Sudden extramedullary and extranodal Philadelphia-positive anaplastic large-cell lymphoma transformation during imatinib treatment for CML:A case report

BACKGROUND Chronic myeloid leukemia(CML)is a malignant hematologic malignancy that can progress to blast phase with a myeloid or lymphoid phenotype.Some patients with CML can also progress to blast crisis phase;however,the transformation of CML into Philadelphia-positive lymphoma is extremely rare.CASE SUMMARY We present a patient with CML who experienced a sudden transformation to anaplastic large-cell lymphoma(ALCL)after 7 mo of treatment with imatinib,during which she had achieved partial cytogenetic response as well as early molecular response.The patient noticed a mass in her left shoulder,the biopsy data of which were consistent with ALCL;moreover,her lymphoma cells exhibited BCR-ABL gene fusion.The patient was diagnosed with Philadelphia-positive ALCL that progressed from CML,and was thus treated with the second generation tyrosine kinase inhibitor nilotinib.Six months later,the mass had totally disappeared and the BCR-ABL fusion gene was undetectable in the peripheral blood.To our knowledge,this is the first patient known to have developed Philadelphia-positive ALCL transformed from CML.CONCLUSION Unexplained lymphadenopathy or an extramedullary mass in a patient with CML may warrant a biopsy and testing for BCR-ABL fusion.

MDR1 Haplotypes and G2677T/A Polymorphism Predict Imatinib Response in Tunisian Patients with Chronic Myeloid Leukemia

Background: The role of human multidrug resistance gene (MDR1) SNPs in the interindividual variability of imatinib mesylate (IM) response has received considerable attention. We aimed to study the association between SNPs of the MDR1 gene (C1236T, G2677T/A, C3435T) and IM response in chronic myeloid leukemia (CML) patients. Method: A retrospective case-control study was conducted on 48 patients with CML undergoing IM therapy. All patients were genotyped using PCR-RFLP method. Results: The genotype and allele frequencies of C1236T and C3435T were not significantly different between CML patients responders and non-responders to IM (p > 0.05). The frequencies of 2677T allele and 2677TT genotype were significantly increased in CML patients IM responders which as compared with IM non-responders (50% vs 26.9%, p = 0.013 and 27.3% vs 3.8%, p = 0.029 respectively). Whereas the 2677AA genotype and CAC haplotype were found only in CML patients IM non-responders (15.4%). Conclusion: Pretreatment genotyping of G2677A/T appears to be useful for predicting IM resistance, which may allow the best choice of drug treatment for CML patients.

Current update on molecular cytogenetics, diagnosis and management of gastrointestinal stromal tumors

Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors of the gastrointestinal(GI)tract and are thought to arise from precursors of the interstitial cells of Cajal.GISTs can arise anywhere in the GI tract,but most commonly originate from the stomach and small intestine.The majority of GISTs occur as a result of activating mutations in two receptor protein tyrosine kinases:KIT and/or platelet-derived growth factor receptor-α.Mutational analyses allow for predicting patient prognosis and treatment response.Clinical presentations can vary from no symptoms,typical in the case of small incidentally found tumors,to GI bleeding,abdominal discomfort,and ulcer-related symptoms when the tumor is enlarged.Imaging plays a critical role in the diagnosis and management of these tumors with multiphasic computed tomography serving as the imaging modality of choice.Magnetic resonance imaging and positron emission tomography-computed tomography can serve as imaging adjuncts in lesion characterization,especially with liver metastases,and subsequent staging and assessment for treatment response or recurrence.Surgical resection is the preferred management for small GISTs,while tyrosine kinase inhibitors−imatinib mesylate and sunitinib malate−serve as crucial molecular-targeted therapies for locally advanced and metastatic GISTs.This review article highlights the clinical presentation,pathology and molecular cytogenetics,imaging features,and current management of GISTs.

Pancreatic extragastrointestinal stromal tumor:A case report and comprehensive literature review

AIM: To provide an overview of the literature on pan-creatic extragastrointestinal stromal tumors(EGISTs).METHODS: We report a case of pancreatic EGIST and review published studies on pancreatic EGIST ac-cessed via the PubMed, MEDlInE, Google Scholar, and Google databases. The keywords used were "pancreas and GIST", "pancreas and extra GIST", "pancreas and gastrointestinal stromal tumor", and "pancreas and ex-tragastrointestinal stromal tumor". literature reviews and/or duplicate studies were excluded. The search included articles published in the English language be-tween January 1, 2000 and May 15, 2014.RESULTS: From our literature survey, 30 manuscripts on pancreatic EGISTs were considered, of which 27met the search criteria and three were excluded. The studies involved 30 patients(15 men, 15 women) with a mean age of 55.3 ± 14.3 years(range 30-84 years). The mean age of the male patients was 50.8 ± 13.7 years(range 30-84 years); that of the female patients was 59.9 ± 13.3 years(range 38-81 years). Tumor dimensions were obtained for 28 cases(mean 114.4 ± 78.6 mm; range 20-350 mm). Tumors were diagnosed incidentally in 23.3% of patients; abdominal discomfort and weight loss were the major complaints in symp-tomatic patients. Risk of aggressive behavior according to Fletcher criteria was determined in 25 of 30 patients(68%: high risk, 28%: intermediate risk, 4%: low risk). Histopathological examination revealed the presence of spindle cells in 96.1% of cases; CD117 and CD34 were present immunohistochemically in 96.6% and 84% of patients, respectively. The most common surgical pro-cedures were distal pancreatectomy with splenectomy(n = 9) and pancreaticoduodenectomy(n = 7). The to-tal follow-up period for the 28 patients ranged from 3-66 mo, during which locoregional or distant metastases were diagnosed in six patients and two patients died.CONCLUSION: Studies on EGISTs have only been published in the last decade. The lack of studies with large patient cohorts and long-term follow-up limits evidence-based commentary. In theory, each case should be assessed individually and further genetic and immunohistochemical studies are needed.

Gastrointestinal tumors in transplantation: Two case reports and review of literature

BACKGROUND Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors of the gastrointestinal tract.As most of them harbor a KIT mutation(75%),selective kinase inhibitors are the therapeutic option and show a sustained objective response among patients with metastatic or unresectable GISTs.A wellknown higher risk of neoplasm has been described among renal transplant recipients(RTRs).Nevertheless,only few cases of GIST onset among transplant patients have been reported in the literature.CASE SUMMARY Here,we describe 2 cases of gastric GIST occurring during the follow-up of RTRs.We also review the existing literature concerning GIST occurrence in transplant patients.In total and in association with our 2 cases,16 patients have been reported.The median age was 59.5 years and 69%were male.With a median tumor size of 45 mm,no patient displayed metastatic dissemination at diagnosis.Time from transplantation to diagnosis was highly variable between 5 mo and 21 years.Histopathological data mostly revealed high risk of progression(43%).Death increased to 29%during follow-up.Surgical treatment was systematically performed when the tumor was operable(94%).The use of adjuvant therapy was uncommon(19%).CONCLUSION GISTs represent rare but potentially severe malignant complication among transplant patients.