Introduction
Epignathus is an extremely rare congenital oropharyngeal teratoma containing fetal organs and structures. It is estimated to occur in 1:35,000–1:200,000 live births with a high incidence in female fetuses compare with male fetuses (3:1-5.1:1).1,2 The teratoma varies from a small pedunculated tumor that can be easily removed to a large mass involving the palate and sphenoid which is present at the mouth during birth, constituting an immediate threat to life.3 Epignathus can cause hydramnios or fetal death in the ante partum period and respiratory distress due to tracheal obstruction in the post-delivery period.4 Antenatal evaluation by ultrasonography and preparation of ex utero intrapartum treatment (EXIT) are necessary to reduce the risk of hypoxic brain injury and death at birth.
In this case report, we present the prenatal diagnosis of fetal epignathus and the immediate successful management of the large oropharyngeal teratoma. Written informed consent was obtained from the parents of the neonate for the publication of this case report and the related images.
Case presentation
The mother was a 26-year-old woman, gravida 3 para 1, with a history of assisted reproductive technology treatment owing to excision of both fallopian tubes following two instances of past ectopic pregnancies. She was referred to our hospital at 24 gestational weeks. Her alpha-fetoprotein (AFP) level was elevated to 6.2 multiples of the median in the second trimester. She underwent ultrasonographic evaluation at 22 gestational weeks at a local hospital. The imaging results showed the presence of a large, mixed, solid and cystic protruding mass in the fetal oral cavity. The mother was referred to our hospital for further ultrasound evaluation which confirmed the presence of the oral mixed solid and cystic mass and the extension outside the fetus’s oral cavity. The mass measured 4.03 cm × 3.23 cm × 4.38 cm. No blood flow was observed on Doppler ultrasound imaging. The fetus’s upper lip skin was continuous without a cleft lip above degree II. Other structures of this fetus were normal (Fig. 1). Subsequently, a fetal teratoma was suspected.
;)
Figure 1: Well-defined mass measuring 4.03 cm × 3.23 cm × 4.38 cm by ultrasonography and arising from the fetal oral cavity at 24 gestational weeks. The arrows indicate the mass.
The patient declined fetal karyotyping out of fear of losing the pregnancy because the fetus was very precious for her. She opted for more counseling about whether the mass could be removed after delivery. An oral and maxillofacial surgeon provided counseling and informed her that there were ways to remove the mass from the neonate. From then on, the patient underwent regular antenatal examinations at our hospital, and was followed-up with serial ultrasound examinations. The patient’s pregnancy progressed normally until 37 weeks and six days of gestation. An ultrasound showed the amniotic fluid index increased to 24.28 cm, and the mass now measured 8.66 cm × 5.76 cm × 6.77 cm. Considering the fetus was mature and the mass would obstruct its airway, we performed a cesarean section to deliver the baby. Fetal magnetic resonance imaging (MRI) before the operation confirmed that there was neither central nervous system involvement nor abnormal nose or tooth in the fetus (Fig. 2).
Figure 2: Magnetic resonance imaging at 36 gestational weeks showed no central nervous system involvement or serious associated malformations. The arrows indicate the mass. A Sagittal section. B Coronal section.
A multidisciplinary team was assembled to secure the airway and carry out EXIT. The team included specialists from the maternal-fetal medicine department, neonatology department, anesthesia department, oral and maxillofacial surgery department, and ear nose and throat department. The plan was that as soon as the fetal head and shoulders were delivered, the neonate would be provided with a tracheal cannula or tracheostomy performed with keeping the placental circulation intact. After that, the neonate would undergo a further thorough evaluation or operation (as needed). Fortunately, the infant cried immediately after its head was delivered. At that moment, it was confirmed that there was no severe airway obstruction and a live female infant was delivered via cesarean section.
The neonate immediately underwent oropharyngeal mass resection with trachea cannula and local anesthesia. Most of the mass was removed. A small cleft palate was diagnosed after the resection (Fig. 3). The excised mass underwent histopathological microscopic examination after the resection, which confirmed the presence of mature tissues that predominantly contained ectopic central nervous tissue, osseous tissue, and bronchial mucosal tissue in most areas (Fig. 4). However, only a few cells were similar to primitive neurons in the focal areas. Immunohistochemistry showed GFAP(+), Olig-2 (+), IDH1(-), p53(-), CD34 vessel(+), H3K27M(-), Calretinin(+), NeuN(+), NSE(+), and Ki-67(+)1%.
Figure 3: The neonate immediately underwent oropharyngeal mass resection at birth. Written informed consent was obtained from the parents of the neonate for the publication of these figures. A Appearance of the neonate with trachea cannula before resection. B Appearance of the neonate with trachea cannula after resection. The arrow indicates a cleft palate. C Appearance of the tumor.
Figure 4: Microscopic examination of histopathological staining (hematoxylin-eosin staining, ×100). A Central nervous tissue-neuroglia. B Central nervous tissue-choroid plexus. C Salivary gland. D Osseous and cartilage tissue.
The neonate was admitted to the neonatal department and discharged after one week. MRI showed that there was a tumor in the right posterior palate. This baby requires reoperation in the future.
Discussion
Oropharyngeal teratoma was classified by Ehrich (1945) based on the location of origin as episphenoid, epipalatine or epiranus, and epignathus tumors.4 Teratomas can be classified into four groups according to histopathological microscopic examination: dermoid cysts, teratoid cysts, teratomas, and epignathi.5 However, the term epignathus tumor is generally understood to denote neonatal oropharyngeal cavity teratomas without specifying the original location.6 The histopathological microscopic examination of this case showed the presence of three highly differentiated germ-layer derivatives.
The etiology of epignathus is still poorly understood. Many studies have reported that fetuses with epignathus had no chromosomal abnormalities.7,8 However, in a few studies, chromosomal abnormalities such as trisomy 13, ring X-chromosome, mosaicism with inactive ring X-chromosome, gonosomal pentasomy 49, and other gene mutations have been found in neonates with epignathus.9-12 Ten percent of epignathus may exhibit associated abnormalities.13 The most common associated malformation is cleft palate, and the likely reason is that the palate is prevented from closing because of the tumor. In our patient, only a small cleft palate was diagnosed, whereas other reported associated malformations such as bifid tongue and/ or bifid nose, diaphragmatic hernias, glossoptosis, and inguinal hernias were absent.14 Fusion of the primitive tongue buds can be impaired by the early development of the epignathus with subsequent anterior positioning of the tongue; this process is known to cause bifidity and glossoptosis. 5
The prognosis depends on the location, volume, pathological classification of the mass, and associated malformations of the fetus. Given that the umbilical cord and placenta perfuse the fetus, a giant epignathus may not cause many significant problems during pregnancy, but it may influence fetal swallowing and result in polyhydramnios However, as the umbilical cord is clamped immediately after delivery, a giant nasopharyngeal teratoma may cause airway obstruction and neonatal mortality. Some authors have reported that epignathus is infrequently associated with an intracranial extension, and prenatal intracranial teratomas have been reported to result in poor prognosis. 14–16
It is necessary to identify chromosomal abnormalities and associated malformations to avoid lethal malformation in neonates. Hence, prenatal diagnosis is extremely important. In this case, we recommended the mother to undergo amniocentesis in the early second-trimester for fetal karyotyping, but she refused. Therefore, we offered a complete ultrasound and MRI examination to evaluate the fetus’s condition, which confirmed that there was no central nervous system involvement or serious associated malformations.
Some studies reported that elevated maternal AFP levels can be detected in the first-trimester3,8,17 as in our case. High serum levels of maternal AFP indicate the presence of a tumor that can be confirmed by ultrasonography.18 The ultrasound can identify the lesion even at a gestational age of 15–17 weeks.19 The reconstructed images from 3D ultrasonography can allow spatial evaluation of the lesion, provide more detailed information about the location and extent of the epignathus, and assess its positional relationship with the anatomical structures of the face and head. Fetal MRI is helpful to assess the relationship between the mass and airway structures and any likely intracranial invasion that can lead to poor prognosis of the fetus.20 Comprehensive assessment during pregnancy provides more details about the developing fetus and allows parents to better understand the condition affecting their unborn child and further counseling to understand the prognosis.15 In our case, the MRI examination did not show any evidence of fetal intracranial extension or central nervous system-related anomalies.
Differential diagnoses of the epignathus include nasal glioma, oro- or nasopharyngeal cystic lymphangioma, giant epulis, sphenoid meningoencephalocele, nasoeth-moid meningoencephalocele, and rhabdomyosarcoma.21 Although it is difficult to distinguish these conditions by prenatal examination, the mode of treatment is rarely affected.
Because the tumor mass can rupture, bleed, or block the birth canal, it is best to perform cesarean section to deliver the baby. If airway obstruction is suspected prenatally, an EXIT procedure should be considered. The EXIT procedure can preserve the intact placental circulation to the fetus and provide enough time to manage the fetal airway. At the time of cesarean section, tracheal intubation or tracheostomy should be performed before the umbilical cord is clamped,13 and the mass can be resected on placental support. This process is called operation on placental support.19 However, during this procedure, placental abruption, placental laceration, or uterine relaxation because of general anesthesia can lead to maternal and fetal hemorrhage.22,23 The duration of placental support to the partially delivered fetus may be less than 60 min.24 The prognosis of the fetus depends on tumor resectability, even though the EXIT procedure can successfully manage the fetal airway. Only cases wherein the tumors are resected after birth can survive until discharge.25
Prenatal assessment of airway status is essential to plan an EXIT procedure and is still not effectively addressed. As in this case, the EXIT procedure was prepared for but was eventually not required, as the neonate cried immediately after its head was delivered. This confirmed that there was no severe airway obstruction. Prenatal ultrasound and MRI are primary methods to assess fetal airway obstruction. The trachea-esophageal index is defined as the degree of displacement between the esophagus and the trachea and can predict the degree of difficulty in securing the airway. A trachea-esophageal index score of <5 predicts a difficult airway.26 Ultrasound static imaging and visualization of the fetus swallowing and further confirmation by fetal MRI can also be used to determine airway patency.27 Mohammad et al. reviewed several specific cases in an attempt to determine whether certain malformations or airway obstruction characteristics could help predict certain airway interventions. They did not observe a clear trend for most of the malformations. The size or anatomical distortion degree of the cervical teratoma did not predict a single type of airway intervention.28 However, prenatal imaging that shows anatomic compression, solid mass, or polyhydramnios is linked with potential airway intervention.29 In this case, the MRI examination did not show any evidence of anatomic compression, which increased our and the parents’ confidence in the successful rescue of the fetus.
In this case report, we discuss the characteristics and outcome of epignathus with a small cleft palate in a fetus. The fetus was diagnosed to have a giant epignathus by ultrasonography in the second trimester. Regrettably, fetal karyotype analysis was not conducted owing to the mother’s refusal. The MRI performed before the operation excluded central nervous system involvement and abnormal nose or tooth. Prenatal ultrasound and MRI evaluation did not show any evidence of anatomic compression. For the safety of the neonate, EXIT was prepared for but was eventually unnecessary. The neonate successfully survived because of immediate and successful management postpartum. Immediate oropharyngeal mass resection with tracheal cannula was performed under local anesthesia, and most of the mass was removed. Nonetheless, the baby still needs a second surgery in the future. More methods for prenatal assessment of airway obstruction would be helpful for prenatal counseling and prognosis assessment of the fetus.
Conclusions
Epignathus is a rare congenital oropharyngeal teratoma that in most cases is associated with malformation and considered fatal death. Prenatal assessments by ultrasound and MRI are very important to facilitate counseling and improve the understanding of prognosis. The EXIT procedure is a good approach to improve survival in neonates with epignathus.
Funding
None.
Conflicts of Interest
None.
Data Availability
Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.
References
1. Tunes RS, Cavalcanti GZ, Squarisi JMO, et al. Oral
epignathus with maxilla duplication: report of a rare case. Craniomaxillofac Trauma Reconstr 2019;12(1):62–66. doi: 10.1055/s-0038-1649497.
2. Kirishima M, Yamada S, Shinya M, et al. An autopsy case of
epignathus (immature
teratoma of the soft palate) with intracranial extension but without brain invasion: case report and literature review. Diagn Pathol 2018;13(1):99. doi: 10.1186/s13000-018-0776-y.
3. Carvalho CHP, Nonaka CFW, Elias CTV, et al. Giant
epignathus teratoma discovered at birth: a case report and 7-year follow-up. Braz Dent J 2017;28(2):256–261. doi: 10.1590/0103-6440201701368.
4. Tuson KW.
Epignathus: basicranial
teratoma. A case report and review of the literature. Br J Surg 1971;58(12):935–937. doi: 10.1002/bjs.1800581219.
5. Jadhav SS, Korday CS, Malik S, et al.
Epignathus leading to fatal airway obstruction in a neonate. J Clin Diagn Res 2017;11(1): SD04–SD05. doi: 10.7860/JCDR/2017/24956.9283.
6. Al-Mahdi AH, Al-Khurrhi LE, Atto GZ, et al. Giant
epignathus teratoma involving the palate, tongue, and floor of the mouth. J Craniofac Surg 2013;24(1):e97–e99. doi: 10.1097/SCS.0b013e3182798f25.
7. Wang AC, Gu YQ, Zhou XY. Congenital giant
epignathus with intracranial extension in a fetal. Chin Med J (Engl) 2017;130(19):2386–2387. doi: 10.4103/0366-6999.215343.
8. Dakpé S, Demeer B, Cordonnier C, et al. Emergency management of a congenital
teratoma of the oral cavity at birth and three-year follow-up. Int J Oral Maxillofac Surg 2014;43(4):433–436. doi: 10.1016/j.ijom.2013.09.004.
9. Witters I, Moerman P, Louwagie D, et al. Second trimester
prenatal diagnosis of
epignathus teratoma in ring X chromosome mosaicism with inactive ring X chromosome. Ann Genet 2001;44(4):179–182. doi: 10.1016/s0003-3995(01)01090-5.
10. Kumar KM, Veligandla I, Lakshmi AR, et al. Congenital giant
teratoma arising from the hard palate: a rare clinical presentation. J Clin Diagn Res 2016;10(7):ED03–ED04. doi: 10.7860/JCDR/2016/18863.8083.
11. Staboulidou I, Miller K, Göhring G, et al.
Prenatal diagnosis of an
epignathus associated with a 49,XXXXY karyotype-a case report. Fetal Diagn Ther 2008;24(3):313–317. doi: 10.1159/000160219.
12. Schwartz S, Raffel LJ, Sun CC, et al. An unusual mosaic karyotype detected through
prenatal diagnosis with duplication of 1q and 19p and associated
teratoma development. Teratology 1992;46(4):399–404. doi: 10.1002/tera.1420460410.
13. Tonni G, De Felice C, Centini G, et al. Cervical and oral
teratoma in the
fetus: a systematic review of etiology, pathology, diagnosis, treatment and prognosis. Arch Gynecol Obstet 2010;282(4):355–361. doi: 10.1007/s00404-010-1500-7.
14. ElSherbiny Hamed M, El-Din MHN, Abdelazim IA, Shikanova S, et al.
Prenatal diagnosis and immediate successful management of isolated fetal
epignathus. J Med Ultrasound 2019;27(4):198–201. doi: 10.4103/JMU.JMU_125_18.
15. Moon NR, Min JY, Kim YH, et al.
Prenatal diagnosis of
epignathus with multiple malformations in one
fetus of a twin pregnancy using three-dimensional ultrasonography and magnetic resonance imaging. Obstet Gynecol Sci 2015;58(1):65–68. doi: 10.5468/ogs.2015.58.1.65.
16. Pasupathy M, Narayanan PV, Mani V, et al. A case report of nasopharyngeal
teratoma with a cleft palate and an inguinal hernia. J Plast Reconstr Aesthet Surg 2011;64(11):1525–1527. doi: 10.1016/j.bjps.2011.03.033.
17. Becker S, Schön R, Gutwald R, et al. A congenital
teratoma with a cleft palate: report of a case. Br J Oral Maxillofac Surg 2007;45(4):326–327. doi: 10.1016/j.bjoms.2005.11.007.
18. Yapar EG, Ekici E, Gokmen O. Sonographic diagnosis of
epignathus (oral
teratoma), prosencephaly, meromelia and oligohydramnios in a
fetus with trisomy 13. Clin Dysmorphol 1995;4(3):266–271.
19. Santana EF, Helfer TM, Piassi Passos J, et al.
Prenatal diagnosis of a giant
epignathus teratoma in the third trimester of pregnancy using three-dimensional ultrasound and magnetic resonance imaging. Case report. Med Ultrason 2014;16(2):168–171. doi: 10.11152/mu.201.3.2066.162.efms1.
20. Ruano R, Benachi A, Aubry MC, et al. The impact of 3-dimensional ultrasonography on perinatal management of a large
epignathus teratoma without ex utero intrapartum treatment. J Pediatr Surg 2005;40(11):e31–e34. doi: 10.1016/j.jpedsurg.2005.07.059.
21. Fotopoulou C, Toennies H, Guschmann M, et al. Prenatal sonographic diagnosis of an oropharyngeal
teratoma (
epignathus) on a stillborn infant: a case report. Z Geburtshilfe Neonatol 2007;211(4):165–168. doi: 10.1055/s-2007-960682.
22. Moldenhauer JS. Ex utero intrapartum therapy. Semin Pediatr Surg 2013;22(1):44–49. doi: 10.1053/j.sempedsurg.2012.10.008.
23. Hirose S, Farmer DL, Lee H, et al. The ex utero intrapartum treatment procedure: looking back at the EXIT. J Pediatr Surg 2004;39(3):375–380. doi: 10.1016/j.jpedsurg.2003.11.011.
24. Cardesa-Salzmann TM, Mora-Graupera J, Claret G, et al. Congenital cervical neuroblastoma. Pediatr Blood Cancer 2004;43(7):785–787. doi: 10.1002/pbc.20190.
25. Masahata K, Soh H, Tachibana K, et al. Clinical outcomes of ex utero intrapartum treatment for fetal airway obstruction. Pediatr Surg Int 2019;35(8):835–843. doi: 10.1007/s00383-019-04494-1.
26. Lazar DA, Cassady CI, Olutoye OO, et al. Tracheoesophageal displacement index and predictors of airway obstruction for fetuses with neck masses. J Pediatr Surg 2012;47(1):46–50. doi: 10.1016/j. jpedsurg.2011.10.022.
27. Prickett K, Javia L. Fetal evaluation and airway management. Clin Perinatol 2018;45(4):609–628. doi: 10.1016/j.clp.2018.07.003.
28. Mohammad S, Olutoye OA. Airway management for neonates requiring ex utero intrapartum treatment (EXIT). Paediatr Anaesth 2020;30(3):248–256. doi: 10.1111/pan.13818.
29. Jiang S, Yang C, Bent J, et al. Ex utero intrapartum treatment (EXIT) for fetal neck masses: a tertiary center experience and literature review. Int J Pediatr Otorhinolaryngol 2019;127:109642. doi: 10.1016/j.ijporl.2019.109642.
