Subglottic ectopic thymus mimicking airway haemangioma

Abstract

Subglottic haemangioma presents as progressive obstruction in the neonatal and infantile airway, with a soft lesion seen during endoscopy. Diagnosis is based on macroscopic findings, biopsy is not usually performed and propranolol is first-line treatment. In contrast, ectopic thymus is a rare differential diagnosis for subglottic mass made by histopathological examination after excision or autopsy. In this article, we present a case of an infant with a subglottic lesion with endoscopic features consistent with haemangioma. After initial clinical response to propranolol, the patient represented with progressive stridor no longer responding to therapy. Open excision of the lesion was performed, and histopathology revealed ectopic thymus tissue. In this case, ectopic thymus tissue mimicked the presentation of subglottic haemangioma, and confirmation bias persisted due to an apparent initial clinical response to treatment with propranolol. In cases of subglottic mass refractory to medical treatment, excision of the lesion should be considered.

Background

Stridor and respiratory distress in neonates should alert clinicians to investigate congenital abnormalities of the laryngotracheal airway. The majority of subglottic masses in infants are benign, and the most common presentation in infants who have never been intubated is congenital haemangioma.^{1 2} Infantile haemangiomas are benign vascular tumours that most commonly present cutaneously but may occur in any body site. The most common airway haemangioma location is the subglottis.³

Aberrant cervical thymus is a rare condition in which thymic tissue is found in any location along the normal pathway of thymic descent, while ectopic thymus is defined as thymic tissue encountered anywhere else in the body.² Ectopic thymus is a rare congenital condition, which typically presents as a cervical mass in children. It can be found in 1% of paediatric autopsies. Most cases follow an indolent course, but in rare occasions, they can present with life-threatening symptoms such as respiratory distress due to airway obstruction.^{1 4}

To date, only a few cases of subglottic ectopic thymus have been reported in literature.1 2 4–6

In this article, a case of subglottic ectopic thymus mimicking haemangioma is described, and the clinical and diagnostic challenges in its management are discussed.

Case presentation

A 14-day-old neonate presented after 1 week of progressive stridor and reduced feeding, which improved following administration of corticosteroids and a short period of continuous positive airway pressure support. A CT neck and chest suggested subglottic stenosis. A small subglottic cyst was identified during microlaryngoscopy, and the airway was otherwise unremarkable. He was discharged home with no support required.

At 4 months of age, the stridor returned and worsened over a fortnight. Repeat microlaryngoscopy demonstrated a soft, compressible, left-sided subglottic mass, partially occluding the airway. Needle aspiration yielded no fluid. The location and dry tap gave the impression of haemangioma, and propranolol was started. The patient had a good clinical response to propranolol; after 1 month of treatment, stridor had resolved, and there was no longer any increased work of breathing.

During the COVID-19 pandemic, the patient’s family was unable to access repeat prescription for propranolol for several months, and at 6 months of age, the patient’s stridor returned again. The lesion was inspected by microlaryngoscopy and had increased in size.

Open excision of the subglottic mass via partial anterior laryngofissure was performed at 7 months of age with complete removal of the lesion from the subglottis.

Histopathological examination of the excised subglottic lesion showed thymic tissue comprising lobules of epithelial cells in the cortex, Hassall corpuscle’s in the medulla and lobules of acinar glands focally. These features are consistent with ectopic thymic tissue, without any evidence of vascular lesion. The initial CT had confirmed a prominent thymus, within normal limits.

Treatment

Treatment with propranolol was initiated with good response. However, after symptom recurrence, open excision of the lesion was performed in theatre.

Outcome and follow-up

The patient’s initial postoperative period was complicated by dehiscence of the laryngofissure sutures (repaired primarily) and reactive mucosal oedema requiring balloon dilatation. After a short period of intubation, the patient was successfully weaned off all respiratory support within a week. At 3-month postoperative follow-up, all stridor had completely resolved. The patient was voicing, eating and drinking normally.

Discussion

Characteristics of haemangiomas

Haemangiomas are a common tumour of infancy. The vast majority of all infantile haemangiomas do not require therapy and involute spontaneously. Approximately 10% exhibit complications, which warrant immediate therapy such as severe cutaneous ulceration, compression of key structures or obstruction if in the airway.⁷ Haemangiomas are characterised by endothelial hyperplasia and increased numbers of mast cells. They occur more commonly in Caucasian newborns and have a higher incidence in girls than boys.

Airway haemangiomas remain uncommon and may affect any location in the airway and, however, are most frequently in the subglottis.⁸ Only 50% of these patients have associated cutaneous lesions, and cutaneous lesions are more likely to appear in a ‘beard’ distribution over the face and neck.³ A subglottic haemangioma usually appears as a spongy, easily compressible sessile lesion causing asymmetry and occlusion of the subglottis. They are more left than right sided and are usually submucosal, so there may be no abnormal vascularity of the mucosa overlying the haemangioma.³

Symptoms include progressive obstruction of the airway as the haemangioma increases. Initially, they may be asymptomatic; however, as the lesion enlarges, patients may present with stridor and increased work of breathing, especially when upset or feeding.³

Characteristics of ectopic thymus

The thymus develops during the sixth week of gestation from bilateral endodermal saccules of the third and fourth branchial pouches. Proliferation of endodermal cells within the outpouchings leads to the formation of paired solid masses, which fuse at the midline by the following week. The descent of the gland continues into the eighth and ninth weeks to its final position in the anterior superior mediastinum, adjacent to the parietal pericardium.^{1 2}

Aberrant thymic tissue is the presence of thymic tissue anywhere along the normal pathway of descent (thymopharyngeal tract), due to an interrupted migration. On the other hand, ectopic thymus is defined by the presence of thymic tissue in any other location outside of the thymopharyngeal tract.²

The aetiopathogenesis of ectopic thymus is still unclear. Possible mechanisms for the ectopic thymus suggested so far include disrupted endodermal–mesodermal interaction during the embryological development of the larynx, metaplasia of pluripotent endodermal cells below the vocal folds, failure of the thymus gland to descend or sequestration and failure to involute.^{1 2 4}

The vast majority of patients with ectopic thymus do not have any symptoms. However, if it’s located in the airway, symptoms can include stridor, dyspnoea or dysphagia due to compression of the trachea or oesophagus. Severe respiratory distress can develop in extreme cases, and death by mechanic obstruction of the airway has been reported.^{1 4}

Differential diagnosis

The differential diagnosis of subglottic lesions in children includes both benign and malignant pathologies. Benign entities are more common and include infantile haemangiomas, subglottic stenosis, respiratory papillomatosis and mucous retention cysts. Rare causes include thyroglossal cysts and ectopic thymic tissue.^{2 9} Malignant lesions of the subglottis are very rare and, however, include carcinoid, sarcomas and mucoepidermoid carcinomas.²

Investigations

Diagnosis of subglottic lesions is most commonly done by direct visualisation, but imaging does play a limited role. Initial diagnostic evaluation for subglottic masses should include a detailed history and an accurate physical examination, including examination of the airway.²

Direct endoscopic visualisation of the airway is required. An awake transnasal flexible laryngoscopy can be performed, but most children will require a formal microlaryngo bronchoscopy (MLB). Ideally, MLB should be performed under general anaesthesia with the patient breathing spontaneously.³ In cases of suspected subglottic haemangioma, biopsy is generally not indicated, and the diagnosis is made based on the MLB findings and response to therapy.³ Biopsy of an airway lesion is performed if the appearance is not in keeping with a haemangioma or there is no response to therapy. Subglottic ectopic thymic tissue is identified only after histological examination of a biopsy or excised specimen obtained by surgical resection or autopsy, as no preoperative examination can accurately recognise ectopic thymus.^{1 2 4}

Radiological evaluation of an airway mass in a small child where spread beyond the airway is suspected is performed by MRI to determine location and size of the lesion, as well as anatomical relation with surrounding structures. Chest X-ray or CT neck and chest may also be used for evaluation of the anatomy of the lesion or staging in the assessment of a malignancy.^{2 3}

Treatment

Subglottic ectopic thymus presents as any subglottic mass does, with recurrent respiratory distress and stridor.² Medical therapy with corticosteroids may offer temporary relief of the symptoms; surgical excision is both diagnostic and therapeutic, as diagnosis is made after excision of the lesion.^{1 2}

Subglottic haemangiomas may cause airway compromise. First-line management is pharmacotherapy with a course of oral propranolol, first discovered in 2008.¹⁰ Studies have demonstrated propranolol therapy is safe and effective, resulting in fewer surgical interventions and demonstrating better tolerance, with minimal adverse effects.7 8 11–14

Propranolol is a non-selective β-adrenergic antagonist, which competitively inhibits β1 and β2 receptors with the same affinity. Propranolol is a pure antagonist without partial agonistic effects.⁷ Despite its widespread use for treatment of haemangiomas, the mechanism of action is still not fully understood. Potential mechanisms include promotion of vasoconstriction, inhibition of vasculogenesis and catecholamine-induced angiogenesis, induction of proliferating endothelial cell apoptosis and inactivation of the renin–angiotensin system.^{8 12 13} There were no vascular lesions present in the specimen obtained from this patient. It is therefore still unclear why the mass initially responded to treatment with propranolol.

Where propranolol is unsuccessful in improving the patient’s symptoms, surgical treatment of subglottic haemangioma by endoscopic or open excision may be undertaken.³ Open excision plays a role in treatment of infants who present at a young age with a large and rapidly growing mass.³ Rarely, an extensive lesion would indicate tracheostomy for airway protection during the growth and plateau phases of growth, awaiting involution.

Our case

In this case, an MLB by the otolaryngology team confirmed a subglottic mass was identified with macroscopic characteristics consistent with haemangioma (figure 1). No biopsy was performed, and trial of medical management was commenced with good initial response, in keeping with a diagnosis of subglottic haemangioma. However, after a short period without propranolol and worsening respiratory symptoms despite recommencing the medication and titration of dose to patient weight, open excision was undertaken and histological examination of the excised tissue revealed ectopic thymus tissue (figure 2). Prognosis following ectopic cervical thymus tissue excision is usually excellent, as there are no reported cases of recurrence.¹

Figure 1.

These photomicrographs taken during microlaryngoscopy and bronchoscopy airway examination show a pale lesion in the subglottis (A and B) and healed, patent airway post excision of the lesion (C and D).

Figure 2.

This microscopic image of the surgical specimen shows H&E-stained thymic tissue comprising lobules of epithelial cells in the cortex and Hassall corpuscle’s in the medulla (white arrows).

Learning points.

• Haemangioma is the most common presentation in infants with subglottic lesion, and diagnosis is made during endoscopic examination of the airway.

• Usual first-line treatment for haemangioma is propranolol.

• In cases of subglottic lesions refractory to medical therapy, excision of the mass should be undertaken.