Abstract
Haemangioblastomas (HBLs) are rare central nervous system tumours accounting for only 1.2–2.5% of all intracranial tumours. While most HBLs occur sporadically, 36–40% of cases are associated with von Hippel-Lindau (VHL) syndrome. Owing to its benign nature, sporadic cases are usually detected only when symptoms occur due to mass effect. Thus, the natural history of HBLs has only been studied in association with VHL syndrome. We present a case of sporadic HBL with a rapid evolution of its small nodule into an enlarging mural nodule with a large pseudocyst that resulted in increased intracranial pressure. Craniotomy for complete tumour removal was performed and the patient fully recovered. This case implies a regular follow-up of HBL might be mandatory even in patients without VHL.
Background
Haemangioblastomas (HBLs) are rare central nervous system tumours accounting for only 1.2–2.5% of all intracranial tumours.1 While most HBLs occur sporadically, 36–40% of cases are associated with von Hippel-Lindau (VHL) syndrome.2 There have been several studies regarding the natural course of HBLs. While most HBLs occur sporadically, a majority of the studies have been performed in patients with VHL syndrome. This, to some extent, is because of the benign nature of HBLs, which delays diagnosis until the symptom develops due to the mass effect of the cyst, especially when it is in patients without VHL.3 The authors present this case not only because this is the second report documented on the transition of solid, sporadic HBL into a pseudocyst with a mural nodule, but also because this case suggests that the developmental course of pseudocysts in sporadic HBL might be consistent with that in VHL syndrome, which implies a necessity for regular follow-up with imaging even for HBL in patients without VHL, since HBL in patients with VHL and without VHL may share the same mechanism in cyst formation.
Case presentation
A 20-year-old man suffering from non-specific headaches was admitted to the army hospital. On MRI, a small solid enhancing nodule was found in the right cerebellum (figure 1). Given the age of the patient, the MRI and the location of the tumour, it was suspected to be a HBL. VHL syndrome was excluded because the patient did not fit the clinical criteria for diagnosis.1 There was no family history suggestive of VHL; however, genetic testing was not performed in any of the family members or the patient. The headache the patient suffered from was non-specific and it later resolved with an ordinary non-steroidal anti-inflammatory drug. It was proven to be not related to the tumour, and because the tumour was benign and too small to operate, the patient was discharged under observation.
Figure 1.
MRI at admission. The enhancing nodule (arrow) is in the right cerebellum.
One year later, follow-up MRI showed very little progress (see online supplemental figure S1). Although some vessels had developed near the tumour, the solid nodule had only slightly grown in size and no cyst was present.
Three years and 6 months later, the patient returned to the hospital, with severe nausea and vomiting.
Investigations
Brain MRI showed obstructive hydrocephalus due to a large cystic mass with an enhancing mural nodule in the right cerebellum (see online supplemental figure S2). The patient was admitted to the emergency room for further examination. He was clinically diagnosed with HBL.
Treatment
Extraventricular drainage was performed to release the increased intracranial pressure, followed by midline suboccipital craniotomy and complete removal of the tumour.
Outcome and follow-up
A subdural haematoma found in the left parietal region on postoperative CT was removed after craniotomy. The patient showed no signs of postoperative complications and was discharged.
Discussion
The irregular growth pattern and transition from a small solid nodule to a cyst with a mural nodule observed in our patient's HBL are consistent with recent studies on the natural history of HBL in patients with VHL. These studies show that HBLs start as small solid nodules and subsequently develop cysts that cause symptoms due to their mass effect.4–6 In their growth, HBLs in VHL syndrome exhibit a stuttering pattern; the arrest and growth intervals last an average of 25 months and 13 months, respectively.5 6 The natural course of HBLs has been studied in large series in patients with VHL, however, in patients without VHL, only one case report has documented the transition of a HBL from a solid nodule to a cyst with a mural nodule.7 A solid cerebellar HBL developed a large cystic component in approximately 2 years and 6 months in a 34-year-old man. The tumour was found incidentally, and the patient was negative for VHL disease, as in our case.
These findings suggest that the four distinct types of radiological classification of HBLs, (1) pure cyst, (2) cyst with enhancing mural nodule, (3) solid and (4) solid with internal cyst formations, act as steps in the course of the development of a HBL in patients without VHL as well as in patients with VHL.8 A HBL presenting as a solid nodule can grow in size but can also rapidly develop into one or multiple cysts in or around the nodule even in patients without VHL. Emerging proteomic analysis data have shown that cyst formation associated with HBL, whether peritumoural or intratumoural, is a consequence of vascular leakage secondary to upregulation of vascular endothelial growth factor (VEGF); and anti-VEGF therapy may effectively control cyst formation.9 Initially, the extravasation of fluid produces a small region of oedema surrounding the tumour and equilibrium is achieved. However, over time, when the absorption of fluid by surrounding tissue exceeds the extravasation of plasma ultrafiltrate, surrounding tissue will swell due to its subjection to solid stress, and this process results in the formation of peritumoural cysts.10–12 The natural history of sporadic, solid HBLs in patients without VHL has yet to be investigated in large series before concluding that all solid nodules eventually develop cysts. However, given that HBL by definition contains irregular vasculature and hypervascularity, which is associated with increased vascular permeability, this disease entity has a fundamental tendency to develop a major peritumoural cyst. The lack of differences in the cytogenetic changes found in VHL-associated HBLs and non-VHL HBLs appear to support this theory.13 There have been a few studies regarding the surveillance guideline for VHL disease with or without HBL based on its natural history. Maher14 suggested that patients with VHL without HBL in the central nervous system should have evaluation that consists of head and spine MRI every 12–36 months, beginning in adolescence. Lonser et al15 16 investigated a mean time of cyst formation (from oedema development to peritumoural cyst formation, 36 months; range 8–72 months) and suggested that regular follow-up is necessary for those cases surgically resected as well as observation in cases without resection. Ammerman et al5 also proposed that HBLs in patients with VHL require long-term follow-up with imaging every 6–12 months even if they are asymptomatic.
Considering the other aforementioned case of rapid growth of a HBL in a 34-year-old man, these two cases together indicate that there is also a risk of acute neurological symptoms because of the HBL's rapid growth or transition into a huge cystic mass not only in patients with VHL but also in patients without VHL. Giving consideration to the data from previous studies by Lonser et al15 and Ammerman et al,5 there might be a necessity for regular follow-up with imaging at least every 6–12 months even for HBLs in patients without VHL, since HBLs in patients with VHL and without VHL may share the same mechanism in cyst formation. Unfortunately, there currently are not enough cases to constitute a surveillance guideline regarding follow-up of HBL in patients without VHL. This case might imply that it would be necessary to make an attempt to establish a follow-up guideline even for the HBL in patients without VHL.
Learning points.
The traditional radiological characteristics (cyst, cyst with mural nodule, solid, solid with internal cyst formation) may help to understand the natural mechanism of cyst formation in haemangioblastomas (HBLs) in patients with and also those without von Hippel-Lindau (VHL) disease.
Though HBLs are generally known to be slow growing and are benign in nature, regular follow-up might be mandatory even in patients without VHL disease.
Genetic testing should always be performed in such type of cases to rule out VHL syndrome.
Footnotes
Competing interests: None.
Patient consent: Obtained.
Provenance and peer review: Not commissioned; externally peer reviewed.
References
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