OBJECTIVE: To investigate and analyze the diagnosis, treatment and prognosis of intracranial hemangioepithelioma.
METHODS: A retrospective analysis of the clinical and imaging manifestations, pathological features, treatment and follow-up results of 18 cases of intracranial hemangiopericytoma admitted to our hospital between 1997 and 2006 was performed.
RESULTS: A total of 23 surgical procedures were performed in 18 patients, including total resection in 10 cases, subtotal resection in 9 cases, and partial resection in 4 cases. There were 6 cases of postoperative adjuvant conventional radiotherapy and 3 cases of adjuvant gamma-knife treatment. 5 of the 15 primary cases recurred, with a recurrence rate of 33.3% and a mean recurrence time of 76.75 months. Intracranial metastasis occurred in 2 cases and extra-neurological metastasis occurred in 2 cases.
Conclusion: Unlike meningioma, intracranial hemangioepithelioma has a high local recurrence rate and can develop neuraxial and extra-neurological metastasis, so total surgical excision + adjuvant radiotherapy with a dose of at least 50 Gy should be the conventional treatment plan. Lifetime follow-up is required for patients with intracranial hemangioepithelial cell tumors.
[Keywords] hemangioepithelial cell tumor; diagnosis; treatment; radiotherapy; prognosis
Hemangioepithelial cell tumor (HPC) is a malignant tumor that originates from Zimmermann’s ependymal cells around capillaries or postcapillary microvessels, mostly in the skin and musculoskeletal system, but rarely in the intracranial area. Intracranial HPC accounts for less than 1% of CNS tumors and approximately 2-4% of tumors of intracranial meningeal origin [1]. Compared with meningioma, intracranial HPC is rich in blood flow, difficult to excise completely, has a high recurrence rate after surgery, and is prone to intracranial and distant metastases, which makes clinical diagnosis and treatment difficult. Among the intracranial HPC admitted to our department from 1997 to 2006, there were 18 cases with perfect data. In this paper, the treatment experience of these 18 cases of HPC combined with the literature is analyzed as follows.
Data and methods
1. general information: 13 male cases, 5 female cases, male:female=2.6:1. age 28~71 years old, average 45.7 years old. among 18 patients, 15 were primary cases, 3 were recurrent cases, duration of primary cases 2 days~1 year, average 1.7 months. Tumor sites: parsagittal sinus in 7 cases, parsagittal cavernous sinus in 4 cases, cerebellar curtain in 3 cases, falx cerebri in 2 cases, temporal area in 1 case, and saddle area in 1 case. Combined with the data of recurrent cases, the age of first onset ranged from 28 to 64 years old, with an average of 42.2 years old.
2. Clinical manifestations: The most common clinical manifestation was headache, with 11 cases. Others included visual acuity loss in 5 cases, diplopia in 5 cases, visual field defect in 2 cases, gait instability in 1 case, hearing loss in 1 case, motoneural nerve palsy in 2 cases, abducens nerve palsy in 1 case, trigeminal nerve dysfunction in 2 cases, unilateral lower limb light palsy in 2 cases, and optic papillar edema in 2 cases.
3. Imaging: 11 cases of CT scan, 6 cases of enhancement, 13 cases of MRI scan, 11 cases of enhancement, 4 cases of DSA examination (1 patient had recurrence of tumor after surgery and 2 DSA examinations were performed.)
4. Treatment: All cases were treated surgically and the pathology was confirmed as HPC. 18 patients were operated 23 times (5 cases were operated twice due to tumor recurrence). In this group, there were 9 cases of postoperative radiotherapy, including 6 cases of postoperative adjuvant conventional external radiotherapy and 3 cases of adjuvant gamma-knife therapy. One case was treated with conventional radiotherapy because of the second recurrence of tumor. Preoperative external carotid artery supply vessel embolization was performed in 4 cases.
5.Follow-up: All 18 cases were followed up by outpatient or telephone, the follow-up time ranged from 12 to 108 months, with an average of 62.1 months.
Results
1, imaging performance: the tumor boundary was clear, all were lobulated, the peritumor edema was more obvious, and there was extensive basal connection with dura, the skull was eroded in 3 cases, 2 cases were accompanied by peritumor hematoma, the CT scan showed high or mixed high and low signal, it could be accompanied by cystic changes, no calcification was seen, the enhanced scan showed obvious enhancement of the lesion, but the internal low density area was not enhanced, the MRI scan showed equal or mixed T1, mixed T2 signal. The tumor was found to have a double blood supply in three cases, mainly from the external carotid branch and partly from the internal carotid branch. In the other case, the blood supply was mainly from the vertebrobasilar branch and partly from the external carotid branch.
2. Intraoperative observations and surgical results: 18 patients underwent a total of 23 operations. The tumors had complete envelope and the surface was red or gray-red nodular. Most of the tumors were tough in texture and the blood supply was extremely rich, and most of them were closely related to intracranial venous sinuses. There were 10 cases of total tumor resection (Simpson grade I and II), 9 cases of near-total tumor resection (Simpson grade III), and 4 cases of partial tumor resection (Simpson grade IV). There were no cases of surgical death, two cases of delayed wound healing after surgery, and one case of postoperative complication of pulmonary infection, all of which improved after corresponding treatment.
All tumors were pathologically confirmed to be HPC, and the tumor specimens were mostly lobulated, red or grayish-red, with intra-tumor vascular cavities or blood sinuses of different sizes. The cytoplasm is lightly stained and may be vacuolated, with round or spindle-shaped nuclei. Some tumors may have interstitial changes. The thin-walled vascular network within the tumor is abundant and can anastomose with each other to form “antler-like” manifestations. Immunohistochemical examination showed positive for vimentin and negative for epithelialmembraneantigen (EMA).
4. Follow-up results: 5 of 15 primary cases had local recurrence of tumor during the follow-up period, with a recurrence rate of 33.3% and a five-year recurrence rate of 13%. Combined with the first surgery time of the three recurrent cases admitted to our group, the first recurrence time was 40-120 months after the first surgery, and the average recurrence time was 76.75 months. Two cases of intracranial metastases, both of which were recurrent cases admitted, occurred 108 and 170 months after the first surgery, respectively, and one of them died 8 months after reoperation due to tumor progression. Two cases of extra-neurological metastases occurred, one case had tumor recurrence in situ 40 months after the first surgery, and was treated with surgery + adjuvant post-operative conventional radiotherapy, and vertebral metastasis occurred 52 months later, and treatment was abandoned. One case had tumor recurrence + vertebral metastasis 94 months after surgery and gave up treatment. The two cases are now 4 months and 1 month after the occurrence of metastasis, respectively, and are still alive. Two cases died, and the other case died of other diseases in addition to the aforementioned cases.
Discussion
Intracranial HPC was once thought to be a subtype of meningioma (angioblastoma meningioma), but HPC has a high rate of local recurrence, can develop intra- and extra-central nervous system metastases, and has clinical features distinct from meningioma. With the development of pathological detection methods, especially the application of immunohistochemical methods, further understanding of intracranial HPC was achieved. 1993 and 2000 WHO classification of CNS tumors separated intracranial HPC from meningioma and classified it as mesenchymal,non-menigothelial meningioma of meningeal origin. menigothelialtumors).
The age of onset of intracranial HPC is mostly 38-45 years old, the duration of disease is mostly less than 1 year, and the most common symptom is headache [2-4] in men than in women. Based on the clinical manifestations and imaging data, it is difficult to make a correct diagnosis of intracranial HPC. Among the 15 primary cases in this group, only two cases were considered preoperatively for HPC, one case was misdiagnosed as glioma, two cases were misdiagnosed as nerve sheath tumor, and the rest were preoperatively diagnosed as meningioma. It is difficult to distinguish HPC from meningioma from imaging data. Based on this group of data combined with the literature, the authors believe that the following features can help in differential diagnosis.
1. intracranial HPC is more common in males and meningioma in females, and the age of onset of HPC is younger than meningioma and the course of the disease is shorter.
2. Intracranial HPC is mostly lobulated, with obvious peritumoral edema. Two cases with peritumoral hematoma are still seen in this group, the cause of which is unknown.
3.The internal cystic necrotic area of the tumor is common.
4. calcification on CT scan is rare, and cranial erosion may be present, but osteomalacia is rare.
5, CT and MRI enhancement is obvious, but internal non-enhanced cystic necrosis area is seen, MRI plain and enhanced scans sometimes see vascular flow space images.
The final diagnosis of HPC depends on pathological examination, which is characterized by a large number of thin-walled blood vessels within the tumor, which can anastomose with each other to form “antler-like”, and the tumor cells are arranged around the blood vessels. It is difficult to see the characteristic changes of meningioma such as vortex-like structures and sand granules. Sometimes it is difficult to confirm the diagnosis by ordinary HE staining, but reticulocyte staining and immunohistochemistry are needed to confirm [1], and there are abundant reticulocytes between HPC tumor cells, which are positive for Vimentin and negative for EMA, while meningioma is positive for both Vimentin and EMA.
Intracranial HPC has a short course and rapid progression, and most of the tumors are already huge at the time of diagnosis, and the tumor blood supply is extremely rich. It has a high recurrence rate and is prone to intra- and extra-neurological distant metastases, making treatment difficult. In the literature, the five-year survival rate of intracranial HPC ranges from 67% to 96%, and the ten-year survival rate ranges from 40% to 75% [2,3,5], with a mean local recurrence time of 40 to 108 months [2,3,5-7]. Among the 15 primary HPC cases in our group, 5 cases recurred, with a recurrence rate of 33.3% and a 5-year recurrence rate of 13%, and the first recurrence time was 40-120 months after the first surgery, with a mean recurrence time of 76.75 months. intra-neurological metastases can occur in HPC, and two cases of in situ recurrence + intracranial multiple metastases were seen in our group, occurring 108 and 170 months after the first surgery, respectively. What is significantly different from other intracranial primary tumors is that HPC has a strong tendency to metastasize outside the nervous system, and the metastasis rate increases significantly with time, and the 15-year metastasis rate can be as high as 64%-79% [3,5], and the mean time to develop distant metastasis is 84-107 months, spanning a time frame of 1-20 years, and the most common metastatic sites are bone, lung, and liver in that order [1-3,5]. The tumor progresses more slowly at the metastatic site after distant metastasis occurs, so it can survive with tumor for a longer period of time, and patients more often die from intracranial tumor progression rather than distant metastasis [8]. In our group, we saw two cases of extra-neurological metastasis, both of which metastasized to the vertebrae, and the time of distant metastasis was 92 months and 94 months after the first surgery, respectively.
The treatment of HPC should strive for total surgical resection, and postoperative adjuvant radiation therapy should be routinely performed regardless of the extent of tumor resection, and it is currently considered that total tumor resection plus postoperative adjuvant radiotherapy at a dose of not less than 50 Gy is the best treatment plan [1,2,8,9]. The effect of preoperative embolization is not as good as that of meningioma because of the involvement of soft meningeal vessels in the blood supply of HPC. Kim et al [2] reported that the degree of resection had a significant effect on the five-year recurrence-free rate, which was 72.7% for total resection and 20.8% for non-total resection, and the average recurrence time was 111 months for total resection and 43 months for non-total resection. In China, Liu et al [10] reported the diagnosis and treatment analysis of 60 cases of intracranial HPC, all of which were operated plus postoperative radiotherapy. The results of the first postoperative follow-up of 28 cases showed that the average follow-up time was 28 months for the group with total tumor resection and the recurrence rate was 6%; the average follow-up time was 27 months for the group with near total tumor resection and the recurrence rate was 71%; the average follow-up time was 19 months for the group with most of the tumor resection and the recurrence rate was 100%. In our group, there were 15 primary cases, 9 cases of total resection, 1 case of recurrence, and the recurrence time was 94 months; 6 cases of non-total resection, 4 cases of recurrence, and the average recurrence time was 57 months; the 5-year recurrence rate was 0% for total resection and 22.2% for non-total resection. The effect of postoperative adjuvant radiotherapy on intracranial HPC is generally affirmed [2,3,5,8,9], and it is believed that the adjuvant radiotherapy dose should not be less than 50 Gy [5,8]. Guthrie et al [5] believed that radiotherapy could delay the time of recurrence and prolong survival, and 9 of their 17 patients who received postoperative adjuvant radiotherapy recurred, with a mean recurrence time of 75 months and a mean survival of 92 months, while Among the 17 patients who received postoperative adjuvant radiotherapy, 7 recurred in 8 cases with doses less than 45 Gy, only 2 recurred in 9 cases with doses greater than 45 Gy, and none recurred in cases with doses greater than 51 Gy. The effectiveness of adjuvant radiotherapy was not observed in 6 of the 15 primary cases (including 1 total resection and 5 partial resections) and 3 recurrences, probably due to the small number of cases and the fact that it was mainly used for cases with unsatisfactory resection. Stereotactic radiosurgery is an excellent treatment for postoperative residual or recurrent tumors and for those who cannot tolerate surgery [2,8,11,12,13]. Galanis [12] applied stereotactic radiosurgery to treat 10 cases of recurrent HPC with 20 tumors ranging from 8 mm to 52 mm in diameter (median 32 mm). 35% of the tumors had a maximum diameter greater than 40 mm.3 In 3 patients who had not been previously treated with external radiation (all <25 mm in diameter), the tumors disappeared completely at a median follow-up period of 3 years, and in the other 17 tumors at a median follow-up period of 12 months, 14 (70%) tumors were partially reduced and 3 tumors remained stable. The group applied γ-knife to treat the residual tumor after surgery in 3 cases, now at 46 months, 31 months and 8 months after treatment respectively, the tumors had shrunk and were well controlled locally, the authors believe that stereotactic radiosurgery is a good choice for intracranial HPC, especially for patients who had received conventional external radiation therapy
It is currently believed that radiotherapy and stereotactic radiosurgery have no significant preventive effect on distant metastases from intracranial hemangioepithelioma [9, 11]. Recurrence and metastasis of intracranial HPC can occur for decades after surgery; therefore, patients with intracranial HPC should be followed up throughout their lives.