Acquired hemophilia (antibodies or inhibitors to factor VIII) is the most common acquired disease affecting clotting factors. It has been described in association with autoimmune disease, malignancy, dermatologic disorders, in the postpartum period, and with drug interactions. Factor VIII inhibitors have been previously described with lung cancer, three with squamous cell and one with adenocarcinoma. A 54-year-old woman presented with weight loss and shoulder pain. A chest X-ray revealed a right hilar mass, confirmed by computed tomography (CT) scan and biopsy revealed small cell lung cancer. Coagulation panel prior to bronchoscopy showed an increased partial thromboplastin time (aPTT). The presence of factor VIII inhibitor was demonstrated at 5 Bethesda units. The patient was treated with fresh frozen plasma twice for hemorrhagic episodes, and six cycles of chemotherapy were begun with carboplatin and etoposide 16. Eight months after the diagnosis, her aPTT was normal and the factor VIII inhibitor titer was undetectable. This is the first case report of small cell lung cancer and acquired hemophilia. A causal relationship between the malignancy and the presence of factor VIII inhibitors is suggested by the response to therapy.
Context.— Even among cases of non–small cell lung cancer (NSCLC) in the most favorable stage (IA), the disease-specific mortality is 25% or greater. One plausible explanation implicates the simplistic standard pathologic procedures used to designate lymph node involvement. A more sensitive assessment of the nodal status may improve staging.
Objective.—To determine the prognostic impact of detecting an abnormal molecular event (promoter hypermethylation in a set of relevant genes) in histologically uninvolved lymph nodes in resected NSCLC.
Design.—In this retrospective analysis of archived material, we examined DNA extracted from lymph nodes of stage I NSCLC (n = 180). Patients underwent surgery between 1991 and 1995 in a single institution. Methylation-specific polymerase chain reaction was used to detect promoter hypermethylation in a panel of 8 genes. Survival data were extracted from the computerized database at the Tumor Registry.
Results.—Evidence of promoter hypermethylation in at least 1 gene was detected in 67% of these N0 nodes. The most commonly hypermethylated gene was E-cadherin (53%). The hypermethylation frequency for the remaining genes were as follows: APC, 5%; p16, 9%; MGMT, 11%; hMLH1, 15%; RASSF1A, 4%; DAP kinase, 9%; and ATM, 19%. The presence of promoter hypermethylation in 2 or more genes did not influence the overall, median, or 5-year survival rates.
Conclusions.—Identifying promoter hypermethylation (in our panel) in N0 lymph nodes in stage I NSCLC cannot be recommended for clinical decision making. Molecular abnormalities, including those found in cancer by qualitative methylation-specific polymerase chain reaction, are not synonymous with established, histologically detectable metastasis.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.