Spindle cell tumor of urinary bladder serosa with phenotypic and genotypic features of gastrointestinal stromal tumor

Most mesenchymal tumors of the gastrointestinal tract are now referred to as gastrointestinal stromal tumors (GISTs). The tumors differ from ordinary leiomyomas and schwannomas in several respects: the GISTs typically express c-kit protein (CD117) and CD34, 30% to 50% of them are (often focally) positive for alpha-smooth muscle actin, and all are negative for desmin and S100 protein. Recently, mutations in the exon 11 of the c-kit gene have been identified and confirmed as a molecular genetic marker for the subset of GISTs. In this report, we describe a mesenchymal tumor removed from the pelvic cavity of a 52-year-old woman, who is alive without disease 36 months after the surgery. The 5-cm tumor was densely attached to the external aspect of the urinary bladder but was attached to small intestine by only filmy adhesions. The tumor grossly resembled a leiomyoma and was histologically composed of sheets of spindle cells with a dense collagenous background. The mitotic activity was low, less then 1 per 50 high-power fields. Immunohistochemically, the tumor cells were negative for alpha-smooth muscle actin and desmin and positive for CD117 and CD34. Molecular genetic analysis of the exon 11 of the c-kit gene revealed a point mutation in the region commonly mutated in GISTs. This mutation substituted T for A in the codon 557, leading to the change of amino acid sequence (tryptophan for arginine) of the KIT protein. This case illustrates that tumors phenotypically and genotypically similar to GISTs may present in sites other than the tubular gastrointestinal tract.     

Gastrointestinal stromal tumors – definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal (GI) tract. They are defined here as KIT (CD117, stem cell factor receptor)-positive mesenchymal spindle cell or epithelioid neoplasms primary in the GI tract, omentum, and mesentery. GISTs typically present in older individuals and are most common in the stomach (60-70%), followed by small intestine (20-25%), colon and rectum (5%), and esophagus (<5%). Benign tumors outnumber the malignant ones by a wide margin. Approximately 70% of GISTs are positive for CD34, 20-30% are positive for smooth muscle actin (SMA), 10% are positive for S100 protein and <5% are positive for desmin. The expression of CD34 and SMA is often reciprocal. GISTs commonly have activating mutations in exon 11 (or rarely exon 9 and exon 13) of the KIT gene that encodes a tyrosine kinase receptor for the growth factor named stem cell factor or mast cell growth factor. Ligand-independent activation of KIT appears to be a strong candidate for molecular pathogenesis of GISTs, and it may be a target for future treatment for such tumors. Other genetic changes in GISTs discovered using comparative genomic hybridization include losses in 14q and 22q in both benign and malignant GISTs and occurrence in various gains predominantly in malignant GISTs. GISTs have phenotypic similarities with the interstitial cells of Cajal and, therefore, a histogenetic origin from these cells has been suggested. An alternative possibility, origin of pluripotential stem cells, is also possible; this is supported by the same origin of Cajal cells and smooth muscle and by the common SMA expression in GISTs. GISTs differ clinically and pathogenetically from true leiomyosarcomas (very rare in the GI tract) and leiomyomas. The latter occur in the GI tract, predominantly in the esophagus (intramural tumors) and the colon and rectum (muscularis mucosae tumors). They also differ from schwannomas that are benign S100-positive spindle cell tumors usually presenting in the stomach. GI autonomic nerve tumors (GANTs) are probably a subset of GIST. Other mesenchymal tumors that have to be separated from GISTs include inflammatory myofibroblastic tumors in children, desmoid, and dedifferentiated liposarcoma. Angiosarcomas and metastatic melanomas, both of which are often KIT-positive, should not be confused with GISTs.     

Mutations in Exon 11 of c-Kit Occur Preferentially in Malignant versus Benign Gastrointestinal Stromal Tumors and Do Not Occur in Leiomyomas or Leiomyosarcomas

Gastrointestinal stromal tumors (GISTs) comprise the largest subset of mesenchymal tumors of the gastrointestinal tract. These neoplasms differ histologically and immunohistochemically from typical leiomyomas and leiomyosarcomas. Most GISTs express CD34 and CD117 (c-kit protein) but not desmin. Recently, gain-of-function mutations of c-kit proto-oncogene have been shown in five solitary GISTs and in tumors and leukocytes from a family with multiple GISTs. An in-frame deletion or a point mutation in exon 11 of c-kit was detected in these cases. Stable transfection of the mutant c-kit complementary DNA was also shown to induce malignant transformation of murine lymphoid cells, suggesting that the c-kit mutations contribute to tumor development. In this study, we evaluated 43 GISTs and 14 smooth muscle tumors for mutations in the exon 11 of c-kit by a PCR-assay. Half of the malignant GISTs (12/24) and only one benign GIST (1/19) revealed mutant bands. No mutant bands were found in 3 leiomyomas and 11 leiomyosarcomas. Sequence analysis confirmed the presence of an in-frame deletion of 3–21 bp in all 13 GISTs with mutant bands. Wild-type bands from 8 malignant and 11 benign GISTs and 7 smooth muscle tumors without mutant bands were cloned and sequenced. Additional mutations were found in 3 malignant and 2 benign GISTs. There were no mutations in 3 leiomyomas and 4 leiomyosarcomas. The mutation status of exon 11 did not correlate with immunohistochemically detectable expression of the CD117, as virtually all GISTs with or without such mutations showed CD117 immunoreactivity. The c-kit mutations occur preferentially in malignant GISTs and might be a clinically useful adjunct marker in the evaluation of GISTs. The conservation of the c-kit mutation pattern, observed in consecutive lesions from the same patients, suggests that these mutations might be useful tumor markers in monitoring recurrence or minimal residual disease.     

Extragastrointestinal stromal tumor of the urinary wall bladder: case report and review of the literature

Most mesenchymal tumours of the gastrointestinal tract are now referred to as gastrointestinal stromal tumours (GISTs). These tumours typically express c-kit (CD117) and CD34; 30-50% are (often focally) positive for alpha-smooth muscle actin, and all are negative for desmin and S100 protein. Recently, mutations in exon 11 of the c-kit gene have been identified as a molecular genetic marker for the subset of GISTs. In this report, we describe a mesenchymal tumour removed from the pelvic cavity of a 34-year-old man. The tumour was strongly attached to the external wall of the urinary bladder. The neoplasm grossly resembled a leiomyoma, and was histologically composed of sheets of spindle cells with a dense collagenous background. The mitotic activity was low (less then 1 per 50 high-power fields). Immunohistochemically, tumour cells were negative for alpha-smooth muscle actin and desmin and positive for CD117 and CD34. This case illustrates that tumours which are phenotypically and genotypically similar to GISTs may present in sites other than the tubular gastrointestinal tract.     

Expression of microtubule-associated protein tau by gastrointestinal stromal tumors.

The purpose of this work was to study the expression in gastrointestinal stromal tumors (GISTs) of various antigens, including the protein tau associated with enteric neuronal differentiation; to compare their expression with that of c-kit, known to be associated with interstitial cell of Cajal differentiation; and to correlate their expression with the observation of ultrastructural features of gastrointestinal autonomic nerve tumors. Twenty-six GISTs of the stomach and 16 GISTs of the small bowel were included in the study group. Thirty-five tumors served as controls. Tissue sections were immunostained with vimentin, CD34, desmin, specific smooth muscle actin, S100 protein, neuron-specific enolase, PGP9.5, neurofilament, bcl-2 oncoprotein, synaptophysin, chromogranin A, c-kit, and tau. Twenty-one of these tumors were also analyzed ultrastructurally. Of the 42 GISTs, 28 were predominantly spindled, 7 were predominantly epithelioid, and 7 were a mixture of epithelioid and spindle cells. Ten primary GISTs were classified as benign, 9 as borderline, and 23 as malignant. Metastatic dissemination was present at primary surgery in 1 case and eventually developed in 6 patients. Six disease-related deaths were counted. In normal submucous and myenteric plexuses of stomach and small bowel, ganglion cell bodies and nerve fibers strongly expressed tau. Twenty (76.9%) GISTs of the stomach and 12 (75%) of the small bowel expressed tau. Tau often showed intense, diffuse staining patterns in both spindled and epithelioid tumors. Ten (100%) of the 10 benign GISTs, 7 (77.8%) of the borderline GISTs, and 15 (65.2%) of the 23 frankly malignant GISTs expressed tau. Thirty-six GISTs expressed at least 2 different neuronal markers. A coexpression of the neuronal markers and c-kit was observed in 90% of GISTs. The expression of tau was observed in 12 of the 15 GISTs with dense core granules, considered as the definitive finding for a diagnosis of gastrointestinal autonomic nerve tumors. Ten of these also expressed c-kit; 9 were malignant. Tau also immunostained other intra-abdominal tumors, including neuroendocrine carcinomas, paragangliomas and desmoplastic round cell tumors. This immunohistochemical study shows that GISTs are specific tumors of the digestive tract and are nearly always characterized by simultaneous neuronal and interstitial cell of Cajal differentiation. Although the loss of tau expression is observed only in borderline and malignant tumors, its prognostic value is not clear cut.     

Malignant stromal tumor, so called "gastrointestinal stromal tumor", with rhabdomyomatous differentiation occurring in the gallbladder

Gastrointestinal stromal tumors (GISTs) constitute the largest category of primary nonepithelial neoplasms of the gastrointestinal tract. It is extremely rare that this tumor occurs in the bile tract, and only a few cases have been reported. Immunohistochemically, the tumor cells revealed a phenotype similar to Cajal cells, occasionally with differentiation to smooth muscle cells or neural cells. We present a case of malignant stromal tumor similar to GISTs with rhabdomyomatous differentiation of the gallbladder in a 68-year-old woman. The resected tumor was predominantly composed of spindle cells with rhabdomyomatous differentiation. Immunohistochemical study revealed diffuse staining of tumor cells using vimentin despite negative staining for desmin or S-100. This indicated a mesenchymal origin of the cells without smooth muscle or neuronal differentiation. Myoglobin-positive cells, in which phosphotungstic acid hematoxylin staining revealed cross striations of the cytoplasm, suggested rhabdomyomatous differentiation. Diffuse positivity for KIT in the cells suggested that the pathogenesis of this tumor may resemble that of GIST. The tumor may have derived from a mesenchymal stem cell that had undergone partial rhabdomyomatous differentiation.     

胃肠间质肿瘤免疫组化及细胞增殖活性研究

研究胃肠间质肿瘤的组织起源,分化以及细胞增殖。方法：应用ＬＳＡＢ法观察ＣＤ３４系系列标记物在２８例ＧＩＳＴｓ中的表达。结果：ＧＩＳＴｓ中ＣＤ３４和Ｖｉｍ的阳性率达８８．５％和９４％,且阳性程度强;肌源性和神经源性标记在部分阳性且相对偏弱;ＣＤ３４和ＰＣＮＡ在良恶性ＧＩＳＴｓ中表达无差异,Ｋｉ６７有一定区别。     

Gastrointestinal spindle cell tumours of the dog: histological and immunohistochemical study

To assess the relevance of spindle cell tumours in the canine gastrointestinal (GI) tract and to classify them, a retrospective study was carried out on haematoxylin and eosin-stained sections from formalin-fixed paraffin wax-embedded samples of 105 primary GI tumours. Seventeen out of 105 (16%) GI tumours were mesenchymal, 48% were epithelial and 36% were round cell tumours. Spindle cell tumours were stained by Masson trichrome, Orcein-Van Gieson and labelled immunohistochemically (vimentin, desmin, smooth muscle actin, protein S100, glial fibrillar acid protein, CD117 and MIB-1) and the histological grade, mitotic index, nuclear size and cellular density were also assessed. The 17 gastrointestinal mesenchymal tumours were classified as 10 leiomyomas (10/10 positive for desmin and smooth muscle actin; 6/10 positive for vimentin) 2 leiomyosarcomas (2/2 positive for desmin, smooth muscle actin and vimentin) and 5 gastrointestinal stromal tumours (GISTs) (5/5 positive for CD117 and vimentin; 3/5 positive for smooth muscle actin). Canine GISTs appeared as densely packed spindle cell tumours, with a diffuse, strong, cytoplasmic immunopositivity for c-kit protein (CD117). GISTs, defined as CD117-positive spindle cell or epithelioid or pleomorphic neoplasms that presumably derive from interstitial cells of Cajal, are reported in recent medical studies as the most common mesenchymal tumours of the GI tract. Our data suggest that GISTs represent a significant portion of canine GI spindle cell tumours, which can be definitely distinguished from leiomyosarcomas only by their expression of CD117.     

L1 (CD171) is highly expressed in gastrointestinal stromal tumors.

The treatment strategy for mesenchymal tumors of the gastrointestinal tract is based upon typing of the tumor. Especially differential diagnosis of gastrointestinal stromal tumors (GISTs) to leiomyomas is crucial for determining radicality of surgery. L1 cell adhesion molecule (CD171) plays an essential role in tumor progression. The aim of this study was to determine expression of L1 in GISTs, smooth muscle tumors, desmoid-type fibromatosis and peripheral nerve sheath tumors (PNSTs). We retrospectively analyzed a total of 129 surgically resected primary tumors or metastases of 72 GISTs, 29 smooth muscle tumors, seven PNSTs and 21 desmoid-type fibromatosis by immunohistochemistry for c-kit, CD34, smooth muscle actin, desmin, vimentin, S-100 and L1 expression. L1 expression was detected in 53 (74%) of 72 GISTs but in none of 29 smooth muscle tumors or 21 desmoid-type fibromatosis (P<0.01 by Fisher's test). In all, four (57%) of seven peripheral nerve sheath tumors were L1-positive. Survival analysis of 55 surgically completely resected GISTs presenting without metastasis at initial diagnosis revealed no tumor-specific death among L1-negative patients (P=0.13 by log-rank test; median follow-up time 41 months) and one recurrence was observed (P=0.12). Interestingly high levels of L1 were seen in tumor vascular endothelial cells of smooth muscle tumors and PNSTs, but not in GISTs. Our data show that L1 is highly expressed in GISTs but not in smooth muscle tumors and desmoid-type fibromatosis being important differential diagnoses. The trend towards a reduced survival of L1-positive patients in this study has to be further evaluated in future trials with higher patient numbers.     

Fine-needle aspiration cytology diagnosis of metastatic gastrointestinal stromal tumor in the liver: a report of three cases

Gastrointestinal stromal tumor (GIST) is the designation for a major subset of gastrointestinal mesenchymal tumors that histologically, immunocytochemically, and genetically differ from leiomyomas, leiomyosarcomas, and schwannomas. GISTs derive from the interstitial cells of Cajal and, in addition to variable expression of smooth muscle and neural markers, they characteristically express CD34 and CD117. The cytological appearance, including immunocytochemical and mutational analysis of c-kit gene in primary GIST has been well described. To our knowledge, only two cases of metastatic GIST diagnosed by fine-needle aspiration (FNA) have been reported. We illustrate three cases of metastatic GIST in the liver. Two cases had no prior history of gastrointestinal tumor and the third case had a 4-yr previous history of duodenal tumor. Consistent immunocytochemistry and ultrastructual studies supported the diagnosis of GIST. We emphasize that in the appropriate clinical and radiological setting, a confident diagnosis of GIST can be established by FNA of metastatic lesions.     

The histopathological differential diagnosis of gastrointestinal stromal tumours

Gastrointestinal stromal tumours (GISTs), initially presumed to be of "true" smooth muscle origin, encompass a heterogeneous, and as yet incompletely understood, group of mesenchymal tumours with respect to their origin, cellular differentiation, and prognosis. Cellular morphology ranges from predominantly spindle shaped to epithelioid in character, whereas differentiation pathways, as determined primarily by immunohistochemistry and ultrastructure, can vary from indeterminate to myoid and/or neural. Recent work has indicated that the interstitial cells of Cajal, a complex cellular network postulated to act as pacemaker cells of the gastrointestinal tract, which exhibit both myoid and neural features, could be candidates for tumour histogenesis. This would provide a plausible and attractive explanation for the variable differentiation pathways identified in the GIST category to date. Nevertheless, the occasional but undisputed location of GISTs outside the gastrointestinal tract (omentum, peritoneum, and retroperitoneum) might mitigate against such an origin, and their histogenesis remains open to debate. The c-kit proto-oncogene, encoding a growth factor receptor with tyrosine kinase activity, has been postulated to play an important role in tumorigenesis because "gain of function" mutations in this gene, localised to chromosome 4q11-21, are being increasingly identified in hereditary and sporadic cases. Monoclonal and polyclonal antibodies directed at the c-kit gene product expressed on the cell surface (CD117/c-kit) appear to be increasingly helpful in resolving the histopathological differential diagnosis between GISTs and true gastrointestinal smooth muscle neoplasms, schwannomas, and other far less frequently occurring mesenchymal tumours at this site. Although tumours with a clinically benign course appear to be more common than their malignant counterparts, no specific histological criteria have as yet been identified to enable an unambiguous prediction of biological behaviour. Increasing tumour size and mitotic activity favour aggressive tumour behaviour, whereas the prognostic value of germline and somatic mutations within the c-kit proto-oncogene remains to be elucidated further. It is the aim of this synopsis to highlight the relevant fundamental and diagnostic developments with respect to this complex group of neoplasms.     

胃肠道间质瘤的光镜、免疫组织化学和超微结构的观察

目的 研究胃肠道间质瘤（GISTs）的光镜,电镜形态特点和免疫组织化学在诊断中的价值,探讨肿瘤的组织来源和分型。方法 对GISTs进行光镜和超微结构的观察,用EnVision二步法免疫组织化学方法检测波形蛋白,CD117（c-kit),CD34等8种抗原标记物在肿瘤中的表达情况。结果 65例GISTs占同期消化系统间叶性肿瘤的85．5％（65／76）;其中梭形细胞为主的有46例,伴有上皮样细胞的有13例,单纯由上皮样细胞组成的有6例,瘤细胞呈长,短梭形和圆形,胞质弱嗜酸,常见核端空泡,有时呈印戒样或透明细胞样;排列呈旋涡状,栅栏状或弥漫性巢状。超微结构表现出树枝样突起,神经内分泌颗粒,桥粒样连接等神经分化特点,或（和）胞质内出现密斑,密体等肌性分化。免疫组织化学显示肿瘤组织中抗原标记物表达阳性率波表蛋白为100％（65／65）,CD11793．8％（61／65）,CD3478．5％（51／65）。结论 GISTs是消化道最常见的间叶性肿瘤,光镜形态与真性肌源性和神经源性肿瘤极为相似,电镜和CD117,CD34等免疫标记物配合使用可对其做作出正确诊断,GISTs可能起源于多潜能的,卡哈尔间质细胞样的前体细胞。     

Gastrointestinal stromal tumors: are they of cajal cell origin?

Recently some reports have suggested that gastrointestinal stromal tumors (GIST) might originate from the interstitial cells of Cajal or differentiate into them because they express c-kit and/or CD34 and indicated that the majority of previously diagnosed smooth muscle tumors (SMT) actually belong to GIST, but are not true SMT. We, therefore, detected c-kit, CD34, SMA, and S-100 in 106 Chinese cases of gastrointestinal tumors, which were histopathologically diagnosed as smooth muscle tumors originally, to demonstrate the immunophenotypes of these tumors. The results showed that 73 cases had immunoreaction with c-kit and/or CD34, of which 48 cases showed coexpression with either SMA or S-100 or with both. A correlation between the immunophenotypes and known histopathological parameters was also shown here based on follow-up data. We suggest that the concept of GIST should not be used as an umbrella to cover all gastrointestinal mesenchymal tumors, but be defined in a narrow term as differing from true smooth muscle tumors.     

Gastrointestinal mesenchymal tumors - immunophenotypic classification and survival analysis

The current definition of gastrointestinal tumors (GIST) as CD117-positive mesenchymal tumors of uncertain malignant potential fails to include a number of cases with similar histology. In an attempt to improve the classification of these neoplasms, we conducted an immunohistochemical analysis of 244 mesenchymal tumors with histological features of GIST. According to their immunophenotype, the tumors were classified as GISTs, which are characterized by CD117 (c-kit) expression; gastrointestinal CD117-negative CD34 positive stromal tumors (GINST); alpha-smooth muscle actin and/or desmin positive gastrointestinal leiomyogenic tumors (GILT); S-100 and glial fibrillary acidic protein positive gastrointestinal glial/schwannian tumors (GIGT); gastrointestinal neuronal/glial tumors (GINT), which are positive for S-100/glial fibrillary acidic protein plus neuronal/glial markers; and gastrointestinal fibrous tumors (GIFT), which are only vimentin positive. The most common type of tumors were GIST, followed in order of frequency by GINST, GILT, GIGT, GIFT, and GINT. GISTs did not show any preferential location, whereas GINSTs occurred almost exclusively in the stomach and duodenum, and GILTs preferentially in the large intestine. Over a median follow-up period of 71 months, malignant behavior, i.e., metastatic spread, was observed in all tumor types except GINTs. Malignancy was associated with distal gut location, high mitotic activity, large tumor size, and nuclear pleomorphism, though none of these criteria alone discriminated between benign and malignant. Kaplan-Meier analysis of disease-specific survival showed significant differences in the long-term outcome of the newly defined subgroups. We conclude that, despite strong morphological similarities, gastrointestinal mesenchymal tumors are heterogeneous in their immunophenotype and biology.     

Diagnosis of gastrointestinal stromal tumor by fine-needle aspiration biopsy: a cytological and immunocytochemical study

The diagnosis of gastrointestinal stromal tumors (GIST) is generally established on histopathologic examination of surgical specimens. The present study was undertaken to characterize the cytologic appearance of these tumors and to assess the utility of fine-needle aspirates, including immunocytochemistry for the demonstration of c-kit (CD117) and CD34, in the preoperative diagnosis. The study comprised preoperative fine-needle aspirates in three cases and aspirates performed on fresh surgical specimens in eight cases. The routinely stained smears revealed a mesenchymal cell population, predominated by spindle cells. In five of six cases a strong positivity for c-kit was demonstrated and in three of five cases a strong CD34-expression was found in the tumor cells. These results show that fine-needle aspiration appears to be a useful method for the recognition and diagnosis of GISTs or ICC (interstitial cell of Cajal) tumors.     

Gastrointestinal stromal tumors and other mesenchymal lesions of the gut.

In the past 5 years, there has been a paradigm shift in our understanding of gastrointestinal stromal tumors (GISTs). Once thought to be smooth muscle tumors, these uncommon neoplasms are now thought to differentiate along the lines of interstitial cells of Cajal, the pacemaker cells of the gut. Along with this understanding comes an exciting new drug therapy (Gleevec) that for the first time offers real hope to patients with malignant stromal tumors. Overall, approximately 60-70% of stromal tumors are from the stomach, 20-30% are from the small intestine, and <10% come from the esophagus, colon, rectum, omentum, and mesentery. Between 10 and 30% of GISTs are malignant. Stromal tumors should be studied in a site-specific fashion, as tumors from a given location in the gut have unique growth patterns and corresponding behaviors. Although the most important tool needed to diagnose a GIST is still a hematoxylin and eosin-stained section, a confirmatory CD117 stain is recommended (and may be required for drug therapy). True smooth muscle tumors, inflammatory fibroid polyps, fibromatoses, schwannomas, inflammatory myofibroblastic tumors, and solitary fibrous tumors all enter into the differential diagnosis of GISTs. This article reviews the histologic features of these tumors in the context of recent molecular genetic and immunohistochemical advances.     

Expression of the intermediate filament nestin in gastrointestinal stromal tumors and interstitial cells of Cajal

It has recently been proposed that gastrointestinal stromal tumors (GISTs) originate from stem cells that differentiate toward a phenotype of interstitial cells of Cajal (ICCs). Nestin is a newly identified intermediate filament protein, and is predominantly expressed in immature cells, such as neuroectodermal stem cells and skeletal muscle progenitor cells, and tumors originating from these cells. In this study, we examined, using immunohistochemistry, the nestin expression in GISTs and ICCs to clarify the origin of GISTs. Strong immunoreactivity for nestin was observed in all 18 GISTs, and its expression was confirmed by Western blot and Northern blot analyses. In contrast, three leiomyomas and a schwannoma that developed in the gastrointestinal tract showed no apparent immunoreactivity for nestin. Among 17 mesenchymal tumors (seven leiomyosarcomas, five malignant peripheral nerve sheath tumors, and five fibrosarcomas) that occurred in sites other than the gastrointestinal tract, only two malignant peripheral nerve sheath tumors were moderately immunoreactive for nestin. Furthermore, with fluorescence double immunostaining of the normal small intestine, nestin expression was demonstrated in ICCs. These results show that nestin may be a useful marker for diagnosis of GISTs, and support the current hypothesis that GISTs are tumors of stem cells that differentiate toward an ICC phenotype.     

Contribution of electron microscopy to understanding cellular differentiation in mesenchymal tumors of the gastrointestinal tract: a study of 82 tumors

Eighty-two mesenchymal tumors of the gastrointestinal tract were examined by electron microscopy for the purposes of subtyping for diagnostic precision and of understanding cellular differentiation. Tumors were subclassified into leiomyoma/leiomyosarcoma, tumors of the interstitial cell of Cajal (equivalent to traditionally defined GISTs [Miettinen et al. Hum Pathol. 1999; 30:1213-1220; Mod Pathol. 2000; 13:1134-1142]), gastrointestinal autonomic nerve tumors (GANTs), and fibroblastic and myofibroblastic tumors, using criteria from the literature. Leiomyoma/leiomyosarcoma were diagnosed by myofilaments, attachment plaques, plasmalemmal caveolae, and lamina; GIST by processes or cell bodies full of intermediate filaments, solitary focal densities amid intermediate filaments, attachment plaques with incomplete lamina, scarce myofilaments, and smooth endoplasmic reticulum; GANTs by neuroendocrine granules, cell bodies/processes full of intermediate filaments (more rarely microtubules), and smooth endoplasmic reticulum; fibroblastic/myofibroblastic tumors by abundant rough endoplasmic reticulum, myofilaments, and fibronexuses. Seventy-three tumors (89%) were successfully subclassified, as 5 leiomyoma/leiomyosarcoma (6%), 36 GISTs (44%), 22 GANTs (27%), 10 fibroblastic and myofibroblastic tumors (12%). Results indicated overlap between poorly differentiated leiomyosarcoma and GIST, and between GIST and GANT. GANT is emphasized as a neuronal tumor identifiable by electron microscopy, and thereby distinguishable from GIST.     

Contribution of Electron Microscopy to Understanding Cellular Differentiation in Mesenchymal Tumors of the Gastrointestinal Tract: A Study of 82 Tumors

Eighty-two mesenchymal tumors of the gastrointestinal tract were examined by electron microscopy for the purposes of subtyping for diagnostic precision and of understanding cellular differentiation. Tumors were subclassified into leiomyoma/leiomyosarcoma, tumors of the interstitial cell of Cajal (equivalent to traditionally defined GISTs [Miettinen et al. Hum Pathol. 1999; 30:1213-1220; Mod Pathol. 2000; 13:1134-1142]), gastrointestinal autonomic nerve tumors (GANTs), and fibroblastic and myofibroblastic tumors, using criteria from the literature. Leiomyoma/leiomyosarcoma were diagnosed by myofilaments, attachment plaques, plasmalemmal caveolae, and lamina; GIST by processes or cell bodies full of intermediate filaments, solitary focal densities amid intermediate filaments, attachment plaques with incomplete lamina, scarce myofilaments, and smooth endoplasmic reticulum; GANTs by neuroendocrine granules, cell bodies/processes full of intermediate filaments (more rarely microtubules), and smooth endoplasmic reticulum; fibroblastic/myofibroblastic tumors by abundant rough endoplasmic reticulum, myofilaments, and fibronexuses. Seventy-three tumors (89%) were successfully subclassified, as 5 leiomyoma/leiomyosarcoma (6%), 36 GISTs (44%), 22 GANTs (27%), 10 fibroblastic and myofibroblastic tumors (12%). Results indicated overlap between poorly differentiated leiomyosarcoma and GIST, and between GIST and GANT. GANT is emphasized as a neuronal tumor identifiable by electron microscopy, and thereby distinguishable from GIST.