Acquired Pancreatic Arteriovenous Malformation.

Pancreatic arteriovenous malformation is a rare vascular anomaly which may cause abdominal pain, acute pancreatitis, gastrointestinal bleeding and portal hypertension. Pancreatic arteriovenous malformation is mostly congenital; however secondary pancreatic arteriovenous malformation due to pancreatitis has been suggested by some authors. We encountered a case which can confirm this presumption. Several imaging modalities are useful for the diagnosis of pancreatic arteriovenous malformation, especially dynamic contrast-enhanced studies. Angiography is the most important diagnostic tool because of the dynamic features of this vascular lesion. Treatment is advised and consists of surgical resection and/or transarterial embolization.

Upregulation of Wilms' tumour gene 1 (WT1) in uterine sarcomas.

AIM: Overexpression of Wilms' tumour gene (WT1) has been proven in several tumours. Previous research of our group on the cell cycle of uterine leiomyosarcoma (LMS) and carcinosarcoma (CS) suggested a possible role for WT1. We therefore intended to further explore the expression pattern of WT1 in uterine sarcomas. METHODS: 27 CS, 38 LMS, 15 endometrial stromal sarcomas (ESS) and seven undifferentiated sarcomas (US) were collected. WT1 expression was evaluated by immunohistochemistry (IHC) in 87 samples, by RT-PCR (m-RNA expression) in 23 random selected samples and by Western blotting in 12 samples, separating cytoplasmic and nuclear proteins. A pilot study to detect mutations (exons 7-10) was performed on eight samples. RESULTS: IHC showed WT1 positivity in 12/27 CS, 29/38 LMS, 7/15 ESS and 4/7 US. All-but-one sample had a positive RT-PCR. All Western blottings were positive with more cytoplasmic expression in 9/12 cases. No mutations were found. CONCLUSIONS: WT1 is overexpressed in uterine sarcomas. Since increased levels of mRNA determine the biological role, WT1 might contribute to uterine sarcoma tumour biology.

Crohn's-like changes in the colon due to mycophenolate?

OBJECTIVE: Mycophenolate mofetil (MMF) is used for prevention of allograft rejection in kidney transplant patients. A subset of patients suffers from chronic diarrhoea of unknown origin. The aim of the study was to investigate the effect of MMF on the colonic mucosa. MATERIALS AND METHODS: Colonic mucosal biopsies from 24 kidney transplant patients receiving MMF and presenting with chronic diarrhoea were analysed using routine stainings and immunohistochemistry for Ki67 and E-cadherin. Results were compared with a control group of 19 kidney transplant patients not receiving MMF. In all patients routine clinical and laboratory investigations were performed in order to explain the diarrhoea. RESULTS: In 11 patients, the diarrhoea seemed to be of infectious origin. Furthermore, 19/24 of MMF-patients showed characteristic histological alterations of the mucosa that were Crohn's disease-like: discontinuous crypt architectural distortion, increased epithelial mucin secretion, mildly active inflammation and focal presence of dilated and inflamed crypts. Ki67 staining was abnormal in 6/24 MMF patients but also in 4/19 control patients. E-Cadherin staining was normal in most MMF and control patients. CONCLUSIONS: Diarrhoea following MMF treatment is frequently infectious in origin and associated with morphological changes with a Crohn's-like pattern in the colonic mucosa in a subset of patients. MMF does not induce major alteration in the proliferative compartment of colonic epithelium. The diarrhoea is not associated with altered E-cadherin expression in the colonic epithelium.

Influence of treatment on morphological features of mucosal inflammation.

Microscopic analysis of endoscopically obtained tissue samples is important for the diagnosis of several gastrointestinal disorders such as gastritis and chronic inflammatory bowel disease (IBD). Histologically disease activity is based on the presence of neutrophilic polymorphonuclear leucocytes in conjunction with epithelial damage. Effective eradication treatment for Helicobacter pylori related gastritis reduces active inflammation rapidly whereas chronic inflammation decreases only slowly. Similar findings have been obtained for IBD. A literature review of clinical drug trials in IBD and the effect of various drugs on the microscopic features of Crohn's disease and immunohistochemistry for different markers was performed. Diagnostic microscopic features and the features characteristic for disease activity vary with time and treatment. The more recently developed drugs used for Crohn's disease can induce mucosal healing.

Vasculitis and the gastrointestinal tract.

Vasculitis, defined as a non-infectious inflammatory disorder of blood vessels, can affect vessels of any type in any organ. The gastrointestinal (GI) tract may thus also be involved. In systemic disorders as mixed connective tissue disease (MCTD) and systemic lupus erythematodes (SLE), patients may present with symptoms of gastrointestinal disfunction such as motility disorders, caused by alterations in the connective tissue. True vasculitis however also occurs in the GI tract. Severe, occlusive damage often leads to ischemia that may result in ulceration and perforation. Non-occlusive vascular disease may lead to vascular leakage resulting in oedema and haemorrhage. Those patients often present with diarrhoea or symptoms of bleeding. GI involvement is frequent in Henoch-Schönlein purpura and also often noted in polyarteritis nodosa (PAN), microscopic polyangiitis, Wegener's syndrome and Churg-Strauss syndrome. Furthermore, GI vasculitis has also been described in giant cell arteritis, Takayasu's disease, Buerger's disease and leucocytoclastic vasculitides as essential mixed cryoglubulinemia, lupus vasculitis, rheumatoid disease, MCTD, drug-induced vasculitis and Behçet's disease. The diagnosis and classification of vasculitis relies upon a combination of clinical, serological, haematological, radiological and histological findings. Establishing a precise diagnosis can be difficult but is important because treatment and prognosis can be highly variable.

Vascular lesions of the gastrointestinal tract.

Vascular lesions of the gastrointestinal (GI) tract include arterio-venous malformations as angiodysplasia and Dieulafoy's lesion, venous ectasias (multiple phlebectasias and haemorroids), teleangiectasias which can be associated with hereditary hemorrhagic teleangiectasia (HHT), Turner's syndrome and systemic sclerosis, haemangioma's, angiosarcoma's and disorders of connective tissue affecting blood vessels as pseudoxanthoma elasticum and Ehlers-Danlos's disease. As a group, they are relatively rare lesions that however may be a major source of upper and lower gastrointestinal bleeding. Clinical presentation is variable, ranging from asymptomatic cases over iron deficiency anaemia to acute or recurrent bleeding that may be life-threatening. Furthermore, patients may present with other symptoms, e.g. pain, dysphagia, odynophagia, the presence of a palpable mass, intussusception, obstruction, haemodynamic problems resulting from high cardiac output, lymphatic abnormalities with protein loosing enteropathy and ascites, or dermatological and somatic features in syndromal cases. Diagnosis can usually be made using endoscopy, sometimes with additional biopsy. Barium radiography, angiography, intraoperative enteroscopy, tagged red blood cell scan, CT-scan and MRI-scan may offer additional information. Treatment can be symptomatic, including iron supplements and transfusion therapy or causal, including therapeutic endoscopy (laser, electrocautery, heater probe or injection sclerotherapy), therapeutic angiography and surgery. The mode of treatment is of course depending on the mode of presentation and other factors such as associated disorders. If endoscopic or angiographic therapy is impossible and surgical intervention not indicated, pharmacological therapy may be warranted. Good results have been reported with different drugs, albeit most of them have not been tested in large trials.

Tenascin and strictures in inflammatory bowel disease: an immunohistochemical study.

Tenascin is an extracellular matrix protein involved in morphogenesis of muscle tissue and in wound healing. In the present study we examined its distribution in tissue from patients with inflammatory bowel disease. Intestinal biopsies from 10 normal controls, 15 patients with Crohn's disease, and 6 with ulcerative colitis were studied. Samples were obtained both from uninvolved and involved areas. Mucosal tenascin is increased in ulcerative colitis and Crohn's disease, especially in areas of ulceration. In Crohn's disease, tenascin is also strongly expressed in the submucosa and in smooth muscle cells of the muscularis mucosae and propria, especially in areas of stricture. We conclude that tenascin is involved in stricture formation in Crohn's disease and that it is a marker of phenotypic change in smooth muscle cells.

Malignant angiomyolipoma of the liver: a hitherto unreported variant.

AIMS: After their original recognition in the kidney, angiomyolipomas (AMLs) have been reported in the liver for more than 20 years. In the kidney, five cases of malignant AML have been reported. We report the first case of malignant hepatic AML. METHODS AND RESULTS: A 70-year-old female patient presented with abdominal discomfort. Clinical examination revealed a palpable liver. CT scan showed a polymorphous hypervascular lesion in the right liver lobe. A biopsy was taken and resulted initially in a differential diagnosis between a hepatocellular carcinoma, a metastatic tumour (possibly of renal origin) and angiomyolipoma (AML). After immunohistochemistry, a hepatic AML was suggested, given the immunoreactivity for HMB45/NKIC-3. The mass was resected 5 years later because of relapsing abscess formation. Gross examination of the resection specimen showed a focally encapsulated brown mass with focal necrosis. Microscopic examination showed a tumour growing in sheets, separated by sinusoidal-like vessels. Most of the tumour cells had a large, polygonal, clear cytoplasm, often with eosinophilic condensation around the nucleus. There was prominent vascular invasion. Immunohistochemistry (reactivity for HMB-45, NKIC-3, S100 and alpha smooth muscle actin, negativity for cytokeratin and vimentin) and electron microscopy confirmed the diagnosis of monomorphic epithelioid AML with prominent vascular invasion. Seven months after tumour resection, the patient died of recurrent disease. CONCLUSIONS: This case highlights the importance of immunohistochemistry and electron microscopy in diagnosing this type of tumour. Possibly, in the past, malignant AML of the liver has been misdiagnosed as HCC.