Ex Utero Intrapartum Treatment (EXIT) in a rare infantile tongue fibrosarcoma and it’s management dilemma

Abstract

Ex utero intrapartum treatment (EXIT) has been described as a safe procedure to secure challenging fetal airways while on placental support. Here we present an extremely rare case of huge infantile tongue fibrosarcoma diagnosed prenatally and successfully delivered via EXIT. Initial diagnosis of infantile tongue haemangioma was made based on physical examination, radiological findings and high incidence of infantile haemangioma in the first year of life hence trial of oral propranolol was given. Tracheostomy was performed at 1 week of life in anticipation of airway compromise and failed extubation. A biopsy of the tongue tumour was performed to rule out soft tissue malignancy. Histopathological examination (HPE) revealed a malignant tumour suggestive of infantile fibrosarcoma. The management of infantile fibrosarcoma is a multidisciplinary team’s involvement. However, non-mutilating surgery should be the primary treatment for infantile fibrosarcoma aiming for complete excision. Neoadjuvant chemotherapy is indicated when upfront resection is unfeasible as in the present case.

Keywords:

• EXIT procedure
• infantile fibrosarcoma
• tongue
• soft tissue tumour

Introduction

Fibrosarcoma has been defined as a malignant tumor of the fibroblasts that shows no other evidence of cellular differentiation and is capable of recurrence and metastasis. There are two types of fibrosarcoma, infantile or congenital (IF) and adult form. Infantile fibrosarcoma is a rare paediatric soft tissue sarcoma and is typically detected in children less than 1 year of age, most commonly presented as a non-tender, poorly circumscribed mass varying in size and consistency. Infantile fibrosarcoma is unique among human sarcomas because it has an excellent prognosis, very low metastatic rate and good chemosensitivity [1].

Case report

A 19-year-old primigravida was referred to our centre at 36^th weeks of gestation following an antenatal ultrasonography finding of a huge fetal oral mass. MRI fetus demonstrated a well-defined mass with smooth margins arising from the tongue filling the entire fetal oral cavity and protruding out from the mouth with differential diagnoses of vascular malformation and tumour such epignathus teratoma (Figure 1 (A and B)). Multidisciplinary consultation was conducted with a team of fetomaternal specialist, paediatric otorhinolaryngologist, neonatalogist and anesthesiologist. Ex utero intrapartum treatment (EXIT) procedure was recommended to the patient in view of the huge fetal tongue mass and airway compromise.

Figure 1. (A) Heterogeneous hypointense lesion (*) on T1 of fetal MRI. (B) Fetal MRI shows mixed signal (*) on T2 with the region of intermediate signal on T2 showing post-contrast enhancement and central hyperintense region on T2 with no enhancement suggestive of the cystic or necrotic component.

At 37 weeks, the baby was delivered via elective ex-utero intrapartum treatment (EXIT) to intubation. Infant’s head was delivered through caesarean section, with its body in utero to maintain fetal-maternal circulation. Direct diagnostic laryngoscopy was performed using a Parson Laryngoscope size 3 (blade length 11 cm). The laryngeal inlet was then visualized followed by a telescope (0-degree Karl Storz 2.7 mm) guided intubation of the infant. The infant was then delivered completely (Figure 2) and was admitted to the Neonatal Intensive Care Unit (NICU). MRI neck was performed on day 2 of life and showed a large expansile solid heterogenous tongue mass around 5.8 cm × 4.5 cm × 4.5 cm associated with increased vascularity, suggestive of congenital intramuscular tongue hemangioma and differential diagnosis of rhabdomyosarcoma of the tongue. There was no regional node seen.

Figure 2. Post EXIT delivery- A huge tongue mass causing expansion of the tongue and oral cavity and protruding out of the mouth.

Oral propranolol was initiated empirically based on physical examination, radiological findings and high incidence of infantile haemangioma in the first year of life. Subsequently, tracheostomy was performed at 1 week of life in anticipation of airway compromise and failed extubation. Examination under anaesthesia and biopsy of tongue tumours was performed in the same setting to rule out soft tissue malignancy (Figure 3(A and B)). Histopathological examination (HPE) of tongue mass later revealed ulcerated tumour tissue composed of sheets of malignant spindle cells with mildly pleomorphic elongated to spindle-shaped dark nuclei with evenly dispersed chromatin and inconspicuous nucleoli. Immunohistochemical study showed positive toward Vimentin, CD99, Bc12 and TLE-1. These findings were suggestive of infantile fibrosarcoma. The oral propranolol was hence stopped.

Figure 3. Open tracheostomy and examination under anesthesia (EUA) and biopsy performed on day 7 of life (A) Lateral view of the huge tongue mass, (B) Anterior view of huge tongue mass.

Surgical excision was not feasible without causing significant morbidity to the baby and because of the chemosensitive nature of the tumour, the Paediatric Oncology team has started a chemotherapy VAC regime consisting of Vincristine sulfate, Actinomycin-D and Cyclophosphamide. The tumour was significantly reduced in size after completing total 6 cycles of chemotherapy. In view of a good response to chemotherapy, she underwent surgical resection (Figure 4 (A and B)) of the tumor 2 months later which show an excellent outcome (Figure 5).

Figure 4. Significant reduction in tumour size post-chemotherapy; surgical excision of the tongue tumour (A) prior to surgical removal of the tumor, (B) post-tumour removal.

Figure 5. Eight months post tumour removal. Tracheostomy was decannulated 4 months after the surgery.

Discussion

Paediatric soft tissue sarcomas (STS) represent about 7% of all childhood malignancies including rhabdomyosarcoma (RMS) which is the more common case, while the other type is the ‘‘non-rhabdomyosarcoma’’ STS (NRSTS) [2]. Infantile fibrosarcoma (IF) is a type of NRSTS with an incidence of 24.5% of all soft tissue sarcomas seen in the first year of life [3]. It is a malignant tumour that arises from the fibroblasts (cells that produce connective tissue). These types of sarcoma may arise at any site but are predominantly found in the area around the bones or in the soft tissue [4]. Among all the fibrosarcoma occurring in humans, only 0.05% occurs in the head and neck region. Of this, 23% of head and neck fibrosarcoma occur within the oral cavity. Rarely it arises from the tongue [4,5].

Generally, there is no gender predilection. The tumours develop with equal frequency in males and females [6]. Clinical features of fibrosarcoma vary depending on the size, location and grade of the tumour. The aetiology of fibrosarcoma remains obscure, however, genetic malformation and radiation may contribute [5,6].

There are two types of fibrosarcoma which are infantile or congenital (IF) and adult form [7]. The presentation of infantile fibrosarcoma is usually at an early age as in our case. Although it is histologically similar to fibrosarcoma in adults, its behaviour is quite different from that in older age groups. In adults, this diagnosis carries a grim prognosis while the 5-year disease-free survival rate in infants is good around 83% to 94% [7,8]. However, this rare lesion of infantile fibrosarcoma of the tongue can cause life-threatening neonatal airway obstruction.

Advances in fetal imaging like antenatal ultrasonography followed by MRI, allow planning in order to improve outcomes and limit hypoxia at delivery [9]. Other options like fetoscopic airway evaluation have been proposed in a study by Beckers et al. [10], to optimize the selection of patients in need of an EXIT procedure which was not practically performed in our centre. The use of the EXIT procedure to facilitate airway securement in a controlled manner on placental bypass has been proposed since 1990s as an optimal delivery strategy for patients with this type of pathology [9,11–13]. The purpose of the EXIT is to convert an emergency neonatal airway situation into an elective-controlled one. Delivery at 37–38 weeks is recommended for the best fetal outcome as the fetus is fully developed [14]. Spontaneous vaginal delivery is not an option here due to the disproportionate ratio between the fetus with oral mass and vaginal introitus. A multidisciplinary approach with proper preoperative planning is essential for the best outcome for the patient [9,11–14].

Infantile fibrosarcoma in the oral cavity is a rare pediatric soft tissue sarcoma and may mimic vascular lesions on clinical grounds and in imaging evaluation. It is most frequently misdiagnosed as an infantile hemangioma or congenital hemangioma contributing to a delay in diagnosis and treatment dilemma as seen in the present case. Our patient was initially started on oral propranolol until the HPE result confirmed IF.

Imaging like CT scan or MRI may point to a solid mass but the exact diagnosis can only be made on histopathology examination powered by immunohistochemistry as seen in our case. Infantile fibrosarcoma can be graded into low, intermediate and high-grade depending on the severity of cellularity, nuclear pleomorphism and mitosis. Infantile fibrosarcoma must be kept in the differential diagnosis of soft tissue tumours like rhabdomyosarcoma and infantile myofibromatosis and its variants.

The management of infantile fibrosarcoma is multidisciplinary which includes surgery, chemotherapy and radiotherapy with rehabilitation if indicated. Parida et al. recommended non-mutilating surgery as the primary modality of treatment for infantile fibrosarcoma and neoadjuvant chemotherapy is indicated in cases in which upfront resection is not feasible. Patients with positive surgical margins also should receive adjuvant chemotherapy [15]. The most commonly used chemo-therapeutic drugs were vincristine, cyclo-phosphamide, actinomycin-D, and doxorubicin; ifosfamide and etoposide [16]. Aggressive local therapy (mutilating surgery or external radiotherapy) is discouraged as it has the potential to impair growth [15]. Our patient was given neoadjuvant chemotherapy for tumour reduction given a huge inoperable tumour. Surgical excision was done after she completed the neoadjuvant chemotherapy.

Conclusion

In conclusion, the EXIT procedure is a safe mode of delivery for patients identified with obstructing oropharyngeal lesions with a potential risk of neonatal airway obstruction. A multidisciplinary team of experienced physicians including the specialities of obstetrics, neonatology, anaesthesia and head and neck surgery are fundamental to ensure a successful surgical outcome. Intraoral fibrosarcoma is a rare tumour but should be kept in the differential diagnoses of soft tissue tumours in infants, even in congenital cases. Accurate diagnosis and prompt treatment of the lesion are mandatory for prolonged disease-free survival, and to avoid tumour recurrence.

Consent for publication

Written informed consent was obtained from the patient’s legal guardian for the publication of this case report and any accompanying images.

Author contributions

NR was involved in the collection of the data, literature search, writing of the original draft, surgical assistance, patient follow-up and the corresponding author. FAR, NG and SSMH were involved in the patient management, operating surgeon, follow-up and review of the draft. GBS was involved in reviewing the final draft. All authors read and approved the final manuscript.

Acknowledgement

The authors would like to acknowledge Dato Dr Bavanandam Naidu (Fetomaternal specialist) and his team for their expertise in managing the mother, Dr Nazuha and the rest of anesthesiologist team for allowing surgery to proceed smoothly. The authors would also like to thank the paediatric intensivist Dr Eric Ang Boon Kuang together with his team who have been tirelessly involved in the care of the patient. We also would like to thank Director- General of Health Malaysia for his permission to publish this article.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This manuscript has not received any external or industrial support or funding.