The patients of odontogenic masses would see a stomatologist or otorhinolaryngologist, thus the odontogenic masses were not discussed here. The fact that most of the cases were benign is consistent with our study, which was in common with that found in the previous studies[5]. The vascular anomalies were the greatest occurrence in children aged under 14 years, which was similar to those of the previous reports in the United States[2]. Some experts believed that the vascular anomalies and hamartoma might be developmental malformations rather than neoplasms[6], if this hypothesis were to be accepted, except for cyst, tumors included 5 teratomas, 2 hamartoma, 2 neurofibroma, 1 papilloma and 1 IMT, with an incidence of 6.4% (11 cases) in our study [Table 1]. Tumors would be less prevalent in oral nonodontogenic masses in children[7]. The tongue was the most common site, meanwhile, some cases of hemangiomas appeared multiple-site lesions not only intraoral but all body locations.
Vascular anomalies
Hemangiomas are benign vascular tumors common in childhood, affecting 5% of all infants [8, 9]. However, few large series of oral hemangiomas were reported in the literatures[10]. In this study we present 109 cases, representing one of the largest series in children to date, although it was not discussed alone. The literature showed it was a female-dominated disease. In this study females were predominant, 69 girls and 40 boys showed in Table 1. This finding is similar to that of other reports[11, 12]. In difference with other authors that lip was the most site of oral hemangiomas[13, 14], in this study the most common location was the buccal mucosa, tongue is the second. Under 3 years and 7 years in Table 2, the ratio of oral hemangiomas were 80.0% and 89.9%, respectively, which is higher than other literature reports[15]. Table 1 indicated that 41.3% oral hemangiomas could be detected similar lesions in multiple intraoral (16 cases) and extraoral regions (29 cases), the most common extraoral site was head and neck. Some reports indicated that multiple infantile hemangiomas in children were associated with hepatic hemangioma[16]. However, it’s still controversial for universal screening hepatic hemangioma in multiple hemangiomas. Because of hemangiomas spontaneous regression[17], conservative observation is usually recommended, these cases were disposed in outpatient department and not included in our study. Aggressive treatment is warranted when complications arise from uncontrolled hemorrhage, pain, ulceration, infection, or airway obstruction[18]. There were many forms of therapies in dealing with hemangiomas, such as oral medication, surgical removal, sclerotherapy and laser surgery. Oral propranolol usually is the first-line management in oral hemangiomas after clinical evaluation[18]. Sometimes single therapy could not achieve a satisfactory result or after failure of a single treatment, repeated treatment with same method or multimodality therapy may be a better choice with less recurrence. Although using a variety of therapy strategies, there were about 8.3% (9/109) patients recurrent during 1-5 years follow-up in present cases.
Lymphatic malformations (LMs), otherwise known as lymphangiomas or macrocystic LMs (formerly cystic hygromas), involve the presence of low-flow vascular anomalies caused by defective embryologic development[19]. Lymphangiomas were rare, benign, congenital malformation of unknown cause originates from lymph vessels. Mucosal lesions appear as small and cystic with a salmon roe appearance. Lymphangiomas is most commonly located on the head and neck region, with an incidence of 50-70%[20]. it is more common in males by a ratio of 1.5 to 1 in Table 1 in our study. In contrast to hemangiomas, spontaneous regression is not seen. Intraoral lymphangiomas occur more frequently on the dorsum of tongue, which is consistent with previous reports[20]. Surgical excision is the treatment of choice. Besides, sclerosing treatment, oral medicines (sirolimus) and laser surgery are alternative methods. A fraction of the complicated cases which were thought partial surgical resection still need following combination therapy. Local oral recurrence occurred in 17.9% (5/28) of patients.
Mix vascular malformations were not common seen in oral cavity, only accounting for 3.5% (5/142) of vascular anomalies. The most frequent clinical type was mixed venous-lymphatic malformation. Its clinical and imaging features were similar to venous malformation and that must careful be distinguished by postoperative pathology.
Cystic masses
Cystic masses included 13 ranulas and 5 mucoceles, as a rate of 10.5% (18/171) in oral nonodontogenic masses in children [Table 1]. Cysts and pseudocysts of the minor salivary glands are considered the most prevalent cysts of the oral cavity[21]. The obstruction of the duct of a salivary gland may lead to an enlarging mass within the floor of the mouth. The gold standard procedure is the as advocated by Pandit and Park[22] suggested that complete excision of the lesion along with excision of the sublingual gland is the best choice for minimizing recurrence. However it followed a wide range of complications, including injury the lingual nerve, damage to submandibular duct, bleeding/hematoma, lead to a recurrent plunging ranula, scarring, and restricted mobility of the tongue, et al[23]. Surgery to conserve the sublingual gland often following high a high recurrence rate. Operative approaches remain disputed. Given the early age children in our department, simple cyst excision was performed. No recurrence was observed in any patients, it could be to do with a small number of cases and rather short-term following up.
Oral mucocele is the most common benign minor salivary gland lesion. The mechanism is that trauma to the excretory duct of the gland, mucoproteins leak into the surrounding tissues leading mucus retention in local tissues[24]. Clinical features included single or multiple, translucent, ill-defined nodules, ranging from the normal colour of the oral mucosa to deep blue. They represent the 17th most common lesion of the oral cavity[25]. The lower lip was the most common site for mucocele and no sex preference in previous reports[25, 26]. Only one of five cases occurred in the lower lip in our study. Complete resection is the first choice of traditional treatments. Microwave, sclerotherapy or laser treatments were alternative techniques[25, 26]. Mucocele has a lower recurrence rate and fewer complications than ranulas.
Other benign tumors
Teratoma
Teratoma is a congenital malformation, accounting for 3% of all childhood tumors[27]. It arising from the oral cavity is extremely rare in the newborn and 2.6% (5/171) of oral teratomas present in oral nonodontogenic masses [Table 1]. They can arise in the base of cranium and have associated craniofacial anomalies including cleft palate, cystic hygroma and other multifocal teratomas[28]. Small tumors can be discovered by accident, some cases were followed by feeding difficulties, partial oral teratomas can cause seriously airway obstruction, even resulting in asphyxia at birth. Congenital teratomas can be detected by the prenatal ultrasound diagnosis in early pregnancy and further MRI examination in the later stages of pregnancy[29]. Other cases were diagnosed by clinical characteristics and imaging expression at birth. Early diagnosis and complete tumor resection are the only means to achieve good survival in children with oral teratomas[29]. Some reports indicated that the risk of malignant transformation up to 90% in the patients of failing to diagnose or treat head and neck teratomas when they grew up[28]. However giant oral teratomas might not be resected completely to prevent serious craniofacial defect and dysfunction. Palliative surgeries were taken and have high risk of recurrence. Alpha-fetoprotein (AFP) is a good marker of malignant transformation and as a screening tool for postoperative follow up[30]. Developing better treatments for these patients is needed in the future.
Hamartoma
Hamartoma is a benign pseudoneoplastic malformation mainly composed of an abnormal arrangement of tissues, such as fat, nerves, and blood vessels[31]. However, smooth muscle predominant (leiomyomatous) hamartomas are rare. The first case in the tongue was reported in 1945 by Stamm and Tauber[32]. Two cases reported in this paper were both leiomyomatous hamartomas. Most of the oral hamartomas occurred at the tongue[33]. At least 50% leiomyomatous hamartoma were known to be present at birth and the most common age of diagnosis was under 12months[34]. The mass of oral hemartoma mostly are asymptomatic. Other masses affecting the tongue that should be considered in the differential diagnosis include thyroglossal duct cyst, lingual thyroid, choristoma, and congenital dermoid cysts. The definitive diagnosis was the postoperative pathological examination. It is generally agreed that complete resection of the tumor is the most effective treatment with better prognosis, and no cases with follow-up data available had tumor recurrence in literature reports, as well as our work.
Neurofibroma
Neurofibroma is an uncommon benign tumour of the oral cavity originating from the nerve sheath, commonly can be found in patients with neurofibromatosis type-1 (NF-1), with an incidence of 72%[35]. Oral cavity involvement by a solitary and peripheral plexiform neurofibroma in patients with no other signs of neurofibromatosis is uncommon[36]. NF-1 is an autosomal dominant and multisystem genetic disorders, known as Recklinghausen syndrome, nearly 50% of NF-1 have a positive family history[37]. It is the most common type of neurofibromatosis which affects approximately 1 in 3500 people and can be seen in 90% of all cases[38]. The oral clinical presentation includes gingival enlargement and pigmentation, dental abnormalities, dental caries, neoplastic lesions and osseous lesions. The tongue is the most commonly affected region of oral neurofibroma[39]. In our study, the symptom of two cases were oral neoplastic lesion of NF-1 patients, both located in tongue, and only one patient’s mother has similar clinical features. Besides oral manifestations, light brown pigmentation spots on the skin and multiple small tumors surround the nerves in other parts of the body. Surgical excision represents the treatment of choice for oral neurofibroma. Although mostly benign, malignant transformation of neurofibromas could be found in some certain NF-1 patients.
Papilloma
Oral squamous papilloma is a benign tumor whose pathogenesis has been associated with human papillomavirus (HPV) usually HPV-6 or HPV-11[40]. The lesions are low proportion in oral benign neoplasms, occupying 22%[41]. The lesion can occur in any site of oral cavity. The most prevalent site was the tongue and the palate, with an incidence of 34%[41, 42]. They appear clinically as asymptomatic and often found by accident. The typical clinical manifestations were an exophytic growth, with a rough surface that appears a cauliflower-like and, usually white but sometimes pink and/or red in color. The frequently occurrence of oral squamous papilloma is adults aged between 30 and 40, predominate in female (75%)[43]. It accounts for 8% of all tumor in children[42]. The correct diagnosis depends on clinical features and histopathology. An alternative means of treating oral squamous papilloma is surgical removal including electrocautery, cryosurgery, laser ablation and intratumoral injection. Solitary papilloma has a relatively low rate of recurrence while a high rate in multiple ones. Oral squamous papilloma caused by HPV may evolve canceration.
Inflammatory Myofibroblastic tumor (IMT)
IMT as a rare mesenchymal tumor composed of myofibroblast differentiated spindle cells and contain inflammatory cells, plasma cells, and/or lymphocytes[44]. It can occur at any age, but common in children and young adults. It shows a high predilection in the lung, however, it has been found anywhere in the body. Head and neck region accounts for 14-18% of extrapulmonary sites of IMT[45]. Oral IMTs are extremely rare and the sites of involvement in oral nonodontogenic IMTs include the buccal mucosa, tongue, hard palate and floor of the mouth. World Health organization (WHO) defined IMTs as tumors of intermediate biological potential associating with a tendency of recurrence and metastasis[44]. The exact etiology and pathogenesis of IMT is unknown. Researchers and social scientists believe that it represents an extravagant immune host reaction to microorganisms, surgery, trauma, tissue damage, foreign bodies or even or radiotherapy[46]. The ALK gene is thought to be participated in the pathogenesis of IMT[47]. It has no specific clinical manifestation. Radiographical depiction can be found the presence of bone absorption or destruction when the lesion involves in certain skeleton and easily misdiagnosed as sarcoma. Moreover, the atypical histologic appearance is much confusing that sometimes overwhelms pathologists. The pathological character shows numerous plasma cells, spindle cells, lymphocytes and myofibroblastic cells. The treatment of the tumor depends on operation, corticosteroid therapy, chemotherapy, radiotherapy and a combination therapy[48]. Complete surgical excision and /or corticosteroid combination is a non-controversial way to treat oral IMTs. There are 80 % cases respond to corticosteroid treatment. However, the remaining cases are no respond to corticosteroid because of few inflammatory cells in tumor tissues[49]. Oral IMTs usually run a more favorable clinical course and respond well to the treatment with no reported recurrence. However, in the present case of our department, having underwent the first surgical excision of oral IMT, the patient received the second and third surgical removal and chemotherapy during 3 months, 9 months after first surgery, respectively. No recurrence was observed in one-year follow up.