The TP53 mutational spectrum and frequency of CHEK2*1100delC in Li-Fraumeni-like kindreds.

Li-Fraumeni syndrome (LFS) is a dominantly inherited cancer predisposition syndrome characterized by a wide spectrum of neoplasms occurring at young age. Germline mutations in the TP53 tumor suppressor gene have been identified in approximately 71 of LFS patients and 22 of Li-Fraumeni-like (LFL) patients. Mutations within the cell cycle checkpoint gene CHEK2 have also been reported in some patients with LFS, LFL, and phenotypically suggestive of LFS (PS-LFS) not carrying a TP53 mutation. In this study, we show that 7 of the 23 patients with LFS/LFL tested positive for deleterious mutations in p53. Fifteen of the remaining sixteen were not found to carry the CHEK2* 1100delCmutation. These results indicate that CHEK2*1100delC is not a common cause of LFS, LFL, or PS-LFS in North American kindreds not carrying a TP53 mutation. Of note, two patients were found to carry p53* R72P, which is of unknown clinical significance. Lack of segregation of this allele in one of these kindreds provides strong evidence that the R72P allele is not disease-causing. While mutations in p53 account for a proportion of patients with LFS/LFL, future studies are needed to determine if other genes are responsible for LFS/LFL families not carrying germline p53 mutations.

"Russell Body Gastroenterocolitis" in a Posttransplant Patient: A Case Report and Review of Literature.

Russell bodies represent a cellular response to overstimulation of plasma cells, leading to the accumulation of abundant, nondegradable, condensed immunoglobulin in dilated rough endoplasmic reticulum cisternae. Russell body gastritis was first described 1998 by Tazawa and Tsutsumi. Since then only 39 cases involving the gastrointestinal tract have been reported in English literature, which include Russell body gastritis, duodenitis, and esophagitis. We report a case of a 44-year-old female with a history of diabetes mellitus, status post kidney and pancreas transplant who presented with multiple episodes of watery diarrhea associated with abdominal pain, nausea, and vomiting. Upper gastroendoscopic examination showed diffuse mild erythema in the gastric body and a clean-based duodenal ulcer. Lower gastroendoscopic examination was normal. Examination of multiple biopsies from duodenal, gastric, terminal ileum, and colonic mucosae revealed numerous plasma cells with abundant eosinophilic granular cytoplasm (Russell bodies) and eccentric nuclei, highlighted by PAS stain and CD 138 plasma cell marker. Helicobacter pylori stains were performed on gastric biopsies and were negative for organisms. To date, there are no cases described in English literature with multifocal Russell body infiltrates in gastrointestinal tract in a single patient including ileum and/or colon. This makes our case the first to be reported with these unique findings; thus, the spectrum of Russell body-associated chronic inflammation of the gastrointestinal tract would be more suitably referred to as "Russell body gastroenterocolitis."

Severe upper airway obstruction from cricoarytenoiditis as the sole presenting manifestation of a systemic lupus erythematosus flare.

Upper airway obstruction due to laryngeal involvement is a known complication of systemic lupus erythematosus (SLE). Laryngeal involvement typically accompanies inflammatory activity involving other sites and varies from mild mucosal inflammation to bilateral vocal cord immobility. Cricoarytenoid arthropathy is a rare cause of severe airway obstruction in patients with SLE and almost always occurs in the presence of other associated symptoms. Furthermore, in contrast to patients with rheumatoid arthritis, in whom chronic involvement of cricoarytenoid joints occurs more commonly and often requires surgical intervention, patients with SLE typically present with acute arthritis of cricoarytenoid joints and respond to corticosteroid therapy alone. We describe a patient with known SLE who presented with severe acute upper airway obstruction as the sole manifestation of active SLE after several years of quiescence. The laryngeal involvement progressed from mucosal inflammation to acute cricoarytenoiditis, despite the administration of high-dose corticosteroid therapy, necessitating emergent intubation and tracheostomy. This case illustrates the importance of considering SLE in the differential diagnosis of patients presenting with acute upper airway obstruction.

The genetics of familial lymphomas.

Whereas familial clustering of malignant lymphoma is well documented, the molecular changes underlying familial lymphoma syndromes remain unclear. An understanding of the hereditary basis of lymphoma may lead to the identification of new molecular markers for disease or novel therapeutic targets. This paper reviews the genetics of familial lymphoma, focusing on germline susceptibilities to lymphoma as well as germline susceptibilities to environmental exposures that have been linked to lymphoma.

Low-molecular weight heparin: treatment failure in a patient with primary antiphospholipid antibody syndrome.

Antiphospholipid antibody syndrome is an acquired autoimmune disorder characterized by vascular thrombosis and/or recurrent pregnancy losses along with laboratory evidence of antiphospholipid antibodies. Anticoagulation rather than immunosuppression is the mainstay of treatment. Despite the effectiveness of oral anticoagulation for the prevention of recurrent thromboembolic episodes, thrombotic complications in the setting of apparently therapeutic oral anticoagulation have been observed; this may at times be due to difficulties in maintaining a consistently therapeutic level of anticoagulation. Low-molecular-weight heparin has been a useful alternative for long-term anticoagulation when there is difficulty in managing oral anticoagulant therapy and has the advantage of a consistent anticoagulant effect. In this report, we describe a woman with primary antiphospholipid antibody syndrome who developed extensive pulmonary embolism despite receiving a proven therapeutic dosage of low molecular weight heparin.

Acute pancreatitis during sickle cell vaso-occlusive painful crisis.

Sickle cell disease is characterized by chronic hemolytic anemia and vaso-occlusive painful crisis. The vascular occlusion in sickle cell disease is a complex process and accounts for the majority of the clinical manifestations of the disease. Abdominal pain is an important component of vaso-occlusive painful crisis and may mimic diseases such as acute appendicitis and cholecystitis. Acute pancreatitis is rarely included as a cause of abdominal pain in patients with sickle cell disease. When it occurs it may result form biliary obstruction, but in other instances it might be a consequence of microvessel occlusion causing ischemia. In this series we describe four cases of acute pancreatitis in patients with sickle cell disease apparently due to microvascular occlusion and ischemic injury to the pancreas. All patients responded to conservative management. Acute pancreatitis should be considered in the differential diagnosis of abdominal pain in patients with sickle cell disease.