A Clinical Observation Report on Prenatal Management and Postnatal Treatment of Congenital Granular Cell Epulis

Introduction Congenital granular cell epulis (CGCE) is a rare, benign tumor that manifests on the mucosal surface of the alveolar ridge in newborns. It was initially described by Neumann in 1871 and has been referred to by various names such as congenital epulis, congenital epulis of the newborn, and congenital granular cell tumor.1 Documentation on larger tumors is limited and reported diameters vary.2 Diagnosis necessitates histological examination and immunohistochemical staining, typically revealing negative immunoreactivity for S-100 and cluster of differentiation 68 (CD68).3,4 This article presents a case of CGCE with weakly positive S-100 and CD68 staining, alongside a relatively large size. Additionally, it conducts a literature review on diverse aspects, encompassing multidisciplinary prenatal diagnosis, antenatal management, choice of delivery mode during childbirth, and postnatal treatment, with the objective of augmenting clinicians' comprehension of the ailment. The study adhered to the guidelines of the Declaration of Helsinki and obtained informed consent from the patient and approval from the medical ethics committee of Chongqing Health Center for Women and Children. Case presentation On June 8, 2023, a 26-year-old pregnant woman at 39+1 weeks of gestation was admitted to our hospital because of the discovery of an oral mass in the fetus over the past 2 days. Prenatal noninvasive genetic testing revealed low-risk results for trisomies 21, 18, and 13. The patient had a history of one previous artificial abortion (G1P0) and no family history of hereditary diseases. All prenatal tests during pregnancy before 37+2 weeks showed no abnormal fetal development, but a prenatal ultrasound at 39 weeks indicated a solid mass in the fetal facial area, measuring approximately 5.2 × 4.3 cm, with abundant blood supply (Fig. 1A). Magnetic resonance imaging (MRI) examination revealed an abnormal signal in the fetal oral cavity, measuring approximately 4.14 × 3.09 × 5.27 cm, with most of it located outside the oral cavity. A portion of the mass, roughly 1.1 × 1.3 cm, was within the oral cavity and closely related to the anterior part of the upper palate and upper lip (Fig. 1B, C).Figure 1: A Ultrasound image indicating abundant blood flow with PSV: 43.8 cm/s, EDV: 18.28 cm/s, PI: 0.86, and RI: 0.58. B&C Axial and sagittal views of fetal intrauterine MRI reveal abnormal signals on T1-weighted and T2-weighted images. The mass shows high signal intensity on diffusion-weighted imaging and elongated T2 signals in a patchy pattern, situated within the oral cavity near the anterior part of the upper palate and upper lip (red arrows). DWI: diffusion-weighted imaging; EDV: end diastolic velocity; MRI: magnetic resonance imaging; PI: pulsatility index; PSV: peak systolic velocity; RI: resistance index.Cesarean section was performed on June 8. A live female infant weighing 3,220 g and measuring 49 cm in length was delivered with Apgar scores of 10-10-10. The newborn exhibited no cyanosis around the lips, and a roughly 5.0 × 4.5 × 3.0-cm irregular mass was observed in the oral cavity (Fig. 2A). Surgical excision of the oral tumor was performed under general anesthesia with endotracheal intubation 3 days after birth (Fig. 2B, C). Postoperative feeding began after 5 hours. Postoperatively, the wound was rinsed with normal saline 4 times a day. Pathological examination after surgery revealed CGCE (Fig. 3). Immunohistochemical analysis showed S100(+), CD68(+), vimentin(+), CR(+), SOX-10(−), neuron-specific enolase− (NSE(−)), HMB45(−), CK(−), CEA(−), SMA(−), desmin(−), and Ki-67(15%+). After 6 months of follow-up, there was no recurrence of the tumor, the appearance of oral skin was normal, and there was teething.Figure 2: A Uneven surface of the mass originating from the upper gum and maxilla (with abundant vascular distribution visible within the mass, and manual reduction not possible). B Gross specimen after complete excision of the tumor. C Sectional view of the tumor, exhibiting a grayish-yellow color and firm consistency.Figure 3: A Surface epithelium showing localized erosion with inflammatory exudates, without pseudoepitheliomatous hyperplasia (H&E, 100 μm). B Tumor cells exhibiting diffuse growth with relatively clear boundaries, abundant eosinophilic granules, and rich capillary stroma (H&E × 200). C S-100 staining showed weak positivity (dark brown). D CD68 staining showed weak positivity (tan). H&E: hematoxylin and eosin.Discussion CGCE is a rare tumor primarily found in fetuses or newborns, originating from the upper alveolar ridge, with the maxilla being more commonly affected than the mandible (ratio approximately 2:1). While typically solitary, multiple lesions have been reported in 5%–16% of cases.5 CGCE usually manifests during late pregnancy, with the earliest detection reported around 26 weeks. The male-to-female ratio is approximately 1:8–10, likely because of the higher prevalence in females.6 The prevailing theory attributes CGCE's pathogenesis to intrauterine exposure to estrogen. After birth, the decline in hormonal levels may halt tumor growth, with rare cases of spontaneous regression.4 CGCE typically presents as nodules with a nonspecific appearance, often smooth or lobulated, pedunculated at the base, and colored similarly to the surrounding mucosa (reddish-brown, purplish-red, or yellow-white). This appearance resembles granular cell tumors (GCTs).7 In this case, B-ultrasound at 37+2 weeks of gestation did not find the mass, and it grew rapidly in only 12 days. The tumor appeared grayish-yellow, with an irregular surface and abundant blood vessels. Doppler ultrasonography plays a vital role in the early detection of CGCE during pregnancy. Typical ultrasound findings include an intramural hyperechoic mass within the oral cavity, featuring a smooth, regular surface, uniform echogenicity, and minimal blood flow signals, which can aid in differential diagnosis. Magnetic resonance imaging complements ultrasound by providing detailed information about the lesion's relationship with surrounding structures like the gingiva and palate. On T1-weighted MRI, the lesion typically exhibits signal intensity similar to or slightly higher than muscles, while T2-weighted images may show variable or uneven signal intensity, with nodular fluid-like signals sometimes observed at the lesion's center.3 The article reported ultrasound findings of a solid lesion with abundant blood flow in the fetal oral cavity's anterior portion, confirmed by abnormal signal intensity on T1 and T2-weighted MRI sequences. Diffusion-weighted imaging revealed high signal intensity, with elongated T2 signal areas within the lesion, aiding in differentiation from other oral cavity masses and treatment planning. CGCE is pathologically distinctive, requiring histological examination and immunohistochemical staining for diagnosis. Histologically, the tumor displays abundant polygonal cell proliferation arranged in sheets, with well-defined cell membranes, small and uniformly located nuclei often with inconspicuous nucleoli, and cytoplasm rich in eosinophilic granules. Cells are arranged in large nests or bands interspersed with rich blood vessels, with occasional infiltration of chronic inflammatory cells like lymphocytes. The squamous epithelium appears thin without signs of pseudoepitheliomatous hyperplasia.8,9 Approximately 40% of cases exhibit immunoreactivity to NSE.10 Immunohistochemical analysis typically shows negative expression for S-100, smooth muscle actin, desmin, calponin, cytokeratin, chromogranin A, inhibin, nerve growth factor receptor, CD31, CD34, laminin, and CD68.2–4,11 CGCE can be easily confused with GCTs in histology. Granular cell tumors are more common in adults, typically occurring between the ages of 20 and 60, with the tongue being the most frequent location.12 Pseudoepitheliomatous hyperplasia of the epithelium is often seen in GCTs, accompanied by minimal inflammatory exudates and vascular structures.7,13,14 Immunohistochemical staining can aid in distinguishing between the two, as GCTs commonly exhibit S-100 positivity,8,15 although a minority may show negativity.13,16 In our case, the immunohistochemical results revealed weak positivity for S-100 and CD68, and positivity for vimentin, while NSE was negative. Similarly, He et al.17 also reported a case of CGCE with positive S-100 expression. Therefore, relying solely on the expression of S-100 for differentiation between the two tumors may not be reliable. While pathological examination is the gold standard for diagnosing CGCE, prenatal diagnosis of tumors in the fetal oropharyngeal region requires differentiation from the following conditions: (1) Teratomas, accounting for 2.4% of pediatric oral and maxillofacial tumors, can also occur in the oropharyngeal region.18 Alpha-fetoprotein levels in the amniotic fluid and ultrasound examinations can aid in diagnosing teratomas. Mature teratomas pathologically typically comprise mature tissue components from two or more germ layers, and ultrasound examinations often reveal heterogeneous solid masses. (2) Hemangiomas generally occur closer to the surface, often within subcutaneous tissues. Doppler ultrasound flow patterns can be used for differentiation. (3) Melanocytic neuroectodermal tumor originates from the neuroectodermal layer and is characterized by pigment deposits. It has a firm texture, high tumor density, bone dissolution, often accompanied by bone destruction. It exhibits invasiveness and a high recurrence rate.19 For the management of CGCE during pregnancy, limited research is available, but experiences from our center have been compiled. In addition to regular prenatal monitoring of tumor growth, assessing fetal swallowing function might be necessary at times. This assessment can determine the presence of gastric bubbles and bidirectional amniotic fluid flow through the nasal cavity, helping identify obstructions. It also serves as an important indication for emergency cesarean section. For cases with abundant blood flow, monitoring cerebral arterial blood flow indices and fetal echocardiography are advisable to evaluate the impact of the tumor on the fetus and identify potential complications such as fetal anemia or edema due to ischemic-hypoxic decompensation. Litwinska et al.20 reported a successful case of fetal endoscopic vascular ablation for treating sacrococcygeal teratomas, which inspired us to consider whether intrauterine treatment using fetal endoscopic vascular ablation could be effective for managing large oral tumors. This approach could potentially prolong gestational weeks, mitigating the risk of premature birth, thus presenting a new challenge in clinical practice. The choice of delivery method should prioritize the safety and well-being of both the mother and the fetus. In cases where the tumor is relatively large and there is a possibility of obstructing the birth canal, cesarean section should be chosen. Kumar et al.21 reported a case of oral mass-causing airway obstruction, where extracorporeal delivery was performed while maintaining uteroplacental blood flow. In this case, the decision to perform a cesarean section was made because of the rapid growth of the tumor within a short period of time, as indicated by prenatal ultrasound and magnetic resonance imaging showing abundant blood flow, suggesting a high possibility of a vascular malformation such as a hemangioma. The decision to proceed with cesarean section was also influenced by the potential risks of ruptured bleeding during vaginal delivery, posing a threat to neonatal circulatory safety, compounded by the substantial size of the tumor, which could impede the delivery of the fetal head. A multidisciplinary team comprising neonatologists, anesthesiologists, and otolaryngologists was convened for the delivery. Because of prenatal diagnosis, the newborn achieved a favorable Apgar score, initiated spontaneous breathing, and did not necessitate tracheal intubation, underscoring the significance of meticulous delivery planning guided by prenatal diagnosis. Predelivery of multidisciplinary consultations facilitated the assessment and mitigation of childbirth-related risks, fostering reassurance within the medical team, and allaying patient anxiety. Tumors in the fetal or neonatal pharyngeal region have the potential to cause respiratory and gastrointestinal obstruction. Their location can lead to the narrowing of the pharynx and upper airway, resulting in respiratory difficulties. Prompt management is essential to prevent respiratory obstruction and potential respiratory failure.14,22 For patients with large-volume tumors, surgical excision is typically the primary treatment method. Surgical removal enables complete resection of the tumor and provides histological confirmation of the diagnosis. In this case, the tumor exhibited a maximum diameter of 5 cm, indicating a significant size that warranted surgical intervention. Despite the newborn's respiratory and circulatory functions remaining unaffected after birth, the tumor impeded the ability to suckle and feed, necessitating surgical excision. Anesthesia for the procedure can be administered via local or general anesthesia. However, given the limited cooperation of the newborn, intravenous anesthesia preserving spontaneous breathing was preferred. This approach ensured the safe and efficient removal of the tumor while mitigating potential risks associated with general anesthesia. Conclusion CGCE, a rare benign tumor, necessitates comprehensive prenatal screening through ultrasound and MRI examinations. These screenings facilitate strategic clinical delivery planning and multidisciplinary diagnosis and treatment. While weakly positive results for S-100 and CD68 provide insights, they alone may not suffice for distinguishing GCTs. Cases with robust blood supply require meticulous pregnancy management, including cerebral arterial blood flow monitoring and potential intrauterine interventions. Surgical excision is advocated for larger tumors posing risks of respiratory or gastrointestinal obstructions. Prenatal diagnostics enable tailored childbirth planning, with multidisciplinary deliberations ahead of delivery serving to evaluate risks, instill confidence in the medical team, and assuage patient concerns.