[Clinicopathologic study of von Hippel-Lindau syndrome-related and sporadic hemangioblastomas of central nervous system].
OBJECTIVE
To study clinicopathologic features, diagnosis, treatment and prognosis of von Hippel-Lindau (VHL) syndrome-related and sporadic hemangioblastomas of the central nervous system (CNS-HB).


METHODS
Histopathological, ultrastructural, immunohistochemical (EnVision method) and clinical features of 21 VHL syndrome and 63 sporadic CNS-HB cases were studied with correlation of the available follow-up information.


RESULTS
Twenty-one VHL patients accompanied with a total of 87 CNS-HBs, including one patient of developing 12 HBs within 13 years. There were 10 patients presenting other lesions related to VHL, including 6 retinal HBs, 4 pancreatic tumors (endocrine tumor and microcystic cystadenoma), 1 clear renal cell carcinoma, 4 renal cysts and 1 endolymphatic sac tumor. One patient developed 5 different tumors related to VHL within a period of 4 years. In the 63 cases of sporadic CNS-HB (34 male and 29 female), the mean age was 43.0 years. Among the 18 VHL syndrome patients with available follow-up information, 14 were still alive and within them, 4 became disabled and 11 had developed new lesions. The other 4 patients died. Among the 42 patients of sporadic HB with follow-up information, 39 were alive including 3 disabled cases, and the other 3 died. Histologically, the tumors showed large and vacuolated stromal cells. Some tumors showed atypical nuclei. Involvement of the brain tissue was seen in 32 cases, among which, 21 patients with available follow-up information were learnt to be alive. Tumor cells of HB stained positive for vimentin, EGFR, Inhibin alpha and D2-40, but negative for CD34 and CD68. In 3 cases of HB, some stromal cells were positive for GFAP. All cases showed a low expression for Ki-67, except 2 cases with 2% and 1 case with 5% Ki-67 indices.


CONCLUSIONS
VHL syndrome is a multisystem disorder with a poor prognosis and a high rate of missed diagnosis. The syndrome is characterized by development of various benign and malignant tumors. The most common tumor is CNS-HB, which occurs predominantly in the cerebellum. Patients with VHL syndrome tend to present at a younger age than patients with sporadic CNS-HBs, and VHL related HB occurs more predominantly in the brain stem and spinal cord. Prognosis of CNS-HB patients is not correlated with the nuclear atypicality, expression for Ki-67 and involvement of the brain tissue. Because new lesions may develop during the patient's lifetime. So that, regular clinical inspection is recommended in order to check up the development of any new lesions.
Zhou
Jing
J
Department of Pathology, Clinical School of Nanjing University Medical College, Nanjing General Hospital of PLA, Nanjing 210002, China.
Li
Nan-yun
NY
Zhou
Xiao-jun
XJ
Zhou
Hang-bo
HB
Wu
Bo
B
Jiang
Shao-jun
SJ
Ma
Heng-hui
HH
Zhang
Ru-song
RS
D000293:Adolescent; D000328:Adult; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D016543:Central Nervous System Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D002648:Child; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018325:Hemangioblastoma / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D006801:Humans; D007265:Inhibins / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D019572:Retinal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D016019:Survival Analysis; D014746:Vimentin / Q000378:metabolism; D055815:Young Adult; D006623:von Hippel-Lindau Disease / Q000378:metabolism / Q000473:pathology* / Q000601:surgery
D005904:Glial Fibrillary Acidic Protein; D019394:Ki-67 Antigen; D014746:Vimentin; C094377:inhibin-alpha subunit; D007265:Inhibins; C512478:EGFR protein, human; D066246:ErbB Receptors