Hemangioblastomas are 2007 World Health Organization Working Group grade 1 tumors of borderline or uncertain behaviour that occur most commonly in the posterior fossa. These tumors were categorised "other neoplasms related to the meninges"
(14). Hemangioblastomas are benign vascular lesions and account for 1 to 2% of primary intracranial tumors. They are approximately make up 5-15% of all posterior fossa tumors in adults. It may occur sporadically (66% of cases) or in association with VHL disease (33% cases). Solitary hemangioblastomas occur sporadically in the absence of family history, whereas VHL-associated hemangioblastomas are usually multiple and associated with additional retinal, brain stem, spinal cord, and/or lumbosacral nerve root hemangioblastomas as well as visceral neoplasms and benign lesions
(9,12). The average age at onset of symptoms in VHL cases is 33 years
(9,23). Sporadic cases of hemangioblastoma tend to present later, with a mean age at presentation of 42 years
(1). These tumors are more common in men
(12). Our patient is likely to represent sporadic case, as there was no relevant family history and none of the other features seen in VHL was noted. The mean age of sporadic disease is 42 years and this patient presented when she was 28 years old.
When associated with pregnancy, these tumors can grow quickly and symptoms may occur. Many theories have been proposed to explain neurological deterioration seen in hemangioblastoma patients. However, pathophysiologic behavior and histogenesis of this disease is still not adequately understood. Plasma volume and cardiac output increases during pregnancy. These changes depend on increased production of oestrogen and progesterone by the trophoblast(16). Possible theories for the increase in size of the hemangioblastoma during pregnancy are: expansion of the tumor vascular bed due to increased maternal blood volume, hormonal influence of the tumor and finding of progesterone receptor protein in the tumor(11,16,21). Some patients spontaneously improve after delivery in the literature(16). We speculated that a critical size of the tumor was present before pregnancy in our patient and then rapidly became symptomatic due to vascular engorgement or hormonal influences of the tumor itself in gestation.
Hemangioblastomas may be purely cystic (5%), purely solid (26%), cyst with a mural nodule (60%) and solid tumor with internal cysts (9%)(17). In our patient, there was a cyst with a mural nodule. Pathogenesis of the cysts is still not well understood. The cyst fluid contains amino acid, nitrogen, mucoprotein and alkaline phosphate levels similar to that of blood, suggesting that the cyst fluid arises by diffusion from the vascular component of the mural nodule(18). Lonser et al. demonstrated with study of 16 VHL patients with 22 hemangioblastomas the protein profiles of peritumoral cyst fluid and serum were similar(13). Also, the mean vascular endothelial growth factor levels determined in peritumoral cysts was 1.5 ng/ml ( range, 0.5-4 ng/ml). These authors showed that histological analysis of the cyst walls was consistent with reactive gliosis devoid tumor cells. Peritumoral cysts develop as a result of a tumor interstitial process that begins with generation of edema. Increased tumor vascular permeability, increased interstitial pressure in the tumor and/or hydrodynamic forces within tumor vasculature promotes plasma extravasation. When these forces overcome the ability of adjacent tissue to resorb fluid, edema and subsequent cyst formation ocur(3,13). Van Velthoven et al. hypothesized that transudation of fluid from the tumor capillaries and tubular dissection along the gray matter near the central canal are the main pathophysiological mechanisms for brain stem and spinal cord hemangioblastomas(20). The cyst wall generally does not enhance on contrast administration and the enhancement indicates neoplastic extension along the cyst wall(15). Bishop et al. presented the case of a VHL patient with a cystic cerebellar hemangioblastoma that recurred twice after removal of the nodule and drainage of the cyst. The cyst wall was excised in the third operation. The cyst wall contained tumor with the same histopathological pattern observed in the nodule. Besides, the enhancing cyst wall contained vascular endothelial growth factor-expressing hemangioblastoma cells intermixed with gliosis(4). Our patient’s MRI scans did not demonstrate nodular enhancement of the cyst wall.
Symptoms of cerebellar hemangioblastomas depend on the tumor’s size and location(2,22). Serial MRI studies of patients with hemangioblastomas have shown that cyst formation can arise from solid tumor(13,17). Solid cerebellar nodules are well tolerated and the onset of symptoms heralds the development of such cysts(17,23). The rate of cyst growth is typically much greater than the rate of tumor growth(23). Ammerman et al. analyzed that the serial clinical and MRI findings in 19 patients with VHL disease (total 143 hemangioblastomas; 68 hemangioblastomas were located in the cerebellum) who were followed up for more than 10 years. The combined tumor and cyst growth rates and the combined tumor and cyst sizes are the significant predictors of symptoms development for hemangioblastomas in the cerebellum(2).
Simple cyst drainage is an inadequate therapy. Total removal of the solid nodule is mandatory to avoid tumor recurrence. The cyst may be entered during tumor resection, but additional removal of the cyst wall is not necessary(8,9,22). Jagannathan et al. in serial MRI studies (60 patients; 126 operations for 164 cerebellar hemangioblastomas; 91 hemangioblastoma-associated peritumoral cysts) demonstrated that tumor resection produced collapse or complete disappearance of the associated peritumoral cyst. Cyst wall removal was not performed in any case. Because the tumor is the source of the cyst, simply removing the tumor elicits cyst collapse. Significant reduction in cyst size within 24 hours of tumor removal and maximal or complete collapse within 24 weeks of removal was noted in all cases. Also, these authors announced that there was no case fluid reaccumulation in peritumoral cysts after resection of the hemangioblastoma associated with the cyst(9). Vougioukas et al. recommended the surgical removal of symptomatic and asymptomatic tumors with validated radiological size progression(22). Nearly all of the tumors (Ammermann’s above-mentioned article) studied showed radiographic progression but only half went on to require therapy. Thus, neither presence of tumor nor radiographic progression is an indication for therapy. Asymptomatic tumors should be followed with serial imaging at regular intervals(2). In the second admission to hospital we did not recommend surgery to our patient. Cyst had grown but there was no mural nodule. There were no clinical and neurological signs of raised intracranial pressure. Antiedema drugs (steroid and/or mannitol) were not given because of continuing pregnancy. Symptoms such as headache and vomiting quickly disappeared. The patient remained neurological intact during hospitalization and discharge home.
In the literature, recurrence has ranged from 20-33%(5-7,10,19). De la Monte and Horowitz documented that an age of less than 30 years on initial diagnosis, the presence of VHL disease, and a multicentric involvement of the central nervous system are independent predictors of hemangioblastoma recurrence(7).
Our patient underwent total removal of the solid nodule and aspiration of cyst without cyst wall excision, but unfortunately, the cyst and symptoms rapidly recurred. We believe that recurrence of the cyst was due to transudation of fluid from the cyst wall capsule during pregnancy. Cyst collapse may be result of the absence of cystic wall fluid excretion because of changes in the hormonal system after birth. In the surgery of cystic cerebellar hemangioblastoma, excision of the cyst capsule together with cyst drainage and excision of the mural nodule may be necessary. When a cyst is seen to be developing and enlarging right after surgery, repeat surgery should be avoided, since spontaneous resolution is possible for pregnancy, as demonstrated by our case report. Also, because of the spontaneous resolution of the cyst for pregnant patient mentioned above, in the patients who do not have neurological deficit or are asymptomatic, the first preference should be a conservative approach.
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