Clinical Challenges

What is your diagnosis? - July 2019

A 32-year-old Filipino woman was referred for endoscopic ultrasound (EUS) imaging of the pancreas from another hospital where she had presented with a history of intermittent abdominal pain with radiation to the back precipitated by alcohol, and recurrent palpitations. During outpatient review before EUS, she gave a background history of previous laparoscopic ovarian cystectomy, as well as multiple previous admissions with supraventricular tachycardia requiring cardioversion on 1 occasion. One of her brothers had undergone brain surgery to remove a cyst, and another had died of an unspecified brain tumor at 25 years of age. Her mother had died of ovarian cancer.

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Physical examination was unremarkable, with a normal pulse rate and blood pressure and no anemia, jaundice, or lymphadenopathy. Laboratory investigations including a full blood count, urea and electrolytes, liver function tests, thyroid function tests, and serum lipase were all normal. Abdominal computed tomography and ultrasound imaging revealed multiple cysts of varying sizes throughout the pancreas (Figure A), as well as multiple small benign-looking cysts in the liver.

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In addition, there was a 17-mm hyperdense solid lesion in the midpole of her right kidney visualized on computed tomography scan (Figure B). EUS revealed multiple thinly septated anechoic cysts throughout the pancreas, the largest measuring 36 mm located in the body, with no associated masses (Figure C).

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What is the likely diagnosis? What other investigations would you do for confirmation?


 

The diagnosis

von Hippel-Lindau disease

The diagnosis is von Hippel-Lindau disease (VHL). Subsequent brain and renal magnetic resonance imaging showed features suggestive of a 5-mm right cerebellar hemangioblastoma and right renal cell carcinoma (RCC), respectively. Fundoscopy showed bilateral small retinal angiomas. Plasma and 24-hour urinary metenephrine levels were normal. Genetic testing confirmed a germline VHL mutation.

VHL is a rare autosomal-dominant hereditary multicancer condition characterized by germline mutations of the VHL tumor suppressor gene, with an incidence of 1 in 36,000 live births. The commonest associated tumors are retinal and central nervous system hemangioblastomas, RCC, pheochromocytoma, pancreatic islet cell tumors, and endolymphatic sac tumors.1 Cystic lesions may also be seen in other viscera such as the liver and ovaries. Clinical diagnostic criteria require the presence of any of these tumors in a patient with a positive family history, or alternatively, at least 2 retinal or cerebellar hemangioblastomas, or 1 hemangioblastoma plus 1 visceral tumor.2

Pancreatic involvement occurs in 65%–77% of patients with VHL, and may be the sole manifestation in 7.6%. Findings include multiple true cysts (91%), microcystic serous cystadenomas (12%), solid pancreatic neuroendocrine tumors (5%–10%), or a combination (11.5%). Most lesions are asymptomatic, but may present with vague symptoms of epigastric pain, diarrhea, dyspepsia, obstructive jaundice, or endocrine and/or exocrine pancreatic insufficiency. Surgery is required for symptomatic cysts or large pancreatic neuroendocrine tumors. The main causes of death are RCC and central nervous system hemangioblastomas.3 Our patient underwent laser therapy for her retinal angiomas, and is currently undergoing close regular surveillance. Clinicians should have a high index of suspicion for diagnosing VHL in patients with multiple pancreatic cysts. Because EUS is now widely used for the evaluation of pancreatic cysts, gastroenterologists may be first in making the diagnosis, as in this patient.

References

1. Lonser R.R., Glenn G.M., Walther M. et al. von Hippel-Lindau disease. Lancet. 2003;361:2059-67.

2. Melmon K., Rosen S. Lindau’s disease. Am J Med. 1964;36:595-617

3. Hammel P.R., Vilgrain V., Terris B. et al. Pancreatic involvement in von Hippel-Lindau disease. The Groupe Francophone d’Etude de la Maladie de von Hippel-Lindau. Gastroenterology. 2000;119:1087-95.

ginews@gastro.org

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