Multiple Cysts, Masses and Tumours—A Syndromic Association?

A 29-year-old female presented with vague abdominal pain for the past two months with occasional vomiting and headache. Patient’s eyes were anicteric with no jaundice. Bilirubin panel was unremarkable. Review of family history revealed occurrence of cranial and abdominal tumours in the maternal side with unrecalled histopathologic diagnoses.

CT scan of the abdomen showed an enlarged pancreas with innumerable cysts replacing the entire parenchyma (Fig.1) and causing mild intrahepatic and extrahepatic biliary obstruction (Fig. 2).

Several well-defined heterogeneously enhancing masses were present in both kidneys (Fig. 3): two in the superior pole of the right kidney and six) in left kidney. No evidence of thrombus formation in both renal veins and inferior vena cava.

Chest and cranial CT scans were subsequently obtained which showed avidly enhancing isodense masses in the left cerebellar hemisphere and vermis measuring 0.8 and 0.4 cm, respectively (Fig. 4). A similar-looking intradural lesion was also seen in the spinal cord (C1 level) measuring 0.5 cm. The rest of the spinal cord and cerebral parenchyma were unremarkable. The temporal horns of both lateral ventricles were mildly dilated, signifying beginning hydrocephalus.

Background: Von Hippel-Lindau disease is an autosomal dominant disorder characterized by development of benign and malignant tumours involving various organ systems such as the kidneys, pancreas and central nervous system [1].

Clinical Perspective

Craniospinal hemangioblastoma is a cardinal feature of VHL, with a reported frequency of 60-80%[2]. It is the most common tumour in VHL with an average age of presentation at 33 years [1,2]. These tumours are usually multifocal and benign but may cause significant morbidity especially when they present with perilesional oedema. They may appear anywhere along the craniospinal axis, most commonly in the cerebellum (44-72%), brainstem (10-25%) or spinal cord (13-50%) [3]. Symptoms related to these lesions depend on their location, size and the presence of associated vasogenic oedema.

Furthermore, mild intrahepatic and extrahepatic biliary ectasia were noted in our patient which may be secondary to extrinsic compression by the cysts. Such a case of biliary obstruction is rare and has only been seen in two reported cases [2, 4]. Among the abdominal manifestations of VHL, renal lesions are most common and come in the form of renal cysts and bilateral renal cell carcinomas. The pancreas may present with cystic lesions like cysts or serous cystadenoma, or solid masses such as neuroendocrine tumours. While the adrenals glands may also be involved and harbour lesions such as pheochromocytoma. [1]

Imaging Perspective

Imaging of the entire neuraxis is recommended as when cerebellar hemangioblastoma is identified a spinal lesion may frequently co-exist. CT appearances of the cerebellar and C1 mass show avidly enhancing isodense tumours with no definite cystic component. The features of these lesions do not coincide with the typical “cyst with a mural nodule” appearance of hemangioblastoma. Different morphologies have been however reported, appearing as a solid tumour (26%) or solid tumour with small internal cyst (9%) [5, 6].

Using a set of criteria described by Melmon in 1964, the diagnosis for VHL disease can be made clinically in the following circumstances: (a) in a patient with family history of VHL and at least one of the characteristic VHL-related tumours; (b) in the presence of two or more retinal or CNS tumours; or (c) in the presence of one retinal or CNS tumour, plus at least one of the characteristic VHL-related visceral tumours [1].

Other typical findings of VHL include pancreatic and renal cysts, renal cell carcinoma, pheochromocytomas and pancreatic cystadenomas in decreasing order of frequency. The various organ systems involved in VHL described by Ganeshan et al. (2018) and Leung et al. (2008) are summarized in figure 5.

Outcome

Due to its autosomal-dominant inheritance, patients have 50% chance of transferring the disease to their children. Strict surveillance for the occurrence of VHL-related tumours and their associated complications must be implemented. Annual abdominal ultrasound and baseline craniospinal MRI are recommended.

Teaching Points

The approach to management should be multidisciplinary and should target clinical problems that cause morbidity and mortality when left untreated. Patients with VHL require lifelong follow-up and anticipatory surveillance.

Written informed patient consent has been obtained.