Recurrent Large Spinal Hemangioendothelioma: A Rare Case Report

Article information

Nerve. 2024;10(2):172-178
Publication date (electronic) : 2024 October 23
doi : https://doi.org/10.21129/nerve.2024.00633
1Department of Neurosurgery, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon, Republic of Korea
2Department of Radiation Oncology, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon, Republic of Korea
3Department of General Surgery, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon, Republic of Korea
4Kangwon National University School of Medicine, Chuncheon, Republic of Korea
Corresponding author: Choonghyo Kim Department of Neurosurgery, Kangwon National University Hospital, Kangwon National University School of Medicine, 156, Baengnyeong-ro, Chuncheon 24289, Republic of Korea Tel: +82-33-258-2410 Fax: +82-33-258-9418 E-mail: jeuelkim@gmail.com
Received 2024 August 13; Revised 2024 September 27; Accepted 2024 October 11.

Abstract

Epithelioid hemangioendothelioma (EHE) is a rare benign vascular tumor, affecting fewer than one in a million individuals. Spinal EHE is exceptionally rare. This case report presents a case of recurrent spinal EHE, focusing on its clinical manifestation and providing a brief overview of its genetic characteristics. Seven years prior, a patient underwent subtotal resection of a lumbar and retroperitoneal EHE. Due to severe intraoperative bleeding, part of the lumbar spine mass was left unresected and subsequently treated with a moderate dose of radiation therapy. More recently, the patient presented with bilateral lower extremity weakness and urinary incontinence. Imaging studies revealed metastases in the thoracic and sacral bones, along with regrowth in the anterior portion of the previously treated spinal EHE. The patient underwent a series of operations to address both the regrowth and metastases, followed by intensity-modulated radiation therapy to target the remaining tumor tissue while minimizing damage to surrounding structures. Although EHE is generally considered benign, this indolent tumor has a tendency for persistent regrowth and metastasis. This case highlights the importance of radical resection and the potential role of higher radiation doses in preventing recurrence. Molecular testing may aid in achieving an accurate diagnosis and guiding effective treatment strategies.

INTRODUCTION

Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor that exhibits characteristics of both hemangioma and angiosarcoma2,4,15). It occurs in fewer than one in a million people and accounts for less than 1% of vascular neoplasms4). EHE of osseous origin is particularly uncommon, with vertebral involvement being even rarer, reported in under 10% of these cases4,10). Recent advances in next-generation sequencing (NGS) have identified mutations in EHE, offering insights into its biology and the dysregulated signaling pathways, suggesting new therapeutic strategies17). Fusion genes such as WWTR1-CAMTA1 and YAP1-TFE3 are recognized as critical drivers of tumorigenesis3,6,7,13,15-17). Despite its generally indolent nature, EHE can display aggressive behavior, particularly in cases of metastasis15).

Given the extreme rarity of EHE, comprehensive data on its clinical course, treatment outcomes, and prognosis remain insufficient. This case report contributes to the limited body of knowledge by presenting an exceptionally rare instance of recurrent spinal EHE. By documenting this case, we aim to enhance our understanding of the disease’s clinical behavior and provide insights to guide therapeutic strategies.

This case report also highlights the importance of aggressive surgical resection combined with curative dose intensity-modulated radiation therapy (IMRT) in the management of spinal EHE.

CASE REPORT

A 49-year-old woman presented to our outpatient clinic with severe lower back pain and sensory disturbances below both knees. The patient was an active smoker with a long-standing history of diabetes and a significant family history of cancer, including her mother, who died of brain cancer. The patient had previously undergone posterior lumbar interbody fusion following a fall 15 years ago. Magnetic resonance imaging (MRI) and computed tomography (CT) scans revealed 12 × 9 × 11 cm lobulated mass in the vertebral body, with extraosseous paravertebral soft tissue extension and posterior element involvement, causing severe canal and neural foramen encroachment from the 3rd to the 5th lumbar spine. Additionally, two paraspinal masses (11 × 8 cm and 6.6 × 5 cm) were identified in the left psoas muscle and probable small bowel mesentery (Fig. 1).

Fig. 1.

(A) Sagittal magnetic resonance imaging (MRI) illustrating the extension of spinal hemangioendothelioma compressing the thecal sac. (B-D) Axial MRI demonstrating multi-lobulated vertebral and abdominal masses at the third lumbar (B), fourth lumbar (C), and sacral (D) vertebral body levels. (E) Coronal computed tomography (CT) image illustrating the extent of the vertebral mass. (F, G) Axial CT scans revealing a lobulated contour vertebral body mass with paravertebral involvement at the fourth lumbar (F) and sacral (G) vertebral body levels.

Spinal angiography and tumor embolization were performed to prevent intraoperative bleeding due to the densely developed peritumoral vasculature. Although a substantial portion of the abdominal mass was removed, the vertebral fungating mass remained unresected due to massive intraoperative bleeding. Postoperative pathological examination confirmed the diagnosis of EHE.

After one month, the patient experienced worsening lower back pain and right leg weakness (motor grade 4+/5). Two-stage operations were performed following tumor embolization. Initially, the fungating mass at L3-5 was resected to decompress the spinal canal, and extensive vertebral fixation from T11 to S2 was completed. Two weeks later, L3-5 corpectomy and tumor removal were performed via a retroperitoneal approach (Fig. 2).

Fig. 2.

(A, B) Computed tomography images showing substantial reduction of the abdominal and vertebral mass following the operation: coronal (A) and axial (B) views. (C) The resected abdominal paraspinal mass. The length of the black line in (C) denotes 10 cm.

One month later, IMRT was administered to the residual mass, delivering a total of 40 Gy over 20 fractions. Three months after radiotherapy (RT), the motor weakness improved, and the patient remained free of neurological problems up to the 6-year postoperative follow-up (Fig. 3).

Fig. 3.

(A, B) Computed tomography images showing the reduced size of the remnant spinal epithelioid hemangioendothelioma 6 years after intensity-modulated radiation therapy: coronal (A) and axial (B) views.

However, paresthesia below the L2 sensory dermatome level and bilateral lower extremity weakness (motor grade 4/5) developed seven years after the first surgery. The patient also experienced dysuria and abnormal cold sensations below the knees. MRI and CT revealed a large mass at the L2-5 level, with multiple bone metastases in the T9, T11, S2 vertebrae, as well as the left 4th rib and bilateral clavicles (Fig. 4).

Fig. 4.

(A) Axial computed tomography image demonstrating an increase in the size of the vertebral body mass. (B) Sagittal magnetic resonance imaging demonstrating metastasis at T9. (C, D) Positron emission tomography revealing metastasis at T9 and the sacrum.

Although immediate RT targeting the L2 to S2 region was initiated, it was eventually discontinued after delivering a total of 14 Gy over 7 fractions, owing to poor compliance resulting from the patient’s general weakness and abdominal pain. Upon discharge, the patient’s bilateral lower extremity weakness improved to the extent that she could walk unaided.

DISCUSSION

This case involves an exceptionally rare instance of spinal EHE with recurrent and metastatic behavior, which is particularly significant given the limited data on the natural history and progression of this tumor type. The aggressive recurrence and metastasis observed underscore the unpredictable clinical course of EHE and the challenges in managing it, highlighting the need for optimized treatment strategies and the integration of emerging molecular diagnostics.

1. Differential Diagnosis

Spinal EHE closely mimics several other conditions, making precise differential diagnosis critical2). Conditions such as metastatic carcinoma, angiosarcoma, and hemangiomas can present similarly but require distinct therapeutic strategies5). The diagnostic approach must consider both the patient’s age and the extent of disease involvement1,2). For patients with multifocal disease, differential diagnoses should consider metastatic carcinoma, lymphoma, and myeloma, especially when disease progression aligns with characteristics of more advanced age1,2). Conversely, multifocal disease in cases presenting earlier in life may suggest conditions such as Langerhans cell histiocytosis and fibrous dysplasia1,2). For solitary lesions, the differential must encompass fibrous dysplasia, Ewing's sarcoma, osteosarcoma, and fibrosarcoma, requiring detailed clinical and radiological evaluation1,2).

2. Comparative Analysis

Given the rarity of spinal EHE, a comparative analysis of cases in the literature offers valuable insights into its clinical behavior. A summary of patient demographics, tumor characteristics, treatments, and outcomes is presented in Table 1.

Comparative overview of documented spinal epithelioid hemangioendothelioma cases

3. Treatment Approach

In the treatment of EHE, surgical resection remains the primary modality, aiming for maximal tumor removal while preserving spinal stability and neurological function4,10). Contemporary treatment typically integrates RT with function-preserving surgery18). Although RT is increasingly utilized for non-resectable primary tumors, and advancements in image-guided RT have expanded therapeutic options, there is no consensus on the optimal dose and fractionation for palliative or curative purposes12,14). Conventionally, curative RT doses for sarcomas range from 50 to 75 Gy, with a median of 60 Gy9). In this case, the patient received 40 Gy of IMRT, a palliative dose aimed at local tumor control. Although initially effective, with stable disease for over seven years, an aggressive recurrence later developed, suggesting that this dose was insufficient for sustained tumor suppression and long-term metastasis prevention. This finding suggests that higher radiation doses may be necessary for sustained tumor control and long-term metastasis prevention and draws attention to the importance of aggressive treatment approaches, including curative doses of IMRT and maximal surgical resection. Further research is required to establish definitive treatment guidelines for this rare and challenging tumor.

4. Clinical Course

This tumor exhibited a peculiar clinical course, remaining well-controlled for seven years before recurring aggressively with distant metastasis. This unusual pattern of progression raises important considerations regarding the adequacy of the initial treatment approach. It suggests that a curative dose of IMRT and maximal resection may be necessary for prolonged disease control and the prevention of late recurrences. This case emphasizes the need for continuous vigilance and potentially more aggressive initial treatment in managing EHE to mitigate the risk of future metastasis.

5. NGS in EHE

NGS is a cutting-edge technique for genetic analysis, but its application remains restricted to specialized centers due to limited availability and high costs. In this case, NGS testing was planned but could not be conducted due to financial and logistical barriers. Despite these challenges, NGS plays a crucial role in identifying the key mutations in EHE, most notably the WWTR1(TAZ)-CAMTA1 and YAP1-TFE3 fusions.

The WWTR1(TAZ)-CAMTA1 fusion reprograms endothelial cells, promoting aggressive tumor behavior, while the YAP1-TFE3 fusion leads to abnormal gene regulation and enhanced oncogenic properties4,15). Patients with the YAP1-TFE3 fusion, though less common, are reported to have a better 5-year overall survival rate (86% vs. 59%) and tend to be younger than those with the WWTR1(TAZ)-CAMTA1 fusion4,6,15,19). Additionally, the recurrence rate for spinal EHE is approximately 13%19).

6. Multidisciplinary Management

Managing spinal EHE requires a multidisciplinary approach involving neurosurgeons, radiologists, and oncologists. Postoperative monitoring of spinal stability and neurological function is critical, with imaging studies indispensable for planning, follow-up, and detecting recurrence or metastasis. This case underscores the importance of administering curative-dose IMRT and performing aggressive surgical resection. Molecular diagnostics play a vital role in achieving a good prognosis and guiding future strategies based on the disease's unique characteristics.

Effective management of EHE, especially when it involves the spine, demands a comprehensive multidisciplinary approach to ensure optimal outcomes. The role of genetic profiling in understanding EHE behavior cannot be overstated, as it provides insights into potential therapeutic targets and prognostic indicators. Future studies should focus on optimizing RT dosing strategies and exploring the benefits of combining novel targeted therapies with conventional treatment modalities.

CONCLUSION

This case underscores the necessity of aggressive maximal resection and higher RT doses in managing spinal EHE. A tailored approach with individualized surgical intervention and adequate curative doses of RT is essential for effectively treating this rare and persistent tumor.

Notes

ACKNOWLEDGEMENTS

We sincerely thank Professor Jiha Kim for his invaluable support during the preparation of this case report.

INFORMED CONSENT

This case study was approved by our institutional ethics committee, with a waiver of informed consent granted (IRB no. 2024-07-016).

No potential conflict of interest relevant to this article was reported.

References

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Fig. 1.

(A) Sagittal magnetic resonance imaging (MRI) illustrating the extension of spinal hemangioendothelioma compressing the thecal sac. (B-D) Axial MRI demonstrating multi-lobulated vertebral and abdominal masses at the third lumbar (B), fourth lumbar (C), and sacral (D) vertebral body levels. (E) Coronal computed tomography (CT) image illustrating the extent of the vertebral mass. (F, G) Axial CT scans revealing a lobulated contour vertebral body mass with paravertebral involvement at the fourth lumbar (F) and sacral (G) vertebral body levels.

Fig. 2.

(A, B) Computed tomography images showing substantial reduction of the abdominal and vertebral mass following the operation: coronal (A) and axial (B) views. (C) The resected abdominal paraspinal mass. The length of the black line in (C) denotes 10 cm.

Fig. 3.

(A, B) Computed tomography images showing the reduced size of the remnant spinal epithelioid hemangioendothelioma 6 years after intensity-modulated radiation therapy: coronal (A) and axial (B) views.

Fig. 4.

(A) Axial computed tomography image demonstrating an increase in the size of the vertebral body mass. (B) Sagittal magnetic resonance imaging demonstrating metastasis at T9. (C, D) Positron emission tomography revealing metastasis at T9 and the sacrum.

Table 1.

Comparative overview of documented spinal epithelioid hemangioendothelioma cases

References Age/Sex Presenting symptom Location Tumor characteristics Genetic profile Treatment Outcome
Present case 49/F Low back pain and abnormal sensory disturbances below the knees L3, L4, L5, paravertebral soft tissue, psoas muscle and, small bowel Severe canal and neural foramen encroachment NA Decompressive surgery with instrumentation, tumor removal followed by IMRT (total of 40 Gy) Recurrence after 7 years
Matamalas et al. (2014)11) 58/F Anemia, weight loss, and cervical pain with no neurologic deficits C2, C3 Left vertebral artery involvement with liver metastasis NA Partial resection and arthrodesis followed by radiotherapy and chemotherapy Locally controlled but distant metastasis occurred 2 years after surgery
Albakr et al. (2017 )2) 34/M Unsteady gait due to lower limb ataxia T5 Compression fracture with cord compression NA T4-T6 bilateral posterior decompression for epidural tumor and T3-T7 instrumentation with pedicle screws followed by radiotherapy Pain and neurologic symptoms improved dramatically
Bialek et al. (2024 )4) 36/M Recurrence of EHE with symptoms of lower extremity weakness, paresthesia, urinary incontinence/saddle anesthesia T7 Left paraspinal mass with extension causing spinal cord compression from T4 to T6, pulmonary metastases Additional copies of both TFE and YAP were observed (not translocation) Repetitive retreatment with surgical resection and decompression of the spinal cord, radiotherapy, and chemotherapy Neurologic improvement
Kerry et al. (2012 )8) 25/M Severe back pain followed by non-traumatic paraplegia T7 Pathologic T7 vertebral body fracture with epidural hematoma, pulmonary and pleural, and lymphonodular metastases NA T7 vertebrectomy and decompression, resection of pulmonary metastases, radiotherapy, and chemotherapy Temporary improvements but eventually died within 8 weeks
Yim et al. (2012)20) 55/M Severe neck pain C2, C3, C4 Infiltrative lesions from C2 to C4, with maximum cranial-caudal distance of 4 cm with no evidence of metastases NA Radical radiotherapy, 55 Gy Remained in remission with no signs of relapse

This table includes a selection of documented spinal epithelioid hemangioendothelioma (EHE) cases. Not all reported cases are represented.

IMRT: intensity-modulated radiation therapy; F: female; M: male; NA: not available.