Introduction

Masses seen on the neck can give an unsightly appearance and can be a telltale sign of various pathological conditions. These masses can result from infectious causes, such as swollen lymph nodes in tuberculosis, or malignant conditions, such as teratomas. This article deals with:

• Basics about embryological germ cell layers
• What are teratomas?
• Why do we need to know about teratomas?
• The role of microscopy and tumour markers in the diagnosis of teratomas
• Complications, treatment, and prognosis of teratomas

The human embryo has 3 layers: 

• The outer layer of the embryo is the ectoderm, which forms skin, brain, nerves, eyes, and inner ears
• The middle layer is the mesoderm, which gives rise to the heart, blood vessels, bones, ligaments, kidneys, and the reproductive system
• The inner layer is the endoderm, from which lungs and intestines form

Stem cells are the pioneer cells that transform themselves to form various mature cells in our body. 

What are ‘Teratomas’?

Teratomas are tumours that originate from pluripotent stem cells of all three germ layers: endoderm, mesoderm, and ectoderm. The incidence of fetal teratomas is 0.07 to 2.8 per 1000 pregnancies.¹ 

How do teratomas occur?

The molecular basis of the occurrence of these tumors is not clear. During embryonic life, the abnormal migration and differentiation of precursor cells can give rise to teratoma formation. Various chromosomal abnormalities (abnormal number of chromosomes) are linked to teratomas, such as trisomy 13, pentasomy 49, and XXXY karyotype. Teratomas can occur as a part of genetic syndromes such as Aicardi syndrome, a rare genetic malformation of the brain, and Pierre-Robin syndrome, a rare birth defect often characterised by underdeveloped jaws.¹

These tumors are more likely to develop in the midline of our bodies. The most common site is the sacrococcygeal region (lowermost part of the spine). However, they can also develop in the head and neck, mediastinum (in between the lungs), heart, and retroperitoneal areas. Head and neck teratomas constitute 30% of the head and neck masses. Mostly, the neck teratomas are benign, but, in rare cases, they can turn malignant.¹

The neck teratomas present with variable symptoms, unusual appearance microscopically, and an unpredictable outcome. These can be so large that they can cause respiratory distress, facial deformity, and even involve the orbits (eye sockets).⁵

On ultrasound, these tumours appear as large irregular masses with both solid and cystic components, along with areas of calcification.¹

Why do we need to know about teratomas?

There are a lot of pathologies that can present as neck masses. The treatment protocol depends upon the location, size, and exact diagnosis of the neck masses. The various conditions are as follows:

• Anterior neck masses: Teratoma, lymphangiomas, epignathus, goiter, bronchogenic cyst, and hemangioma 
• Posterior neck masses: Cystic hygroma, cervical meningocele (spina bifida), occipital encephalocele, hemangioma, and cervical neuroblastomas⁴

Every neck mass has a unique clinical presentation, radiological features, gross appearance, and microscopic features. Thus, a correct diagnosis is essential for adequate treatment and outcome. Radiological investigations, including an MRI or CT scan, help reach the diagnosis. For example, on ultrasound, the cervical lymphangiomas appear as fluid-filled cystic spaces, divided by fine septae, and don’t have areas of calcification. They are less vascularised and do not invade adjacent tissues as compared to cervical teratomas.

On the other hand, cervical teratomas are usually irregular masses, unilateral, with more vascularity. Most are multiloculated, partially solid, partially cystic, and have calcifications.^1,4

Features exhibited by teratomas microscopically

On gross appearance, the teratomas may be completely cystic, predominantly solid, or partially solid and cystic with variable areas of necrosis.⁸

Microscopically, the teratomas are classified as mature, immature, or teratomas with malignant transformation.

• The mature teratomas are composed of well-differentiated tissues such as skin, hair, sebaceous glands, intestinal tissue, and pancreatic tissue, present in an unusual pattern⁸
• The immature teratomas contain small regions, called foci, of immature (embryonal) structures or undifferentiated tissues such as primitive neuroectodermal tissue, and yolk sac tumor cells. The treatment and prognosis of immature teratomas depend upon the type of tissue present. For example, tumours with malignant yolk sac tumour (germ cell tumour) cells have chances of relapse if the teratomas are incompletely resected and adjuvant chemotherapy is recommended to eradicate them⁸ 
• The teratomas with malignant transformation: These are the rare tumours in which there are preexisting teratomatous structures transform into non-germ cell malignancies, such as myeloid leukemias, carcinomas, or soft tissue sarcomas⁸

A thorough sampling of the excised mass is required for grading of the teratomas. The grading is done according to the Gonzalez-Crussi grading system: 

• Grade 0: Microscopically, the sampled tissue contains well-differentiated components
• Grade 1: Less than 10% of the sampled tissue contains occasional microscopic foci of  undifferentiated components
• Grade 2: 10-50% of sampled tissue contains immature components
• Grade 3: More than 50% of the sampled tissue comprises immature components 

Grade 0 and 1 are classified as mature teratomas, whereas grade 2 and 3 are categorised under immature teratomas.⁶

Role of tumour markers in diagnosis

Tumour markers, also called oncofetal proteins, are the proteins or carbohydrate molecules expressed in or released from the tumour tissues. They are released in such quantities into circulation or body fluids that are easily detectable. Their levels correspond to the tumour burden, thus helping in the diagnosis and choice of treatment of tumours. 

Alpha-fetoprotein (AFP) is one such protein produced by the fetal yolk sac, liver, and the gut. In fetal life, its function is similar to that of albumin, i.e. maintains plasma oncotic pressure, acts as a carrier for bilirubin and estrogen, and has a role in immunosuppression or growth stimulation. The levels can be from 10,000 ng/ml to as high as 70,000 ng/ml at birth. Afterwards, the levels start declining and normal adult levels of < 10 ng/ml are reached anywhere between 8 months - 1 year of age. The elevated levels are seen in various conditions such as liver tumours, germ cell tumours, and pancreatoblastoma.³

1. Alpha-fetoprotein (AFP) has utility in the diagnosis, for assessment of the response to treatment, and monitoring of disease response post-chemotherapy and/or teratomas of the head and neck resection 
2. The levels of AFP tell about the aggressiveness of the disease 
3. AFP presence further plays a definitive role in surveillance of tumor recurrence and clinical monitoring to predict early recurrence and treatment outcomes⁷

The final diagnosis can be confirmed by immuno-histochemical staining of cytoplasmic AFP in frozen and paraffin tumor sections.⁷

Limitations of AFP as a tumour marker

• The absence of elevation of AFP levels does not negate the possibility of a congenital tumour because perinatal AFP levels are directly influenced by both birth weight and perinatal age⁷
• AFP is a non-specific marker as its levels are increased in other tumours such as hepatoblastoma, pancreatoblastoma, and hemangioendothelioma. Even the non-malignant conditions such as chronic hepatitis, cirrhosis, cholestasis, ataxia telangiectasia, and hereditary tyrosinemia can also show elevated serum AFP levels²
• The recurrence or malignant transformation of mature teratomas may go unnoticed sometimes, as they do not produce significantly high quantities of AFP⁴

Complications of teratomas

In the intrauterine life, fetal neck teratomas can lead to compression of adjacent structures, such as trachea and oesophagus, causing significant airway obstruction and the fetus’s inability to swallow, resulting in polyhydramnios respectively. The lungs of the fetus don’t develop properly, leading to severe lung hypoplasia (reduced lung mass due to abnormal development), which can cause fetal death.¹

The cervical teratomas have a rich blood supply, that’s why there is always a risk of significant blood loss.¹

Treatment

Surgery is the mainstay of treatment for cervical teratomas, as these neck masses present with airway obstruction. 

When the fetus has a small non-obstructing neck mass while in the uterus, as detected on ultrasound, expectant management is considered. The neck mass is resected after birth depending upon size, complexity of the mass, and overall condition of the newborn’s airway.¹

Sometimes, the neck masses are so large in intrauterine life that they can cause significant airway collapse, leading to fetal death. Two approaches are used for the management: EXIT-to-airway (Ex-utero intrapartum treatment) and fetal endoscopic tracheal intubation (FETI). After birth, the follow-up visits include repeated imaging and alpha-fetoprotein levels. The rise in AFP levels can indicate metastasis or recurrence.¹

If the newborn’s airway is secured before surgery, then these newborns with isolated cervical teratoma have a good prognosis. However, if the fetus has developed pulmonary hypoplasia secondary to a huge neck mass as a complication, even if an adequate airway is maintained, death is imminent due to respiratory insufficiency.⁴

In case the benign teratomas develop malignancy, the tumour is completely excised, and chemotherapy is given. Serial measurements of AFP levels are done, and the levels of AFP should fall to normal after successful completion of the chemotherapy.⁵

FAQ

Can cervical teratomas be cured completely?

It depends upon many factors such as age, size of teratoma, the histological type, grade, invasion of adjacent neck structures like trachea, oesophagus, and blood vessels. The treatment is planned taking into account these factors. If the definitive diagnosis is made timely, then cervical teratomas have a good prognosis.

Summary

The cervical teratomas are the congenital neck masses that arise from the pluripotent stem cells and contain tissues derived from all three germ cell layers of an embryo. Other tumours, such as cystic hygroma, hemangiomas, neuroblastomas, can mimic teratoma. Therefore, it's important for clinicians to identify them properly as the treatment, outcome, and prognosis depend upon the definitive diagnosis of neck mass. Although the cervical teratomas are mostly benign, malignant transformation can occur rarely. Ultrasound, MRI, or CT scan are helpful in differentiating these tumours. The histopathology of the excised neck masses confirms the diagnosis. Serum AFP levels aid in diagnosis, monitoring post-surgery and post-chemotherapy response, and recurrence of the tumour.