Neurofibromatosis type 1, recurrent pulmonary embolism, and a periampullary carcinoid tumor: is there a link?

Neurofibromatosis type 1 (NF1), a relatively common autosomal dominantly inherited condition with complete penetrance but extremely variable phenotypic expressivity, is caused by mutations in the NF1 gene. The disease is defined clinically by its cutaneous (cafe-au-lait macules, inguinal and axillary freckles) and neural (neurofibromas, plexiform neurofibromas, Lisch spots, optic nerve gliomas) signs, but it can involve many other systems including the gastrointestinal, pulmonary, respiratory, skeletal and vascular systems. Involvement of these other systems can sometimes manifest itself in clinically confusing ways. For example, the literature includes reports of patients with NF1 that has caused pulmonary hypertension, spontaneous hemothorax, and gastrointestinal bleeding. We present the case of a man with NF1 who presented with recurrent unexplained thromboembolic disease and died suddenly in the hospital. In addition to confirming his suspected massive pulmonary thromboembolus (PE), an autopsy revealed an unsuspected periampullary duodenal carcinoid tumor. The potential connections between the patient's NF1, duodenal tumor, and fatal PE are discussed. The case highlights the importance of bearing in mind the protean clinical manifestations of NF1.