Neurofibromatozis type 1 is a complex disease, with patients having an increased prevalence of benign and malignant neoplasms throughout the body due to mutations of the NF gene leading to abnormal tumor suppression.10
The association between von Recklinghausen's disease and tumors of neurogenic and neuroendocrine origin, such as meningiomas and pheochromocytomas is well known. Pheochromocytoma occurs in about 1% of NF1 patients, the incidence of pheochromocytomas is much higher in patients with duodenal somatostatin producing endocrine tumors associated with NF1.8,11
The composite tumors in this syndrome are much rare, with isolated case reports. The coincidence of multiple GISTs and pheochromocytoma and NF1 is described as a few case reports within the literature.12,13
Our patient had both pheochromocytoma and multiple GISTs with NF1 ().
Figs. 3 and 4
Neurofibromatozis type 1 with multiple neurofibromas and cafe au lait spots.
In one study performed in Swedish population,14
malignant tumors were reported significantly more often in the NF1 patients than was expected in the general population. Pheocomocytomas are well recognized with NF1 and it is said to be 10 times more common than the general population. In a Korean study,15
among 125 NF1 patients, 9 carcinomas and 8 sarcomas were detected. All three GISTs were multiple in small bowel and they concluded that NF1 patients had a high risk of developing malignant tumors.
Gastrointestinal stromal tumors in NF1 patients have been reported to be the most common lesions of gastrointestinal tract, but symptomatic cases account for less than 5% of patients.2,16,17
The incidence of GIST in NF1 patients is varying from 4% to 25%.6,7,9
Although most GISTs arise in the stomach, GISTs in NF1 patients tend to be multiple and mostly located within the small bowel.6,7,16,18
Clinical symptoms related to the size and location of tumor, initial clinical manifestations varies; nonspecific abdominal pain, bleeding from gastrointestinal tract, palpable abdominal mass, perforation etc. In this case, melena was the initial clinical manifestation of the patient and duodenal GIST was detected in upper gastrointestinal tract endoscopy ().
Duodenal tumoral mass lesions.
In NF1 patients, predisposition of tumorgenesis might be explained by overexpression of a tumor suppressor gene called neurofibromin.12
In patients with NF1, pheochromocytomas and GISTs are well known neoplasms seen with increased incidence than the general population. Most of the lesions cause no symptoms until they grow large in size and therefore it is difficult to detect them preoperatively. In patients with NF1, any gastrointestinal symptoms should be managed carefully. Early diagnosis of abdominal symptoms is very important because of the risk of malignancy and complications of tumors such as hypertension, bleeding and perforation.