{'fraction_non_alphanumeric': 0.038399024786672085, 'fraction_numerical': 0.025396180414465664, 'mean_word_length': 5.231012658227848, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Progression of aggressive vertebral hemangiomas during pregnancy

Abstract Rationale: Vertebral hemangiomas (VHs), one of the most common benign tumors of the spine, can be aggressive, which is a rare condition and causes neurological deficits. Pregnancy is related to the worsening of aggressive VHs. The diagnosis and treatment of aggressive VHs remain challenging, especially for pregnant cases. Patient concerns: We report 3 cases of aggressive VH in women who developed progressive neurological deficits during pregnancy among 95 patients treated for aggressive VH in our hospital in the past 15 years. Diagnoses and Interventions: All 3 patients experienced progressive deterioration of neurological function and pain at 13, 28, and 41 weeks’ gestation. On radiological examination, VHs were the suspected radiological diagnoses in 2 patients; 1 patient was preoperatively misdiagnosed with a spinal metastatic tumor. All 3 patients underwent decompression surgery with intraoperative vertebroplasty and/or postoperative radiotherapy. The pathological diagnosis after surgery was all hemangiomas. Outcomes: In all 3 patients, there were no tumor recurrences, and neurological functions remained normal at the last follow-up of 75, 38, and 15 months after the treatment, respectively. Lessons: Pregnancy might lead to the onset of aggressive VHs. The diagnosis and treatment of VHs during pregnancy remain controversial due to concern for both maternal and fetal safety. Timely surgery could preserve neurological function. Decompression surgery by laminectomy followed by adjuvant therapies require less skill and have a shorter surgery time, and can be considered more appropriate for aggressive VHs with pregnancy.


Introduction
Vertebral hemangiomas (VHs), one of the most common benign spinal tumors, are vascular malformations that comprise rich blood vessels. [1,2] Frequently affecting the thoracic spinal columns, the incidence of VHs is 10% to 26%. The majority of VHs are asymptomatic, and only 0.9% -1.2% of patients develop symptoms. [1][2][3][4] In addition to pain, some VHs may be aggressive (Enneking Stage 3 [5] ), extending into the spinal canal and paravertebral space to cause spinal cord compression and neurological deficit. [1,3,6,7] Pregnancy results in increased blood volume and hormone changes, which may lead to the worsening of aggressive VHs. [8][9][10][11][12][13][14] Although aggressive VH during pregnancy is a rare condition, its diagnosis and treatment remain challenges because both maternal neurological functions and fetal safety must be considered. [15] There are a few case reports in the literature that discuss the treatment of aggressive VHs during pregnancy; however, most are sporadic case reports, and the treatment remains controversial. [8][9][10][11][12][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] Our hospital has treated 95 patients with aggressive VHs in the past 15 years, including 3 with progressive neurological deficits that developed during their pregnancies. Here, we report our experience of aggressive VHs during pregnancy and the results of a literature review of articles published in the past 30 years. The study was approved by the ethics committee of Peking University Third Hospital. Informed consents for publication of the case details were obtained from the reported patients.

Case 1
A 27-year-old woman in her 13th week of gestation was referred to our department for progressive numbness of her right arm and Editor: N/A. Ethical approval: The study was approved by the ethics committee of Peking University Third Hospital. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consents for publication of the case details were obtained from the reported patients.
The manuscript submitted does not contain information about medical device(s) or drug(s). paralysis and numbness of her bilateral lower extremities for 3 weeks. She also complained of neck pain, and her visual analog score (VAS) was 4/10. She was otherwise healthy previously. She had sensory deficits below the level of her xiphoid, and the muscle strength of her lower limbs was 2/5 (modified Frankel grade C). Radiological imaging revealed a C7 lesion and VH was the suspected radiological diagnosis. Preoperative embolization was performed to reduce intraoperative blood loss, followed by laminectomy, intraoperative injection of ethanol, and posterolateral fusion. [33] The estimated blood loss was 1200 mL. The pathological report after surgery revealed a hemangioma. Her pregnancy was later terminated; she underwent radiotherapy. At 75 months follow-up, there was no sign of recurrence; she was the mother of a 3-year-old boy and free of neurological symptoms (Fig. 1).

Case 2
A previously healthy 29-year-old woman in the 28th week of her gestation experienced intermittent back pain (4/10 by VAS) that was relieved with rest. At week 39 of her gestation, her pain suddenly worsened (9/10 by VAS), with weakness and numbness of her lower limbs. She could only walk with assistance. After delivery of a healthy baby, the muscle strength of her lower limbs was 0/5 with bowel and bladder dysfunction (modified Frankel B). Emergency magnetic resonance imaging (MRI) and computed tomography (CT) revealed bony destruction and pathological fracture at T7 (Fig. 2), suggestive of malignancy. Her blood tests revealed cancer antigen (CA)-125 (82.45 U/mL) and 15-3 (30.5 IU/mL) levels above the normal ranges. Positron emission tomography (PET-CT) was performed, revealing a suspected malignant mass in her right breast in addition to the tumor on T7. She underwent separation surgery [34] for suspected spinal metastasis tumor with intraoperative radiofrequency ablation and vertebroplasty. The estimated blood loss was 1200 mL. The pathological diagnosis was a hemangioma. No mass was detected in her right breast by ultrasound in her follow-up after surgery. She underwent adjuvant radiotherapy 3 months after surgery. At 38 months follow-up, there was no sign of recurrence on the spine and her neurological function was Frankel D3 (slight weakness but normal function) (Fig. 2).

Case 3
After a normal uneventful 40-week gestation and delivery, a 35year-old woman experienced sharp back pain (8/10 by VAS) the day after delivery, which was not relieved by rest or analgesics. She had progressive numbness and weakness in the bilateral extremities. On the 20th day after delivery, she could not stand up and had bowel and bladder dysfunction; thus, she was referred to our hospital. She had sensory reduction below the level of T6, and the muscle strength of her lower extremities was 3/5 (modified Frankel D2). MRI and CT revealed a pathological vertebral fracture of T5. VH was the suspected radiological diagnosis. She underwent decompression and fixation with intraoperative vertebroplasty. The estimated blood loss was 300 mL and the pathological diagnosis was a hemangioma. At 15 months followup, she had no neurological deficits and was without recurrence (Fig. 3).

Discussion
This report described in detail 3 rare cases of aggressive VHs during pregnancy. We also summarized a total of 32 cases published in the past 30 years (including the present cases).
Pregnancy plays an important role in the pathogenic mechanisms of VHs in 2 main ways. [8][9][10][11][12][13][14] Increased blood volume during pregnancy, especially in the third trimester (which may explain why 62.5% of cases were in the third trimester). After delivery, uterine contractions may lead to a rapid volume increase and fast progression of aggressive VHs (2/32, 6.3%). Pregnancy changes levels of hormones, such as estrogen and progesterone, which may lead to VH angiogenesis and growth.
The diagnosis and treatment of aggressive VHs during pregnancy is controversial due to considerations for both maternal and fetal safety. [15] Typical VH lesions have vertical trabeculation and a honeycomb appearance on CT and a saltand-pepper appearance on MRI. MRI is usually performed first for pregnant patients. CT should be used with caution due to the potential radiation harm to the fetus, [15] although CT is valuable. For patients with atypical imaging feature, percutaneous CTguide biopsy may be helpful. [35] However, cautious consideration by both the doctors and patients are necessary due to the potential radiation harm of CT. Moreover, for patients with rapidly progressing VHs, timely decompression prior to CTguided biopsy may save neurological function.
The choice of surgery is also controversial. Complete tumor resection (intralesional vertebrectomy or total en bloc spondylectomy) is recommended by some surgeons to reduce the possibility of recurrence. [3,6,15,37] However, long surgery time and blood loss increase risk in pregnant patients. In our cases and the reviewed cases, decompression surgeries by laminectomy were usually performed, a technique requiring less skill and a shorter surgery time, which may suitable for pregnant patients. With intraoperative vertebroplasty and adjuvant radiotherapy after surgery and delivery, laminectomy may reduce blood loss and the likelihood of recurrence. [20,36,38] Although radiotherapy has been successfully used for the treatment of aggressive VHs with neurological deficits, [39][40][41] we do not recommend its use in pregnant patients due to potential harm to fetuses, [42] unless radiotherapy is performed after delivery.
Due to limitations inherent to a case study, additional research with more patients is warranted to completely evaluate the management of aggressive VHs during pregnancy.