Surgical and Non-Surgical Treatment of Head and Neck Haemangioma: A Retrospective Study and Literature Review
Header Dakhel AL- Muala - HDD, MSc, FICMS
Oral & Maxillo-Facial Surgeon, Kufa College of dentistry | Baghdad, Iraq
Certificate Oral & Maxillofacial Surgery, Bristol University Hospital Foundation trust | UK
Membership of Arabic Scientific Council of Maxillofacial Surgery | Iraq
Certificate Dental Implant Charite University Hospital | Germany | email@example.com
Hemangiomas are lesions that are not present at birth. They manifest within the first month of life, exhibit a rapid proliferative phase, and slowly involute to near complete resolution. Hemangiomas exhibit both a proliferating phase and an involution phase, whereas vascular malformations are more stable and fail to regress.
Patients and methods: The retrospective study was done on ninety patients with hemangiomas, eighty patients treated with intralesional triamcinolone acetonide injection at age 6 years to 45 years and ten patients who were treated surgically considered as a control group at al-sadder teaching hospital –Al Najaf and department of oral and maxillofacial surgery, Kufa, college of dentistry 2007 to 2014.
Results: Examined group eighty patients with hemangiomas were treated with intralesional triamcinolone acetonide injection thirty six cases were male and forty four cases were female. our results revealed that (10-19) years was most common age group with heamangiomas twenty cases and revealed that females were most common than males forty four cases which were complaint heamangiomas.
Discussion: our results revealed that (10-19) years was most common age group with heamangioma twenty cases (25%) and revealed that females was most common than males forty four cases (55%) which was in agreement with Zheng Jia-wei et al. 2008 reported that females are affected more often than males and in agreement with Steven Brett Sloan et al. 2012, they reported that Heamangioma are approximately 3-5 times more common in females than in males.
Conclusions: The treatment of heamangioma is dependent on stages of growth, primary site, size and depth of heamangioma. Each treatment option has limited therapeutic benefit with its own side-effect profile and risks. There is no gold-standard treatment applicable to all patients.
Surgical and Intralesional injection therapy of heamangioma.
Bioceramics Hemangiomas are tumors identified by rapid endothelial cell proliferation in early infancy, followed by involution over time; all other abnormalities are malformations resulting from anomalous development of vascular plexuses. The malformations have a normal endothelial cell growth cycle that affects the veins, the capillaries, or the lymphatics, and they do not involutes. Hemangiomas are lesions that are not present at birth. They manifest within the first month of life, exhibit a rapid proliferative phase, and slowly involutes to near complete resolution.1
Hemangiomas exhibit both a proliferating phase and an involution phase, whereas vascular malformations are more stable and fail to regress Hemangiomas are benign vascular anomalies which may occur in various areas throughout the body with 50% being located in the head and neck. Vascular anomalies are the most common head and neck tumor in infancy and childhood with hemangiomas.2 In the oral cavity, the bones and the muscles are affected as well as the mucosa and the skin.3 The most commonly affected facial bones are the mandible, the maxilla, and the nasal bones. Intraosseous lesions affect the mandible more often than the maxilla, with a ratio of 2:1 reported in one study.4 Involvement of the zygoma is rare.5 The possible sites of occurrence in oral cavity are lips, tongue, buccal mucosa, and palate, despite its benign origin and behaviorr.6
Intramuscular hemangiomas in the oral region are most commonly seen in the masseter, compromising 5% of all intramuscular hemangiomas.7 Hemangiomas are approximately 3-5 times more common in females than in males.8 Etiology of vasoformative tumors are unknown.1 Vascular anomalies arise from genetic, environmental, mechanical, and/or hormonal factors. Some are inherited in a Mendelian fashion whereas others result from abnormal chromosomal segregation during gametogenesis or appear sporadically during various stages of life. Understanding the molecular basis of vascular development and vascular anomalies provides potential tools for diagnosis and treatment of the diseases.9
Aim of study: to evaluation the effect of intralesional injection therapy comparison with surgery in the treatment head and neck hemangiomas.
There are many ways to classify haemangiomas. According to Enzinger and Weiss,10 haemangiomas are broadly classified into capillary, cavernous, and miscellaneous forms like verrucous, venous, arteriovenous haemangiomas.The International Society for the Study of Vascular Anomalies (ISSVA) has recently provided guidelines to differentiate these two conditions, according to the novel classification first published by Mulliken et al. in 1982.11 Vasoformative tumours are broadly classified into two groups: haemangioma and vascular malformation. Mulliken’s scheme divides hemangiomas into two categories, capillary and cavernous. Capillary hemangiomas are the most common with an incidence of 1-1.5% in infants. They are characterized by raised, circumscribed, red lesions that are often lobulated. On histology, they are composed of small thin-walled vessels of capillary size that are lined by single layer of flattened or plump endothelial cells and surrounded by discontinuous layer of pericytes and reticular fibers. In general, they are low flow lesions. Cavernous hemangiomas on the other hand can be high flow lesions, and they consist of deep, irregular, dermal blood-filled channels. They typically impart a purple-blue hue to the overlying skin. Further classification includes a mixed hemangioma containing both components which may be more common than the pure cavernous lesions.2 B. W. Neville,12 reported that Capillary haemangioma is composed of many small capillaries lines by a single layer of endothelial cells supported in a connective tissue stroma of varying density, while cavernous haemangioma is formed by large, thin walled vessels, or sinusoids lined by epithelial cells separated by thin layer of connective tissue septa.12 Hemangiomas are further categorized into two types: “infantile” or “congenital.” The rare “congenital” hemangioma is less understood and present at birth. Congenital hemangiomas either rapidly involute (rapidly involuting congenital hemangioma (RICH)) over a very brief period in infancy or never involute (noninvoluting congenital hemangioma; (NICH)). The natural course of the infantile hemangioma has 3 distinct phases: proliferative, involution, and involuted phase.13 Hemangiomas can be superficial, deep, or compound. The superficial hemangioma is red and nodular with no subcutaneous component. A deep hemangioma presents as a protrusion with an overlying bluish tint or telangectasia. Compound hemangiomas have both deep and superficial components.14 Waner M, Suen JY. 199915 reported that hemangiomas are subdivided into superficial, deep-seated, and mixed type, is more practical and easily used clinically.
Hemangiomas are antedated by a pale, well-circumscribed flat area that may contain some central telangiectasia. The actual hemangioma will appear within the first month and will continue to increase in size for the next 3-8 months. A stable phase of relatively no growth then occurs over the next 6-12 months followed by slow involution of the tumor by ages 5-7 years. They can occur just about anywhere in the head and neck, but are more common in the parotid, lip, oral cavity, perinasal region, and larynx or subglottis.11 Central jaw lesions can show hypermobility of the teeth and distortion of the arch form.4 Presentation of central hemangiomas of the maxilla and the mandible common and clinical findings include gingival bleeding, post extraction bleeding, swelling, pain, mobility of the teeth, and bony expansion.16
Vascular malformations need to be understood in terms of their embryology and development. The classic sequence of events usually falls into 3 stages: (1) the undifferentiated capillary network stage, (2) the retiform developmental stage, and (3) the final developmental stage. In the undifferentiated capillary network stage, the primitive mesenchyme is nourished by an interlacing system of blood spaces without distinguishable arterial and venous channels. Separate venous and arterial stems appear on either side of the capillary network in the retiform developmental stage. The retiform developmental stage begins at about 48 days of embryonic development. The final developmental stage begins at 2 months’ development and involves the gradual replacement of the immature plexiform network by the mature vascular channels.The more common capillary hemangioma represents an arrest in the development of the mesenchyme primordia in the undifferentiated capillary network stage. As differentiation progresses, primitive vessels penetrate deeper into the subcutaneous layer, the muscle, or the bone tissue and give rise to capillary hemangiomas. Termination of development in the retiform developmental stage may produce venous, arterial, or capillary malformations because this stage is characterized by an established venous, arterial, and capillary system. In the final developmental stage, the maturation of the venous and lymphatic systems predominates. Aberrations in this mature stage of development result in venous malformations and lymphangiomas. Proliferating hemangiomas have been shown to have estradiol-17 beta-receptors in the cytoplasm,17 and corticosteroid treatment has been theorized to block these receptors. Lack of estradiol receptors in stable or involuting lesions has supported this theory, and steroid treatment has become a first line of treatment for proliferating lesions. A number of growth factors, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factor-beta (TGF-beta), and interleukin 6 (IL-6), have been demonstrated as regulators of angiogenesis.18 Takahashi et al.19 outlined a number of cellular markers that distinguish the phases of hemangiomas; these markers include tissue metalloproteinase (TIMP-1), bFGF, proliferating cell nuclear antigen, type IV collagenase, VEGF, and urokinase. Another theory suggests that the endothelial cells of hemangiomas are derived from a distant population of endothelial precursors carried by existing vascular pathways to a small embolic nidus of placental endothelial cells could reach fetal tissues through the permissive right-to-left fetal shunt of fetal circulation. This occurrence could, in part, explain the 3-fold increased risk of hemangiomas observed in infants subjected in utero to chorionic villus sampling, because local placental injury might predispose the shedding of cells into the fetal circulation. At least 5 markers of hemangiomas are uniquely co-expressed in the placenta: GLUT1, merosin, Lewis Y antigen, Fc-R11b, and type III iodothyronine deiodinase. Recently, a comparison of the transcriptomes of the human placenta and infantile hemangiomas supported a placental origin of the tumors.20
The Complications of these lesions are ulceration, infection, bleeding, compression syndromes (airway compromise), thrombocytopenia, and even high output cardiac failure. Psychiatric problems are not uncommon given the sever cosmetic deformities that are associated with facial tumors.11 Complications of oral vasoformative tumors can be divided into 2 general types: complications related to the disease process and complications from treatment. Complications from the disease process include hemorrhage, high-output states, infection, function problems (eg, airway, vision, and hearing), thrombocytopenia, and ulceration,21 ulceration is the most common complication of capillary hemangiomas and typically occurs centrally in large lesions. It may result in scarring and does not hasten resolution of the lesion. Ulceration may become secondarily infected and is readily treated with local wound care. Treatment of the nonproliferating lesion with minimal functional impairment becomes a risk-to-benefit decision. With all treatments, a common complication is persistence or recurrence of disease. With the 2 medical treatments, steroids and interferons, the complications are the well-known adverse effects of the drugs. With embolotherapy, complications can range from minor to life threatening. Complications are often related to specific kinds of embolizing devices and techniques. For embolization in general, the commonly reported complications include the risks of superselective catheterization, which include pain, infections, fever, organ infarction, and abscesses related to the introduction of external agents; exclusion of a vital segment of the blood supply; release of pyrogenic materials into the circulation; migration of emboli into other parts of the body; and general effects of drugs, such as thrombin and ethanol. Complication rates for ethanol embolization are 7.5-23%, including nerve palsies and at least 2 reported fatalities.22 When used permucosally for the treatment of oral hemangiomas, the only reported complication was a mucosal slough that spontaneously healed.23 O’Donovan et al.24 reported that 3 of 21 patients had minor skin ulceration following sclerosis with STS. Others have reported no complications with the use of STS injected intralesionally.25-27
Complications Related to Sclerotherapy include the followings: skin necrosis (4%), temporary myoglobinuria (2%), and airway compromise (1%). As lesions become larger and, more importantly, as the flow in the lesions becomes greater, the complications increase.1 Most infantile hemangiomas are benign and do not cause any morbidity or mortality. Ulceration of certain areas (eg, diaper area, neck, mucosal surfaces) is not uncommon. Excessive bleeding is infrequent and rarely, if ever, life threatening.28,29
Ttreatment Options for problematic hemangiomas include systemic or intralesional corticosteroids, chemotherapeutic agents (vincristine, alpha-interferon), laser, surgery, or a combination of these therapies.30-32 The principles of management of hemangiomas are accelerating the resolution of the lesions, minimizing the psychosocial distress caused by the lesions, and minimizing any morbidity related to the treatment of the lesions. Many treatment modalities are currently available for management of head and neck hemangiomas, including careful observation, drug therapy, laser and operative therapy. Controversies still exist as to when and how to treat based on these treatment tools.33 Intralesional steroid treatment is also an option for focal hemangiomas of the parotid, nasal tip, subglottis, and eyelid. Systemic side effects are limited.34 Embolization has been used for the treatment for hemangiomas.35 The range of treatment includes surgery, flash lamp pulsed laser, intralesional injection of fibrosing agent, interferon alpha-2b, and electrocoagulation and cryosurgery.36 The oral route generally is preferred over intralesional therapy.37
Investigation most vascular anomalies are recognized with various imaging modalities. Radiography, ultrasonography (US), CT, or MRI is usually performed to confirm the suspected diagnosis, to determine the extent of the vascular anomaly and to search for associated abnormalities.38 On ultrasound, infantile hemangiomas (the most common type of vascular tumor) appear as hypoechoic, heterogenous, well-defined lesions. They contain small cystic and sinusoidal elements. Doppler ultrasound often reveals fast flow, while hemangiomas are in their proliferative phase. Ultrasound of vascular malformations depends upon the type of lesion. Some exhibit small cystic spaces with minimal or no flow (microcystic lymphatic malformations). Others exhibit high flow through enlarged, ectatic vascular channels (arteriovenous malformations). Still other lesions exhibit low or no flow within larger cystic spaces. These may be macrocystic lymphatic malformations or venous malformations. MRI is the mainstay for radiographic evaluation of deep vascular lesions of the head and neck and can aid in the differentiation of vascular tumor from vascular malformation. In addition, this modality allows differentiation of lesion from normal tissue, elucidates the flow pattern of the lesion (low vs high flow), and defines extent of the lesion. Proliferating hemangiomas and arteriovenous malformations have high-flow patterns on MRI and characteristic patterns of signal and enhancement, while venous and lymphatic malformations have low-flow patterns and their own characteristic patterns of signal and enhancement. In addition, 3-dimensional techniques in CT angiography are gaining acceptance as a useful tool in diagnostic and preoperative evaluation of vascular lesions.39
PATIENTS AND METHODS
The retrospective study was done on ninety patients with hemangiomas, eighty patients treated with intralesional triamcinolone acetonide injection at age 6 years to 45 years and ten patients who were treated surgically considered as a control group at Al-Sadder teaching hospital –Al Najaf, department of oral and maxillofacial surgery, kufa, college of dentistry 2007 to 2014. Data were collected from interviews, examinations, medical records, photographs and telephone conversations. Clinical examination with investigation were recorded, blood pressure, CBC, FBS, BUN, Ultrasonographically, colour Doppler sonography, MRI and / or CT Scan were checked before injection and histopathological examination was done after surgery and / or intralesional triamcinolone acetonide injection. The hemangioma sizes were classified into small (> 0-3cm), medium (> 3-6cm) and large (> 6-9cm) according to Waner M, Suen JY 199915 classification, also divided into superficial, deep and mixed hemangimas according to Gresham T. Richter 2012.14 Indications for the treatment were rapidly growing lesions, lesions with visual problems, bleeding, ulceration, cosmetic concern and lesions interfere with mastication where lesions presented orally. Intralesional injection of triamcinolone acetonide was given in a dose of 2 mg/ml for small size, 40mg/ml for medium size and 60mg/ml for large size (maximum of 60mg).40 Three to 6 injections of triamcinolone acetonide, the drug was injected at low pressure, using a 3ml syringe and 25-gauge needle. The interval between the treatments varied from 4 weeks. Most patients were followed up at monthly interval at least 18 months through clinic visits; follow-up was range 18 months to 3 years. If there is necrotic tissue and/or secondary infection, the injections should not be undertaken. The results were assessed one month after completion the maximum injections were 6 injections (one injection per month) followed by surgical excision to the ruminant heamangioma.
Assessment of healing was based on visual evaluation of physicians in charge, identifying patient’s satisfaction (by using forms that divided patient’s satisfaction to four groups including poor, acceptable, good and excellent) and comparing serial photographs and ultrasonography indicating reduction of lesion’s size, flow, dimension, asymmetry and change of color. Regarding score of prognosis post surgery or post intralesional triamcinolone acetonide injection, poor when lesions was recurrence after eight months after surgery (control group) or no reduction in size after injection (examined group), acceptable when lesions was appears eighteen months duration with small size of lesion post surgery and 20% reduction in size son graphically post intralesional therapy, good when no sign and symptom of recurrence after eighteen months post surgery and 40% reduction in size sonographically post intralesional therapy, excellent when no sign and symptom of recurrence after thirty six months post surgical treatment and 50% reduction in size sonographically post intralesional therapy.
1. Control Group: Results of control group (Ten patients) which were treated surgically revealed that four cases were small size (> 0-3cm) heamangioma, two cases good ,one case was excellent and one case was acceptable. Three cases were medium (> 3-6cm) size of heamangioma revealed one case was acceptable, other one was good and one case was excellent. Three cases were large (> 6-9cm) size heamangioma and all three cases were poor (heamangioma was recurrent after eight months after surgery) (Table 1).
Regarding to our results according to superficial, deep and mixed heamangioma classification Gresham T. Richter 2012, superficial heamangioma six cases were revealed one case was acceptable post-surgery, three cases were good prognosis post operatively and two cases were excellent prognosis post surgery. Three cases of deep heamangioma results revealed that two cases were poor prognosis post surgery and one case was acceptable prognosis. While one case of mixed heamangioma was poor prognosis post operatively (Table 2).
2.Examined Group: Eighty patients with hemangiomas were treated with intralesional triamcinolone acetonide injection thirty six cases were male and forty four cases were female. our results revealed that (10-19) years was most common age group with heamangiomas twenty cases and revealed that females were most common than males forty four cases which were complaint heamangiomas (Table 3). Eighty patients with hemangiomas were treated with intralesional triamcinolone acetonide injection, according to Waner M, Suen JY 1999 classification our results revealed that small (> 0-3cm) size hemangiomas was 57 (71.2%) of total cases, 32 cases was excellent prognosis post intralesional triamcinolone acetonide injection, sixteen cases were good post intralesional injection and nine cases were acceptable post therapy. Medium (> 3-6cm) size sixteen (20%) cases heamangiomas, results revealed six cases were excellent, five cases were good, three cases were acceptable and two cases were poor prognosis post intralesional triamcinolone acetonide treatment. While large (> 6-9cm) size seven (8.8%) cases of heamangiomas revealed that five cases were poor, one case was acceptable and one case was good prognosis (Table 4). According to Gresham T. Richter 2012 classification of heamangiomas, our results revealed that sixty three (78.75%) cases were Superficial type of heamangiomas, thirty eight cases were showed excellent prognosis, twenty tow cases showed good prognosis, three cases were acceptable prognosis post therapy. Eleven cases were deep type of heamangiomas one of them was poor and ten cases were showed acceptable prognosis post treatment. Six cases which were mixed type of heamangiomas were poor prognosis post therapy (Table 5). Complication of treated heamangiomas with intralesional triamcinolone acetonide injection, twelve patients complained off intra operative oozing which was treated by pressure pack, seven patients complained off swelling post injection which was treated by reassurance of the patient and odema was subsided after 3-4 days and some cases covered with anti-inflammatory mefanimic acid. Three patients complained off slight difficulty of mouth opening one week post injection and such complication was not reported, patients were treated by physiotherapy and get improvement gradually.
Heamangioma is of benign origin and behavior, but heamangioma in the oral cavity is of clinical importance, they most often affect the area of the head and neck,41 it often mimics other lesion clinically and requires appropriate clinical diagnosis and proper management. Heamangioma are usually not present at birth but are antedated by a pale, well-circumscribed flat area that may contain some central telangiectasia. The actual heamangioma will appear within the first month and will continue to increase in size for the next 3-8 months. A stable phase of relatively no growth then occurs over the next 6-12 months followed by slow involution of the tumor by ages 5-7 years. Endothelial cell sensitization to catecholamine is the mechanism by which intralesional corticosteroids exert their effects. Although there may be a period of temporary enlargement, blanching usually is noted within 2-3 days and involution is seen by 2-4 weeks. Their effectiveness is most pronounced 2 weeks after injection but can be seen up to 2 months later. Steroid injections can be repeated, but, ideally, they should be separated in time by 2-3 months to allow for maximum benefit to be seen. Risks of injection include swelling, depigmentation and oozing. The injection should be distributed throughout the tumor to avoid embolization by injection into arterial channels. A technically slower injection of corticosteroid or a smaller volume of solution may lessen the risk.
Our results revealed that (10-19) years was most common age group with heamangioma twenty cases (25%) and revealed that females was most common than males forty four cases (55%) which was in agreement with Zheng Jia-wei et al. 200833 reported that females are affected more often than males and in agreement with Steven Brett Sloan et al. 2012 reported that Heamangioma are approximately 3-5 times more common in females than in males.1
Our results revealed that 57 cases small (> 0-3cm) size of heamangioma, 32 cases showed 50% reduction in size, 16 cases showed 40% reduction in size after injection and 9 cases showed 20% reduction in size after injection by sonography, i.e. 100% of small (> 0-3cm) size of heamangioma showed reduction in size ( 50%-20 %) post injection which was in agreement with MT Chen et al. 200042 they reported that eighty-five percent of the lesions showed greater than 50% reduction in volume. Varied treatment response was noted in different classes of heamangioma, so small size of heamangioma which was treated by intralesional triamcinolone acetonide injection accompanied by surgical excision revealed best prognosis.
Our results revealed that medium (> 3-6cm) size of heamangioma sixteen cases, six cases were excellent, five cases were good, three cases were acceptable and two cases were poor prognosis, (87.5%) of medium (> 3-6cm) size showed reduction (50%-20%) post injection, large (> 6-9cm) size seven cases of heamangioma revealed that (28.6%) only showed reduction in size (50%-20%) post injection and (71.4%) no reduction in size after injection, which might be due to tumor at involution phase (stages of growth) or technical error that injection could not reach lesions precisely, medium size heamangioma revealed better prognosis than deep type and small size was the best prognosis.
Our results revealed that sixty three cases were superficial type of heamangioma, thirty eight cases were showed Excellent prognosis, twenty tow cases showed good prognosis, three cases were acceptable prognosis post therapy. So superficial type of heamangioma which was treated by intralesional triamcinolone acetonide injection accompanied by surgical excision revealed best prognosis which was in agreement with M T chin 200042 reported that superficial hemangiomas yield the best results. Eleven cases were deep type of heamangioma one of them was poor and ten cases were showed acceptable prognosis post treatment. Six cases which were mixed type of heamangioma were poor prognosis post therapy. Our results revealed that (95.2%) of the superficial and (90.9%) of the deep showed (50% -20%) reduction in volume. Further growth was not found after treatment, which were in agreement with M.T. Chen et al. 200042 in agreement with Kushner BJ43 reported 25 patients with periocular heamangioma treated with intralesional corticosteroid injections; 21 patients (84%) had a marked to moderate involution of the tumor. Our results in agreement with Richard J Antaya et al. 2012 that reported oral and intralesional corticosteroids are effective at slowing the growth and decreasing the size of proliferating infantile heamangioma. Response vary widely, from less than 40% to greater than 90%.44
Non Matastatic benign congenital tumor, treatment of hemangiomas should be dependent on the location, extent, growing phase of the lesions and techniques available, corticosteroid should be administered during the proliferative phase because they have a negligible effect on involuting otherwise stable lesions. Surgical treatment should not be used as the first choice of treatment specially with 8-9 years. Intralesional corticosteroid injections are safe and effective in arresting heamangioma proliferation for reduction size of heamangioma and to be more localize and preferred to be accompanied with surgery. Small (> 0-3cm) size of heamangioma and superficial type was better prognosis than large and deep and mixed type of heamangioma. The treatment of heamangioma is dependent on stages of growth, primary site, size and depth of heamangioma. Each treatment option has limited therapeutic benefit with its own side-effect profile and risks. There is no gold-standard treatment applicable to all patients.
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