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.
Adult ; Aged ; Autonomic Nervous System/*pathology/ultrastructure ; Comparative Study ; Cytoplasm/pathology/ultrastructure ; Female ; Gastrointestinal Neoplasms/*pathology/ultrastructure ; Human ; Immunohistochemistry ; Male ; Microscopy, Electron ; Middle Aged ; Peripheral Nervous System Neoplasms/*pathology/ultrastructure ; Stromal Cells/*pathology/ultrastructure ; Support, Non-U.S. Gov't ; Tumor Markers, Biological ; Vacuoles/pathology/ultrastructure

OBJECTIVETo explore the histogenesis and neural differentiation of gastrointestinal stromal tumor (GIST).

METHODSThe ultrastructural morphology and neural differentiated antigen expression were studied in 20 cases of GIST using electron microscopy and immunohistochemistry.

RESULTSAll of the 20 cases mentioned were positive for c-kit expression. The ultrastructural features of neural differentiation were observed in 7 cases, while no neural or myogenic differentiation seen in 12 cases. Myogenic differentiation to smooth muscle was observed in one case. The ultrastructural features of neural differentiation included scattered or cluster distribution of dense core granules in cytoplasm and cytoplasmic processes; formation of synaptic construction of cell processes; and neurogenic-like processes. In some cases pinocytotic vesicles under the cell membrane and skenoid fibers were seen. Neural differentiation with dense core granules was seen in one case in benign, one case in borderline and five cases in malignant group. The positive reactivity of neural differentiated antigen NSE, CD99, S-100p and CD56 in cases of the neural differentiation group appeared in seven, seven, five and four cases respectively, which were significantly higher than that of the undifferentiated group.

CONCLUSIONSIt's rather difficult to differentiate GIST accompanying with neural differentiation from gastrointestinal autonomic nerve tumor if depending only on its histology and immunophenotype appearance, since many features were overlapping in both tumors. Examination of the neural ultrastructures and neural differentiated antigen in GIST might be helpful to clarify the neural differentiation and potential behavior of GIST.

12E7 Antigen ; Adolescent ; Adult ; Aged ; Antigens, CD ; metabolism ; Autonomic Nervous System Diseases ; metabolism ; pathology ; Biomarkers, Tumor ; metabolism ; CD56 Antigen ; metabolism ; Calcium-Binding Proteins ; metabolism ; Cell Adhesion Molecules ; metabolism ; Cell Differentiation ; Child ; Diagnosis, Differential ; Female ; Gastrointestinal Stromal Tumors ; metabolism ; ultrastructure ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neoplasm Proteins ; metabolism ; Proto-Oncogene Proteins c-kit ; metabolism ; Stromal Cells ; ultrastructure ; Synapses ; ultrastructure