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.     

Ultrastructural studies of gastrointestinal stromal tumors

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the gastrointestinal tract (GIT). Although interstitial cells of Cajal has been suggested as origin of this tumor, the cytological and ultrastructural features of GISTs are heterogeneous and unclear. A total 10 cases of normal gastrointestinal tissue (control), 13 GISTs of the stomach (8), small intestine (3), mesocolon (1) and liver (1), and 2 gastrointestinal autonomic nervous tumor (GANT) of small intestine were ultrastructurally studied. Normal interstitial cells of Cajal (ICC) were abundantly present around the myenteric plexuses or individually scattered through the wall of GIT. ICC was characterized by slender cytoplasmic processes, well-developed endoplasmic reticulum (ER), mitochondria, Golgi apparatus, caveolae and intermediate filaments. The GISTs and GANTs had overlapping ultrastructures. The most common and important ultrastructural features of GISTs were rich villous cytoplasmic processes, dispersed intermediate filaments and abundant SER, and those of GANTs were neurosecretory granules and skenoid fibers. Compared with ICC, the GISTs and GANTs had remarkably reduced caveolae and gap junctions. Our study suggested that ultrastructural analysis gives much information to investigate lineage differentiation of neoplastic cells and make a differential diagnosis of these tumors from other mesenchymal tumors and between GISTs and GANTs.     

Subclassification of Gastrointestinal Stromal Tumors Based on Evaluation by Electron Microscopy and Immunohistochemistry

Fifty-six gastrointestinal stromal tumors (GIST) were subclassified by ultrastructural examination and by immunophenotypic analysis using a panel of 13 antibodies. Eighty percent of the tumors originated in the stomach and small intestines. The neoplasms were classified as follows: 42.9% smooth muscle tumors (4 leiomyomas, 9 spindle cell and 8 epithelioid leiomyosarcomas, and 3 mixed spindle cell and epithelioid leiomyosarcomas); 37.5% gastrointestinal autonomic nerve tumors (GANT), 47.6% of which arose in the small intestines; 8.9% mixed leiomyosarcoma/neurogenic tumors; and 10.7% undifferentiated GIST, not otherwise specified. The muscle common actin antibody HHF-35, variably reactive with tumor cells composing 23 of 24 smooth muscle tumors, was found to be the most sensitive marker of leiomyocyte differentiation. One immunophenotypically questionable spindle cell leiomyosarcoma was diagnosed by electron microscopy. Since neuron specific enolase positive cells were found in 1/3 of the leiomyosarcoma cases, the ultrastructural demonstration of synapse-like structures and neurosecretory granules was required for diagnosing GANTs. The immunophenotype of the ultra-structurally undifferentiated GIST was vimentin and CD34 +. Variable numbers of ultrastructurally undifferentiated cells also were found in all of the tumors except 2 leiomyomas. CD34 was also expressed in smooth muscle (54%) and GAN (62%) tumors. Despite their similar light microscopic appearance, GIST are phenotypically heterogeneous, requiring both ultrastructural and immunohistochemical studies for accurate characterization.     

Gastrointestinal stromal tumors: recent advances in understanding of their biology.

Gastrointestinal stromal tumor (GIST) is the preferred term for mesenchymal tumors specific for the gastrointestinal tract (60% in stomach, 30% small intestine, 10% elsewhere). GISTs include most tumors previously designated as leiomyoma, cellular leiomyoma, leiomyoblastoma, and leiomyosarcoma. However, in the esophagus, leiomyoma is the most common mesenchymal tumor. GISTs are composed of spindle (70%) or epithelioid (30%) cells, and 10%-30% are malignant showing intra-abdominal spread or liver metastases. They are immunohistochemically positive for c-kit (CD117), CD34, and sometimes for actin but are almost always negative for desmin and S100-protein. The malignant GISTs especially show activating mutations in the c-kit gene. GISTs and gastrointestinal autonomic nerve tumors (GANT) overlap. The cell of origin is not fully understood, but resemblance to the interstitial cells of Cajal, expression of some smooth muscle markers, and occurrence outside of the GI-tract suggest origin from multipotential cells that can differentiate into Cajal and smooth muscle cells.     

Myofibroblastom a of Breast: Evidence Favoring Smooth-Muscle Rather Than Myofibroblastic Differentiation

A histopathological study of two cases of the tumor known in the literature as myofibroblastoma of the breast is presented. The tumors occurred in Caucasian males aged 57 and 62 years. Histologically, these were moderately cellular, lobulated spindle-cell lesions, each with a reasonably well-delineated edge with surrounding fatty connective tissue. No breast ducts or lobules were present. Tumor cell nuclei were bland, with small nucleoli and some nuclear grooving. Nuclear atypia and mitoses were absent. Immunostaining revealed positivity for alpha -smoothmuscle actin, desmin, and CD34. Tumor cells contained rough endoplasmic reticulum, bundles of myofilaments with focal densities, intermediate filaments, attachment plaques alternating with plasmalemmal caveolae, and focal lamina. Ultrastructural findings pointed to true smooth-muscle differentiation, and the cell-surface in particular lacked surface features of myofibroblasts (fibronectin fibrils [microtendons] and fibronexus junctions). These and published data suggest that at least some of the lesions referred to in the literature as myofibroblastoma may not be myofibroblastic and may be better designated as myogenic stromal tumors or as variants of leiomyoma.     

Myofibroblastom a of Breast: Evidence Favoring Smooth-Muscle Rather Than Myofibroblastic Differentiation

A histopathological study of two cases of the tumor known in the literature as myofibroblastoma of the breast is presented. The tumors occurred in Caucasian males aged 57 and 62 years. Histologically, these were moderately cellular, lobulated spindle-cell lesions, each with a reasonably well-delineated edge with surrounding fatty connective tissue. No breast ducts or lobules were present. Tumor cell nuclei were bland, with small nucleoli and some nuclear grooving. Nuclear atypia and mitoses were absent. Immunostaining revealed positivity for alpha -smoothmuscle actin, desmin, and CD34. Tumor cells contained rough endoplasmic reticulum, bundles of myofilaments with focal densities, intermediate filaments, attachment plaques alternating with plasmalemmal caveolae, and focal lamina. Ultrastructural findings pointed to true smooth-muscle differentiation, and the cell-surface in particular lacked surface features of myofibroblasts (fibronectin fibrils [microtendons] and fibronexus junctions). These and published data suggest that at least some of the lesions referred to in the literature as myofibroblastoma may not be myofibroblastic and may be better designated as myogenic stromal tumors or as variants of leiomyoma.     

Fibroblast Phenotype Plasticity: Relevance for Understanding Heterogeneity in "Fibroblastic" Tumors

Cellular transformations, reflecting phenotypic plasticity, characterize embryonic life, would-repair, physiological adaptation, and neoplasia. Fibroblastic tumors show a range of cellular differentiation, which can be rationalized in terms of phenotypic plasticity of the “normal” fibroblast. In this paper, the various kinds of fibroblast transformation are discussed, and some insights provided into the molecular mechanisms involved. Comparable molecular events may take place in neoplastic fibroblasts to produce the heterogeneous tumors nevertheless identified as fibroblastic. The following transformations are discussed: histiocytic, and fibrohistiocytic tumors; adipocytic, and lipogenic tumors; myofibroblastic, and myofibroblastic tumors. A definition of the fibroblast is required. This consists of spindle-cell morphology, vimentin-staining, and abundant rough endoplasmic reticulum. Transformation to histiocytic, lipogenic and myofibroblastic phenotypes requires the development of lysosomes, lipid droplets and lamina, and peripheral myofilaments and fibronexuses respectively. These occur in non-malignant transforming (transdifferentiating) fibroblasts, and also in tumors identified as fibrohistiocytic, lipogenic and myofibroblastic. The molecular basis of the myofibroblast transformation is probably the best studied. It is driven primarily by transforming growth factor β. Investigations into the mechanisms of differentiation in normal fibrobiasts could prove fertile ground for defining comparable differentiation in tumors. In this respect, there are very few publications on the presence of growth factors in tumors or tumor-like lesions. There is, however, increasing investigation into gene expression and gene products in tumors, which bear on the differentiation process. Ultimately, our understanding of the molecular events controlling differentiation in cancer will lead to control, cure and prevention.     

Myofibroblastic,fibroblastic and myoid lesions of the breast

Myofibroblastic, fibroblastic and/or myoid lesions are rare in the breast but comprise the majority of mammary mesenchymal spindle cell lesions. Whereas most have similar features to their counterparts at extramammary sites, pseudoangiomatous stromal hyperplasia is considered a breast-specific myofibroblastic proliferation on the same spectrum as myofibroblastoma. Other lesions with myofibroblastic/fibroblastic differentiation include fibromatosis and nodular fasciitis, as well as more aggressive tumors such as the rarely reported myofibrosarcoma, inflammatory myofibroblastic tumor and fibrosarcoma. Lesions with myoid differentiation include benign leiomyoma, myoid hamartoma and leiomyomatous myofibroblastoma, but primary leiomyosarcoma and rhabdomyosarcoma may also rarely arise in the breast. Furthermore, fibroepithelial lesions and metaplastic carcinomas can demonstrate myoid metaplasia. Diagnosis can be challenging, particularly on core biopsy, but benign lesions with or without recurrence potential must be distinguished from more aggressive tumors, especially metaplastic carcinoma and phyllodes tumors. This article will review lesions with myofibroblastic, fibroblastic and myoid differentiation in the breast, with special emphasis on differential diagnosis.     

Leiomyosarcoma showing partial synthetic-phase differentiation

An unusual leiomyosarcoma in the thigh of a 53-year-old woman is described. Tumor cells were spindled and positive for muscle immuno-markers. Some cells exhibited typical smooth-muscle ultrastructure - abundant myofilaments, focal densities, attachment plaques, plasmalemmal caveolae, and lamina. Others had fewer myofilaments and prominent rough endoplasmic reticulum. These features indicated a variable phenotype that included synthetic-phase (matrigenic) differentiation. Synthetic-phase cells were distinguished from myofibroblasts by typical smooth-muscle surface features in the absence of fibronexus junctions. In a subset of cells myofilaments were absent, but structures resembling solitary focal densities were identified. These are discussed as possible indicators of a primitive level of smooth-muscle differentiation.     

胃肠道间质瘤起源和分化的探讨

目的 探讨胃肠道间质瘤(GIST)的起源或分化。方法 采用免疫组织化学EnVision和电镜的方法对GIST进行研究。结果 212例GIST CD117、CD34、α—平滑肌肌动蛋白(SMA)、肌特异性肌动蛋白、结蛋白阳性率分别为96．7％,77．3％,19．3％,15．6％,1．9％,其中S—100和PGP9．5的阳性反应分别为16．3％及12．3％。超微结构显示瘤细胞含丰富的线粒体,粗面内质网、游离核糖体和中间丝,有的细胞切面可见溶酶体和脂滴,高尔基复合体在核周分布,质膜处偶尔不规则地分布着一些微饮泡、密斑样结构及不连续的基板。部分病例细胞有多量细长指状突起,突起内有胞内成分如线粒体、粗面内质网延续,突起之间或突起与细胞膜有连接结构。细胞外间质内可见胶原原纤维或团丝样纤维。结论 GIST免疫表型及超微结构特征与胃肠壁成熟卡哈尔间质细胞相似,提示GIST可能是起源于幼稚间充质细胞向卡哈尔间质细胞分化的肿瘤,并具有一定的肌性特征。     

Fibroblast phenotype plasticity: relevance for understanding heterogeneity in "fibroblastic" tumors

Cellular transformations, reflecting phenotypic plasticity, characterize embryonic life, would-repair, physiological adaptation, and neoplasia. Fibroblastic tumors show a range of cellular differentiation, which can be rationalized in terms of phenotypic plasticity of the "normal" fibroblast. In this paper, the various kinds of fibroblast transformation are discussed, and some insights provided into the molecular mechanisms involved. Comparable molecular events may take place in neoplastic fibroblasts to produce the heterogeneous tumors nevertheless identified as fibroblastic. The following transformations are discussed: histiocytic, and fibrohistiocytic tumors; adipocytic, and lipogenic tumors; myofibroblastic, and myofibroblastic tumors. A definition of the fibroblast is required. This consists of spindle-cell morphology, vimentin-staining, and abundant rough endoplasmic reticulum. Transformation to histiocytic, lipogenic and myofibroblastic phenotypes requires the development of lysosomes, lipid droplets and lamina, and peripheral myofilaments and fibronexuses respectively. These occur in non-malignant transforming (transdifferentiating) fibroblasts, and also in tumors identified as fibrohistiocytic, lipogenic and myofibroblastic. The molecular basis of the myofibroblast transformation is probably the best studied. It is driven primarily by transforming growth factor beta. Investigations into the mechanisms of differentiation in normal fibrobiasts could prove fertile ground for defining comparable differentiation in tumors. In this respect, there are very few publications on the presence of growth factors in tumors or tumor-like lesions. There is, however, increasing investigation into gene expression and gene products in tumors, which bear on the differentiation process. Ultimately, our understanding of the molecular events controlling differentiation in cancer will lead to control, cure and prevention.     

Fibroblast Phenotype Plasticity: Relevance for Understanding Heterogeneity in “Fibroblastic” Tumors

Cellular transformations, reflecting phenotypic plasticity, characterize embryonic life, would-repair, physiological adaptation, and neoplasia. Fibroblastic tumors show a range of cellular differentiation, which can be rationalized in terms of phenotypic plasticity of the “normal” fibroblast. In this paper, the various kinds of fibroblast transformation are discussed, and some insights provided into the molecular mechanisms involved. Comparable molecular events may take place in neoplastic fibroblasts to produce the heterogeneous tumors nevertheless identified as fibroblastic. The following transformations are discussed: histiocytic, and fibrohistiocytic tumors; adipocytic, and lipogenic tumors; myofibroblastic, and myofibroblastic tumors. A definition of the fibroblast is required. This consists of spindle-cell morphology, vimentin-staining, and abundant rough endoplasmic reticulum. Transformation to histiocytic, lipogenic and myofibroblastic phenotypes requires the development of lysosomes, lipid droplets and lamina, and peripheral myofilaments and fibronexuses respectively. These occur in non-malignant transforming (transdifferentiating) fibroblasts, and also in tumors identified as fibrohistiocytic, lipogenic and myofibroblastic. The molecular basis of the myofibroblast transformation is probably the best studied. It is driven primarily by transforming growth factor β. Investigations into the mechanisms of differentiation in normal fibrobiasts could prove fertile ground for defining comparable differentiation in tumors. In this respect, there are very few publications on the presence of growth factors in tumors or tumor-like lesions. There is, however, increasing investigation into gene expression and gene products in tumors, which bear on the differentiation process. Ultimately, our understanding of the molecular events controlling differentiation in cancer will lead to control, cure and prevention.     

The myofibroblast: an assessment of controversial issues and a definition useful in diagnosis and research

Some interpretational problems associated with the myofibroblast, which affect how this cell is identified, are discussed. Questions addressed include distinguishing between "external" lamina ("basement membrane") and the fibronectin fibril of the fibronexus; the nature of stress fibers (bundles of smooth-muscle myofilaments with focal densities); the utility of some of these features to distinguish between myofibroblastic and smooth-muscle cell surfaces; and cytoskeletal immunophenotype. The following points are emphasized. Myofibroblasts have a surface characterized by prominent fibronectin fibrils and fibronexus junctions, which are distinct from lamina ("basement membrane"). This can permit a distinction to be made between smooth-muscle and myofibroblastic lesions and tumors. Myofibroblasts are typically positive for vimentin and alpha-smooth-muscle actin, but desmin is not a useful discriminant between smooth-muscle and myofibroblastic lesions. The main features for defining the myofibroblast are abundant rough endoplasmic reticulum; modestly developed peripheral myofilaments with focal densities (stress fibers); fibronexus junctions; vimentin and smooth-muscle actin immunostaining. Other features include a Golgi apparatus and collagen secretion granules, gap junctions, and actin-associated nondesmosomal junctions. Illustrations of the usefulness of these criteria in the diagnosis of soft-tissue lesions (myofibrosarcoma, so-called myofibroblastoma) are given.     

Electron microscopy in the study of myofibroblastic lesions

Electron microscopy in the diagnosis and academic study of myofibroblastic lesions is discussed. Myofibroblasts from granulation tissue and tumor stroma are regarded as the nearest equivalent to a "normal" myofibroblast population with which to define myofibroblastic differentiation in tumoral and pseudotumoral lesions. Histological features include a plump-spindle-cell morphology, with an ill-defined cytoplasm paler and less fibrillar than in smooth-muscle cells, and matrix collagen. Myofibroblasts stain for alpha-smooth-muscle actin, fibronectin, and vimentin. Desmin is found in some lesional myofibroblasts. The main ultrastructural features are prominent rough endoplasmic reticulum, modestly developed myofilaments with focal densities ("stress fibers"), and fibronexus junctions. The latter are foci on the cell surface where intracellular myofilaments and extracellular fibronectin filaments converge. Myofibroblastic lesions vary in the extent to which they mirror this overall phenotype. Hypertrophic scar, Dupuytren's disease, nodular fasciitis, the fibromatoses, and inflammatory myofibroblastic tumors have the most developed myofibroblastic features. Keloid, postoperative spindle-cell nodule, and fibroma of tendon sheath are less well differentiated. Myofibroblastoma is among many lesions described as myofibroblastic which, however, appear to show a kind of smooth-muscle differentiation. Some spindle-cell malignancies express myofibroblastic features.     

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.     

Actin filaments in human renal tubulo-interstitial fibrosis: significance for the concept of epithelial-myofibroblast transformation

Epithelial-myofibroblast transformation has been argued as playing a role in tubulo-interstitial fibrosis. To investigate this hypothesis, we examined 9 renal biopsy specimens from patients with chronic renal disease by light and electron microscopy. In all cases, electron microscopy confirmed light microscope observations in relation to tubulo-interstitial fibrosis-tubular atrophy, accumulation of extracellular matrix and of mesenchymal interstitial cells, and infiltration by inflammatory cells. Tubular epithelial cells (TECs) contained bundles of actin filaments: mostly lacking the focal densities typical of smooth-muscle myofilaments. The interstitium contained collagen and inflammatory cells. Some endothelial cells showed bundles of myofilaments. Free mesenchymal cells in the matrix were spindled and had sparse rough endoplasmic reticulum (rER), small attachment plaques, few actin filaments and no lamina. In one case, myofibroblasts (defined by abundant rER, myofilaments and fibronexuses) were present. Most of the mesenchymal cells, therefore, did not correspond to myofibroblasts, nor to classical fibroblasts because of the sparse rER and the presence of actin filaments. We therefore called these cells myoid stromal cells, regarding them as stromal mesenchymal elements showing partial activation towards a smooth-muscle phenotype. This paper demonstrates a greater phenotypic complexity of actin-containing stromal cells in the interstitium than previously appreciated, with only a minority conforming to true or fully differentiated myofibroblasts. The widespread presence of actin (as filaments or immunoreactivity) in both TECs and interstitial cells, combined with the absence of evidence of intermediate forms or of migration from epithelium into interstitium, may point to epithelium and interstitium as separate targets for actin upregulation as an alternative hypothesis to epithelial-myofibroblast transformation.     

A Study of Spindle Cell Sarcomas Showing Myofibroblastic Differentiation

Five diagnostically problematic spindle cell sarcomas showing invasive character, cellular pleomorphism, and high mitotic rate were studied clinically and histopathologically by conventional light microscopy, immunohistochemistry, and transmission electron microscopy. They showed varied clinical courses, with two causing death within 5 years and three showing recurrent and metastatic behavior. All lacked a clearly defined line of differentiation by conventional light microscopy. By immunohistochemistry, all were positive for vimentin and α-smooth muscle actin; in addition, one showed focal S-100 protein positivity, and one stained for desmin. All were cytokeratin negative. By electron microscopy, the great majority of spindle cells in all cases showed abundant rough endoplasmic reticulum and fine myofilaments with focal densities; collagen secretion granules were also found in all cases but in fewer cells. The fine structure and immunophenotype were considered consistent with myofibroblastic differentiation; these tumors, therefore, were designated as sarcomas of myofibroblasts or myofibrosarcomas. The suitability of the alternative diagnostic label of myofibroblastic or matrix-secreting variant of leiomyosarcoma is discussed. Comparisons with similar tumors documented in the literature are drawn.     

A study of spindle cell sarcomas showing myofibroblastic differentiation.

Five diagnostically problematic spindle cell sarcomas showing invasive character, cellular pleomorphism, and high mitotic rate were studied clinically and histopathologically by conventional light microscopy, immunohistochemistry, and transmission electron microscopy. They showed varied clinical courses, with two causing death within 5 years and three showing recurrent and metastatic behavior. All lacked a clearly defined line of differentiation by conventional light microscopy. By immunohistochemistry, all were positive for vimentin and alpha-smooth muscle actin; in addition, one showed focal S-100 protein positivity, and one stained for desmin. All were cytokeratin negative. By electron microscopy, the great majority of spindle cells in all cases showed abundant rough endoplasmic reticulum and fine myofilaments with focal densities; collagen secretion granules were also found in all cases but in fewer cells. The fine structure and immunophenotype were considered consistent with myofibroblastic differentiation; these tumors, therefore, were designated as sarcomas of myofibroblasts or myofibrosarcomas. The suitability of the alternative diagnostic label of myofibroblastic or matrix-secreting variant of leiomyosarcoma is discussed. Comparisons with similar tumors documented in the literature are drawn.     

Loss of heterozygosity on chromosome 22q in gastrointestinal stromal tumors (GISTs): a study on 50 cases

Mutational activation of KIT or PDGFRA is considered an early step in pathogenesis of gastrointestinal stromal tumors (GISTs); however, other nonrandom genetic changes have also been identified. At least three common regions of deletions on chromosome 22q, which may harbor putative tumor suppressor genes, have been defined. However, mapping of these regions has been inconsistent. It has also been speculated that GI autonomous nerve tumors (GANTs), GISTs with ultrastructural features suggestive of autonomic nerve differentiation, are characterized by a specific deletion involving 22q13 cytogenetic region. This study was undertaken to evaluate loss of heterozygosity (LOH) on chromosome 22q in 50 GISTs, including 10 GANTs. Four tumors were incidental minimal lesions 相似文献   

Oesophageal mesenchymal tumours: clinicopathological features and absence of Epstein-Barr virus

BACKGROUND: Recent studies have suggested that the Epstein-Barr virus (EBV) is associated with smooth muscle tumours (leiomyoma and leiomyosarcoma) in patients with human immunodeficiency virus and in organ transplant recipients. Leiomyoma is the most common mensenchymal tumour found in the oesophagus. AIM: To report a single institution experience on oesophageal mesenchymal tumours and to determine whether EBV is associated with these tumours. METHODS: 40 sporadic oesophageal mesenchymal tumours were studied and their diagnosis confirmed on pathological review and immunohistochemical studies. Formalin fixed, paraffin was embedded tissues from these tumours were analysed for EBV using in situ hybridisation for two messenger RNA (mRNA) probes, EBER and BamH1 W. RESULTS: The oesophageal mesenchymal tumours comprised 36 leiomyomas, two undifferentiated stromal tumours, and two gastrointestinal autonomic nerve tumours (GANTs). Median age of the patients with leiomyoma (26 men, 10 women) was 62 years (range 30 to 85) and 81% of them had an asymptomatic lesion. The median longitudinal size was 1.2 cm. Multiple leiomyomas were seen in 11% of the patients and calcification was noted in one tumour. Coexisting squamous cell carcinoma was found in one third of cases. The stromal tumours were small, asymptomatic, and located in the lower third of the oesophagus, while the GANTs were large, symptomatic, and found in the upper third of the oesophagus. EBV mRNAs were not detected in all these tumours. CONCLUSIONS: The clinicopathological features of oesophageal leiomyoma, undifferentiated stromal tumour, and GANT were different. Some oesophageal leiomyomas were associated with oesophageal squamous cell carcinomas. EBV is not associated with sporadic oesophageal mesenchymal tumours.