Introduction

Alpha-fetoprotein (AFP) is a plasma protein, present in marked amounts only during fetal life and up to 2 years after birth.¹ This glycoprotein is mainly produced by the fetal liver and plays a significant role in fetal medicine. It enables the early detection of neural tube defects, Down syndrome, and other chromosomal abnormalities during the initial stages of fetal development.² AFP is one of the markers utilized in the diagnosis of cervical teratomas in the fetus and newborn stage. 

Cervical teratomas are congenital tumours seen in the neck region of the fetus and neonates.³ Even though cervical teratomas are rare, they can create a potential risk to the fetus due to airway obstruction and fetal distress at the time of labour. Hence, early diagnosis opens up a chance for timely surgical intervention at the time of labour. AFP with imaging tests helps in diagnosing cervical teratomas in the fetus.

Understanding alpha-fetoprotein

Alphafeto protein plays a role similar to that of albumin in the fetal circulation. It is produced by the yolk sac in the preliminary embryonic stage of fetal life, and by the 13th week, the main source of AFP is the fetal liver. During fetal circulation, AFP crosses the placenta and reaches the maternal blood circulation.⁴ AFP screening is performed on maternal blood serum for the assessment of neural tube abnormalities, Down syndrome, and cervical teratomas. 

AFP enters the maternal circulation through two pathways. 

• Trans placental pathway - Here, AFP crosses the fetal blood vessels through the chorionic villi to reach maternal serum
• Transfusion across the tissues - In this indirect route, AFP is secreted into the amniotic fluid through fetal urine to cross the fetal membranes and finally enter maternal serum

The clinical significance of AFP lies in its diagnostic, screening, and monitoring roles in prenatal medicine. It is included as a part of triple or quadruple prenatal screening based on the gestational age to detect fetal anomalies, estimate gestational age, and assess risks for aneuploidy. For screening purposes, AFP testing is usually performed during the second trimester, ideally between 15 to 20 weeks of gestation, with the optimal window being 16 to 18 weeks.⁵ The normal AFP range between 15 to 21 weeks of gestation is 10 to 150 ng/mL. Beyond the 21st week, the AFP levels drop consistently until birth. If the test result is negative with AFP level falling in the normal range, there is no need for further tests. 

However, iIf there is any elevation in the maternal serum alphafetoprotein levels, an ultrasound will be carried out to identify the probable cause. Ultrasound scanning helps confirm the gestational age and the number of foetuses, as naturally the AFP levels would be elevated in twin and multiple pregnancies and can give a false positive result if the gestational age is not correct.⁶ After multiple pregnancies and incorrect gestational age are ruled out, the next step would be to test AFP levels in the amniotic fluid. This is done on a sample obtained through trans-abdominal amniocentesis, where a small needle is used to aspirate a small volume of amniotic fluid under aseptic conditions. It is performed by an experienced obstetrician under ultrasound guidance.⁷ AFP levels may also be assessed using fetal cord blood, either arterial or venous, if further clarification is needed. However, these are more invasive procedures. 

Role of AFP in cervical teratomas

Elevated AFP levels serve as a marker for germ cell tumours, including cervical teratomas. AFP levels are typically higher in immature cervical teratomas as they contain yolk sac elements that consistently secrete AFP. In contrast, mature cervical teratomas have AFP levels within the normal range. 

As AFP can also be elevated in other fetal abnormalities, it is essential to differentiate the cause through ultrasound findings and appropriate clinical correlation.

Cervical teratomas: clinical features

Cervical teratoma is an infrequent germ cell tumor seen behind the neck region. Congenital cervical teratomas are even rarer, with an estimated incidence of 1 in 20,000 to 40,000 live births.⁸ The exact cause of cervical teratomas is unknown. 

Scientific studies are ongoing to find the exact reason for this condition. A hypothetical theory suggests that during embryogenesis germ cells migrate to other sites instead of the developing gonads, where they proliferate through mitosis to form teratomas.⁹ Mst congenital teratomas are non-harmful (i.e.benign) in nature, and the major risk associated with them is the closure of the windpipe due to compression of adjacent structures by the growing teratoma. This can ultimately result in respiratory distress in the baby at the time of labour.¹⁰ 

Prenatal diagnosis of cervical teratomas is primarily achieved through ultrasound, where large tumours are easily visible. Also in USG, a notable feature is Hyperextension of the neck due to the mass is another notable feature on ultrasound. Additionally, in some cases, an increase in amniotic fluid amount (polyhydramnios) might be evident, as the fetus may develop difficulty in swallowing secondary to the mass. Magnetic Resonance Imaging(MRI) can be used to gather further information regarding the exact anatomical location and extension of the tumour. 

Monitoring and management

Once cervical teratoma is diagnosed in the second or third trimester, repeated ultrasound imaging or MRI should be done to analyse the growth and vascularity of the tumour. Maternal serum AFP levels should be measured regularly to understand the nature of the teratoma. Regular assessment of fetal well-being through non-stress tests, fetal doppler studies, and biophysical profile is also essential during this period. Surgical intervention has to be planned at the time of delivery with a combined team of skilled obstetricians, neonatologists, and paediatric surgeons. EXIT (Ex Utero Intrapartum Treatment ) will be performed if there is a high risk of airway obstruction. Once the newborn is stable, surgical excision of the tumour can be carried out.¹² Based on the histological findings, further treatment will be planned. The presence of features of cancer will necessitate the administration of chemotherapy.

Limitations and considerations

As cervical teratomas are a rare condition, so far only a few cases have been reported in the literature. Although AFP is elevated in cervical teratomas, it can also rise in other conditions such as neural tube defects and chromosomal abnormalities. In addition, variations in the calculated gestational age can give rise to false positive results.¹³ Therefore, AFP alone cannot be considered as a definitive diagnostic parameter in cervical teratomas. Multimodal assessment with AFP, ultrasound imaging, and clinical history is essential for an accurate confirmatory diagnosis. 

Summary

Cervical teratomas are among the rarest types of fetal teratomas, representing less than 5% of all teratomas. Survival rates have improved with advancements in prenatal diagnosis and surgical techniques, including the use of EXIT procedures. Maternal serum Alpha-fetoprotein is a valuable tool in the early detection of cervical teratomas alongside ultrasound findings. Elevated AFP levels are associated with immature cervical teratomas and, polyhydramnios is frequently observed in most of these cases. Elevated AFP has also been reported in a few cases of neonatal cervical teratomas. However, not all cervical teratomas produce elevated AFP levels, particularly immature teratomas without yolk sac elements. Due to their rarity, only a small number of fetal cervical teratoma cases have been reported in medical literature till now. Therefore, there is a significant need for further research to better understand the role of AFP in the diagnosis and management of cervical teratomas.