Large parotid and cheek infantile hemangiomas refractory to medical treatment: Is there a role for embolization?

INTRODUCTION

Infantile hemangiomas (IHs) are the most common tumors of childhood. There are three types of IHs: Superficial, deep, or mixed. Superficial and mixed IHs appear in the first few weeks of life and grow rapidly, reaching their maximum size when the child is between 6 months and 8 months of age. The proliferative phase of deep IHs, however, could last up to 2 years. Deep IHs may proliferate for 12–14 months, although some cases have lasted up to 2 years. The onset of involution has not been clearly established, but it is usually signaled by a change in color from bright red to purple or gray.^[1] Involution may begin by about 1 year of age and continue for 5–10 years.^[2] At the end of the involutive phase, superficial and mixed IHs often leave disfiguring scars.^[3] Rarely, a congenital hemangioma is seen fully developed at the time of birth.^[4]

Most patients with IHs do not require any treatment because the IHs enters the involution phase and disappear. Only 10% of all patients will need therapy. Corticosteroid therapy was traditionally used, but since 2008, propranolol has become the first-line treatment for IHs. Studies have shown that propranolol stops the growth and triggers remission in most parotid IHs.^[5,6] However, 2–20% of patients with IHs may be resistant to propranolol or show contraindications.^[7] Surgery may be prescribed to treat IHs that are in critical locations such as those that obstruct the airway or the visual axis, that are bleeding, or that are associated with Kasabach–Merritt syndrome. Large facial IHs that cause an aesthetic deformity also warrant excision to avoid psychological sequelae, although there is a risk of leaving a post-operative disfiguring scar.^[8,9] To avoid excessive blood loss during the excision of large IHs, pre-operative transarterial embolization (TAE) may be prescribed.^[4] Laser therapy can also be used to treat ulcers and scars from involuted IHs.^[10] Radiation therapy is not used to treat patients with IHs because of its unclear correlation with long-term tumorigenesis.^[11]

It can be challenging to assemble experienced head and neck, vascular, esthetic, and reconstructive surgeons to treat patients with IHs while ensuring that the necessary equipment for an embolization procedure is available. Since 1996, we have performed pre-operative TAE for selected patients with head and neck IHs that were found to be refractory to medical treatment or were prone to significant intraoperative bleeding. From our first cases, parents and surgeons noticed a rapid and remarkable shrinkage of the tumors after the TAE was performed, which caused the surgery to be deferred; for these patients, a wait-and-see strategy was adopted as surgery was not required and embolization remained as the sole treatment for IHs.

There is a scarcity of papers on the effectiveness of pre-operative TAE and even fewer reports on treating IHs only with TAE. Thus, the aim of this paper was to report on our experience with TAE as an upfront and definitive treatment of parotid and cheek IHs after failed medical treatment.

MATERIAL AND METHODS

RESULTS

Our six patients ranged in age from 4 months to 4 years (mean 16.33 months and median 8.5 months); all patients were female. The extent of the tumor in relation to the hemiface ranged from 50% to 70% (mean 58.33%). Four of the IHs were in the proliferative phase (66.66%). Table 1 summarizes the patient demographics, the clinical and angiographic features of the IHs, and the embolization and clinical results [Figures 1-6].

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Figure 1:

(Case 1): A 4-month-old baby girl with a large and rapidly growing, deep parotid/cheek IH. (a) and (b) Pre-embolization pictures. The tumor caused aesthetic disfiguring and pain. (c) and (d) The IH was embolized, notice the angiographic lobulated pattern of cotton wool appearance. (e) and (f) two months later the tumor was no longer visible, patients pain and irritability disappeared. The infant did develop a left facial hypoesthesia probably due to ipsilateral Gassers ganglion infarction with partial improvement over two years follow-up.

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Figure 2:

(Case 2): A 5-month-old baby girl with a right mixed parotid/cheek IH. (a) Pre and (b) 4 months post TAE. Surgical excision had been scheduled after embolization. The mother refused surgery due to the rapid and progressive shrinking of the tumor post TAE.

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Figure 3:

(Case 3): A 4-year-old girl with a deep left parotid/cheek IH with facial deformity. (a) Before, and (b) At 4 months’ follow-up after 100% devascularization. The tumor regressed completely.

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Figure 4:

(Case 4): A 2-year-old little girl with a large left parotid/ cheek IH. (a) and (b) Before, and (c) and (d) 5 months after TAE. Embolization had been scheduled previous to surgical excision. Patient’s mother refused the surgery due to the rapid and progressive shrinkage of the tumor observed as early as 3 weeks after TAE.

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Figure 5:

(Case 5): An 8-month-old baby girl with a large right mixed parotid/cheek IH. (a) and (b) Clinical pictures before TAE. (c) Lateral external carotid artery angiogram shows profuse arterial supply to the tumor. (d) Post-TAE angiogram shows ≥ 95 devascularization. (e) The tumor began to shrink one month later and disappeared after 6 months (photo not shown). The last picture was taken at 2 years’ follow-up.

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Figure 6:

(Case 6): A 9-month-old girl with a large superficial non-involuting congenital cheek IH with a doughnut appearance. She had had intratumoral injections of triamcinolone in another institution, developing central tumor necrosis. (a) Before TAE. (b) Superselective endovascular PVA injection in the facial artery. (c) Clinical picture at 5 months’ follow-up showed dramatic regression of the tumor. Patient was sent to Cosmetic Surgery for skin grafting.

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Some patients had been previously treated with oral corticosteroids, while two patients had received oral corticosteroids and propranolol. One patient also received previously an intralesional injection of triamcinolone in another hospital and developed central necrosis of the tumor (Patient 6).

All six patients were treated for aesthetic deformities and tumor hypersensitivity; one patient was also treated for pain. The arterial supply of the tumors was the branches of the external carotid artery, mainly the facial artery and the transverse facial artery. The mean devascularization rate achieved after TAE was 99.17%. Follow-up at 2–6 months (mean 4.33 months) after TAE showed that the tumor volume had shrunk by 100%.

Each patient underwent a single TAE. In one patient, a post-procedural neurological examination showed moderate ipsilateral facial hypoesthesia, which may have corresponded to trigeminal ganglion ischemia [Figure 1]. Thus, in this study, there was an overall short-term partially reversible complication rate of 16.66%.

DISCUSSION

About 60% of all IHs are located in the maxillofacial region.^[12] The management of IHs that causes disfigurement is very difficult, and the negative emotional effects of IHs on parents should not be underestimated.^[1,4,6] Surgical excision of IHs in the head and neck is limited to small lesions due to the risks of scar deformities, as well as potential injury to the facial and trigeminal nerves or to the facial muscles. Surgery is mainly used for the management of residual deformities left after natural or drug-induced tumor involution to improve cosmesis and function. TAE before surgery is advisable in large and richly vascularized tumors to decrease the tumor size and intraoperative bleeding.^[4,13-17] Occasionally, TAE has been used as a primary therapy to treat bleeding IHs, large cervical or peripheral IHs, those that are associated with Kasabach–Merritt syndrome, and as an urgent treatment for alarming IHs.^[18-25]

Embolization has been suggested as an upfront treatment of maxillofacial IHs, although the supporting evidence has been limited to case reports and studies of a series of cases that involve direct puncture and bleomycin sclerotherapy.^[25-27] Few studies have investigated the effects of TAE using different embolic materials on IHs.^[23-25] For example, Demuth et al. treated three patients with maxillofacial IHs with isobutyl cyanoacrylate.^[23] Two patients developed skin necrosis and required further surgery; one patient developed post-operative ipsilateral loss of vision. The third patient did not require surgery. Patel et al. performed TAE in 10 patients, most of them children, who had non-involuting congenital IHs.^[24] The embolization involved the use of 4F catheters and a wide array of embolic materials, including 25% n-butyl cyanoacrylate (n-BCA) dissolved in lipiodol, ethylene-vinyl alcohol copolymer, or microparticles of an inert PVA foam. Most of the patients also received direct percutaneous sclerotherapy of sodium tetradecyl sulfate, 98% ethanol, microfibrillar collagen, thrombin hemostatic matrix, and n-BCA. To achieve 12 months without lesion recurrence or progression, most patients required 1–2 treatments. Eight patients (80%) did not require surgery after treatment. Jianhong et al. treated 10 out of their series of 17 patients with IHs with TAE using both coils and the embolic mixture of n-BCA and lipiodol. Their other 7 patients had direct puncture and sclerotherapy with bleomycin.^[25] During the follow-up period, their IHs that did not shrink to a satisfactory size were additionally treated with intratumoral injections of bleomycin in lipiodol until the tumor reached a surgically manageable size. The mass of the tumors shrank ≥75%. Complications ranged from local pain to dyspnea that was associated with the migration of the embolic material to the lungs and was resolved after conservative treatment. There were no recurrences of the IHs during the follow-up period of 5–86 months, although five patients required surgery. The authors concluded that TAE plus bleomycin sclerotherapy is an effective therapy either alone or as a pre-operative adjunctive treatment for patients with extensive maxillofacial IHs.

In our study, we found that the tumor shrank 100% in six patients with deep or mixed IHs in the parotid or cheek region who were given TAE. Five of the patients did not require further treatment. Only one patient experienced complete involution after TAE; the patient had a mixed IH and had developed central necrosis of the tumor after an intralesional triamcinolone injection. Since the patient had a superficial scar, a surgical skin graft was recommended [Patient 6 of the table and Figure 6].

TAE should be performed with extreme caution. Selective arteriography and superselective microcatheterization are difficult in infants because their vessels are short, thin, and prone to arterial spasm, dissection, and thrombosis. TAE in IHs may have serious and potentially fatal consequences and, therefore, should only be performed by trained teams.^[28,29] Since the extracranial arterial anastomoses with the intracranial and ophthalmic circulation are wide open in babies and children, the embolic material may migrate and produce infarction of the brain or retina.^[30] TAE can cause mild complications, such as transient local pain and fever, or major complications, such as skin necrosis, embolism and stroke, vision loss, and cranial nerve palsies. The main causes of complications include using the wrong embolic material, reflux of embolic particles, and failure to recognize dangerous anastomoses.^[31] In this study, our complication rate was 16.66% and consisted of a single case of facial hypoesthesia, which was probably due to trigeminal ganglion ischemia which partially improved after 1 year. It is worth noting that this was the only complication in our overall series of 38 embolized head and neck IHs; the readjusted complication rate for the total series was 2.6%. The complication probably occurred due to reflux of embolic particles and the occlusion of the trigeminal ganglion artery, which is an extracranial branch of the middle meningeal artery.^[32] There are concerns about the long-term effects on the central nervous system, the optic apparatus, and the thyroid gland from radiation given to an infant or child during TAE. Thus, we limited our procedures to one whenever possible and minimized radiation exposure.^[33]

We studied six patients with parotid and cheek IHs that were refractory to medical therapy. After the patients were treated with TAE, there was a rapid and complete response by the tumor and surgery was avoided. The responses occurred after a near 100% devascularization rate of the tumors, which were in the proliferating phase. Our results were similar to other experiences with TAE and/or sclerotherapy for maxillofacial IHs. It should be noted that we used inert non-bioactive embolic material (PVA particles), which means that ischemia itself may lead to IH involution regardless of the embolic agent used. Our results were contrary to the findings by Enjolras and Gelbert that TAE gave inconstant results.^[29] However, our results agreed with Patel et al. and Jianhong et al., who suggested that TAE alone may be an effective treatment for large proliferating and richly vascularized parotid and cheek IHs.^[24,25] The results from our small series showed that TAE could be used to treat parotid and cheek IHs that were refractory to medical therapy.

CONCLUSION

Our early experience using TAE to treat parotid/cheek IHs that were resistant to medical treatment yielded good results with few complications. Complete tumor devascularization led to the termination of the proliferative phase and triggered a rapid involution in all of our patients without producing scars. Only one patient experienced a partially reversible complication. This paper contributes to the literature on TAE as an upfront therapy for IHs that could help avoid surgery. Larger studies on the effects of TAE on IHs should elucidate these preliminary findings.