BACKGROUND: Acquired deficiency in C1-inhibitor (C1-INH) associated with malignancy is often asymptomatic because clinical manifestations are not dependent on a critical complement threshold (in contrast to hereditary C1-INH deficiency). Increased complement consumption involving different kinds of antibodies is the postulated mechanism for this disease, but other factors must play an important role. CASE REPORT: A 76-year-old woman with unremarkable medical history experienced three episodes of angioedema over 6 months. Investigations revealed a complement profile characteristic of acquired deficiency in C1-INH, a hemolytic anemia, and a signet ring cell adenocarcinoma (linitis plastica). A gastrectomy and a splenectomy were performed. The postoperative course was characterized by a complete disappearance of the symptoms of angioedema and hemolytic anemia. A local recurrence of the tumor 5 months later could not be resected. The patient died 17 months after the initial surgery was performed. RESULTS: Quantitative and functional analyses of the complement factors showed persistent excessive complement consumption. Markers of hemolytic anemia disappeared after tumor removal but recurred in the second part of the disease evolution. Immunohistochemical findings in tumor tissue showed loss of normal blood group antigens but expression of Lea antigen, as well as C1q deposition. CONCLUSION: To explain the whole clinical and laboratory picture, we hypothesize a connection between tumor immunohistochemical profile, complement consumption, and hemolytic anemia. Tumor cell surface antigens might lead to a permanent but asymptomatic complement consumption that is worsened and becomes clinically manifest by superimposed hemolytic anemia caused by cross-reactive antibodies to newly expressed blood group antigens on tumor cells. This hypothesis should be confirmed by other observations.
BACKGROUND: Acquired deficiency in C1-inhibitor (C1-INH) associated with malignancy is often asymptomatic because clinical manifestations are not dependent on a critical complement threshold (in contrast to hereditary C1-INH deficiency). Increased complement consumption involving different kinds of antibodies is the postulated mechanism for this disease, but other factors must play an important role. CASE REPORT: A 76-year-old woman with unremarkable medical history experienced three episodes of angioedema over 6 months. Investigations revealed a complement profile characteristic of acquired deficiency in C1-INH, a hemolytic anemia, and a signet ring cell adenocarcinoma (linitis plastica). A gastrectomy and a splenectomy were performed. The postoperative course was characterized by a complete disappearance of the symptoms of angioedema and hemolytic anemia. A local recurrence of the tumor 5 months later could not be resected. The patient died 17 months after the initial surgery was performed. RESULTS: Quantitative and functional analyses of the complement factors showed persistent excessive complement consumption. Markers of hemolytic anemia disappeared after tumor removal but recurred in the second part of the disease evolution. Immunohistochemical findings in tumor tissue showed loss of normal blood group antigens but expression of Lea antigen, as well as C1q deposition. CONCLUSION: To explain the whole clinical and laboratory picture, we hypothesize a connection between tumor immunohistochemical profile, complement consumption, and hemolytic anemia. Tumor cell surface antigens might lead to a permanent but asymptomatic complement consumption that is worsened and becomes clinically manifest by superimposed hemolytic anemia caused by cross-reactive antibodies to newly expressed blood group antigens on tumor cells. This hypothesis should be confirmed by other observations.