LONG‐TERM FOLLOW UP OF PATIENTS WITH SMALL GASTROINTESTINAL STROMAL TUMORS IN THE STOMACH USING ENDOSCOPIC ULTRASONOGRAPHY‐GUIDED FINE‐NEEDLE ASPIRATION BIOPSY

Background: Gastrointestinal stromal tumors (GIST) are one of the most common mesenchymal tumors of the gastrointestinal tract. GIST are defined by positive immunohistochemical staining for KIT or CD34 and thus are generally diagnosed after surgery. Because small GIST are rarely diagnosed before surgery, the clinical course of these small tumors is not clear. The aim of the present study was to follow changes in size and configuration of small GIST that were pathologically confirmed using endoscopic ultrasonography‐guided fine‐needle aspiration biopsy (EUS‐FNAB). Methods: Between July 1997 and December 2003, 16 tumors in 16 patients (10 men and 6 women) with an immunohistochemical diagnosis of GIST were regularly followed in our hospital. The median patient age when EUS‐FNAB was performed was 62 years (range 26–82 years) and the median follow‐up period was 4.9 years (range 0.5–9.6 years). Results: Fourteen tumors showed no remarkable changes in size and shape during follow up compared with the initial diagnosis. Two tumors enlarged: one tumor approximately doubled its diameter in 8 years and the other tumor increased from 1.8 cm at diagnosis to up to 10 cm after only 2 years. Doubling time of the latter tumor was calculated as 3.1 months. Conclusions: We conclude that EUS‐FNAB might be a good modality for final diagnosis of GIST without surgery, and that GIST without rapid growth on follow up can be endoscopically followed.     

Gastrointestinal stromal tumours: a regular origin in the muscularis propria, but an extremely diverse gross presentation

Background Gastrointestinal stromal tumours (GISTs) are thought to arise from the interstitial cells of Cajal (ICCs). ICCs form a network surrounding the myenteric plexus and between-muscle fibres of the muscularis propria of the tubular GI tract. The cell of origin of so-called extra-gastrointestinal stromal tumours (EGISTs) is not known.Aim and methods To study the diversity of gross presentation of GISTs and to critically assess the incidence of EGISTs and their relationship to mural GISTs, a total of 200 neoplasms with typical morphologic and immunohistochemical features of GISTs were reviewed, looking for any degree of association with the muscularis propria of the gut wall.Results There were 130 gastric (65%), 9 duodenal (4.5%), 48 small intestinal (24%), 9 colorectal (4.5%), 1 appendiceal (0.5%) and 3 unclassifiable GISTs (1.5%). Fourteen cases (7%) were initially submitted as EGISTs (four mesenteric, four omental, one pararectal/prostatic, one pelvic/Douglas, one perivesical, one located between root of mesentery and tail of pancreas, one involving the mesentery, omentum and abdominal wall extensively and one located between liver and stomach). After critical re-evaluation of surgical reports and remote clinical history and a careful search for residual muscular tissue from the gut wall in the tumour pseudocapsule (in some cases supported by desmin immunoreactivity), it was possible to reclassify most of these cases (11/14) as either GISTs with extensive extramural growth resulting in loss of contact to the external muscle coat of the gut (8/14) or as metastases from an inoperable GIST (2/14) or from a previously resected deceptively benign tumour (1/14).Conclusion EGISTs are probably rarer than previously reported (1.5% or less in this study). We concluded that most so-called EGISTs represent apparent EGISTs that should have arisen from the outermost muscle coat, but have lost their contact to the point of origin due to extensive extramural growth pattern. From a surgical point of view, it is crucial to document and mark any focal attachment or adhesions to the gut wall noticed during surgery for an apparent EGIST. In contrast to most other neoplasms, GISTs should be defined by virtue of any degree of association with the muscularis propria (no matter how minimal), but not by localisation of the bulk of the tumour.     

胃肠间质瘤的CT诊断及治疗评价

目的:探讨胃肠间质瘤(GIST)的CT表现及分子靶向药物甲磺酸伊马替尼(STI571)对胃肠间质瘤疗效的CT评价。方法:选择经手术及病理证实的胃肠间质瘤病例32例进行回顾性分析。对19例接受STI571治疗者进行定期CT检查随访,观察病灶大小、形态及密度变化,评价药物疗效。结果:32例GIST中,发生于胃部的18例,小肠11例,肠系膜1例,直肠2例。①CT特征:恶性度较高的胃肠间质瘤CT表现为:肿块相对较大,密度不均,肿瘤中央坏死及囊变多见;肿瘤边缘多不光整,可呈分叶状。增强扫描肿瘤呈不均匀强化;少数巨大肿瘤密度较低,极少数可见高密度出血及钙化灶。良性GIST体积较小,密度均匀,肿瘤坏死及囊变少见,病灶边缘光整,增强扫描多呈均匀强化;②19例接受STI571治疗者定期CT检查疗效评价为(肿瘤缩小):疗效达PR(部分缓解)者9例,占47.4%,疗效为SD(疾病稳定)者8例,占42.1%,病灶进展(PD)者2例,占10.5%。术后2年内复发及转移者19例。结论:①螺旋CT扫描是诊断胃肠间质瘤最常用和最有价值的影像检查手段,其定位诊断率达81%以上;②应用CT扫描观察测量病灶变化是评价药物(STI571)治疗胃肠间质瘤疗效最重要和最直接的方法之一;对指导临床治疗具有重要意义。     

True smooth muscle neoplasms of the gastrointestinal tract: morphological spectrum and classification in a series of 85 cases from a single institute

BACKGROUND AND AIM: True smooth-muscle neoplasms of the GI tract have been only rarely studied in the KIT era. Their incidence among other GI mesenchymal tumours and their clinicopathological spectrum have not been sufficiently analysed. MATERIALS AND METHODS: We reviewed all GI mesenchymal lesions at the Pathology Institute of the Nuremberg Clinic Centre from 1994 through 2005. RESULTS: Among 262 lesions, there were 142 GISTs (54%) and 85 true smooth muscle neoplasms (32%). Smooth muscle neoplasms comprised 72 polypoid leiomyomas (78%, 5 oesophageal and 67 colorectal), 10 intramural leiomyomas (11%, 5 oesophageal, 4 gastric and one ileal), two intramural leiomyosarcomas in the sigmoid colon and ileum (2%) and one polypoid leiomyosarcoma involving the stomach, descending colon and the retroperitoneum concurrently. None of the leiomyomas with available follow-up have recurred or metastasised. CONCLUSION: Smooth muscle neoplasms are the second most common mesenchymal neoplasms in the GI tract after GISTs. They may arise either from the muscularis mucosae or proper muscle layer forming polypoid and intramural lesions, respectively. Polypoid leiomyomas are more common in the rectosigmoid, while intramural ones mainly arise in the vicinity of the oesophagogastric junction. Polypoid leiomyomas are sufficiently treated by endoscopic resection, and local surgical excision is the treatment of choice for intramural leiomyomas. Intramural leiomyosarcomas are rare high-grade sarcomas that commonly have infiltrated into the surrounding tissue or metastasised by the time of diagnosis.     

Deposition of keinoid fibers in gastrointestinal stromal tumors of the small intestine. Report of two cases and review of the literature

Skeinoid fibers are interstitial collections of a pathological collagen, most often seen in gastrointestinal stromal tumors. They were first described in 1991. We report two cases of intestinal stromal tumors, one in an exceptionally young patient with excessive skeinoid fiber deposition. The microscopic as well as the ultrastructural findings of skeinoid fibers are demonstrated and their role is discussed considering the newest literature.     

p53 expression in gastrointestinal stromal tumors

The understanding of gastrointestinal stromal tumors (GIST) is complex because of their divergent differentiation and unpredictable behavior. However, our understanding is becoming clearer, despite some cases of tumors which are exceptions from the typical cases. Tumor size, mitotic rate and, to a lesser degree, location, are the most important predictive parameters for the behavior of GIST. In this study, expression of p53 protein was evaluated in 15 cases of GIST. Tumors were divided into three groups: (i) benign (mitotic index [MI] < 5/50 high-power fields [HPF] and size < 5 cm); (ii) borderline (MI < 5/50 HPF and size > or = 5 cm); and (iii) malignant (MI > or = 5/50 HPF, irrespective of size). The mean values of p53 expression in the three groups were significantly different (benign, 10.6%; borderline, 33.8%; and malignant, 71%). The conclusion of the present study is that p53 overexpression correlates well with the malignant potential of GIST.     

Gastrointestinal stromal tumours (GISTs) negative for KIT (CD117 antigen) immunoreactivity

Gastrointestinal stromal tumours (GISTs) are currently defined as mesenchymal tumours of the gastrointestinal tract that express KIT receptor tyrosine kinase. However, a small subgroup of tumours that fulfil the clinical and morphological criteria for GISTs lack KIT expression. So far, the biological features of these tumours have rarely been addressed. The present study describes seven gastrointestinal stromal neoplasms that presented clinicopathological features typical of GISTs but showed absence of CD117 expression as detected by immunohistochemistry. The tumours originated from the stomach (n = 5), duodenum (n = 1), and colon (n = 1), showing histologically either predominantly epithelioid (n = 3), mixed spindled and epithelioid (n = 2), or anaplastic/spindle cell (n = 2) type features. CD34 and alpha-smooth muscle actin (alpha-SMA) positivity was present in four and three tumours, respectively. Chromosomal analysis was performed in two cases, both showing losses of chromosomes 14, 22, and 1p, which is the characteristic feature of GISTs. Dual-colour interphase fluorescence in situ hybridization (FISH) analysis, utilizing chromosome 1p-, 14-, and 22-specific probes, revealed a similar cytogenetic profile in the remaining five tumour specimens. Mutational analysis of exons 9, 11, 13, and 17 of KIT, and exons 12 and 18 of PDGFRA was performed in all cases by denaturing high-pressure liquid chromatography (DHPLC) pre-screening, followed by direct sequencing. None of the tumours showed KIT mutant isoforms. Three tumours harboured PDGFRA exon 18 activating mutations; two were Asp --> Val(842) missense substitutions and one was a DIM842-844 amino acid deletion. KIT and PKC theta (protein activated in interstitial cells of Cajal and GISTs) expression was determined by western immunoblotting of the total cell lysates from three tumour biopsies. None of these three tumours expressed KIT, while all specimens showed expression of PKC theta protein. These findings indicate that there is a subgroup of KIT-negative GISTs that exhibit the same morphological, cytogenetic, and molecular features as KIT-positive tumours. While intragenic PDGFRA activating mutations are present in some of these tumours, the oncogenic events underlying the pathogenesis of the others remain unknown.     

Positive microscopic surgical margins: Is there an association with survival in resected small gastrointestinal stromal tumors?

BackgroundFew studies evaluate the relationships between surgical approach, histologic margin, and overall survival in gastrointestinal stromal tumor. We test the hypothesis that margin positive resection is associated with compromised overall survival.MethodsWe queried the National Cancer Data Base to identify patients undergoing resections for gastrointestinal stromal tumors ≤3 cm in size between 2010 and 2015. Multivariable logistic regression was used to identify factors associated with positive microscopic margins on final pathology. Cox proportional hazard methods were used to evaluate factors associated with overall survival.Results2064 patients met inclusion criteria; 135 (6.5%) had a microscopically positive surgical margin. On multivariable regression, minimally invasive approach was not associated with risk of a positive margin (OR 1.06 95% CI [0.71, 1.59]). On Cox analysis, positive margin status was not associated with OS (R1: 1.03, CI [0.46–2.31], reference R0).ConclusionsPositive microscopic surgical margins are not associated with compromised overall survival in patients undergoing resection of small gastrointestinal stromal tumors. Minimally invasive surgical approaches do not compromise oncologic outcomes in these cases.     

Laparoscopic resection for a large gastrointestinal stromal tumor (GIST) with diaphragm invasion following preoperative imatinib treatment: A case report

IntroductionNeoadjuvant imatinib for large GISTs may prevent tumor rupture and the need for extended surgery by reducing tumor size. In this study, we present a case of large gastric GIST with diaphragm invasion, due to the patient receiving laparoscopic resection following preoperative imatinib treatment.Presentation of caseA 72-year-old woman was hospitalized with left hypochondriac pain for a month. Examinations revealed a large heterogeneous gastric mass measuring 80 mm in size, arising from the greater curvature of the corpus. The mass invaded the left thoracic diaphragm. Treatment with imatinib at an initial dosage of 400 mg/day was initiated. After a further two months of follow-up, the lesion had sustained reduction to 50 mm in size, however, the invasion to the diaphragm remained. The patient eventually underwent laparoscopic partial gastrectomy and partial resection of the diaphragm with curative intent. Adjuvant chemotherapy was initiated at one month after the surgery, however, was discontinued due to nausea. After one-year follow-up, no recurrence was noted.DiscussionNeoadjuvant imatinib may shrink tumor size remarkably and prevent tumor rupture during surgery, and thus lead to increased rates of complete resection. To date, several publications have directly compared the oncologic results between laparoscopic and open resection for GISTs. In the present case, the tumor was movable, and moderately fixed on diaphragm. It was favorable condition for laparoscopic surgery.ConclusionsThis is the first report of a large gastric GIST invading the diaphragm that was successfully treated by laparoscopic resection after tumor reduction by neoadjuvant imatinib.