Congenital granular cell epulis (CGCE), also referred to as congenital gingival granular cell tumour, congenital epulis or Neumann’ tumor [1–3], is a benign lesion that exclusively occurs in newborns, and has an incidence rate of approximately 0.0006% [4, 5]. The lesions frequently occur in the maxillary alveolar ridge, which is three times more common than in the mandibular alveolar ridge [6]. Females are affected 8 to 10 times more frequently than males [7]. The lesion typically appears as a solitary mass. Multiple lesions are sporadic and account for approximately 10% [8]. Clinically, the lesion presents as a lobular, sessile or pedunculated swelling with a smooth surface. Due to its origin in the oral cavity, large lesions may interfere with feeding and breathing. The histogenesis of the lesion remains unclear and controversial. Several hypotheses have been proposed regarding the origin of the lesion, including pericyte [6], fibroblast [9], histiocyte [10], nerve-related [11] and undifferentiated mesenchymal cells [12, 13]. The lesion may be diagnosed by ultrasound during pregnancy, especially during the third trimester [14]. Although spontaneous regression has been reported in the literature, surgical excision remains the most common treatment with negligible recurrence and malignant transformation [8].

In this article, we report on two cases of CGCE, which presented in the prenatal period with oral masses protruding from the mouth. We provide a detailed account of the prenatal diagnosis, clinical and histopathological characteristics, and the management of the lesions. This report underscores the significance of a sequential treatment approach for the lesions.

We have obtained the patient’s guardian’s informed consent for them to undergo surgery, as well as for the disclosure of clinical data, imaging, and other relevant information pertinent to this report.

CGCE was initially described by Neumann in 1871 [3]. CGCE exclusively occurs in newborns and exhibits features of spontaneous regression, lack of recurrence and malignant transformation. Thus, it is not considered to be a real neoplasm but rather a reactive hyperplasia [15, 16]. This condition is uncommon, with an incidence rate of 0.0006% [4, 5]. In our hospital, the two cases reported in this article mark the only occurrences in the past 20 years. The lesion commonly develops in the anterior alveolar ridge of the maxilla, particularly in the area of canine and lateral incisors (which is more frequent than in the mandible, with a 3:1 ratio) [6]. Approximately 10% of cases involve both the maxilla and mandible [8]. The lesion occurs more frequently in females than in males (8-10:1), which may be associated with the stimulation of endogenous hormones in the uterus [17]. The lesion is solitary, lobular, sessile or pedunculated, firm, and has a pink color with a smooth surface. The diameter of the lesion can vary from a few millimeters to tens of millimeters, with the largest reaching a diameter of 9 cm [18]. Small lesions generally have no impact on the infant, while larger ones may cause respiratory obstruction and difficulties with breastfeeding.

CGCE can be detected through prenatal obstetric ultrasound [19, 20]. The ideal time for prenatal ultrasound testing is typically during the third trimester, with no reports prior to the 26th week of gestation [21]. All of the current cases were identified at approximately the 34th week of gestation. Although previous ultrasound examinations were normal, the presence of lesions should not be assumed to be non-existent, as they may have been too small to detect. The presence of these lesion may affect fetal swallowing which could cause excessive amniotic fluid [8, 22]. While the two cases we reported here exhibited normal amniotic fluid, this may be attributed to the fetus’s ability to swell [14]. Although prenatal ultrasound observations have been obtained, the findings are nonspecific, making it difficult to make an initial diagnosis of CGCE. Differential ultrasonic diagnoses may include congenital malformations and intraoral tumors such as teratomas, hemangiomas, and lymphangiomas [22, 23]. As mentioned above, the primary prenatal impression of the mass was likely a congenital teratoma rather than CGCE. Nonetheless, prenatal ultrasound examination plays a crucial role in facilitating early communicating with parents and in alleviating parental anxiety. Furthermore,a multidisciplinary consultation can be organized to ensure a safe delivery and to devise a well-considered treatment plan.

The gross specimen of CGCE presents as a solid, smooth mass with a pink hue, which is congruent with the surrounding gums. Bang KO had documented a case where the tumor exhibited a red appearance due to the prominent blood vessels covering its surface [24]. The cross-section appears homogeneous, presenting as yellowish white or greyish, as previously reported. Histologically, CGCE is characterized as a benign tumor composed of large, polygonal cells with abundant eosinophilic, granular cytoplasm, small and round nuclei, and no mitotic figures. Currently, there are several theories regarding the origin of these lesions, including odontogenic, myogenic, epithelial, histiocytic, neural, and mesenchymal origins [6, 25–28]. However, there is still no consensus opinion. Currently, the majority of scholars support the theory of mesenchymal or neurogenic origin. Regarding immunohistochemistry, numerous documents have been reported, and the results have varied. Among the markers, a positive reaction for vimentin is the most frequently reported. Therefore, the majority of scholars believe that CGCE originates in mesenchymal cells [2, 12, 29, 30]. While others concur that the lesion is derived from nerve cells, based on the presence of NSE immunopositivity [11, 31, 32]. However, it’s worth noting that NSE is not specific to tumor cells, so this hypothesis must be further discussed. Additionally, according to one report, the presence of S-100 immunopositivity supports the notion that CGCE arises from Schwann cells and originates in nerve cells [14]. Nevertheless, most prior studies have yielded negative results for S-100, which contradicts the neural origin [25–30]. In the current study, the Immunohistochemical stains were strongly positive for vimentin and negative for NSE. These results support the hypothesis of mesenchymal origin. CGCE is typically diagnosed based on its clinical features, with spontaneous regression being a common one [15, 32]. One explanation for spontaneous regression is the stimulation of the tongue during the embryo stage and the sucking effect after birth, which can transform CGCE from a granular to a fibrous mass with the help of macrophages [12]. Additionally, maternal estrogen and fetal ovarian hormone levels may play a role. The absence of estrogen stimulation after birth leads to the tumor’s spontaneously regresses [17]. In addition to the aforementioned factors, it is important to consider the blood supply to the lesion. During the removal of the lesions, no significant supply vessels were identified. Consequently, as the growth environment changes, the blood supply to the lesion gradually diminishes, leading to spontaneous regression. Furthermore, the characteristic spontaneous regression of CGCE may contribute to its low incidence rate. Small lesions typically exhibit no symptoms and regress spontaneously after birth, often going unnoticed by both obstetricians and parents, resulting in a lack of case statistics. The primary differential diagnosis of CGCE is granular cell tumor (GCT) due to their comparable histological morphology, albeit with distinct clinical behaviors. GCT primarily affects the tongue of adults and may reappear post-resection, Whereas CGCE is exclusively observed in newborns and spontaneously regress without the risk of recurrence following removal [16]. Furthermore, GCT is derived from Schwann cells and exhibits positive S-100 reaction, while CGCE does not. Studies have indicated that cases with positive S-100 reaction should be diagnosed as GCT instead of CGCE [16]. However, we maintain that S-100 reaction should not be the sole diagnostic criterion, as histological and clinical characteristics, such as occurrence exclusively in newborns, spontaneous regression, and non-recurrence post-surgical removal, are adequate to differentiate GCT.

The treatment for CGCE encompasses observation for spontaneous regression and surgical resection. The spontaneous regression of CGCE has been documented in literature [20]. However, not all lesions undergo spontaneous regression, as Ritwik et al reported a case which did not regress after 6-month observation period [33]. Additionally, other scholars have also noted that tumor regression was not clearly evident [34, 35]. According to reports, lesions with a diameter of less than 2 cm are permissible to wait for spontaneous regression [33]. However, larger ones may cause interference with breastfeeding or respiration and necessitate removal. Some individuals opt to undergo the surgery several months after birth to ensure its safety [34]. In the two cases we reported, early and immediate operations were chosen for the following reasons: 1. The lesions were diagnosed prenatally, and a multidisciplinary consultation was organized to make a therapeutic plan. 2. The hospital’s perfect anesthesia technology for newborns ensured the safety of the operation. 3. Although there was no ventilation obstruction, breastfeeding difficulties appeared in both infants. 4. To prevent rupture and bleeding caused by the baby’s scratching. 5. To alleviate parents’ anxieties regarding breastfeeding difficulties, tooth eruption, local deformities, and ugly appearance. The operations were successfully completed with a short duration and minimal bleeding. The infants remained stable post-surgery and commenced breastfeeding the following day. Follow-up visits revealed normal tooth eruption, with no signs of tumor recurrence or local abnormalities.

CGCE is a rare benign tumor that arises in newborns. Prenatal diagnosis is beneficial as it allows for prior communication with parents and reduces parental anxiety. Additionally, a multidisciplinary consultation can be arranged to ensure a safe of delivery and comprehensive management of the lesion. Early or immediate surgical intervention is advocated as it may lead to respiratory tract obstruction, feeding difficulties, infant discomfort and parental anxiety.