Masquerading in the midgut: a rare diagnosis in a patient with recurrent abdominal pain.

A 38-year-old woman who had been previously diagnosed with irritable bowel syndrome was seen in the outpatient clinic with a 2-year history of intermittent cramp-like abdominal pain which was often followed by watery diarrhoea. She had presented several times previously to the emergency department with episodes of severe pain and collapse although on arrival examination findings were mostly unremarkable other than some mild lower abdominal tenderness. On each occasion, the symptoms resolved spontaneously with conservative management. She had been extensively investigated by her general practitioner to establish the cause of her symptoms but all laboratory findings, cross-sectional imaging, ultrasound and oesophagogastroduodenoscopy to date were unremarkable. After being seen in gastroenterology outpatients' clinic, a colonoscopy was performed and was described as being macroscopically normal but microscopic evaluation of colonic biopsies suggested a possible 'resolving infection'. She was treated symptomatically, but within 6 months she represented to hospital with progressively worsening symptoms of severe abdominal pain, now associated with vomiting, followed by watery diarrhoea and then resolution of the symptoms. An abdominal CT scan was performed which showed a small intraluminal-filling defect in the mid-terminal ileum. A wireless capsule endoscopy was organised to further characterise the lesion although this was reported as showing no abnormality. Prior to any further outpatient investigations, she represented as an emergency to hospital in small bowel obstruction, underwent further cross-sectional imaging followed by surgical resection of the lesion. Histological characterisation revealed a small bowel inflammatory fibroid polyp.

Aberrant succination of proteins in fumarate hydratase-deficient mice and HLRCC patients is a robust biomarker of mutation status.

Germline mutations in the FH gene encoding the Krebs cycle enzyme fumarate hydratase predispose to hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome. FH-deficient cells and tissues accumulate high levels of fumarate, which may act as an oncometabolite and contribute to tumourigenesis. A recently proposed role for fumarate in the covalent modification of cysteine residues to S-(2-succinyl) cysteine (2SC) (termed protein succination) prompted us to assess 2SC levels in our existing models of HLRCC. Herein, using a previously characterized antibody against 2SC, we show that genetic ablation of FH causes high levels of protein succination. We next hypothesized that immunohistochemistry for 2SC would serve as a metabolic biomarker for the in situ detection of FH-deficient tissues. Robust detection of 2SC was observed in Fh1 (murine FH)-deficient renal cysts and in a retrospective series of HLRCC tumours (n = 16) with established FH mutations. Importantly, 2SC was undetectable in normal tissues (n = 200) and tumour types not associated with HLRCC (n = 1342). In a prospective evaluation of cases referred for genetic testing for HLRCC, the presence of 2SC-modified proteins (2SCP) correctly predicted genetic alterations in FH in every case. In two series of unselected type II papillary renal cancer (PRCC), prospectively analysed by 2SCP staining followed by genetic analysis, the biomarker accurately identified previously unsuspected FH mutations (2/33 and 1/36). The investigation of whether metabolites in other tumour types produce protein modification signature(s) that can be assayed using similar strategies will be of interest in future studies of cancer.

Human AlkB homologue 5 is a nuclear 2-oxoglutarate dependent oxygenase and a direct target of hypoxia-inducible factor 1α (HIF-1α).

Human 2-oxoglutarate oxygenases catalyse a range of biological oxidations including the demethylation of histone and nucleic acid substrates and the hydroxylation of proteins and small molecules. Some of these processes are centrally involved in regulation of cellular responses to hypoxia. The ALKBH proteins are a sub-family of 2OG oxygenases that are defined by homology to the Escherichia coli DNA-methylation repair enzyme AlkB. Here we report evidence that ALKBH5 is probably unique amongst the ALKBH genes in being a direct transcriptional target of hypoxia inducible factor-1 (HIF-1) and is induced by hypoxia in a range of cell types. We show that purified recombinant ALKBH5 is a bona fide 2OG oxygenase that catalyses the decarboxylation of 2OG but appears to have different prime substrate requirements from those so far defined for other ALKBH family members. Our findings define a new class of HIF-transcriptional target gene and suggest that ALKBH5 may have a role in the regulation of cellular responses to hypoxia.

Hepatic progenitor cells in chronic hepatitis C: a phenomenon of older age and advanced liver disease.

Hepatic progenitor cells (HPC) appear in a variety of liver diseases. Their occurrence in chronic hepatitis C (CHC) remains unclear, and triggering factors have to be elucidated. The presence of HPC in CHC was examined in relation to histological and virological parameters and patient age. Fifty liver biopsies of HCV-infected patients were examined. The presence of HPC was evaluated by immunohistochemical expression of keratin 7 (K7). Double immunostaining with K7 and cell proliferation marker Ki-67 was undertaken. Ductular reaction at the limiting plate, mean number of isolated progenitor cells (IPC) and isolated ductular structures (IDS) were quantified. The predominant distribution pattern of IPC and IDS and the presence of K7(+) hepatocytes were registered. Relationship between ductular reaction, IPC, IDS, presence of K7(+) hepatocytes, and patient age, hepatitis grade and stage, HCV RNA, and HCV genotype was examined. Prominent ductular reaction and increased numbers of IPC and IDS correlated significantly with older age and severe fibrosis/cirrhosis. The above HPC subtypes were not proliferating. Periportal/periseptal distribution pattern of IPC and IDS and presence of K7(+) hepatocytes were significantly more frequent in advanced hepatitis stages and in patients older than 40 years. Intraparenchymal distribution pattern correlated with younger age, lobular activity, and early fibrosis stage. K7(+) hepatocytes were encountered almost exclusively in the periportal pattern and in the presence of interface hepatitis and were more frequent among HCV genotype-1 patients. HPC activation in CHC is a common but diverse phenomenon closely related to patient age and hepatitis stage.

Differential expression of CKS-1B in typical and blastoid variants of mantle cell lymphoma.

Mantle cell lymphoma is a distinct type of B-cell lymphoma characterized by the t(11;14)(q13;q32). Mantle cell lymphomas exhibit a spectrum of morphologic findings, of which a subset of tumors is clinically aggressive with a high proliferation rate. These neoplasms are known as aggressive variants of which there are blastoid and pleomorphic subsets. CKS-1B (CDC28 protein kinase regulatory subunit 1B) is essential for the ubiquitination and degradation of p27 and cell cycle progression. We analyzed CKS-1B expression in mantle cell lymphoma cell lines and tumors by Western blot and immunohistochemical analysis. In 4 mantle cell lymphoma cell lines, CKS-1B was expressed at variable levels and correlated inversely with p27 expression. In mantle cell lymphoma tumors, CKS-1B was positive in 10 (28.6%) of 35 typical versus 14 (87.5%) of 16 blastoid/pleomorphic cases (Fisher exact test, P = .0002). Analyzed as a continuous variable, the percentage of CKS-1B-positive cells significantly correlated with blastoid/pleomorphic morphology (Mann-Whitney U test, P = .001). Twelve (23.5%) of 51 mantle cell lymphoma tumors expressed p27. Proliferation rate (Ki-67) was higher in blastoid/pleomorphic variants than in typical mantle cell lymphoma tumors and was inversely associated with p27 levels in typical mantle cell lymphoma. However, CKS-1B expression did not correlate with p27 expression, proliferation rate, or prognosis in the entire study group. Fluorescence in situ hybridization analysis of 10 CKS-1B-positive mantle cell lymphoma tumors showed no evidence of CKS-1B gene amplification. We conclude that CKS-1B is commonly expressed in mantle cell lymphoma, particularly in aggressive histologic variants, and may be involved in pathogenesis.

T cell lymphoblastic lymphoma in parotidectomy for Warthin's tumor: case report and review of the literature.

Lymphomas associated with Warthin's tumor (WT) are extremely uncommon and the majorities are of B cell type. We report the simultaneous occurrence of T-cell lymphoblastic lymphoma (T-LBL) and WT in an 81-year-old patient, who presented with fever, night sweats and enlargement of the right parotid gland. The parotidectomy specimen showed a WT with extensive replacement of the lymphoid stroma by T-LBL, but preservation of the oncocytic epithelium. Staging investigations revealed mediastinal and abdominal lymphadenopathy, bilateral pleural effusions and bone marrow infiltration, in keeping with stage IVB disease. The patient received combination chemotherapy treatment but responded poorly, and died three months after diagnosis. To our knowledge, this is the first case report of T-LBL involving WT. The present study indicates that the lymphoid stroma in WT belongs to the systemic lymphoid tissue and can be involved in disseminated lymphoma. It highlights the importance of careful examination of WT's lymphoid stroma for the possible presence of any coexistent malignancy.

Incidental pathologic extracardiac uptake of 99mTc-tetrofosmin in myocardial perfusion imaging.

Technetium-99m-tetrofosmin ((99m)Tc-TF) myocardial perfusion studies have incidentally detected various extracardiac abnormalities. The interpretation of these findings may be essential for early diagnosis and treatment of important diseases. We present a rare case of a mediastinal thymoma incidently detected during myocardial perfusion imaging. A 60 year-old woman, with precardiac symptoms of possible myocardial ischemia, underwent a (99m)Tc-TF stress-rest single photon emission tomography test. Intense uptake of the radiotracer in the left paracardiac area, was observed. The computerized tomography and the magnetic resonance imaging tests revealed a mass in the left lower anterior mediastinal area. Biopsy and subsequent histology showed that this mass was a thymoma.

Acute abdomen due to primary omentitis: a case report.

BACKGROUND: Idiopathic segmental infarction of the greater omentum (ISIGO) is an uncommon cause of acute abdomen in children and adults and its etiology is rather vague and speculative. The clinical presentation is usually with atypical acute or subacute abdominal pain. In a number of cases radiologic imaging allows proper preoperative diagnosis and treatment. CASE PRESENTATION: We report a case of ISIGO in a 31 year old patient, who presented with acute abdominal pain, nausea, vomiting and leukocytosis. Radiologic investigation was non-specific. The patient underwent surgical resection of the infracted omentum with compete recovery. CONCLUSION: ISIGO should be considered in the differential of acute abdomen especially when presentation is atypical and all other causes have been excluded. In cases with non-specific radiologic findings, laparotomy is necessary for proper diagnosis and treatment. Surgical resection of the infracted omentum results in uneventful recovery in the majority of cases.