A ganglion-rich gastrointestinal stromal tumor: A case report.

We report a case of an extremely rare type of duodenal gastrointestinal stromal tumor (GIST) that included neuronal components. Although gastrointestinal autonomic nerve tumors (GANTs), a subtype of GISTs, exhibit ultrastructural features of the nerve plexus, neuronal cells have not been observed within GANTs or GISTs. GISTs originate from interstitial cells of Cajal (ICCs), which are markedly different from the progenitor cells of neural elements and neural-crest-derived stem cells. This may explain why GISTs typically lack neuronal elements. It remains unclear that the neuronal components of this tumor are neoplastic or hyperplastic, but proliferation and survival of ICCs have recently been reported to be closely related to neurons. Although we could not find the KIT, PDGFR, and BRAF mutation as far as we examined, it may have had a rare mutation in NF1, a fusion of EVT6-NTRK3, or an as-yet-unknown KIT mutation that affected neurogenesis. Further investigation of related genetic mutations and accumulation of data from other similar cases is needed.

Primary hepatic gastrointestinal stromal tumor with right adrenal gland invasion: A case report and systematic literature review.

INTRODUCTION: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors that mainly occur in the gastrointestinal tract. The GISTs that are sporadically reported in extra-gastrointestinal regions are named as extra-gastrointestinal stromal tumors (EGISTs). However, the primary EGISTs that originate from the liver are rare. PATIENT CONCERNS: A 64-year-old female presenting with right upper abdominal pain and thirsty for more than 20 days. DIAGNOSIS: A diagnosis of a 15 × 14 × 7 cm liver mass located in the posterior right lobe of liver and spread to the right adrenal gland was confirmed. Pathological results showed that the tumor was mainly composed of epithelial cells and tested positive for CD117 and SDHB (succinate dehydrogenase complex iron sulfur subunit B). The gene mutational analyses for c-Kit and platelet-derived growth factor receptor alpha exons revealed negative results. Fluorescence in situ hybridization of murine double minute 2 produced negative fluorescence results which distinguished it from dedifferentiated liposarcomas. The postoperative gastroduodenal and colorectal endoscopy did not find any neoplastic lesions. To this end, the diagnosis of primary hepatic EGIST of wild type nature was confirmed. INTERVENTIONS: The patient received right hepatectomy and adrenalectomy, no postoperative chemotherapy was administered. OUTCOMES: The patient died 11 months after surgery due to tumor metastasis. CONCLUSION: Primary hepatic EGIST is a rare and complicated disease of liver, a multidisciplinary team is necessary in diagnosis and treatment of primary hepatic EGIST.

Biogenesis of a new type of extracellular vesicles in gastrointestinal stromal tumors: ultrastructural profiles of spheresomes.

Extracellular vesicles (EVs) have emerged as an intercellular communication mediator in cancer. They seem to be involved in tumor processes by means of transformation of surrounding cells previous to metastasis by transferring miRNAs and oncogenic proteins. It is known that EVs, depending on their source, can be exosomes or ectosomes. Although the first type constitutes a specific population formed from the endosomal system, via multivesicular bodies, the ectosome biogenesis is not yet well known. In this study, we report a new type of EVs which has been termed spheresomes. While exosomes come from multivesicular bodies and ectosomes from direct budding of plasma membrane, spheresomes present a new mechanism of shedding from a spherical membrane structure which we have named multivesicular spheres. These EVs are first described in gastrointestinal stromal tumor cells in the present study. But moreover, these new membrane spherical structures appear not only next to tumoral cells but also different distances from them. Since some other authors have evidenced oncogenic KIT-containing EVs, it is also suggested here that surrounding cells uptake of these first described EVs, GIST-derived spheresomes, could induce tumor invasiveness. That is why the prevention of signaling processes developed by these new EVs may represent an alternative approach for GIST treatment.

Nuclear morphometry and proliferative activity evaluation in the gastrointestinal stromal tumors.

Twenty-two cases with gastrointestinal stromal tumors (GISTs) have been studied, sized from 2 cm to invasive gigantic tumors and also from low to high degree of malignancy. The altering of the form and the size of the nucleus is a reference point of malignancy, being used in the histological grading of many types of tumors and also as an appreciating parameter of the tumoral prognosis, with a high degree of accuracy in the colorectal, uterine, prostatic or ovarian cancers, as it was pointed in the previous researches. The aim of this study is to evaluate the dimensional characteristic of the nuclei and the mitosis in GIST with a cholic and gastric localization, attempting a quantitative differentiation of the two tumors, by studying the following aspects: nuclear dimensions, mitotic activity index and the mitotic density. The results of the proliferative activity quantification (mitotic activity index and mitotic density) have shown that this can be a decisive criterion for the precocious appreciation of the evolution. The most important morphological criterion with a predictive role is the mitotic activity index, but is recommended to be applied correlated with the size and the localization of the tumor. Although various nuclear morphometry studies in different types of malignant tumors have been performed, the data in gastrointestinal stromal tumors is scarce and only few similar studies have been reported in the specialty literature; from this point of view, the present study is new and original and is also trying to point out that even with GIST, such analysis and prognosis is as valuable as in any other malignant diseases.

Primary cilia in gastric gastrointestinal stromal tumours (GISTs): an ultrastructural study.

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal (non-epithelial) neoplasms of the human gastrointestinal (GI) tract. They are thought to derive from interstitial cells of Cajal (ICCs) or an ICC progenitor based on immunophenotypical and ultrastructural similarities. Because ICCs show primary cilium, our hypothesis is based on the possibility that some of these neoplastic cells could also present it. To determine this, an exhaustive ultrastructural study has been developed on four gastric GISTs. Previous studies had demonstrated considerable variability in tumour cells with two dominating phenotypes, spindly and epithelioid. In addition to these two types, we have found another cell type reminiscent of adult ICCs with a voluminous nucleus surrounded by narrow perinuclear cytoplasm with long slender cytoplasmic processes. We have also noted the presence of small undifferentiated cells. In this study, we report for the first time the presence of primary cilia (PCs) in spindle and epithelioid tumour cells, an ultrastructural feature we consider of special interest that has hitherto been ignored in the literature dealing with the ultrastructure of GISTs. We also point out the frequent occurrence of multivesicular bodies (MVBs). The ultrastructural findings described in gastric GISTs in this study appear to be relevant considering the critical roles played by PCs and MVBs recently demonstrated in tumourigenic processes.

Tumores del estroma gastrointestinal (GIST): características clinico-morfológicas y perfil inmunohistoquímico / Gastrointestinal stromal tumors (GIST): clinical-morphological features and immunohistochemical profile

Los tumores del estroma gastrointestinal (GIST) son neoplasias de origen mesenquimático que representan aproximadamente el 0,3 por ciento de todas las neoplasias del tubo digestivo, caracterizadas inmunohistoquímicamente por expresar CD117 en el 95 por ciento de los casos y afectando más frecuentemente estómago e intestino delgado. El objetivo de este estudio fue describir aspectos clínicos, morfológicos y de inmunohistoquímica en pacientes con diagnóstico de GIST en la Unidad de Anatomía Patológica del Hospital Hernán Henríquez Aravena de Temuco, Chile. Estudio de cohorte retrospectiva. Se estudiaron 30 pacientes con diagnóstico de GIST intervenidos entre 1999 y 2010 en el Hospital Hernán Henríquez Aravena de Temuco. Las variables clínicas y morfológicas estudiadas fueron edad, género, localización y tamaño tumoral, tipo histológico, índice mitótico, compromiso de mucosa, grado de pleomorfismo nuclear y presencia de necrosis. El estudio inmunohistoquímico consideró c-KIT, CD34 y S-100. Se utilizaron estadísticas descriptivas y analíticas; aplicando chi-cuadrado de Pearson y exacto de Fisher para las variables categóricas; y, T-test para variables continuas. El promedio de edad fue 60 años (17-81 años), verificándose un 60 por ciento de mujeres en el grupo estudiado. El 90 por ciento correspondió a tumores de localización gastro-intestinal, representando estómago e intestino delgado el 80 por ciento de los casos. El tamaño tumoral promedio fue 75,9 mm. Correspondió a patrón fusocelular el 77 por ciento, observándose necrosis en el 37 por ciento de los casos. El 50 por ciento presentó > 5 mitosis/50 CAM, verificándose compromiso de la mucosa en un 67 por ciento. Según el grupo pronóstico se verificó 7 por ciento grupo 1, 23 por ciento grupo 2, 20 por ciento grupo 3, 0 por ciento grupo 4, 10 por ciento grupo 5 y 40 por ciento grupo 6. El 100 por ciento expresó positividad para c-KIT, 63 por ciento para CD34 y 3 por ciento para S-100. Los GIST afectan mayormente...

Gastrointestinal stromal tumors (GIST) are mesenchymal neoplasms that represent approximately 0.3 percent of all malignancies of the gastrointestinal tract, characterized immunohistochemically for CD117 expression in 95 percent of cases and most commonly affects the stomach and small intestine. The aim of this study is to describe the clinical, morphological and immunohistochemical diagnosis of gist patients in the unit of pathology Hernán Henríquez Aravena Hospital in Temuco. Retrospective cohort study. We studied 30 patients with gist who underwent surgery between 1999 and 2010 in the Hernan Henríquez Aravena Hospital in Temuco. The clinical and morphological variables studied were age, gender, location and tumor size, histological type, mitotic index, commitment mucosa, degree of nuclear pleomorphism and necrosis. immunohistochemical study found c-KIT, CD34 and S-100. Descriptive statistics and analytical, using Pearson chi-square and Fisher exact tests for categorical variables, and T-test for continuous variables. The average age was 60 years (17-81 years), verified 60 percent of women in the study group. 90 percent corresponded to tumors located gastro-intestinal, stomach and small intestine represents 80 percent of cases. The average tumor size was 75.9 mm. spindle pattern accounted for 77 percent, with necrosis in 37 percent of cases. 50 percent had> 5 mitosis/50 cam, mucosal involvement verified by 67 percent. according to the prognostic group was observed 7 percent group 1, group 2 23 percent, 20 percent in group 3, 0 percent in group 4, 10 percent and 40 percent group 5 group 6. 100 percent expressed positive for c-KIT, CD34 63 percent and 3 percent for S-100. GIST mostly affect patients from the 4 th -6 decade of life with a slight female predominance, stomach and small intestine being the organs most commonly affected. Immunohistochemical study showed positivity for c-KIT and CD34 in 100 percent and 63 percent of cases.

Clinicopathologic factors and nuclear morphometry as independent prognosticators in KIT-positive gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms found in the gastrointestinal tract. The purpose of this study was to evaluate whether morphometric measurements could complement tumor size and mitotic activity in risk evaluation. Nuclear roundness and ellipse axis ratio were found to correlate with tumor size, mitotic activity, nuclear atypia, and hemorrhage. Morphometric variables in 422 GISTs were significant for overall survival in univariate analyses but did not retain independent significance in multivariate analyses incorporating mitotic count and tumor size. Traditional variables, together with sex, location of primary tumor, and nuclear atypia, seem to be the best parameters for prognostic evaluation.

[Ultrastructural features and platelet-derived growth factor receptor A gene mutations in CD117-negative gastrointestinal stromal tumor].

OBJECTIVE: To explore the ultrastructural features and mutation status of platelet-derived growth factor receptors A (PDGFRA) and c-kit in gastrointestinal stromal tumors that were immunohistochemically negative for CD117 antigen. METHODS: Six cases of gastrointestinal stromal tumors that were CD117 immunostain negative were studied by electron microscopy. Direct PCR sequencing was used to investigate the mutation status of c-kit gene exons 9, 11, 13, 17 and PDGFRA gene exons 12 and 18. RESULTS: The ultrastructural features of all 6 cases were similar to those of the interstitial cell of Cajal (ICC). None of the 6 cases were found to have c-kit gene mutations. However, three tumors were found to harbor PDGFRA exon 18 activating mutations, including two tumors having an Asp-->Val842 missense mutation and one having an Arg-->Ser841 missense mutation. CONCLUSIONS: PDGFRA mutations may provide an important alternative molecular mechanism for the development of gastrointestinal stromal tumor.

[Study on gastrointestinal stromal tumors by electron microscopy and immunohistochemistry].

OBJECTIVE: To explore the histogenesis and neural differentiation of gastrointestinal stromal tumor (GIST). METHODS: The ultrastructural morphology and neural differentiated antigen expression were studied in 20 cases of GIST using electron microscopy and immunohistochemistry. RESULTS: All 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. CONCLUSIONS: It'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.

[Study on the origin and differentiation of gastrointestinal stromal tumors].

OBJECTIVE: To explore the origin and differentiation of gastrointestinal stromal tumors (GISTs). METHODS: Immunohistochemistry staining and electron microscopy were adopted. RESULTS: In 212 cases of primary GISTs, the positive rates of CD117, CD34, alpha-SMA, MSA, desmin, S-100, PGP9.5 were 96.7%, 77.3%, 19.3%, 15.6%, 1.9%, 16.3%, and 12.3% respectively. Among them, GISTs showed a diffuse and strong positivity for CD117. Electron microscopy of tumor cells demonstrated numerous mitochondria, prominent perinuclear Golgi complex, smooth and rough endoplasmical reticulum and intermediate filaments. Irregular caveolae, dense plaque, incontinuous basal lamina were observed occasionally. Cytoplasmic processes were often observed accompanying with local adhesion present between the processes or between the processes and the cell membrane. CONCLUSIONS: Data from both immunophenotype and electron microscopy suggest that GIST might originate from the mesenchymal cells, differentiating to be ICC afterwards, and possessing myoid characteristics in various extent.