gastrointestinal stromal tumors (GISTs), the specific KIT-positive mesenchymal tumors of the gastrointestinal tract, have been sporadically reported in the rectum, but there are few clinicopathologic series. In this study we analyzed the clinicopathologic features of 133 anorectal GISTs, 3 intramural leiomyomas (LMs), and 8 leiomyosarcomas (LMSs) from the files of the Armed Forces Institute of Pathology and the Haartman Institute of the University of Helsinki. Ninety-six GISTs were documented as KIT-positive and three additional ones as CD34-positive. Thirty-four tumors were included by their histologic similarity to KIT- or CD34-positive cases. GIST-specific c-kit gene mutations, mostly in exon 11, were documented in 18 of 29 cases (62%). The GISTs occurred in adults with the age range of 17-90 years (median 60 years) with a significant male predominance (71%). The tumors ranged from small asymptomatic intramural nodules to large masses that bulged into pelvis causing pain, rectal bleeding, or obstruction. They were mostly highly cellular spindle cell tumors; four tumors had an epithelioid morphology. The tumors coexpressed CD34 and KIT and were rarely positive for smooth muscle actin or desmin and never for S-100 protein. Seventy percent of patients with tumors >5 cm with more than 5 mitoses/50 high power fields (HPF) (n = 31) died of disease, whereas only one tumor <2 cm with <5 mitoses/50 HPF (n = 21) recurred and none caused death. Long latency was common between primary operation and recurrences and metastases; either one occurred in 60 of 111 patients with follow-up (54%). Distant metastases were in the liver, bones, and lungs. Three benign actin- and desmin-positive and KIT-negative intramural LMs, similar to those seen in the esophagus, were identified. There were eight LMSs, six of which formed a polypoid intraluminal mass and were actin-positive and KIT-negative. Despite high mitotic counts, only one LMS patient died of disease. A great majority of rectal smooth muscle and stromal tumors are GISTs, which have a spectrum from minimal indolent tumors to overt sarcomas. Intramural LMs are exceptional, and true LMSs are rare, and similar to colonic ones, often present as intraluminal polypoid masses that appear to have a better prognosis than GISTs with similar mitotic rates.     

Gastrointestinal stromal tumor versus intra-abdominal fibromatosis of the bowel wall: a clinically important differential diagnosis

Intra-abdominal fibromatosis (IAF) is an uncommon benign neoplasm that usually occurs in the mesentery or retroperitoneum and may, on occasion, mimic a gastrointestinal stromal tumor (GIST). Differentiating between these two entities is important clinically because IAF is a benign tumor whereas GISTs frequently have malignant potential. In this study, the authors identified 13 cases of IAF with prominent involvement of the bowel wall as well as 35 GISTs of the small intestine, colon, or mesentery and analyzed their clinical, gross, histologic, immunophenotypic, and ultrastructural characteristics to identify important distinguishing features. Patients with IAF were younger (mean, 34 yrs) than patients with GIST (mean, 54 yrs). Both types of tumors tended to be large, but GISTs were soft and lobulated with hemorrhage, necrosis, or cystification whereas IAFs were firm, tan, and homogeneous. Histologic features characteristic of GIST included the presence of spindle or epithelioid cells with variable architecture, mitotic activity (range, <1-95 mitoses/50 high-power fields [hpf]; mean, 15 mitoses/50 hpf), nuclear atypia, and myxoid or hyalinized stroma. Necrosis and hemorrhage were seen in 16 and 25 tumors, respectively. In contrast, IAFs were composed of broad, sweeping fascicles of monotonous spindle cells with mitotic activity (range, <3-11 mitoses/50 hpf; mean, 4 mitoses/50 hpf), bland nuclear features, and finely collagenous stroma. Necrosis, hemorrhage, and myxoid degeneration were not seen. Immunohistochemical studies performed on a limited number of GISTs and IAFs demonstrated that cells expressed vimentin (100% GIST and IAF), CD117 (88% GIST and 75% IAF), CD34 (42% GIST and 0% IAF), smooth muscle actin (63% GIST and 75% IAF), muscle actin (75% GIST and 75% IAF), desmin (8% GIST and 50% IAF), and S-100 protein (16% GIST and 0% IAF). Ultrastructural analysis of 21 GISTs revealed incomplete smooth muscle differentiation in some tumors whereas IAFs were shown to have complete myofibroblastic/fibroblastic differentiation. Information regarding clinical outcome was available on 29 patients and revealed that three patients with histologically benign GISTs were alive with no evidence of disease at 5 months to 6 years (mean, 3.5 yrs) and one patient with a histologically benign tumor died of disease after 7 years. Of patients with histologically malignant GIST, one died of surgical complications, 10 were alive without disease at I to 13 years (mean, 5.4 yrs), four were alive with disease at 4 months to 15 years (mean, 3.8 yrs), three had disseminated disease at operation, and seven were dead of disease at 10 months to 3 years (mean, 2.2 yrs). Follow up of eight patients with IAF demonstrated that five were alive without disease at 4 months to 15 years (mean, 5.3 yrs) and three had recurrences at 1 (two patients) and 2 years (one patient). In summary, IAFs can have many features (large size, infiltration of adjacent structures, mitotic activity) that can cause diagnostic confusion with GISTs and, importantly, the degree of mitotic activity present in IAFs may overlap that seen in malignant GISTs. These entities can be distinguished primarily by their light microscopic and ultrastructural features but there is a notable overlap in their immunohistochemical profiles. The distinction between these neoplasms is important because there are important clinical implications for the patient.     

Primary giant cell tumor of soft tissues: a study of 22 cases

Twenty-two cases of giant cell tumor of soft tissues (GCT-ST) identified in the Mayo Clinic files and the consultation files of two of the authors (A.G.N., C.D.M.F.) were analyzed clinicopathologically. Age at presentation ranged from 5 to 80 years (median, 43 years), and there was no sex predilection (12 male, 10 female). Duration of symptoms ranged from 2 to 12 months (median, 4.5 months), and a painless growing mass was the most common complaint. The lower limbs were the most frequent location (50%), followed by the trunk (31.8%) and the upper limbs (13.6%). The size of the tumors ranged from 1 to 10 cm, and they tended to be superficial (86.4%), forming well-circumscribed (72.7%), multinodular (86.4%) masses. Histologically, all tumors consisted of a mixture of mononuclear cells showing vesicular, round to oval nuclei and osteoclastlike, multinucleated giant cells distributed uniformly throughout the tumors. Foci of stromal hemorrhage were observed in 11 tumors (50%); nine tumors (40.1%) showed metaplastic bone formation and six (27.2%) showed aneurysmal bone cystlike areas. Necrosis was absent in all but one tumor. Mitotic figures were present in all but one tumor, ranging from two to more than 30 mitoses per 10 high-power fields (HPFs; median, 9.5 mitoses per 10 HPFs) and were typical in aspect. Vascular invasion was identified in seven tumors (31.8%), and none of the tumors showed marked cellular atypia or pleomorphism. The tumors were treated surgically, and follow-up information was available for 16 patients (duration of follow-up, 2 to 130 months; median, 51 months). Only one of the 16 patients (6.2%) had local recurrence and lung metastases; this patient died of the tumor. In conclusion, GCT-ST occurs as a primary soft-tissue neoplasm and is identical clinically and morphologically to giant cell tumor of bone. Provided that GCT-ST is treated adequately by complete excision, a benign clinical course is expected because episodes of distant metastasis and tumor-associated death seem to be exceedingly rare.     

Esophageal stromal tumors: a clinicopathologic, immunohistochemical, and molecular genetic study of 17 cases and comparison with esophageal leiomyomas and leiomyosarcomas

Although rare elsewhere in the gastrointestinal tract, leiomyomas (LMs) are the most common esophageal mesenchymal neoplasms. In contrast, gastrointestinal stromal tumors (GISTs) predominate in the stomach and intestines but have not been documented in the esophagus. This study was undertaken to determine the clinicopathologic features and frequency of esophageal GISTs compared with LMs and leiomyosarcomas (LMSs) of the esophagus. A total of 68 stromal/smooth muscle tumors from the Armed Forces Institute of Pathology and the Haartman Institute of University of Helsinki were reclassified by current histologic and immunohistochemical criteria. There were 17 GISTs, 48 LMs, and three LMSs. The esophageal GISTs occurred in 12 men and five women with a median age of 63 years (range, 49-75 years). All tumors were from the lowest third of the esophagus, and the most common complaint was dysphagia, whereas two tumors were detected incidentally. Histologically the tumors had an overall basophilic appearance and showed combinations of solid, myxoid, and perivascular collarlike patterns with a spindle cell histology in 13 patients and epithelioid histology in four patients. All tumors were positive for CD117 and for CD34, whereas two patients were also positive for alpha-smooth muscle actin (SMA) and three patients were positive for desmin. One patient showed a unique immunophenotype with coexpression of CD117, CD34, SMA, and desmin. Nine patients died of disease, including all who had a tumor larger than 10 cm, and also one patient whose tumor showed five mitoses per 50 high-power fields. In comparison, esophageal LMs (n = 48) occurred in a younger population (median age, 35 years) but, similar to the GIST group, men predominated (67%). All LMs were clinically indolent tumors with no tumor-related mortality. The LMs showed eosinophilic cytoplasm, and were positive for desmin and SMA, and negative for CD117 and CD34. All three LMSs were large high-grade tumors that showed muscle cell markers but no CD117. All patients died of disease. Esophageal GISTs showed mutations in exon 11 of c-kit as described previously in gastric and intestinal GISTs. The separation of GISTs from esophageal LMs is important diagnostically because the former group has a high risk of malignant behavior.     

Multiple sporadic gastrointestinal stromal tumors (GISTs) of the proximal stomach are caused by different somatic KIT mutations suggesting a field effect

Multifocal gastrointestinal stromal tumors (GISTs) are observed in patients with germline KIT or PDGFRA mutations, and in those with neurofibromatosis 1. However, the pathogenesis of apparently sporadic multifocal gastric GISTs in adults is poorly understood. We analyzed 27 GISTs from 11 patients (mean age, 75 y) with 2 to 4 tumors each. All tumors represented incidental findings in surgical (n=8) and autopsy (n=3) specimens and were located in the gastric body or fundus within < or =4 cm distance from each other. The 8 surgical cases represented 10% of GISTs involving the proximal stomach in our case material. Tumor size ranged from 1.5 mm to 45 mm (mean, 9 mm). Histology revealed a uniform spindle cell morphology with a variable sclerosis/calcification and a low mitotic activity (<5 mitoses/50 high-power fields). All tumors were KIT+/CD34+. Nineteen of 22 tumors (79%) revealed mutations in KIT exon 11 (13 deletions and 6 point mutations). Individual lesions from the same patient displayed different mutations in all, but 1 case, thus ruling out germline mutations and neurofibromatosis 1. Our findings indicate that multifocal gastric GISTs in elderly patients are unrelated to hereditary GIST syndromes. Clustering of these lesions in the proximal stomach, their close proximity, and the demonstration of different KIT mutations in individual lesions from the same patient point to the existence of distinct subsets of interstitial cells of Cajal with a higher propensity for different somatic KIT exon 11 mutations, possibly as a result of a field effect involving premutational epigenetic alterations or yet unidentified etiologic factors.     

Laparoscopic resection of small gastric submucosal tumors

Background

No consensus exists regarding the necessity of operative resection for patients with small, asymptomatic gastric submucosal tumors (SMTs). The purpose of this study is to evaluate clinical outcomes of resection by minimally invasive surgery.

Methods

The medical records of 20 consecutive patients who had undergone laparoscopic or robotic wedge resection for small (<5?cm) gastric SMTs between March 2008 and February 2009 were reviewed. Operative indications included all SMTs unquestionably visible by endoscopy, irrespective of symptoms. The operative procedures, clinicopathologic features, and operative results were assessed.

Results

Out of a total of 20 patients, 17 were asymptomatic, and 3 presented with vague abdominal discomfort. One patient had two tumors, therefore 21 total lesions were resected and evaluated (19 by laparoscopy and 2 by robotic procedures). There were 12 exogastric and 9 transgastric wedge resections. Mean operative time was 84?±?28?min, and mean length of hospitalization was 4.7?±?1.6?days. There were no major peri- or postoperative complications or mortalities. Mean tumor size was 2.4?±?1.2?cm (range 0.6?C4.8?cm). All lesions had microscopically negative resection margins. There were 16 gastrointestinal tumors (GISTs) and 5 other benign lesions. Fifteen of the GISTs had mitotic count (MC) <5 per 50 high-power fields (HPFs), and one lesion measuring 2.5?cm in size had MC of 38 per 50 HPFs.

Conclusions

Small size cannot guarantee a specific malignant risk for gastric SMTs. Laparoscopic/robotic wedge resection is safe and effective in treating small, asymptomatic lesions. Therefore, an active surgical approach should be considered for management of patients with small gastric SMTs.     

Transvaginal excision of a large rectal stromal tumor: an alternative

BACKGROUND: Gastrointestinal stromal tumors (GISTs), the specific kit-positive mesenchymal tumors of the gastrointestinal tract, are rarely found in the anorectum and account for only 0.1% of all colorectal tumors. The main stem of therapy remains surgical excision. The standard surgical approach for anorectal GISTs includes transanal resection or enucleation for smaller and anterior or abdominoperineal resection for larger tumors. METHODS: We present an alternative, transvaginal approach for a local excision of a large rectal GIST. In our case, a 5 x 5 x 8 cm large GIST located 3 cm above the dentate line in the anterior rectal wall was removed through the vagina. RESULTS: In our experience, this approach enables a safe alternative even for larger tumors in the anterior rectal wall with a very low morbidity, sparing the patient from an unnecessary abdominoperineal resection.     

腹内胃肠外间质瘤30例临床病理分析

目的研究腹内胃肠外间质瘤(EGIST)临床病理特点及预后。方法复阅1986年7月至2003年6月47例经病理诊断为腹腔或腹膜后平滑肌瘤、平滑肌肉瘤、平滑肌母细胞瘤、许旺细胞瘤和间质瘤患者的组织切片,重新诊断,免疫组织化学染色检测CD117、CD34、SMA、Desmin及S-100 5种蛋白表达,分析其临床病理变量与预后的关系。结果30例患者最终确诊为EGIST。肿瘤位于肠系膜12例,腹膜后8例,小网膜囊6例,其余4例肿瘤病例记载为腹腔来源。肿瘤中位直径12.5(4～30)cm,其中梭形细胞为主型23例,上皮为主型4例,混合型3例。随访中位时间44个月。随访率90%。全组患者1、3、5年生存率分别为79.7%、59.5%和45.4%。单因素分析结果显示.肿瘤位于腹膜后和肠系膜及腹腔、肿瘤直径超过10cm、肿瘤有坏死、核分裂像数目超过5个/ 50HPF、肿瘤细胞异型性和中、低分化的肿瘤,其预后不佳。结论EGIST有其特有行为谱,预后评价除参照GIST的指标外;肿瘤直径超过10cm和肿瘤的生长部位有助于对EGIST预后的判断。     

A gastrointestinal stromal tumor of the third portion of the duodenum treated by wedge resection: A case report

A 65-year old woman was admitted to our hospital with abdominal pain. Computed tomography showed a tumor measuring about 3 cm in diameter with no metastatic lesion or signs of local infiltration. Gastroduodenal endoscopy revealed the presence of a submucosal tumor in the third portion of the duodenum and biopsy revealed tumor cells stained positive for c-kit. These findings were consistent with gastrointestinal stromal tumors (GISTs) and we performed a wedge resection of the duodenum, sparing the pancreas. The postoperative course was uneventful and she was discharged on day 6. Surgical margins were negative. Histology revealed a GIST with a diameter of 3.2 cm and < 5 mitoses/50 high power fields, indicating a low risk of malignancy. Therefore, adjuvant therapy with imatinib was not initiated. Wedge resection with primary closure is a surgical procedure that can be used to treat low malignant potential neoplasms of the duodenum and avoid extensive surgery, with significant morbidity and possible mortality, such as pancreatoduodenectomy.     

Surgical Management of Small Gastrointestinal Stromal Tumors of the Stomach

Small gastrointestinal stromal tumors (GISTs) (<3 cm) occasionally are found in the stomach during endoscopy. There is no consensus about the surgical management of these small tumors, although this clinical issue is crucial because some of the tumors show unexpected malignant behavior. In this study, we evaluated the clinical management of patients with gastric GISTs who underwent surgical resection. Altogether, 31 patients with gastric GISTs were examined retrospectively. Surgical resection was fundamentally indicated for the patients with gastric GISTs suspected to be malignant by endoscopy or endoscopic ultrasonography (EUS). The malignant grade of the GISTs was evaluated by the mitotic rate, tumor size, and MIB-1 index. EUS was useful for differentiating benign from malignant GISTs; but by limiting the study to patients with small tumors (<3 cm), the diagnostic value of EUS was not satisfactory for defining the surgical indication. Tumors that were <50 mm were successfully treated by laparoscopic surgery. Of the 31 patients, 4 had a relapse of the disease, and 1 of those 4 patients had a small tumor (30 mm). All of the recurrences were classified in the high risk category. Surgery is indicated for gastric GISTs that are ≥20 mm or are suspected to be malignant based on EUS findings. Laparoscopic resection is feasible and is recommended as the treatment of choice for patients with tumors < 50 mm. Risk assessment can be most useful for predicting recurrence.     

Cellular fibromas of the ovary: a study of 75 cases including 40 mitotically active tumors emphasizing their distinction from fibrosarcoma

Cellular fibroblastic tumors of the ovary are currently classified as either cellular fibroma (CF) or fibrosarcoma. The former are characterized by bland nuclei, 3 or fewer mitotic figures per 10 high-power fields (MFs/10 HPFs), and a low malignant potential, whereas fibrosarcomas usually have severe nuclear atypia, > or = 4 MFs/10 HPFs, and an aggressive clinical course. The prognosis of cellular fibromatous tumors with > or = 4 MFs/10 HPFs and low-grade cytology is not established and it is the purpose of this study to investigate that aspect. It has been our anecdotal experience that otherwise typical CFs with > or = 4 MFs/10 HPFs usually have a benign clinical course, suggesting that such tumors should be regarded as "mitotically active cellular fibroma" (MACF) rather than fibrosarcoma. Seventy-five cellular fibromatous neoplasms were analyzed to determine their clinicopathologic features and the appropriateness of "MACF" as a designation for otherwise typical CFs with > or = 4 MFs/10 HPFs. The mean age of patients with CF (n = 35, 0 to 3 MFs/10 HPFs) and MACF (n = 40, > or = 4 MFs/10 HPFs) was 51 and 41 years, respectively. Patients most commonly presented with symptoms related to a pelvic mass. All tumors were unilateral. The mean tumor size of CFs was 8.0 cm and 9.4 cm for MACFs. The majority of the tumors were solid; approximately one-third of them had a cystic component. Ovarian surface adhesions, involvement of the ovarian surface, or both, was present in 6% of CFs and 10% of MACFs. Eleven percent of CFs and 13% of MACFs were associated with extraovarian involvement. All tumors consisted of cellular, intersecting bundles of spindle cells with bland nuclear features. The mean highest mitotic count for MACFs was 6.7 MFs/10 HPFs (range 4 to 19 MFs/10 HPFs). Follow-up of 3 months to 12 years (mean 4.75 y) was available in 18 of the 40 patients with MACFs and was uneventful in all cases. We conclude that cellular fibromatous neoplasms with bland cytology and elevated mitotic counts are associated with favorable patient outcome and should be diagnosed as MACF rather than fibrosarcoma, which usually have moderate to severe atypia and elevated mitotic rates. As prior observations have shown that even typical CFs can occasionally recur locally, particularly if they are associated with rupture or adherence, long-term follow-up for patients with CFs and MACFs is appropriate.