History Of Gastrointestinal Stromal Tumor Research Articles

Inclusion body myositis triggerred with long-term imatinib use.

Imatinib is an orally administered tyrosine kinase inhibitor with wide clinical use in different indications from solid tumors to hematologic malignancies. Inclusion body myositis (IBM) is an acquired myopathy of both inflammatory and degenerative nature. We present an 81 years old male with a history of gastrointestinal stromal tumor (GIST) operated 8 years ago and was evaluated for the progressive loss of weight and muscle strength leading to total immobilization in 6 months. He was under imatinib for 8 years despite the remission of GIST. Physical examination disclosed diffuse loss of muscle strength, most prominently involvement of distal upper and proximal lower extremity in an asymmetrical pattern with normal serum creatinine kinase level (CK). Further investigations including bilateral thigh MRI, electromyography (EMG), and PET/CT suggested myositis and degenerative myopathy and ruled out any malignancy. Quadriceps femoris biopsy proved the diagnosis of IBM and no trigger except for imatinib was displayed. Clinical improvement in terms of weight loss and muscle weakness was achieved after the discontinuation of imatinib. This is the first case of IBM associated with prolonged use of imatinib not reported in the literature so far. Since imatinib is widely used in different conditions, it is important to be aware of even its rare adverse effects. Poor response of IBM to conventional immunosuppressive agents enhances the value of etiology identification to relieve symptoms in addition to supportive care.

Inherited Germline DNA Repair Gene Defects Are Prevalent Among Thai Patients with Myeloid Neoplasms

Certain germline mutations increase the risk of developing myeloid neoplasms (MNs) accompanied by second hit somatic events, such as therapy-related or oxidation-induced DNA damages. Aberrancy in DNA damage response (DDR) pathways leads to genomic instability giving rise to cancer. Previous data showed that the prevalence of pathogenic germline mutations in young adult Caucasian MN patients was 13-19%.1, 2 The most commonly affected pathways were involved in telomere biology and transcription factors, while the defects in DDRs were found in 15-25%. However, data in Asians are limited. In this study, we investigated the prevalence and landscape of germline variants in cancer predisposition genes in a cohort of Thai patients diagnosed with MNs. Targeted next generation sequencing of 23 germline predisposition genes was performed using the SureSelect custom kit and the Illumina HiSeq 2500 system. The total of 127 unselected adult (> 15 years old) patients from 3 medical centers comprising MDS (66%), MDS/MPN (14%) secondary AML (sAML, 20%) were enrolled. The median age was 66 years old (range 16-93) and 50% were male. Variants reported in COSMIC, the frequency of higher than 0.01% in the Genome Aggregation Database (gnomAD) or Thai exome database (consisted of 1084 Thai exome controls) and variant allelic frequency of less than 30% were excluded. New or exceeding rare nonsense variants or indels, as well as missense variants predicted to be deleterious by at least 4/6 in silico software, were included. The variants were classified according to American College of Medical Genetics (ACMG) classification. 14pathogenic and likely pathogenic germline variants were identified in 15 patients (15/127; 12%). One patient had 2 variants including heterozygous CEBPAP75fs and MSH2A604G. Of the 16 variants, there were 8 (50%) missense, 7 (44%) frameshift, and 1 (6%) nonsense, with a median VAF of 51%, ranging 36-83%. The variants affected the DDR pathway (8/16; 50%), transcriptional regulation pathway (4/16; 25%) and signal transduction pathway (2/16; 13%). Two variants were recurrent i.e.,FANCAAla1219GlyfsTer59 and BRCA2Glu626delinsAspPro and the others were identified in BRCA1/2, MSH2, MSH6, GATA2, CEBPA, DDX41, CBL and NF1. The median age of patients harboring germline variants was younger (58 vs. 66 years old) than those who did not. Half of the cases (6/12) were characterized by normal cytogenetics without enrichment of -7 or complex karyotype, comparable to patients with no germline variants. Of note, 28% (4/14) patients had previous history of gastrointestinal stromal tumor, Graves’ disease, Immune thrombocytopenia, and aplastic anemia (FANCA mutation) for years before MNs were diagnosed. None of the patients reported family history of hematological malignancies. In conclusion, the prevalence of germline predisposition to MNs in Southeast Asian populations is as high as in Caucasians and the identified variants are more commonly involved in the DDR pathway. The defects in the DDR pathway suggested an important role of genomic instability in leukemogenesis. This subset of patients should preferably receive non-cytotoxic treatments to avoid oxidative damages that possibly lead to further clonal evolution. ReferencesKeel SB, Scott A, Sanchez-Bonilla M, Ho PA, Gulsuner S, Pritchard CC, et al. Genetic features of myelodysplastic syndrome and aplastic anemia in pediatric and young adult patients. Haematologica 2016 Nov; 101(11): 1343-1350. Feurstein S, Churpek JE, Walsh T, Keel S, Hakkarainen M, Schroeder T, et al. Germline variants drive myelodysplastic syndrome in young adults. Leukemia 2021 2021/08/01; 35(8): 2439-2444.

November 2022 Imaging Case of the Month: Out of Place in the Thorax

No abstract available. Article truncated after 150 words. History of Present Illness: A 30-year-old woman presented with complaints of left-sided back pain and numbness. She denied any history of trauma. PMH, SH, FH: No significant past medical history. She denied smoking and use of illicit substances. Her family history was largely unremarkable, positive only for a history of gastrointestinal stromal tumor affecting her father. Medications: Her medications included fluoxetine, spironolactone, and Celebrex (celecoxib). Physical Examination: The patient’s physical examination showed her to be afebrile with pulse rate and blood pressure within the normal range. Laboratory Evaluation: A complete blood count showed a hemoglobin and hematocrit value of 14.3 gm/dL (normal, 13.2-16.6 gm/dL) and 41.5% (normal, 38.3-48.6%) and a platelet count of 253 x x109/L (normal, 135-317 x109/L). The white blood cell count was normal at 6.9 x109/L (normal, 3.4-9.6 x109/L), with no left shift. The eosinophil count was normal. Liver function studies were entirely normal. Serum chemistries were …

Metachronous occurrence of gastrointestinal stromal tumor and acute promyelocytic leukemia in a patient with ankylosing spondylitis: A case report

Gastrointestinal stromal tumors are the most common mesenchymal tumor of the alimentary canal. Acute promyelocytic leukemia (APL) is a unique subtype of acute myeloid leukemia. A 57-year-old male patient with a previous record with history of gastrointestinal stromal tumors (GIST) and ankylosing spondylitis, was hospitalized with right ankle and foot swelling and pancytopenia. A diagnosis of APL was made by bone marrow aspiration and cytogenetic study. After a combined treatment with all-trans retinoic acid and arsenic trioxide, the patient achieved cytogenetic and molecular remission. According to past studies, the synchronous or metachronous coexistence of GISTs with other malignancies, such as lymphoma, liver cancer and pancreatic tumors has been widely reported. This study describes a patient with the metachronous occurrence of a CD34 positive GIST and APL. We suggest, the minor alterations in hematological parameters must be taken into consideration for such cases.

Massive Multifocal Familial GIST: A Case Report

Gastrointestinal stromal tumors (GIST) are uncommon mesenchymal neoplasms of the gastrointestinal tract. The majority of GISTs are the result of sporadic mutations, most commonly of the KIT proto-oncogene. Germline mutations account for 5% of GISTs and result in rare familial syndromes. We present a 66-year-old male with a family history of GIST who presented with mild abdominal pain and was found to have a massive, multifocal GIST. The main tumor was resected via laparotomy and the weight was found over 2 kg. He was commenced on adjuvant therapy with imatinib and will be closely monitored. Familial GISTs tend to be larger, multifocal and diagnosed at a younger age. Familial GISTs are extremely rare conditions. There is little to no evidence on the long-term outcomes of treatment on which to base management decisions.

Inguinal GIST: A Systematic Literature Review of Primary and Metastatic Cases.

Gastrointestinal stromal tumor (GIST) has a wide spectrum of clinical manifestations. Involvement of the groin region can cause interesting presentations but, as of 2020, has rarely been investigated. Our aim was to assess the clinicopathological and prognostic features of GIST appearing in this specific part of the body. We investigated the world literature dealing with primary or metastatic GIST appearing in the inguinal region (IGIST). A case of metastatic IGIST from our clinical records was also included. We found only six cases of primary and nine of metastatic IGIST. All were of male gender, and most aged 60 years or more (10 cases). Inguinal hernia (11 cases) was the patient type most frequently affected. The association between metastatic IGIST and inguinal lymphadenopathy was statistically significant (p=0.049). IGIST is a rare entity with particular clinical manifestations. Inguinal hernia and inguinal lymphadenopathy should be carefully investigated in patients with a history of GIST.

Determination of the absolute bioavailability of oral imatinib using a stable isotopically labeled intravenous imatinib-d8 microdose

PurposeThe aim of this study was to ascertain whether the absolute bioavailability of oral imatinib (Glivec®) during steady state plasma pharmacokinetics in cancer patients could be determined through a concomitant intravenous administration of a single 100 μg microdose of deuterium labeled imatinib (imatinib-d8). Secondly, the usefulness of liquid chromatography–tandem mass spectrometry (LC-MS/MS) was investigated for simultaneous analysis of orally and intravenously administered imatinib.MethodsIncluded patients were on a stable daily dose of 400 mg oral imatinib prior to study participation. On day 1, patients received a 100 μg intravenous imatinib-d8 microdose 2.5 h after intake of the oral dose. Plasma samples were collected for 48 h. Imatinib and imatinib-d8 concentrations were simultaneously quantified using a validated LC-MS/MS assay. The absolute bioavailability was calculated by comparing the dose-normalized exposure with unlabeled and stable isotopically labeled imatinib in plasma.ResultsA total of six patients were enrolled. All patients had a history of gastrointestinal stromal tumors (GIST). The median absolute bioavailability of oral imatinib at steady state was 76% (range 44–106%). Imatinib and imatinib-d8 plasma concentrations were quantified in all collected plasma samples, with no samples below the limit of quantification for imatinib-d8.ConclusionThe absolute bioavailability of imatinib was successfully estimated at steady state plasma pharmacokinetics using the stable isotopically labeled microdose trial design. This study exhibits the use of a stable isotopically labeled intravenous microdose to determine the absolute bioavailability of an oral anticancer agent in patients with LC-MS/MS as the analytical tool.

2667 Can't You GIST Move Over?

INTRODUCTION: Gastrointestinal stromal tumors (GISTs) are a common mesenchymal tumor of the GI tract. Here we present a case of a 60-year-old male with a 33.5 × 27 cm GIST arising from the greater stomach curvature, increased in size from 18.1 × 13.4 cm in five months; an alarming growth rate for a tumor known to grow slowly. CASE DESCRIPTION/METHODS: 60-year-old male with history of GIST and HTN presented to the hospital with abdominal pain and shortness of breath. Physical exam revealed decreased bowel sounds and diffuse tenderness to palpation in the right and left lower quadrants. Patient had previously been diagnosed with a 18.1 × 13.4 cm GIST 5 months prior, and was positive for CKIT (CD117) and DOG1, with 6 mitotic figures/21 HPFs (Figure 1). The patient was lost to follow up and never started on Imatinib. Over a span of five months, the necrotic mass had doubled in size with a repeat CT scan on admission showing a 33.5 × 27 cm GIST (Figures 2 and 3) arising from the greater stomach curvature, invading the left hepatic lobe and compressing the inferior vena cava (IVC). During this admission, he was also found to have bilateral pulmonary embolism, with large clot burden and right heart strain. An IVC filter would have been ideal for prevention of further clot migration, however the compression of the IVC by enlarging GIST prevented intervention. Patient was treated with heparin and started on Imatinib as an outpatient, patient is doing well and following with oncology. DISCUSSION: GISTs can be found in any part of the gastrointestinal tract, with predominance in the stomach. GISTs are often asymptomatic and diagnosed incidentally or they may present with nonspecific symptoms such as early satiety, abdominal pain, anemia, GI bleed or gastric outlet obstruction. Treatment options are dictated by risk of progression which is determined by size (≥3 cm), location, and mitotic count. [1] While the exact rate of tumor growth is unknown, studies have shown a range of 1.2 to 50.7% per annum [2]. On representation to the hospital five months after initial diagnosis, our patients’ mass had increased in size by 54% which surpasses documented growth rates. His mass also created significant compression and prevented integral placement of an IVC filter. While GIST tumors are traditionally thought to be slow growing tumors our case highlights the importance of earlier intervention in high-risk patients; metastatic and compressive complications could have been avoided for this patient had he returned for initial follow-up.

Metastatic Cutaneous Duodenal Gastrointestinal Stromal Tumor: A Possible Clue to Multiple Metastases

We report a case of a 69-year-old man with metastatic cutaneous duodenal gastrointestinal stromal tumor, which led to find multiple metastases on orbital muscle and scalp. The patient presented with a rapidly growing chest nodule with mild tenderness. He underwent surgical resection for duodenal gastrointestinal stromal tumor and had been treated with imatinib for three years. Histopathological examination of the chest nodule was consistent with gastrointestinal stromal tumor. A brain magnetic resonance imaging of follow work-up revealed multiple metastases at the left superior rectus muscle and occipital scalp. Under the diagnosis with imatinib-resistant duodenal gastrointestinal stromal tumors, a second-line therapy with sunitinib was tried. After six weeks, his skin lesion was completely improved and other metastatic cancers showed a response of stable disease. This is the first reported case of a cutaneous metastasis from duodenal GIST. This report emphasizes the importance of a full-skin examination in patients with a medical history of gastrointestinal stromal tumor which leads to find multiple metastases.

Management of obstructive jaundice in stage IV cholangiocarcinoma with peritoneal carcinomatosis and history of gastrointestinal stromal tumor

Management of obstructive jaundice in stage IV cholangiocarcinoma with peritoneal carcinomatosis and history of gastrointestinal stromal tumor

A case of multiple gastrointestinal stromal tumors caused by a germline KIT gene mutation (p.Leu576Pro)

Multiple gastrointestinal stromal tumors (GISTs) caused by germline KIT gene mutations are an extremely rare autosomal dominant disorder. We report a case of a 21-year-old woman who presented to the emergency department with a 2-week history of asthenia, palpitations and upper gastrointestinal bleeding. After further clinical evaluation one gastric and two small bowel GISTs were diagnosed, which were surgically resected after neoadjuvant therapy with Imatinib. Diffuse hyperplasia of the interstitial cells of Cajal was also seen in the background gastric and small intestinal walls. Somatic mutational analysis of the KIT gene revealed a substitution at codon 576 in exon 11 (p.Leu576Pro) in all tumors and normal ileal mucosa. The germline nature of this mutation was confirmed by mutation analysis in peripheral blood leukocytes. However, she had no familial history of GISTs and her parents did not carry the respective germline mutation.

A Case Report of Post-Operative Jöd-Basedow Phenomennon Following Oral and IV Iodine Contrast Administration

This is a case of thyrotoxicosis, due to the Jöd-Basedow phenomenon following administration of oral and IV iodinated contrast in a patient with history of gastrointestinal stromal tumor (GIST) and small bowel obstruction. The patient developed atrial fibrillation and had an extended stay in the intensive care unit. Given the aging population with possible subclinical hyperthyroidism, multinodular goiter, and the rise in contrast administration for routine diagnostic studies, this case serves to raise awareness of the risks of “routine” tests administered to our aging patient population.

Familial gastrointestinal stromal tumor with germ line mutation of the juxtamembrane domain of the KIT gene observed in relatively young women

Familial gastrointestinal stromal tumor (GIST) is an extremely rare autosomal dominant disorder, and approximately 20 families have been reported to date. In this article, we present one additional family. A 25-year-old Japanese woman presented with abdominal pain, and subsequent image analyses disclosed multiple tumors measuring 12 cm in maximum diameter in the lower digestive tract. The postoperative histologic examination showed multiple GISTs and diffuse hyperplasia of interstitial cells of Cajal. Her mother had a history of GIST in the digestive tract. Three members of this family including her younger sister and mother had cutaneous hyperpigmentation of external genitalia and axilla. Their DNA samples showed identical missense mutation at exon 11 in the juxtamembrane domain of the KIT gene, and this mutation site was considered to be a hot spot in familial GIST. One year after, her younger sister suffered from multiple GISTs in the digestive tract at the age of 25 years. To correctly diagnose familial GIST, mutual information should be exchanged among clinicians, pathologists, and molecular scientists.

Gastric carcinoid tumor in a patient with a past history of gastrointestinal stromal tumor of the stomach

Gastrointestinal stromal tumor is the most common mesenchymal tumor in the gastrointestinal tract. It may coexist with other type of cancers, and if so, the tumors usually involve the stomach. The most common associated cancers are gastrointestinal carcinomas. We report a 65-year-old woman with a history of gastric gastrointestinal stromal tumor who had undergone subtotal segmental gastrectomy. New polypoid lesions were detected on a follow-up gastroscopy one year later. The lesions were biopsied and found to be carcinoid tumors. There was serum hypergastrinemia, and type 1 gastric carcinoid tumor was diagnosed. A total gastrectomy was performed. Pathologic examination revealed both carcinoid tumors and a recurrent gastrointestinal stromal tumor.

Left Extended Hepatectomy for a Metastatic Gastrointestinal Stromal Tumor After a Disease-Free Interval of 17 Years: Report of a Case

Gastrointestinal stromal tumors (GISTs), although rare, are frequently diagnosed with liver metastasis. These metastatic GISTs are poorly responsive to conventional chemotherapy; however, recent studies report improved survival after complete surgical resection of liver metastases. On the other hand, few reports describe the treatment of delayed liver metastasis after resection of a primary GIST. We report the case of a 55-year-old woman found to have liver metastasis from a GIST after a 17-year disease-free interval. The patient underwent a left extended hepatectomy for a complete resection of the metastatic GIST and is alive and well 30 months later. To our knowledge, this is the longest disease-free interval reported in the literature, and emphasizes the importance of considering late metastasis when evaluating patients with a history of GIST. Thus, surgical resection of delayed liver metastasis from a GIST should be considered as primary therapy.

Expression of Bcl‐2 in gastrointestinal stromal tumors

The natural history of gastrointestinal stromal tumor (GIST) has been revolutionized by imatinib mesylate (imatinib) therapy. Before imatinib, Bcl-2 expression in GIST was associated with a worse prognosis or added no additional prognostic value. To the authors' knowledge, the current study is the first to evaluate Bcl-2 expression in pre-imatinib GIST tissue samples as a prognostic marker of progression-free survival (PFS) time in patients treated with imatinib. The cases of 81 patients with GIST who were evaluated between December 15, 2000 and September 1, 2001 were retrospectively reviewed. Clinicopathologic variables were reviewed. GIST cell morphology and patterns of Bcl-2 expression were described. The methods of Kaplan-Meier and the Cox proportional hazards regression model were used for statistical analysis. Sixty-one (75%) patients had tumors that expressed Bcl-2, and 20 (25%) patients had tumors that were negative for Bcl-2. All epithelioid tumors (n = 12) expressed Bcl-2 and tumors with mixed morphology exhibited Bcl-2 expression in the epithelioid component. A trend toward longer PFS for patients whose tumors expressed Bcl-2 at a greater immunohistochemical intensity was observed (20.6 mos for no Bcl-2 expression; 28.3 mos for 1++Bcl-2 expression; 31.9 mos for 1.5++Bcl-2 expression; 40.8 mos for 2++Bcl-2 expresssion; and 35.9 mos for 3++Bcl-2 expression). In contrast to studies performed in the preimatinib era, in which Bcl-2 was found to be a negative prognostic indicator, the current study suggests a trend toward better PFS with increasing Bcl-2 expression level in GISTs from patients subsequently treated with imatinib. Larger studies may help elucidate the influence of Bcl-2 expression on PFS after therapy with imatinib.