Venetoclax combined with avapritinib for treatment of refractory/relapsed acute myeloid leukemia with KIT gene mutation: report of 2 cases and review of literature / 白血病·淋巴瘤

Objective:To investigate the therapeutic efficacy of venetoclax combined with avapritinib in treatment of refractory/relapsed acute myeloid leukemia (AML) with KIT gene mutation.Methods:The clinical data of 2 AML patients with KIT gene mutation who received venetoclax combined with avapritinib admitted to Canglang Hospital of Suzhou in October 2022 and November 2022 were retrospectively analyzed, and the relevant literature was reviewed.Results:Both patients with high-risk relapsed/refractory AML and KIT gene mutation were females; the one was 53 years and the other was 17 years. Case 1 was diagnosed with AML-M 2, and genetic testing revealed positive mutations in ASXL1, KIT, and RUNX1. The patient relapsed after transplantation and then was treated with venetoclax combined with avapritinib achieving morphologic leukemia-free status (MLFS). Case 2 was diagnosed with AML, and RUNX1-RUNX1T1 (AML1-ETO) fusion gene and KIT and DX15 gene mutations were detected. The patient was treated with venetoclax combined with avapritinib regimen after relapse, and the treatment regimen significantly reduced the tumor load. Complete remission was achieved after bridging to allogeneic hematopoietic stem cell transplantation. Conclusions:AML with KIT gene mutation is heterogeneous and some patients are difficult to treat with very poor prognosis. Bridging (secondary) hematopoietic stem cell transplantation can be the better treatment choice for relapsed patients achieving MLFS or complete remission after venetoclax combined with avapritinib treatment regimen.

Identificación de una deleción causante de tumor del estroma gastrointestinal (Gist) por el análisis de los genes KIT y PDGFRA / Identification of a causative deletion of gastrointestinal stromal tumor (gist) by the analysis of the KIT and PDGFRA genes

Optimizar la detección de mutaciones en los genes KIT y PDGFRA en una muestra de tumor del estroma gastrointestinal (GIST). Material y Métodos: Se analizó una muestra de tumor GIST fijada y embebida en parafina. Mediante la técnica de reacción en cadena de la polimerasa (PCR) se amplificaron los exones 9, 11, 13 y 17 del gen KIT y los exones 12 y 18 del gen PDGFR que contienen las mutaciones causales de GIST. Se confirmó la amplificación mediante electroforesis en gel de agarosa al 2%. Los fragmentos amplificados, fueron purificados y secuenciados en un analizador genético. Se detectó una sobreposición de bases propio de una deleción por lo que se tuvo que clonar los productos del exón 11 para identificar el alelo mutado. Resultados: Se determinó la presencia de una mutación patogénica en el exón 11 del gen KIT. Dicha mutación es una deleción de 15 pares de bases que genera la pérdida de 5 aminoácidos en el receptor tirosina kinasa KIT. Se encontraron polimorfismos neutrales en los exones 11 del gen KIT y en el exón 18 del gen PDGFRA. Conclusión: El análisis molecular mediante secuenciación automática, permitió identificar una mutación en el gen KIT en una muestra de tumor GIST. Esta técnica puede ser aplicada para caracterizar las mutaciones genéticas de casos peruanos de GIST y así poder establecer un tratamiento adecuado según su perfil mutacional...

Objective: To optimize the detection of mutations in the genes KIT and PDGFRA in a sample of gastrointestinal stromal tumor (GIST). Material and Methods: We analyzed a GIST tumor sample fixed and embedded in paraffin. Using the technique of the polymerase chain reaction (PCR) we amplified exons 9, 11, 13 and 17 of the KIT gene and exons 12 and 18 PDGFR gene which contain tha causal mutations of GIST. PCR amplification was confirmed by gel electrophoresis on 2% agarose. The amplified fragments were purified and cloned for subsequent sequencing. An overlap of baeses, characteristic of a deletion was detected, so we had to clone the exon 11 products to identify mutated allele. Results: We determined the presence of a pathogenic mutation in exon 11 of KIT gene. The mutation is a deletion of 15 base pairs and generates a loss of 5 amino acids in the KIT receptor tyrosine kinase. Neutral polymorphisms were also found in exon 11 of KIT gene and exon 18 of PDGFRA gene. Conclusion: Molecular analysis by automatic sequencing identified a mutation in the KIT gene in a tumor sample GIST. This technique can be applied to characterize genetic mutations Peruvian cases of GIST and thus establish adequate treatment by mutational profile...

A Case of an Extragastrointestinal Stromal Tumor of the Pelvic Cavity Presenting with Hematuria / 대한내과학회지

Although gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract, it also occurs in the non-gastrointestinal tract, and is referred to as extragastrointestinal stromal tumor (EGIST). In this report, we describe a 48-year-old female patient who presented with hematuria, and who was finally diagnosed with a primary extragastrointestinal stromal tumor of the pelvic cavity involving the bladder, vagina and left ureter. Tumor cells were positive for immunohistochemical staining for CD117 antigen (proto-oncogene protein c-kit), CD34, and vimentin, whereas they were negative for desmin, smooth muscle actin, and S-100 protein. These findings provide histopathological and immunohistochemical evidence for diagnosing this tumor as EGIST.

Gene mutation and prognosis of extragastrointestinal stromal tumor / 中华普通外科杂志

Objective To evaluate prognostic significance of c-kit and PDGFR-α gene mutation in extragastrointestinal stromal tumors(EGIST). Methods Paraffin embedded tissue specimens from 23 EGISTs were tested for CD117,CD34 and Ki-67 expression by immunohistochemical method.EGIST cases were also tested for the presence of c-kit exons 9,11,13,17 mutations and PDGFR-α exons 12,18 mutations.Kaplan-meier survival rate was used to evaluate the prognostic factors. Results Of 23 cases of EGIST,23(100%)were positive for CD117,17(74%)were positive for CD34.For Ki-67 labeling index(Ki-67 LI):30%were＜1%,44%were between 1%-5%,26%were＞5%.C-kit mutations were detected in 44% of EGIST patients and all were of exon 11 mutations.PDGFR-α mutations were found in 13%of all the 23 cases and all were of exon 18 mutations(The commonest type of mutation D842V).Survival analysis indicated that mitotic count and Ki-67 index were significant predictors for survival.Conclusion The pattern of c-kit and PDGFR-α mutation in EGIST was essentially similar to that in GIST.But the mutation frequency of PDGFR-α was slightly higher in EGIST than in GIST.EGIST could be a special subtype of GIST.The results of this study also show combination of mitotic counts and Ki-67 labeling index may be useful for predicting the prognosis of EGIST.

Analysis of c-Kit Gene Polymorphism in NK/T Cell Lymphoma in Korean Population / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The proto-oncogene c-KIT encodes a receptor tyrosine kinase (KIT) whose ligand is a stem cell factor. KIT is expressed and critical for the development and growth of mast cells, melanocytes, hematopoetic stem cells, and the interstitial cells of Cajal. In this study, c-kit gene mutations were analyzed in 27 cases of NK/T cell lymphoma. SUBJECTS AND METHODS: During 1995 to 2002, 27 patients with NK/T cell lymphoma in the head and neck area were selected for this study. The nasal cavity were predominant sites (15 cases), followed by 6 nasopharynx cases, 4 tonsil 4 cases, and 2 hard palate cases. Gene mutation was analyzed by PCR-SSCP and direct sequencing. RESULTS: c-kit gene mutation was found in 5 of 27 cases by the PCR-SSCP method. Among the 5 cases, 2 cases exhibited no mutation by direct sequencing. Consequently, the mutation of c-kit gene was detected in 3 of 27 cases. CONCLUSION: The frequency of c-kit gene mutation (11%) indicated in the present cases is lower than that reported in north China but higher than that in Japan.

Malignant Gastrointestinal Stromal Tumor of the Gallbladder

Gastrointestinal stromal tumors (GISTs) of the gallbladder are representative of an extremely rare group of tumors. We have encountered a patient with a malignant GIST of the gallbladder and presented it with a review of some articles. A 72-yr-old woman initially presented with right upper quadrant abdominal pain, fever and chills. Emergency cholecystectomy was performed under the impression of gallbladder empyema. Liver metastasis was found at 7 months postoperatively and the patient expired 9 months after the surgery. At the time of cholecystectomy, the gallbladder showed a necrotic serosal surface with an irregular thickened wall. A mass, 6 cm in length and 3 cm in width, encircled the whole wall of the neck and upper body of the gallbladder. Microscopic findings revealed frequent mitotic figures (more than 20/50 HPF) and tumor necrosis. Hyperchromatic, pleomorphic and spindle shaped neoplastic cells that were arranged in a pattern of short fascicles infiltrated the entire layer of the gallbladder. The tumor cells were immunoreactive for CD117 antigen (c-kit protein) and vimentin. They were negative for desmin, smooth muscle actin and S-100 protein. Mutations of the c-kit proto-oncogene were not found in this case. These findings were sufficient to provide enough clinical, histopathological and immunohistochemicalevidence in diagnosing our case as a malignant 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.

Immunohistochemical Expression of CD117, CD34, Vimentin and alpha-Smooth Muscle Actin in Gastrointestinal Stromal Tumors

BACKGROUND: The interstitial cell of Cajal (ICC), the cell of origin for gastrointestinal stromal tumor (GIST), expresses CD117 (c-kit) which is a receptor for KIT ligand in cell membranes. It is immunohistochemically positive for CD117, CD34 and vimentin, but not for alpha-smooth muscle actin (SMA). METHODS: We performed the immunohistochmical study with anti-CD117, anti-CD34, anti-VMT and anti-alpha-SMA in paraffin-embedded tissue of 28 GISTs and 19 smooth muscle tumors arising in the gastrointestinal tract, mesentery, omentum and retroperitoneum (GISMT) to determine the precise nature of GIST cells. RESULTS: The positive rates of CD117, CD34 and vimentin in extraGISTs were significantly higher than in GISMTs. The positive rate of alpha-SMA in GIST was not significantly different than in GISMTs. CONCLUSIONS: A subset of GISTs may express alpha-SMA as well as CD117 and the cell of their origin may be a ICC precursor cell which is capable of differentiating bidirectionally into ICC and smooth muscle cell. This explains why GISTs may arise out of gut where ICC is not present and that they may represent the tumors arising from ICC precursor cell present around the gastrointestinal tract.

Primary Extragastrointestinal Stromal Tumor (EGIST) of the Greater Omentum

Gastrointestinal stromal tumors (GISTs) were recently defined as spindle cell, epithelioid, or occasionally, pleomorphic mesenchymal tumors of the gastrointestinal tract that express the CD117 (proto-oncogene c-kit protein, stem cell factor receptor), as detected using immunohistochemistry. And they show a new tendency to include the CD117-positive mesenchymal spindle cell or epithelioid neoplasms primary in the omentum and mesentery, and is so termed extragastrointestinal stromal tumors (EGISTs). Omental EGISTs are very rare and similar to their gastrointestinal counterpart. We present a case of primary EGIST of the greater omentum in a 58-year-old man. The resected tumor mass measured 20X15X5 cm and weighed 1,150 g. The cut surface displayed a central cystic change and partial mural nodules. Microscopically, most parts of the tumor were composed of round or polygonal cells, with many of them containing perinuclear vacuoles. The mitotic count was less than one per 50 high-power-fields. Immunohistochemically, the tumor cells were diffusely positive for CD117 and vimentin, and focally for smooth muscle actin and CD34. Ultrastructurally, partially smooth muscle differentiation was confirmed in this case.

Expression of cell kit on peripheral blood monocytes of patients with systemic lupus erythematosus / 中华风湿病学杂志

0 05).Conclusion C kit level may be more closely related to the clinical parameters in SLE patients,which may reflect the clinical status of SLE patients.

Clinical analysis of the CD_(117)-weak and CD_(117)-negative gastrointestinal stromal tumors:a report of 13 cases / 肿瘤研究与临床

Objective To explore the CT features in CD_(117)-weak and CD_(117)-negative gastrointestinal stromal tumors(GIST).Methods The CD_(117)-weak and CD_(117)-negative Gist proved by pathologically and sur- gically in 13 cases were retrospectively analyzed.Results The tumor was located in the stomach in 6 cases, small intestine in 4 cases,colorectum in 2 cases,greater omentum in one case.The most common clinical manifestations were abdominal pain or discomfort in 6 cases,hematemesis or melena in 3 cases.Malignant tu- mors occurred in 8 cases.Benign tumors occurred in 5 cases.A soft tissue was identified in all 13 cases in CT examination.The CT examinations revealed cystic regions and bleeding in 5 cases.Calcification was not noted within the masses in all cases.The mean diameter of benign tumors was 3.4 cm?2.8 cm while that of malig- nant tumor was 7.5 cm?6.2 cm.All the cases underwent operation,the resection rate was 100%.After follow up from 6 months to 4 years in 10 cases,1 case died of tumor recurrence and metastasis,the others survived. Conclusion CD_(117)-weak and CD_(117)-negative Gist occurred more common in the stomach.CT is useful in lo- cation and differentiation of CD_(117)-weak and CD_(117)-negative gastric stromal tumors with regard to benign or malignant.Surgery is the main method for final diagnosis and treatment.

Significance of CD117 and CD34 expression in gastrointestinal stromal tumors / 中国病理生理杂志

AIM: In this article, gastrointestinal tumor-related historical archives of pathology in our hospital were reviewed in order to acknowledge gastrointestinal stromal tumors (GIST). METHODS: These cases were rediagnosed correctly , these tissues were labeled with some antibodies such as CD117, CD34, ?-SMA, S-100, and their clinical characteristics were explored. RESULTS: CD117, CD34 were expressed widely in GISTs ,the percentage of positive expression was CD117 (50/56, 89.3%), CD34 (37/56, 66.1%), respectively, ?-SMA, S-100 were (17/56, 30.4%), (4/56, 7.1%), respectively, desmin was negative in these cases. Among them, 29 cases were benign and borderline, 27 cases were malignant. The percentage of occurring in stomach and intestine was 91.1%. CONCLUSION: CD117, CD34 are expressed significantly in GIST, these might be assistant markers for GIST diagnosis. GISTs mostly occurred in stomach and intestine.