A Single-Institution Experience with Eight CD117-Positive Primary Extragastrointestinal Stromal Tumors: Critical Appraisal and a Comparison with Their Gastrointestinal Counterparts

Introduction  Gastrointestinal stromal tumors (GISTs) arising from outside the gut wall also termed extragastrointestinal stromal tumors (EGISTs) are reported to be rare. Presently, their pathogenesis remains controversial, and recently, it has been proposed that EGISTs may be the result of extensive extramural growth of GISTs which lose contact with the gut wall. This study presents a single-institution experience with eight EGISTs and compares their clinicopathological features with mural GISTs in order to determine further insight to their possible origin. Methods  Between 1997 and 2008, 156 patients with pathologically proven CD117-positive primary GISTs were retrospectively reviewed. Eight tumors were identified as EGISTs, 104 were gastric GISTs, and 44 were small-bowel GISTs. Mural GISTs were classified as extramural or intra/transmural according to their gross pattern of growth. Results  There were five male and three female patients with a median age of 58 years (range, 42–81 years). All patients were symptomatic, and the tumors were located in the greater omentum (n = 2), lesser sac (n = 2), lesser omentum, retroperitoneum, small-bowel mesentery, and pancreas. The median tumor size was 140 mm (range, 55 to 220 mm). Seven of eight EGISTs were found to be in close association to the adjacent gut wall. Pathological examination demonstrated that two tumors demonstrated focal involvement of the muscularis propria of the adjacent gut wall. Four tumors demonstrated tumor abutting or adherent to the serosa but no muscle involvement and one tumor was separated from the serosa. Comparison between the clinicopathological features of EGISTs with extramural GISTs and intra/transmural GISTs demonstrated that EGISTs were significantly larger [140 range (55–220) mm vs 80 (5–260) mm vs 50 (15–190) mm, P = 0.049, P < 0.001 respectively]. Conclusion  The occurrence of true EGISTs is rare. Most cases demonstrate some form of communication or contact with the gut wall, and EGISTs are significantly larger than extramural or intra/transmural GIST. These observations suggest that most, if not all, cases of EGISTs are likely to represent mural GISTs with extensive extramural growth with eventual loss of contact with the muscle layer of the gut.     

Pancreatic gastrointestinal stromal tumor: A case report

IntroductionGastrointestinal stromal tumors (GISTs) are the most common gastrointestinal tract (GIT) tumors of mesenchymal origin. GISTs tend to arise with a higher frequency in the stomach and the small intestine. GISTs that originate from outside of the GIT are defined as extra-gastrointestinal stromal tumors (EGISTs). Among them pancreatic EGISTs are very rare.Case presentationA 30 years old male patient presented with abdominal pain. Triphasic abdominal computed tomography scan with contrast revealed large well defined mass at the pancreatic tail, about 12 × 11.6 cm. Laparoscopic distal pancreatectomy and splenectomy was performed. Postoperative pathological examination revealed positive CD 117 and Dog 1 confirming the diagnosis of EGISTs.DiscussionGIST is a rare mesenchymal tumor. EGISTs arising in the pancreas are extremely rare, about, 5% of EGISTs. Its origin remains controversial. Some authors believe that GISTs and EGISTs arise from the common cell origin of interstitial cells of Cajal. Others suggest that EGISTs are at the beginning, mural GISTs with extensive extramural growth, resulting in later on, loss of their connection with the GIT wall.ConclusionWe report a rare case of large pancreatic tail EGIST, which was resected, safely and effectively by laparoscopic approach.     

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。     

Extragastrointestinal stromal tumour of the lesser omentum: A case report and literature review

IntroductionExtragastrointestinal stromal tumours (EGISTs) are very uncommon compared to their gastrointestinal counterparts. Most of them originate from the intestinal mesentery and the omentum.Case reportA 70 year-old Caucasian woman presented with a bulky abdominal mass which on laparotomy was found to originate from the lesser omentum and was completely resected. Histological examination revealed spindle cells with severe pleomorphism and high mitotic activity. Immunohistochemically, the tumour cells showed strong positivity for c-kit (CD117), DOG-1 and human haematopoietic progenitor cell antigen (CD34). An exon 11 deleterious mutation was identified and thus regular dosing of 400 mg imatinib mesylate was initiated.DiscussionThere have been only a few previous reports of EGISTs arising in the lesser omentum. Although EGISTs seem to have morphological and immunohistochemical similarities with GISTs, their pathogenesis, incidence, genetic background and prognosis are not completely known because they are extremely rare. It is strongly believed that such tumours originate from cells, which have similar pathological characteristics and biological behaviour as the intestinal cells of Cajal. In most series of EGISTs, a female predominance, a greater size and a higher mitotic index than GISTs were observed.ConclusionEGISTs are very rare mesenchymal tumours which originate from cells outside the gastrointestinal tract and tend to have a more aggressive biological behaviour than their GI counterparts. Complete surgical resection is the most effective treatment associated with the use of imatinib in the presence of adverse prognostic factors. In any case a strict follow-up is necessary due to high recurrence rates.     

"Seedling" mesenchymal tumors (gastrointestinal stromal tumors and leiomyomas) are common incidental tumors of the esophagogastric junction

Gastrointestinal stromal tumors (GISTs) are the most common nonepithelial neoplasm of the gastrointestinal tract and show a predilection for the stomach. Most are detected because of symptoms, but some are incidental findings at autopsy or surgery for other reasons. Incidental GISTs tend to be smaller at diagnosis, but even small (<1 cm) GISTs have been shown to harbor activating KIT mutations at rates similar to advanced GISTs. However, the prevalence and characteristics of small GISTs in surgical resections of the esophagogastric junction (EGJ) remains unclear. We studied 150 esophagogastric resections for esophageal or EGJ carcinomas (100 with preoperative chemoradiation and 50 untreated cases) that had been extensively embedded for histologic examination (mean 30 sections/case). Number, size, morphology, and location of all GISTs and leiomyomas were recorded. All potential GISTs were evaluated with CD117 and CD34 immunohistochemistry, and a subset (35) leiomyomas with smooth muscle actin, desmin, and CD117. We found 18 incidental GISTs in 15 of 150 (10%) patients; 3 patients harbored 2 separate lesions. Prevalence of GIST was identical in treated (10 of 100) and untreated (5 of 50) cases. All (100%) showed positivity for both CD117 and CD34 and all were of spindle cell morphology. Lesions ranged from 0.2 to 3.0 mm in size (mean 1.3 mm). Eight (44%) were based in the outer muscularis propria, 7 (39%) in inner muscularis, and 3 (17%) between the muscle layers. The lesions tended to cluster near the EGJ, with 8 (44%) on the gastric side, 9 (50%) on the esophageal side, and 1 (6%) undetermined owing to overlying ulceration. Leiomyomas were even more common than GIST, occurring in 47% of patients (44% of treated and 52% of untreated, P=0.39), with a mean of 3 leiomyomas per patient (range 1 to 13) and mean size of 1.7 mm (range 0.2 to 12 mm). Unlike colorectal leiomyomas, most (91%) EGJ leiomyomas were located in the inner muscularis propria and only rarely (1%) in muscularis mucosa. These results suggest that GIST and leiomyoma are common incidental "seedling" lesions of the EGJ, found in 10% and 47% of patients undergoing surgery for esophageal carcinoma. The common occurrence of microscopic GISTs compared with the rarity of clinically manifest and malignant esophagogastric GISTs suggests that additional genetic or epigenetic alterations must happen for neoplastic progression.     

胃肠道外间质瘤7例临床分析

目的探讨胃肠道外间质瘤(EGISTs)的临床特征、诊断及治疗。方法回顾性分析1999年9月~2004年12月我院收治的EGISTs的临床病理资料。结果发生于小肠系膜2例、腹膜后5例,表现为腹部肿块7例(100%)、腹部不适3例(42.9%)、体重减轻3例(42.9%)。免疫组化检查:CD117、CD34、Vimentin阳性率分别为100%(7/7)、57.1%(4/7)、100%(7/7)。手术切除6例,活检术1例。1、3、4年生存率分别为85.7%(6/7)、42.9%(3/7)、14.3%(1/7),1例复发后服格列卫获得部分缓解。结论EGISTs少见,预后差,完整的外科手术切除是最有效的治疗方法,格列卫是有效的靶向治疗药物。     

KIT-negative gastrointestinal stromal tumors: proof of concept and therapeutic implications

The diagnosis of gastrointestinal stromal tumor (GIST) is currently based on morphologic features and immunohistochemical demonstration of KIT (CD117). However, some tumors (in our estimation approximately 4%) have clinicopathologic features of GIST but do not express KIT. To determine if these lesions are truly GISTs, we evaluated 25 tumors with clinical and histologic features typical of GIST, but with negative KIT immunohistochemistry, for KIT and PDGFRA mutations using DNA extracted from paraffin-embedded tissue. Most tumors originated in the stomach (N = 14) or omentum/mesentery (N = 5). The neoplasms were composed of epithelioid cells (13 cases), admixed epithelioid and spindle cells (8 cases), or spindle cells (4 cases). Absence of KIT expression was confirmed by immunoblotting in 5 cases. Tumor karyotypes performed in 4 cases were noncomplex with monosomy 14 or 14q deletion, typical of GIST. Mutational analysis revealed PDGFRA and KIT mutations in 18 and 4 tumors, respectively, whereas 3 tumors did not have apparent KIT or PDGFRA mutations. The PDGFRA mutations primarily involved exon 18 (N = 15) and included 11 tumors with missense mutation in codon 842 (PDGFRA D842V or D842Y). In conclusion, a small subset of GISTs with otherwise typical clinicopathologic and cytogenetic features do not express detectable KIT protein. When compared with KIT-positive GISTs, these KIT-negative GISTs are more likely to have epithelioid cell morphology, contain PDGFRA oncogenic mutations, and arise in the omentum/peritoneal surface. Notably, some KIT-negative GISTs contain imatinib-sensitive KIT or PDGFRA mutations; therefore, patients with KIT-negative GISTs should not, a priori, be denied imatinib therapy.     

Accurate pathological staging of urothelial neoplasms requires better cystoscopic sampling

PURPOSE: The frequency with which muscularis propria was sampled by urologists and the sources of interpretive discrepancies among pathologists were studied in a community practice setting. MATERIALS AND METHODS: A total of 217 consecutive cases of urothelial neoplasm were independently reviewed by 3 pathologists. The presence or absence of muscularis propria as well as interpretive discrepancies were recorded. RESULTS: Despite clinical emphasis on accurate pathological staging portions of muscularis propria were absent from samples of histologically documented urothelial neoplasms in up to 51% of cases. Failure to obtain muscularis propria varied widely among urologists but was most often associated with cases of low grade papillary neoplasms, in which invasion is less likely. Muscularis propria was usually present in cases of noninvasive carcinoma in situ but this may have represented inadvertent sampling of structures in close proximity. The incidence of interpretive discrepancies among pathologists who are required to assess the status of muscularis propria was significant (24%). Almost all problems were related to artifacts and most may have been avoided if careful attention had been given to specimen sampling and processing. CONCLUSIONS: The well documented tendency toward cystoscopic under staging has not necessarily resulted in a high incidence of muscularis propria in bladder cases of urothelial neoplasms. Even when muscle may have been sampled, artifacts that were often due to thermocoagulation hampered accurate pathological staging.     

Congenital interstitial cell of cajal hyperplasia with neuronal intestinal dysplasia

Interstitial cells of Cajal (ICCs) are intestinal pacemaker cells that initiate peristalsis in the stomach and intestine, and are considered to be precursors of gastrointestinal stromal tumors (GISTs). We report a 2-year-old girl who suffered from scanty stool passage since birth. On barium enema, the distal colon was rigid with narrow lumen, whereas the proximal colon was dilated and atonic. She received right hemicolectomy and ileostomy. Histopathologically, there was continuous proliferation of spindle cells located between the layers of the muscularis propria throughout the right colon. These spindle cells were positive for c-kit and CD34 but negative for myogenic or neurogenic markers, indicating they are ICCs. No germline or somatic mutation of the juxtamembrane domain of c-kit gene was detected. In addition, the changes of the submucosal plexus fulfilled the histologic criteria of neuronal intestinal dysplasia type B. To our knowledge, this is the first reported case of congenital ICC hyperplasia. Further studies of ICC development may contribute to better understanding of the pathogenesis of this congenital malformation and the tumorigenesis of GIST.     

Bladder cancer: Analysis of the 2004 WHO classification in conjunction with pathological and geographic variables

ObjectivesBladder cancer (BCA) is a worldwide disease and shows a wide range of geographical variation. The aim of this study is to analyze the prevalence of schistosomal and non-schistosomal associated BCA as well as compare our findings with the 2004 WHO consensus classification of urothelial neoplasms and with other publications.Patients and methodsThe archival materials of 180 urinary bladder specimens were collected from Department of Pathology, King Abdul-Aziz University Hospital (KAUH), Jeddah, Western region, Saudi Arabia. The regional prevalence of this cancer was identified and studied, and a comparison between schistosomal and non-schistosomal associated BCA was made. Additionally, the study revised and classified these neoplasms according to the most recent 2004 WHO classification of urothelial neoplasms. The type of mural invasion either muscularis mucosae (MM) or muscularis propria (MP), other associated lesions as carcinoma in situ (CIS) as well as, metaplasia and schistosomal infestation were assessed.ResultsUrothelial cell neoplasms (UCN) comprised 161 cases (89.4%), squamous cell carcinoma (SCC) represented 12 cases (6.7%), adenocarcinoma 5 cases (2.8%), and sarcomatoid carcinoma detected in 2 cases (1.1%). Among all these cases schistosomal associated BCA represented 13 cases (7.2%), while the remaining 167 cases (92.8%) were non-schistosomal associated BCA. In the former category, 11 cases (6.1%) were squamous cell carcinoma and 2 (1.1%) urothelial cell carcinoma (UCC) whereas, non-schistosomal associated cancer that included UCN, SCC, adenocarcinoma, and sarcomatoid carcinoma found in 159, one case, 5, and 2 cases. Invasion of muscularis propria was detected in 30 cases (16.7%) and muscularis mucosae invasion in 45 cases (25%).ConclusionAccording to WHO classification of urothelial neoplasms accurate categorization of BCA is very important for both diagnostic and therapeutic values.     

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.     

Gastrointestinal stromal tumors (GIST) of the stomach as a cause of upper gastrointestinal bleeding

Gastrointestinal stromal tumors (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. GIST is currently defined as a gastrointestinal tract mesenchymal tumor containing spindle cells (less commonly epitheloid cells or rarely both) and showing CD 117 (c-kit protein) positivity in more than 95% of cases. Although they may arise throughout the gut, the commonest site are stomach (60-70%), small intestine (20-30%), colorectum (5%) and esophagus (up to 5%). Rarely, GISTs develop in the retroperitoneum, omentum or mesentery. GIST originates from the intestinal cell of Cajal (ICC). ICCs are located in and around the myenteric plexus and are thought to function as intestinal pacemaker cells. Historicaly, GIST were often misclassified as leiomyomas or leiomyosarcomas. Subsequently, it has been determined that GISTs have distinct ultrastructural features and immunophenotypical markers compared with smooth muscle and smooth muscle tumors. GIST predominantly occur in middle aged and older patients, with no significant difference in the sex incidence. Data from the recent population study suggest an incidence of about 10-22 cases per million persons per year. Clinical presentation of GIST varies widely, and depends on tumor size and location. GISTs that caused symptoms tended to be larger with an average size of 6cm versus 2cm for asymptomatic GISTs. Symptoms are most commonly related to mass effect or bleeding. GISTs can grow very large before producing symptoms. Commonest symptom of gastric GIST is manifest or occult bleeding. Abudant, life-threateting bleeding that require urgent surgery is rare. For patient with primary, localized, nonmetastatic GIST, complete surgical resection represents the only chance for cure. Lymhadenectomy is not necessary, because lymph node metastasis is very rare. The 5 year survival rate in patients with resected primary GISTs ranges from 48-65%. Conventional chemotherapy and radiation therapy is ineffective in the treatment of GIST. Imatinib mesilate (a tyrosine kinase inhibitor) was confirmed to be effective against metastatic or unresectable GISTs.     

Expression of androgen and oestrogen receptors and its prognostic significance in urothelial neoplasm of the urinary bladder

What's known on the subject? and What does the study add? Steroid hormone receptor signals have been implicated in bladder tumourigenesis and tumour progression. The expression of androgen and/or oestrogen receptors has been assessed in bladder cancer, leading to conflicting data of expression levels and their relationship to histopathological characteristics of the tumours. We simultaneously analyze three receptors in non‐neoplastic bladder tissues as well as in primary and metastatic bladder tumour specimens. Our data demonstrate that the expression status correlates with tumour grades/stages and patients’ outcomes.

OBJECTIVE

• ? To assess the expression of the androgen receptor (AR) and oestrogen receptors (ERs) in bladder tumours because recent studies have shown conflicting results and the prognostic significance of their expression remains unclear.

PATIENTS AND METHODS

• ? We investigated the expression of AR, ERα and ERβ in 188 bladder tumour specimens, as well as matched 141 non‐neoplastic bladder and 14 lymph node metastasis tissues, by immunohistochemistry.
• ? We then evaluated the relationships between their expression and the clinicopathological features available for the present patient cohort.

RESULTS

• ? AR/ERα/ERβ was positive in 80%/50%/89% of benign urothelium, 50%/67%/41% of benign stroma, 42%/27%/49% of primary tumours and 71%/64%/71% of metastatic tumours.
• ? Significantly lower expression of AR/ERα was found in high‐grade tumours (36%/23%) and tumours invading muscularis propria (33%/19%) compared to low‐grade tumours (55%; P= 0.0232/38%; P= 0.0483) and tumours not invading muscularis propria (51%; P= 0.0181/35%; P= 0.0139), respectively.
• ? Significantly higher expression of ERβ was found in high‐grade tumours (58%) and tumours invading muscularis propria (67%) compared to low‐grade tumours (29%; P= 0.0002) and tumours not invading muscularis propria (34%; P < 0.0001), respectively.
• ? Kaplan–Meier and log‐rank tests further showed that positivity of ERβ (but not AR or ERα) was associated with the recurrence of low‐grade tumours (P= 0.0072); the progression of low‐grade tumours (P= 0.0005), high‐grade tumours not invading muscularis propria (P= 0.0020) and tumours invading muscularis propria (P= 0.0010); or disease‐specific mortality in patients with tumours invading muscularis propria (P= 0.0073).

CONCLUSIONS

• ? Compared to benign bladders, a significant decrease in the expression of AR, ERα or ERβ in bladder cancer was seen.
• ? Loss of AR or ERα was strongly associated with higher grade/more invasive tumours, whereas ERβ expression was increased in high‐grade/invasive tumours and predicted a worse prognosis.

     

Intravesical adipose tissue: a quantitative study of its presence and location with implications for therapy and prognosis

Accurate pathologic staging of carcinomas of the urinary bladder involves assessment of invasion by the tumor into the bladder wall and beyond into perivesical soft tissue. The presence of tumor within perivesical soft tissue implies pathologic stage pT3 (AJCC/UICC system, 1997). In traditional textbooks of histology, anatomy, pathology, and in the literature, other than a single case report and a brief reference in another paper, there is no information on the presence of adipose tissue in the lamina propria or muscularis propria of the urinary bladder. Nine hundred forty-three sections from 139 cystectomy specimens were evaluated for the presence, location, and quantity of adipose tissue within the lamina propria and muscularis propria. The histology of the perivesical soft tissues and the nature of its delineation from muscularis propria were also analyzed. Adipose tissue was seen within the lamina propria in 53% (74 of 139) of cystectomies and in 17.6% (166 of 943) of the examined sections. It was located predominantly in the deep lamina propria (at or below the muscularis mucosae) in 81.1% (60 of 74) of the cystectomies and in 91% (151 of 166) of the sections. Within the lamina propria it was predominantly seen as small localized aggregates in 92% (153 of 166) of sections. All cases showed adipose tissue within the muscularis propria. Adipose tissue was identified within the superficial (inner) muscularis propria in 54% (512 of 943) of sections and was predominantly in small aggregates in 80.5% (412 of 512) of sections. It was in moderate to abundant quantities within the deep (outer) muscularis propria in 60.7% (572 of 943) of sections. The perivesical soft tissue was almost exclusively composed of adipose tissue with variable vascularity. Delineation of the perivesical adipose tissue from the deep (outer) muscularis propria was typically indistinct because muscle bundles of the latter haphazardly merged with the perivesical adipose tissue. Based on these findings, we conclude that adipose tissue is frequently present in the lamina propria and muscularis propria of the urinary bladder wall, and is usually scant in the former location and frequently abundant in the latter. Awareness of the high frequency of adipose tissue within the urinary bladder wall has prognostic and therapeutic implications. In transurethral resection of bladder tumor (TURBT) specimens, misinterpretation of tumor infiltrating adipose tissue within lamina propria (pT1) as perivesical soft tissue involvement (pT3) may potentially result in unwarranted aggressive management. Substaging of muscle invasive tumors should be performed in cystectomy specimens only, because the junction of muscularis propria and the perivesical adipose tissue is typically ill-defined. Muscularis propria adipose tissue in TURBT specimens may be erroneously assumed to be perivesical adipose tissue, potentially leading to overstaging of the primary tumor.     

Microscopic gastrointestinal stromal tumors in esophageal and intestinal surgical resection specimens: a clinicopathologic, immunohistochemical, and molecular study of 19 lesions

Microscopic gastrointestinal stromal tumors (GISTs) (synonyms: sporadic interstitial cell of Cajal hyperplasia, seedling GISTs, minimal GISTs) are common incidental findings in gastroesophageal resections (9% to 35%). To our knowledge, their frequency, clinicopathologic features, and molecular pathogenesis from nongastroesophageal sites have so far not been sufficiently analyzed. We studied 19 lesions from distal esophagus (n=8), gastroesophageal junction (n=2), sigmoid colon (n=5), and vermiform appendix, cecum, rectum, and small intestine (1 each). Microscopic GISTs were detected in 0.2%, 0.1%, and 0.01% of routinely processed resection specimens from sigmoid colon, vermiform appendix, and rectum, respectively. Patients were 11 men and 8 women with a mean age of 66 years (range, 57 to 86 y). Thirteen patients had GI cancers and 5 had diverticular disease. None has a family history of GIST or features of neurofibromatosis 1. Lesions were 0.5 to 4 mm in size (mean, 1.12 mm), were all spindled and had noncircumscribed infiltrating borders. All arose in the muscularis propria and 2 were predominantly subserosal. Immunohistochemistry revealed a CD117/CD34/smooth muscle actin-negative phenotype in 18/19 lesions. Three KIT exon 11 mutations (2 point mutations and 1 deletion, all involving W557) were detected in 3/12 lesions with successful molecular analysis. In conclusion, incidental microscopic GISTs are uncommon in intestinal resections (< or =0.1%), contrasting with their gastroesophageal counterparts (> or =9%). Somatic KIT mutations are early initiating molecular events in a subset of them. The remarkable variation in the incidence of microscopic GISTs at different GI sites suggests an origin from heterogeneous subsets of interstitial cells of Cajal with varying potentials for neoplastic transformation.     

Lamina muscularis propria thickness of renal pelvis predicts radiological outcome of surgical correction of ureteropelvic junction obstruction

PURPOSE: We examine if there is a relationship between the histopathology of the renal pelvis and postoperative radiological findings in children with ureteropelvic junction obstruction. MATERIALS AND METHODS: The records of 220 patients who underwent pyeloplasty for isolated ureteropelvic junction obstruction between 1988 and 1996 were retrospectively reviewed, and 41 (42 kidneys) were identified who had adequate histological specimens and postoperative radiographic studies (ultrasonography and/or well tempered renogram) for examination. Histological features of the lamina muscularis propria from the renal pelvis were correlated with the radiographic outcome after pyeloplasty. RESULTS: Lamina muscularis propria thickness of the renal pelvis correlated significantly with radiological improvement. All kidneys with renal pelvic lamina muscularis propria thickness less than 250 microm. showed radiological improvement at 3 to 6 months postoperatively, those with thickness between 250 and 350 microm. had improvement at 9 months and those with lamina thickness greater than 350 microm. had a significantly worse outcome at all observation points. At 3 and 6 months postoperatively 16 of 30 (53%) and 23 of 34 (68%) children with radiological improvement had a mean lamina muscularis propria thickness of 252 +/- 131.5 microm. and 263 +/- 122.8 microm., respectively, while the remaining unimproved 14 and 12 patients had a mean thickness of 374 +/- 64.3 microm. (p <0.01) 372 +/- 66.1 microm. (p <0.05), respectively. CONCLUSIONS: The lamina muscularis propria thickness of the renal pelvic wall can provide insight to the expected time of postoperative improvement on radiological studies in children with ureteropelvic junction obstruction.     

Carcinosarcoma of the bladder: case report and review of the literature

Primary osteosarcomas of the bladder account for about 0.04% of bladder neoplasms. Most of the patients in the literature expired within 6 months and, in almost all of the cases in the literature, radical cystectomy with postoperative chemotherapy was the treatment choice. A 79-year-old gentleman presented with gross hematuria. Cystoscopy demonstrated a 2- to 3-cm tumour along the lateral wall of the bladder. The tumour was resected incompletely via initial transurethral resection of bladder tumour (TURBT), and a second TURBT was subsequently performed to fully resect the residual mass. Surgical pathology from these 2 resections revealed osteosarcoma with invasion into the muscularis propria. A cystoprostatectomy was performed and final pathologic specimen revealed high-grade CIS without evidence of residual osteosarcoma. Postoperatively, the patient did not receive chemotherapy or radiation and currently remains disease-free 2 years post-radical cystectomy. Only 33 well-documented cases of primary osteosarcoma of the bladder have been reported to date. However, there are only 3 cases in which TURBT resulted in complete resection.     

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.     

Secondary recurrent multiple EGIST of the mesentary: A case report and review of the literature

INTRODUCTIONGastrointestinal stromal tumors (GISTs) are rare intra-abdominal tumors arising from mesenchymal stromal cells. EGISTs are mesenchymal tumors that originate outside the GI tract and tend to have similar characteristics to GISTs. To the best of our knowledge, few cases of long standing recurrent EGIST have been reported.PRESENTATION OF CASEWe present the case of a rare recurrent EGIST in the mesentery of a 39 year old female patient. The tumor was symptomatic at the time of complaint and measured 8.4 cm × 7.7 cm × 7.6 cm. Histological analysis revealed a spindled pattern with fusiform cells arranged in long fascicles and little atypia. Immunochemistry showed positivity for CD117 and was negative for CD34, S-100, Desmin, and MSA. B-catenin was weakly positive. A Ki-67 staining shows approximately 5% positivity revealing a low proliferative rate. The patient was doing well postoperatively and was discharged on 400 mg imanitib regimen.DISCUSSIONWhile GISTs are the most common tumors of the GI tract, recurrent EGISTs of the mesentery are extremely rare. Factors that indicate poor prognosis include tumor size greater than 5 cm, mitotic rate greater than 1–5/10 HPF, presence of tumor necrosis or metastasis and most recently the c-kit mutation. Our patient had a very long time between recurrence of disease.CONCLUSIONThe current literature on EGISTs is limited. Our patient presents a very interesting case due to the time elapsed between disease recurrence and lack of metastasis or excessive growth.     

KIT-negative gastrointestinal stromal tumor of the abdominal soft tissue: a clinicopathologic and genetic study of 10 cases

Gastrointestinal stromal tumor (GIST) typically occurs in the gastrointestinal (GI) tract, and expresses KIT protein that is associated with KIT or platelet-derived growth factor receptor-α (PDGFRA) gene mutation. Extragastrointestinal stromal tumors (EGISTs) are a minor subset of GIST that occurs in the soft tissue outside the GI tract, and in very rare cases, these tumors can be KIT negative. We examined the clinicopathologic and molecular characteristics of 10 cases of KIT-negative EGIST by using immunohistochemical staining and gene mutation analysis. The tumors occurred in the omentum (n=5), mesentery (n=2), retroperitoneum (n=1), pelvic cavity (n=1), and not otherwise specified regions of the abdominal cavity (n=1). They ranged from 4 to 33 cm (median, 15 cm) in maximum diameter with relatively low mitotic counts (median, 3.5 per 50 high-power fields). Morphologically, most cases were of epithelioid cell (n=9) or mixed epithelioid and spindle cell (n=1) type, accompanied by variable amounts of myxoid stroma. By immunohistochemical staining, the tumors were positive for CD34 (80%), protein kinase C (PKC) θ (90%), and discovered on GIST-1 (DOG1) (90%), but were negative for KIT (0%). The majority of the examined cases (7 of 9 cases; 78%) had PDGFRA mutations in exon 12 (n=1) or exon 18 (n=6). One case (11%) had a mutation in KIT exon 11, and the remaining 1 had no mutation in either KIT or PDGFRA. Distant metastasis and local recurrence occurred in 1 (10%) and 2 (20%) patients, respectively, and adverse outcome was correlated with larger (>10 cm) tumor size and high mitotic counts (>5/50 high-power fields). Therefore, KIT-negative EGISTs can be characterized by preferential omental origin, epithelioid cell type, low mitotic activity, and mutation of the PDGFRA gene, and these features are similar to those of KIT-negative gastric GISTs. As KIT-negative EGISTs should be considered to be a potential abdominal soft tissue neoplasm, immunohistochemical staining panel and molecular analysis are necessary not only to confirm the diagnosis but also to determine the therapeutic strategy.