Academic literature on the topic 'Abdominal neoplasms Genes'

This case report describes the history of a 41 year-old woman with a solid pseudopapillary neoplasm (SPN) of the pancreas and a metachronous abdominal desmoid tumor (DT) that occurred two years after the SPN surgical resection. At next-generation sequencing of 174 cancer-related genes, both neoplasms harbored a CTNNB1 somatic mutation which was different in each tumor. Moreover, two BRCA2 pathogenic mutations were found in both tumors, confirmed as germline by the sequencing of normal tissue. The BRCA2 mutations were c.631G>A, resulting in the amino-acid change p.V211I, and c.7008-2A>T, causing a splice acceptor site loss. However, as the two neoplasms showed neither loss of heterozygosity nor somatic mutation in the second BRCA2 allele, they cannot be considered as BRCA-dependent tumors. Nevertheless, this study highlights the important opportunities opened by extensive tumor molecular profiling. In this particular case, it permitted the detection of BRCA2-germline mutations, essential for addressing the necessary BRCA-related genetic counseling, surveillance, and screening for the patient and her family.

Abstract Casestudy: Pancreatic neuroendocrine neoplasms (PanNEN) are rare accounting for 2-5% of pancreatic tumors. Although mostly sporadic, 10-20% are associated with inherited syndromes, notably MEN-1, Von Hippel- Lindau disease, neurofibromatosis type 1, and tuberous sclerosis (TS). When compared to sporadic cases, PanNEN in hereditary syndromes occur at a younger age, are often multifocal, cystic, and may show characteristic microscopic patterns. TS is an autosomal dominant multi-system disorder with mutations involving TSC1 or TSC2 genes which function as tumor suppressors by inhibiting mTORC1 kinase. PanNEN is observed in 1.5-1.8% of patients with TS and no surveillance guidelines for the assessment of pancreatic lesions are established. Compared to other syndromes, PanNEN associated with TS are solitary. To our knowledge, only two cases of multifocal PanNEN in TS patients have been reported. We present a case of a 67-year-old gentleman with a history of TS also affecting two daughters. He presented to the emergency department with severe abdominal pain. Abdominal ultrasound suggested acute appendicitis and an incidental 2.0 cm solid lesion was noted in the head of the pancreas. Follow-up MRI revealed two additional non-cystic masses in the pancreatic tail. Endoscopic ultrasound-guided biopsy of a tail lesion revealed monomorphic tumor cells with stippled chromatin without cytologic atypia. Immunohistochemical staining was positive for synaptophysin and chromogranin. Ki-67 labelling index was under 1%. Diagnosis of a well-differentiated neuroendocrine tumor (G1) was made. The patient denied symptoms of the carcinoid syndrome and no biologically active hormones were detected. Gallium PET scan revealed multiple foci of radiotracer uptake throughout the pancreas in addition to those described on MRI. Although PanNEN are rare in TS, malignant behavior has been reported. This case reinforces the importance of early detection through active surveillance, especially as surgical options may be limited in multifocal disease.

Muir-Torre syndrome (MTS) is a rare genodermatosis, diagnosed by the presence of sebaceous neoplasms along with an internal malignancy, most commonly colorectal carcinomas. MTS is most commonly caused by microsatellite instabilities of the hMLH1 and hMSH2 mismatch repair genes, and is rarely caused by mutations of the hMSH6 gene. We describe the case of a 56-year-old male who presented with an enlarging mass on his back as well as hematochezia. The back mass was excised, and pathology confirmed microsatellite instability in MSH2 and MSH6. Abdominal CT and colonoscopy confirmed the presence of synchronous masses in the cecum, ascending colon, and the transverse colon. He refused any further workup or treatment, only to return 8 months later complaining of hematochezia and discomfort due to an enlarging mass protruding from the rectum. After consenting to surgical intervention, he agreed to outpatient chemotherapy treatment. The presence of sebaceous neoplasms should raise suspicion for the possibility of an associated internal malignancy.

AbstractImmunoproliferative small intestinal disease (IPSID) was recently added to the growing list of infectious pathogen-associated human lymphomas. Molecular and immunohistochemical studies demonstrated an association with Campylobacter jejuni. IPSID is a variant of the B-cell lymphoma of mucosa-associated lymphoid tissue (MALT), which involves mainly the proximal small intestine resulting in malabsorption, diarrhea, and abdominal pain. Geographically, IPSID is most prevalent in the Middle East and Africa. IPSID lymphomas reveal excessive plasma cell differentiation and produce truncated α heavy chain proteins lacking the light chains as well as the first constant domain. The corresponding mRNA lacks the variable heavy chain (VH) and the constant heavy chain 1 (CH1) sequences and contains deletions as well as insertions of unknown origin. The encoding gene sequence reveals a deletion of V region and parts of CH1 domain. Cytogenetic studies demonstrated clonal rearrangements involving predominantly the heavy and light chain genes, including t(9;14) translocation involving the PAX5 gene. Early-stage IPSID responds to antibiotics (30%-70% complete remission). Most untreated IPSID patients progress to lymphoplasmacytic and immunoblastic lymphoma invading the intestinal wall and mesenteric lymph nodes, and may metastasize to a distant organ. IPSID lymphoma shares clinical, morphologic, and molecular features with MALT lymphoma, lymphoplasmacytic lymphoma, and plasma cell neoplasms.

Adrenocortical tumors (ACTs) are rare in childhood, particularly in the neonatal period. ACTs in children usually secrete hormones that can cause virilization, precocious puberty, or Cushing syndrome. However, in many cases the diagnosis is delayed because of the generally healthy appearance of the child and the lack of a palpable abdominal mass. ACTs can also be misdiagnosed as congenital adrenal hyperplasia (CAH) especially if 17-hydroxyprogesterone (17-OHP) is elevated. We describe a case of neonatal ACT diagnosed in an asymptomatic newborn with positive/elevated 17-OHP on newborn screening. On examination there were no signs of virilization, Cushing syndrome, hemihypertrophy, or hypertension, and there was no palpable abdominal mass. While awaiting confirmatory results of an elevated 17-OHP level, an abnormally low adrenocorticotropic hormone level was noted. Abdominal ultrasound, obtained to evaluate the adrenal glands, showed a right adrenal mass with peripheral calcification. MRI revealed a 3.6 x 3.5 x 3.4 cm heterogeneously enhancing ovoid mass in the right adrenal gland. Diagnosis of an ACT was also confirmed by laboratory data, and histopathology of the tumor. Surgical resection was safely performed with perioperative steroid replacement. Genetic analysis of CYP21A2 and CYP11B1 genes was negative. A germ-line point mutation in the TP53 region was discovered, suggesting Li-Fraumeni syndrome. ACTs should be considered in the differential diagnosis of neonates with elevated 17-OHP detected by newborn screening for CAH. Adrenal ultrasound is recommended in cases of significantly abnormal CAH screen results to rule out or treat adrenal neoplasms.

Introduction: Indolent T-cell lymphoproliferative disorder of the gastrointestinal tract (ITCLD-GT) is a newly recognized entity in the 2016 revision of the World Health Organization (WHO) classification of lymphoid neoplasms. ITCLD-GT is defined as a clonal T-cell proliferation occurring in the GT, mostly in colon and small bowel. So far only 52 ITCLD-GT cases have been reported. It has a pathologically nondestructive expansionary growth pattern, a less than 10% Ki67 proliferative index and an indolent clinical course. However, the pathological characteristics of ITCLD-GT in lesions except the small and large intestines, its clinical progress/transformation and pathogenetic mechanisms and molecular alterations remain unknown. Methods: Nine ITCLD-GT cases were collected from one center in southwest China, and their clinicopathological were analyzed. Of these patients, 7 had indolent clinical courses; one had lymph node metastasis in the late stage; and another one transformed into diffuse large B-cell lymphoma (DLBCL) after 16 months (Figure A). In one patient, neoplastic cells involved most of the digestive tract from esophagus to rectum. Whole-exome sequencing was performed in 9 samples from 7 cases. Genome-wide mutation landscape was analysed on these ITCLD-GT samples and pairwise comparison was made between stomach and colon lesions as well as between ITCLD-GT and transformed DLBCL samples. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed. Results: The median age of the patients was 47 years, and the male/female ratio was 7:2. Clinically, these patients presented with diarrhea with or without abdominal pain, abdominal distension, fatigue or hematochezia. Colonoscopy showed thickened intestinal mucosa in 8 cases, with small nodularity and folds in 7 cases and polyps resembling in 1 case. Intestinal mucosa surfaces showed patchy erythema, erosion or superficial ulcer with diameter ≥ 2.5cm. Endoscopy showed thickened gastric mucosa, nodular protrusion or multiple wide pedicle polyps. Microscopically, the lamina propria was displaced by the infiltrate of dense, monotonous and small lymphocytes, but the mucosal glands were not destroyed. All the infiltrated lymphocytes were positive for CD3p and TIA-1, mostly positive for CD2, CD5 and CD7 and negative for CD20 and Granzyme B. 8 cases were positive for CD8 and 1 case expressed CD4. In the case with esophagus and GT involvement, CD56 was positive in gastric and intestinal lesions, but negative in esophageal and colon. The proliferative index of Ki67 was less than 10% in all cases at diagnosis, but in one case it increased to 20% after 4 years (Figure B). In all cases, monoclonal TCR gene rearrangement was positive and EBER1/2 was negative. The landscape of gene alterations using WES in these patients were analysed (Figure C). The recurrent mutated genes included cancer-related gene PDE4DIP, transcription regulatory genes BAZ2B and CNOT6L, signaling transduction-related genes MUC17 and PIEZO2, metabolism regulatory genes PLA2G4D and FRG2C, cytoskeleton and cell adhesion-associated genes COL14A1, DNAH5 and many other genes were shown in Figure C. GO analysis showed that mutated genes were significantly enriched in microtubule cytoskeleton organization. KEGG pathway analysis indicated that the mutated genes were mostly enriched in focal adhesion and ECM-receptor interaction, both associated with cancer development. Pairwise comparison analysis of lesions from the stomach and colon showed that there was almost no genetic difference between the two lesions. JAK3, NRAS and SETD2 mutations and BCOR deletion may contribute to the entire digestive tract distribution of ITCLD-GT. The transformed aggressive DLBCL sample carried 253 more mutated genes than the indolent ITCLD-GT sample. Mutations of TP53, ARID1A, KMT2D and M2P2K1 only in the DLBCL sample may contribute to the transformation of ITCLD-GT to DLBCL. Conclusion: Our study summarized the clinicopathological characterization of 9 cases of ITCLD-GT. ITCLD-GT is generally inert, but it may develop with an increased Ki67 proliferation index in the late stage or even turn into aggressive DLBCL. We characterized the genomic alterations in ITCLD-GT and revealed its molecular pathogenesis and progression, which might be helpful for diagnosis, prognosis and treatment of this rare lymphoid neoplasm. Figure 1 Disclosures No relevant conflicts of interest to declare.

<b><i>Background:</i></b> Several studies have reported an association between microRNAs (miRNAs) and hypertension or cardiovascular disease (CVD). In a previous study performed on a group of 38 patients, we observed a cluster of 3 miRNAs (miR-378a-3p, miR-100-5p, and miR-486-5p) that were functionally associated with the cardiovascular system that predicted a favorable blood pressure (BP) response to continuous positive airway pressure (CPAP) treatment in patients with resistant hypertension (RH) and obstructive sleep apnea (OSA) (HIPARCO score). However, little is known regarding the molecular mechanisms underlying this phenomenon. <b><i>Objectives:</i></b> The aim of the study was to perform a post hoc analysis to investigate the genes, functions, and pathways related to the previously found HIPARCO score miRNAs. <b><i>Methods:</i></b> We performed an enrichment analysis using Ingenuity pathway analysis. The genes potentially associated with the miRNAs were filtered based on their confidence level. Particularly for CVD, only the genes regulated by at least 2 of the miRNAs were studied. <b><i>Results:</i></b> We observed that the miRNAs studied regulate 200–249 molecules associated with several functions and diseases, including extracranial solid tumors and abdominal neoplasms, among others. The cardiac hypertrophy and NF-kB signaling pathways were identified as the cardiovascular pathways most influenced by these 3 miRNAs. <b><i>Conclusions:</i></b> The mechanisms by which CPAP treatment decreases the BP in OSA patients with RH could be related to the cardiac hypertrophy and NF-kB signaling pathways. Further investigations will be necessary to confirm these findings, contributing to the elucidation of new therapeutic targets in patients who do not respond to CPAP treatment.

Abstract CALR mutations are present in 70-84% of JAK2 wild-type myeloproliferative neoplasms (MPN) and 67% and 88% of essential thrombocytopenia (ET) and primary myelofibrosis (PMF) respectively. Most cases of MPN are apparently sporadic, but 7-11% have evidence of familial predisposition. While germline mutations in ET-associated genes, MPL and JAK2, have been described in hereditary thrombocytosis, germline mutations in CALR have not been described in any setting. Two types of CALR mutations are common in MPN: a 52-base pair deletion (bp) and a 5 bp insertion, both in exon 9. With rare exceptions, CALR mutations are generally mutually exclusive with JAK2 or MPL mutations and have very rarely been reported in conjunction with the BCR-ABL1translocation. Here, we report a patient with a germline CALR mutation, thrombocytosis, and subsequent development of BCR-ABL+ CML. A 67-year-old female with no significant medical history presented with severe abdominal pain and nausea. Peripheral blood analysis revealed a marked leukocytosis composed of 66% neutrophils, 16% myelocytes, 6.5% monocytes, 3.5% basophils, 2.5% promyelocytes, 2.5% metamyelocytes, 1.5% lymphocytes, 1.5% blasts, and no eosinophils. The patient was non-anemic and had a normal platelet count (340,000/mm3). Bone marrow biopsy revealed a hypercellular marrow with myeloid predominant trilineage hematopoiesis and 1-2% blasts with morphology consistent with chronic myelogenous leukemia (CML). Fluorescence in-situ hybridization analysis of peripheral blood identified a BCR-ABL1fusion in 98.5% of interphase cells. After 3 months of standard imatinib therapy, quantitative RT-PCR showed a reduction of BCR-ABL1/ABL1 in the peripheral blood, however platelet count was elevated at 539,000/mm3. Thrombocytosis persisted over 2 years with a maximal platelet count of 584,000/mm3. Given the patient's thrombocytosis, her peripheral blood was subjected to a next generation sequencing of JAK2, MPL, and CALR genes. A 52-bp out-of-frame deletion in exon 9 of the CALR gene was detected (52% allele frequency) in peripheral blood. In addition, the same 52-bp CALR deletion (63% allele frequency) was present at the time of diagnosis and within a buccal specimen (47% allele frequency) when the BCR-ABL1 transcript was 1% in the peripheral blood. Immunostain of the buccal sample was strongly positive for cytokeratin (CK) AE1/AE3 but CD45 was not detected indicating no leukocyte contamination. This case reports the first instance of a germline CALR mutation associated with thrombocytosis and is the fourth report of the co-occurrence of BCR-ABL1 and CALR mutation in a single patient. Evolution to BCR-ABL1+ CML suppressed the CALR-mutant thrombocytosis phenotype, emphasizing the effect of these genes on lineage determination in abnormal myeloid proliferation. Disclosures No relevant conflicts of interest to declare.

Synovial sarcoma is a ubiquitous neoplasm predominantly affecting soft tissues of young adults of any gender; few cases have been described in the digestive system, mostly in the stomach. The (X;18)(p11.2; q11.2) translocation yields unique SS18-SSX fusion genes. Synovial sarcoma has been related to radiotherapy, but no synovial sarcoma has been associated with the digestive system. This article describes the case of a synovial sarcoma arising along the extrahepatic biliary tree, 10 years after the application of an abdominal radiotherapy schedule due to a retroperitoneal metastatic seminoma in a male who developed progressive obstructive jaundice. Ninety percent of the analyzed cells carried the SS18 gene with separation of sequences, thus denoting a translocation. There are only 8 post-radiotherapy synovial sarcomas that have been reported previously, and this is the first report of a radiotherapy-related synovial sarcoma arising from the extrahepatic biliary tree, and the second case described in this anatomic region.

Paragangliomas are rare neuroendocrine tumors that arise in the sympathetic or parasympathetic nervous system. Sympathetic paragangliomas are mainly found in the adrenal medulla (designated pheochromocytomas) but may also have a thoracic, abdominal, or pelvic localization. Parasympathetic paragangliomas are generally located at the head or neck. Knowledge concerning the familial forms of paragangliomas has greatly improved in recent years. Additionally to the genes involved in the classical syndromic forms:VHLgene (von Hippel-Lindau),RETgene (Multiple Endocrine Neoplasia type 2), andNF1gene (Neurofibromatosis type 1), 10 novel genes have so far been implicated in the occurrence of paragangliomas/pheochromocytomas:SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127, MAX, EGLN1, HIF2A,andKIF1B. It is currently accepted that about 35% of the paragangliomas cases are due to germline mutations in one of these genes. Furthermore, somatic mutations ofRET, VHL, NF1, MAX, HIF2A,andH-RAScan also be detected. The identification of the mutation responsible for the paraganglioma/pheochromocytoma phenotype in a patient may be crucial in determining the treatment and allowing specific follow-up guidelines, ultimately leading to a better prognosis. Herein, we summarize the most relevant aspects regarding the genetics and clinical aspects of the syndromic and nonsyndromic forms of pheochromocytoma/paraganglioma aiming to provide an algorithm for genetic testing.

Chronic lymphocytic leukaemia (CLL)/small lymphocytic lymphoma is the most prevalent lymphoid neoplasm in Europe and North America. The ‘cell of origin’ is a mature B lymphocyte with a rearranged immunoglobulin gene. CLL cells express modest amounts of surface immunoglobulin, and are characterized by defective apoptosis. The cause of CLL is unknown. Most patients show no specific clinical features of disease and are diagnosed during evaluation of an incidental finding of peripheral blood lymphocytosis, lymphadenopathy, or splenomegaly. A small percentage of patients (<10%) present with symptomatic disease resulting from (1) tissue accumulation of lymphocytes such as disfiguring lymphadenopathy, splenomegaly with abdominal discomfort, profound fatigue, drenching night sweats, weight loss, and fever; or (2) manifestations of marrow failure with cytopenias including anaemia and thrombocytopenia. All CLL patients have an increased risk of infection, autoimmune cytopenias, and second haematological (e.g. diffuse large B-cell lymphoma) and nonhaematological malignancies. Diagnosis is usually made by analysis of the immunophenotype of the monoclonal circulating cells in the peripheral blood. In patients with the small lymphocytic variant of CLL without a detectable circulating monoclonal B-cell population, the diagnosis is made using tissue from the bone marrow, lymph nodes, or spleen. Treatment—there is no standard curative therapy and patients should not be treated until they have progressive and symptomatic disease or develop anaemia or thrombocytopenia due to bone marrow failure. If a decision is made to treat, then the best initial treatment should be given, based on evaluation of the patient’s disease characteristics with specific attention to the integrity of TP53 (coding for p53) and patient fitness.