Pinealoblastoma in a Patient With Familial Adenomatous Polyposis: Variant of Turcot Syndrome Type 2? Report of a Case and Review of the Literature

Abstract We report a case of a 23-year-old Turcot female patient who was first diagnosed as having a pinealoblastoma. Thyroid papillary carcinoma was diagnosed a few months later, and multiple colonic polyps were detected three years after that. A genetic workup revealed an APC gene mutation in her family. Long-term survival (i.e., >5 years) of pinealoblastoma is considered to be 20 percent. A review of 25 documented Turcot cases determined that the average age at death is 20.3 years, raising the difficult question of whether she should undergo restorative proctocolectomy. Restorative proctocolectomy may itself cause major morbidity but is currently the only way to prevent colon cancer. Presented at the Joint Meeting of the Leeds Castle Polyposis Group and International Collaborative Group for Hereditary Nonpolyposis Colorectal Cancer, Cleveland, Ohio, September 4 to 6, 2003     

CASE REPORT: Spontaneous Intrahepatic Portal—Systemic Venous Shunt in the Adult: Case Report and Review of the Literature

Intrahepatic portal-systemic venous shunt is defined as a communication between the portal and the systemic-venous circulation, measuring more than 1 mm in diameter and at least partially located inside the liver. This is a rare condition, and the etiopathogenesis is unclear. Of the various types, Type I, with patent paraumbilical veins, located in the liver, is commonly encountered in portal hypertension. Other types are much less common. Only 47 cases have been reported in the entire French and English literature. Shunts may be congenital or acquired. This report describes a case of portal-systemic encephalopathy due to a spontaneous large-caliber portal-hepatic venous shunt in the right lobe of the liver confirmed by percutaneous transhepatic portography and hepatic venous angiogram. The treatment with coil embolization was successful, and hepatic encephalopathy resolved postoperatively with normalization of ammonia level. The etiology of the shunt was unclear. Given the age of the patient, the shunt was thought to have developed spontaneously.     

A Case Report of Hepatocellular Carcinoma 5 Years After HBsAg Loss in Chronic Hepatitis Delta: How Long Surveillance is Required?

BackgroundHepatitis delta virus infection occurs as acute coinfection or as superinfection in patients with preexisting chronic hepatitis B. Chronic hepatitis delta leads to more severe disease than chronic hepatitis B, with more rapid progression of fibrosis and increased risk of hepatocelullar carcinoma.Case reportWe report a case of hepatocelullar carcinoma 5 years after spontaneous clearance of Hepatitis B surface antigen in a patient with previous chronic hepatitis delta. He had been diagnosed with acute hepatitis delta superinfection 30 years ago which evolved to chronic delta infection and subsequently development of liver cirrhosis. Despite no specific antiviral treatment, he lost HBsAg persistently with later regression of cirrhosis.ConclusionsIn patients with cirrhosis due to chronic hepatitis delta who cleared HBsAg with improvement of liver fibrosis by non invasive techniques, it remains unknown how long hepatocelullar carcinoma surveillance has to be maintained.     

S-Nitrosation of β-Catenin and p120 Catenin: A Novel Regulatory Mechanism in Endothelial Hyperpermeability

Rationale: Endothelial adherens junction proteins constitute an important element in the control of microvascular permeability. Platelet-activating factor (PAF) increases permeability to macromolecules via translocation of endothelial nitric oxide synthase (eNOS) to cytosol and stimulation of eNOS-derived nitric oxide signaling cascade. The mechanisms by which nitric oxide signaling regulates permeability at adherens junctions are still incompletely understood. Objective: We explored the hypothesis that PAF stimulates hyperpermeability via S-nitrosation (SNO) of adherens junction proteins. Methods and Results: We measured PAF-stimulated SNO of β-catenin and p120-catenin (p120) in 3 cell lines: ECV-eNOSGFP, EAhy926 (derived from human umbilical vein), and postcapillary venular endothelial cells (derived from bovine heart endothelium) and in the mouse cremaster muscle in vivo. SNO correlated with diminished abundance of β-catenin and p120 at the adherens junction and with hyperpermeability. Tumor necrosis factor-α increased nitric oxide production and caused similar increase in SNO as PAF. To ascertain the importance of eNOS subcellular location in this process, we used ECV-304 cells transfected with cytosolic eNOS (GFPeNOSG2A) and plasma membrane eNOS (GFPeNOSCAAX). PAF induced SNO of β-catenin and p120 and significantly diminished association between these proteins in cells with cytosolic eNOS but not in cells wherein eNOS is anchored to the cell membrane. Inhibitors of nitric oxide production and of SNO blocked PAF-induced SNO and hyperpermeability, whereas inhibition of the cGMP pathway had no effect. Mass spectrometry analysis of purified p120 identified cysteine 579 as the main S-nitrosated residue in the region that putatively interacts with vascular endothelial-cadherin. Conclusions: Our results demonstrate that agonist-induced SNO contributes to junctional membrane protein changes that enhance endothelial permeability.     

A Case Report of Compound Heterozygosity for β0/β+-Thalassemia Resulting from under Diagnosed β-Thalassemia Found in a Hb A'2 Sample

Hb A'₂ (or Hb B₂) (HBD: c.49G>C) is the most frequent δ chain variant that has been described in Africa but not in Thailand. We report here a 10-month-old Thai infant with compound heterozygosity for β⁰ codon 17 (A>T; HBB: c.52A>T) and β⁺ IVS II-654 (C>T; HBB: c.316-197C>T). Under diagnosed β-thalassemia (β-thal) in her father, who carries Hb A'₂ and a heterozygous β⁰ codon 17 mutation, and the mother, who carries a heterozygous β⁺ IVS II-654 mutation, was noted. Although Hb A'₂ does not cause any problems, heterozygosity for Hb A'₂ can lead to under diagnosis of β-thal in Hb A'₂ samples. This case highlights the importance of Hb A'₂ in prenatal diagnosis (PND). Thus, molecular analysis for β-thal mutations should be carried out when a small peak presents at the retention time (RT) of 4.71?min. on high performance liquid chromatography (HPLC) and the summation level of this peak and Hb A₂ was equal or higher than 4.0%.     

Persistence of the Left Superior Vena Cava in a Patient with Duplication of Chromosome 8p—A Case Report

The authors report a child born with duplication of chromosome 8p. Associated findings have included an interhemispheric cyst with hydrocephalus, persistent left superior vena cava, large secundum-type atrial septal defect, bilateral inguinal hernias, right preauricular skin tag, hypertelorism, cleft palate, cortical thumbing, syndactyly of the toes, and clinodactyly. At three years of age, the patient does not crawl, is developmentally delayed, and has a ventriculoperitoneal shunt to treat his hydrocephalus. With further reports, this case may shed light on a genetic locus related to regression of the left superior vena cava.     

Congenital Scoliosis in Smith–Magenis Syndrome: A Case Report and Review of the Literature

The Smith–Magenis syndrome (SMS) is a complex and rare congenital condition that is characterized by minor craniofacial anomalies, short stature, sleep disturbances, behavioral, and neurocognitive abnormalities, as well as variable multisystemic manifestations. Little is reported about spinal deformity associated with this syndrome.This study is to present a case of scoliosis occurring in the setting of SMS and explore the possible mechanisms between the 2 diseases.The patient is a 13-year-old Chinese female with congenital scoliosis and Tetralogy of Fallot, mental retardation, obstructive sleep apnea, hypertrophy of tonsil, conductive hearing loss, and agenesis of the epiglottis. An interphase fluorescent in situ hybridization at chromosome 17p11.2 revealed a heterozygous deletion, confirming a molecular diagnosis of SMS. She underwent a posterior correction at thoracic 1-lumbar 1 (T1-L1) levels, using the Moss-SI spinal system. At 6-month follow-up, the patient was clinically pain free and well balanced. Plain radiographs showed solid spine fusion with no loss of correction.Congenital cardiac disease, immunodeficiency, and severe behavioral problems can affect the surgical outcome following spine fusion and need to be taken into consideration for the surgeon and anesthesiologist. Scoliosis is not uncommon among patients with SMS, and there is a potential association between congenital scoliosis and SMS. The potential mechanisms in the pathogenesis of congenital scoliosis of SMS included retinoic acid-induced 1 (RAI1) microdeletion and RAI1 gene point mutation.     

Cardiovascular Involvement in Erdheim–Chester Disease: A Case Report and Review of the Literature

Erdheim–Chester disease (ECD) is a rare, multiorgan, non-Langerhans cell histiocytosis of uncertain origin, characterized by systemic xanthogranulomatous infiltration from CD68+CD1a- histiocytes. Skeletal involvement is present in up to 96% of cases with bilateral osteosclerosis of meta-diaphysis of long bones. Furthermore, in more than 50% of cases there is 1 extraskeletal manifestation. In this case report, we describe an interesting case of ECD with an extensive pan-cardiac and vascular involvement, in addition to skeletal, retro-orbital, and retroperitoneum one.A 44-year-old woman with a long history of exophthalmos referred to our hospital for elective surgical orbital decompression. At preoperative examinations a large pericardial effusion was discovered. Echocardiography, computed tomography (CT), and magnetic resonance imaging (MRI) described an inhomogeneous mass involving pericardium and the right heart, abdominal aorta and its main branches and the retroperitoneum, suggestive for a systemic inflammatory disorder. Histological examination on a biopsy sample confirmed the diagnosis of ECD. Radiology showed the pathognomonic long-bone involvement. Surgical orbital decompression was performed and medical therapy with interferon-α (INF-α) was started.Among extraskeletal manifestations of ECD, cardiovascular involvement is often asymptomatic and thus under-diagnosed but linked to poor prognosis. This is why clinician should always look for it when a new case of ECD is diagnosed.     

Do Genetic Polymorphisms Modulate Response Rate and Toxicity of Cisplatin Associated With Radiotherapy in Laryngeal Squamous Cell Carcinoma?: A Case Report

Cisplatin (CDDP) plus radiotherapy (RT) has been used to treat advanced laryngeal squamous cell carcinoma (LSCC) patients. Single nucleotide polymorphisms (SNPs) may be responsible for differences in chemo/radiosensitivity and side effects in those patients. We reported an advanced LSCC patient, who obtained durable complete response and unexpected pronounced toxicity during CDDP and RT, possibly due to SNPs in genes that modulate the effects of this therapeutic modality. Case presentation: A 30-year-old man with advanced LSCC obtained durable complete response and severe alopecia and pancytopenia after standard and reduced doses of CDDP and RT. Analyses of SNPs revealed that the patient presented GSTT1 deletion, variant MSH3 1045ThrThr, wild GSTP1 105IleIle, and wild BAX -248GG genotypes, which were previously described in association with abnormal detoxification, DNA repair, and damaged cell apoptosis, respectively. Seven other advanced LSCC patients with GSTT1 gene, MSH3 AlaAla or AlaThr, GSTP1 IleVal or ValVal, and BAX GA or AA genotypes served as controls of the study. Only 1 control presented complete response; the other 6 controls obtained partial response of short duration. Four and 3 controls presented grade 1 or 2 and grade 3 anemia or leukopenia during treatment, respectively. The CDDP level in urine collected after CDDP infusion in the reported patient was lower than the median value obtained in controls, suggesting a higher amount of intracellular CDDP in the reported case.The data suggest, for the first time, that inherited abnormalities in intracellular detoxification of CDDP, DNA repair of lesions induced by CDDP and RT, and damaged cell apoptosis may alter treatment response and toxicity in LSCC, but should be confirmed by large pharmacogenomic studies.     

Krüppel-Like Factor 1 Gene Mutations in Thalassemia Patients from North Iran: Report of a New Mutation Associated with β-Thalassemia Intermedia

Thalassemia is a hereditary disease with an autosomal recessive inheritance pattern resulting in reduced production of globin chains. Mutations in modifier genes can cause or affect thalassemia. Krüppel-like factor 1 (KLF1) is a modifier gene that was investigated in this study. Thirty-five Iranian β-thalassemia (β-thal) minor patients with hematological symptoms including Hb A₂ 3.0%, mean corpuscular volume (MCV) <75.0 fL, mean corpuscular hemoglobin (Hb) (MCH) <25.0?pg, and two β-thal intermedia (β-TI) patients in 50 subjects who carried no mutations on the HBB and HBA2 or HBA1 genes were investigated for all exons of the KLF1 gene by polymerase chain reaction (PCR) and sequencing methods. Of the 35 patients with a β-thal minor phenotype, one patient was heterozygous for the c.544T>C mutation in exon 2 of KLF1 and HBB: c.380T>G variant, Hb Dhonburi [also known as Hb Neapolis or codon 126 (T>G)]. The c.340T>C mutation was also found in exon 2 of the KLF1 gene with an allele frequency of 16.6% in the studied β-thal carriers. The two β-TI patients were homozygous for a new mutation c.942delA in exon 3 of KLF1. Mutations in modifier genes can cause or affect thalassemia. Therefore, exact investigation of globin genes and modifiers such as KLF1 is necessary in areas where globin gene disorders are most prevalent to understand the reason of clinical and hematological symptoms of thalassemia and facilitate newborn screening or prenatal diagnosis (PND) programs.     

A New β0 Frameshift Mutation,HBB: c.44delT (p.Leu14ArgfsX5), Identified in an Argentinean Family Associated with Secondary Genetic Modifiers of β-Thalassemia

β-Thalassemia intermedia (β-TI) patients present with a wide spectrum of phenotypes depending on the presence of primary, secondary, and tertiary genetic modifiers which modulate, by different mechanisms, the degree of imbalance between α and β chains. Here we describe a new β⁰ frameshift mutation, HBB: c.44delT (p.Leu14ArgfsX5), identified in four members of a family, associated with secondary genetic modifiers in three of them. The different genotype present in this family was suspected after hematological analysis and thorough observation of blood smears highlighting their importance in the identification of β-TI patients among members of the same family.     

A Novel Frameshift Mutation at Codon 2 (–T) (HBB: c.9delT) and First Report of Three New β-Globin Mutations From Azerbaijan

Abstract

We identified a novel mutation of β-thalassemia (β-thal) in a heterozygous carrier from Azerbaijan. Phenotypical data and molecular mechanisms of codon 2 (–T) (HBB: c.9delT) was relevant to β⁰-thal. Additionally, we here report two new mutations on the HBB gene, not observed previously, in the local population as well as a non causative promoter mutation –198 (A>G) (HBB: c.-248A>G).     

Solid Serous Cystadenoma of the Pancreas: A Case Report of 2 Patients Revealing Vimentin, β-Catenin, α-1 Antitrypsin,and α-1 Antichymotrypsin as New Immunohistochemistry Staining Markers

Solid serous cystadenoma (SCA) of the pancreas is a rare type of pancreatic solid tumors. Postoperative pathological evaluation is of particular importance for distinguishing solid SCA of the pancreas from other pancreatic solid tumors.Here we present 2 cases of solid SCA of the pancreas, both preoperatively diagnosed with pancreatic neuroendocrine tumors. One case had positive OctreoScan test.Surgical resections were done for both cases. Postoperative immunohistochemistry assays were conducted with marker panels for SCA and 2 types of pancreatic solid tumors, which were neuroendocrine tumor (pNET) and solid pseudopapillary tumor (SPT).Two cases showed typical staining patterns for SCA markers. Notably, both cases showed positivity for 4 SPT markers (vimentin, β-catenin, α-1 antitrypsin, and α-1 antichymotrypsin).Emphasis should be paid to those 4 new markers for future pathological diagnosis of solid SCA of the pancreas.