Branchial cleft anomalies: a pictorial review of embryological development and spectrum of imaging findings

The branchial arches develop between the fourth and seventh week of gestation and form the embryological precursors of the ear and muscles, blood vessels, bones, cartilage and mucosal lining of the face, neck and pharynx (Fig. 1). In total, six pairs of branchial arches form on either side of the pharyngeal foregut in cranio-caudal succession. The fifth pharyngeal arch is usually only rudimentary, or never forms, so ultimately only five arches formulate adult structures [1, 2]. The fifth arch does not contribute to anatomical structures in humans. Schematically, the sixth arch is often represented as part of the fourth arch due to its small size.

Each branchial arch is lined externally by an ectoderm-lined recess, referred to as a pharyngeal/branchial cleft, and internally by a layer of endoderm, referred to as a pharyngeal/branchial pouch (Fig. 1). Between the branchial cleft and branchial pouch is a core of mesenchyme derived from a combination of lateral plate mesoderm, somites and neural crest cells. Clefts and pouches are gradually obliterated by invasion of mesenchyme to form various adult structures (Table 1). Each arch has its own central cartilaginous/skeletal supporting element, an aortic arch artery and an arch-associated cranial nerve. The first arch is supplied by the trigeminal nerve (V), the second arch by the facial nerve (VII), the third arch is supplied by the glossopharyngeal nerve (IX) and the fourth and sixth arches by the superior laryngeal and recurrent laryngeal branches of the vagus nerve (X), respectively [3]. Each nerve innervates structures derived from its associated arch.

The pharyngeal cleft associated with the first branchial arch forms the external auditory meatus. The corresponding first pharyngeal pouch gives rise to the tubotympanic recess which forms the tympanic cavity of the middle ear and eustachian tube. The associated cleft between these structures forms the tympanic membrane. The tympanic membrane is, therefore, trilaminar and composed of ectoderm, mesoderm and endoderm [4]. The first branchial arch splits distally to form the mandibular and maxillary processes of the jaw. The muscles of mastication, auditory ossicles (malleus and incus) and multiple bony and cartilaginous facial structures are also derived from the first arch.

The first arch and cranial aspect of the second pharyngeal arch enlarge and thicken combining with the third and fourth pharyngeal arches to form an ectoderm-lined cavity called the cervical sinus of His (or cervical cyst). The prominent ridges around the cavity form various caudal structures in the face and neck that are detailed below. The sinus of His rapidly involutes during embryogenesis. In an adult, the angle between the sternocleidomastoid muscle anteriorly and the infrahyoid strap muscles represents the obliterated sinus [1, 5].

Each of the pharyngeal pouches gives rise to an adult structure. Derivatives of the second pharyngeal arch structures include the tonsillar fossa, palatine tonsils, stapes, lesser horn of the hyoid, adjacent muscles of facial expression and floor of the mouth. The third pharyngeal pouch gives rise to the greater horn of the hyoid, thymus and pyriform fossa. The thymic gland precursors migrate inferiorly and ventral to the thyroid to fuse in the midline, forming a bilobed structure. The inferior parathyroid glands also develop from the third pharyngeal pouch; the superior parathyroid glands, paradoxically, arise more inferiorly from the fourth pharyngeal pouch. The fourth pharyngeal pouch also contributes to the apex of the pyriform fossa, as well as laryngeal cartilages and laryngeal muscles. The ultimobranchial body (ultimopharyngeal body/ultimobranchial gland) is a derivative of the ventral recess of the fourth pharyngeal pouch, technically fifth, but that one is rudimentary and merges with the fourth (Fig. 1). It gives rise to the calcitonin-producing cells (parafollicular cells/C cells) of the thyroid gland. The sixth pharyngeal arch contributes towards the sternocleidomastoid and trapezius muscles.

Branchial arch anomalies are the second most common head and neck congenital lesions in children with thyroglossal duct remnants being the most common. They represent approximately 20 % of cervical masses, hence branchial arch anomalies are considered in the differential diagnosis of head and neck masses in children [6]. Second branchial arch anomalies are the most common and account for approximately 95 % of cases. First branchial arch anomalies account for 1–4 % cases with third and fourth branchial arch anomalies being extremely rare [6]. Branchial arch anomalies may present as cysts, fistulas, sinuses or cartilaginous remnants. Branchial cysts typically present in older children/young adults, whereas fistulas typically present in infants/young children. Branchial arch anomalies may be bilateral in 2–3 % of cases where they are often familial [7]. A sinus is a blind ending tract and in the context of a branchial arch anomaly, may connect with either the skin (branchial cleft sinus) or with the pharynx (branchial pouch sinus). A fistula is a communication between two epithelialised surfaces and with regard to branchial arch anomalies, requires communication between a persistent pouch and cleft. If no communication occurs with the inner mucosa or outer skin, then the trapped branchial arch remnant forms a cyst. There are a number of theories proposed to account for the formation of these anomalies, the most widely accepted theory being that they result from incomplete obliteration of the branchial apparatus, primarily the cleft [8]. In the case of sinuses and fistulae, the pharyngeal membrane and pouch are also implicated.

Second branchial cleft anomalies most commonly present as cysts followed by sinuses and fistulae [9]. Most are present within the submandibular space but they can occur anywhere along the course of the second branchial arch tract which extends from the skin overlying the supraclavicular fossa, between the internal and external carotid arteries, to enter the pharynx at the level of the tonsillar fossa [2]. They have previously been classified into four different sub-types by Bailey in 1929 [10]:

A fistula or cyst in the lower anterior or lateral region of the neck is most likely to represent a second branchial cleft anomaly (Fig. 2). Fistulae are usually diagnosed in infancy/childhood with drainage of secretions or purulent material from an opening at the anterior border of the sternocleidomastoid within the lower third of the neck. Cysts are most often diagnosed as a painless, compressible lateral neck mass in a child/young adult that may become tender and/or increase in size if they become infected (Fig. 3) [9]. Histologically, they are filled with a turbid yellow fluid containing cholesterol crystals and are lined by stratified squamous epithelium. In adult patients, the main diagnostic consideration is whether the cystic lesion represents a metastatic lymph node and subsequent imaging is directed at identifying a primary neoplastic lesion (Fig. 4). This is particularly true if there is no history of chronic neck fullness and no history of a recurrent mass following upper respiratory tract infections. In the authors’ institution, this is achieved with a combination of cross-sectional imaging [magnetic resonance imaging (MRI) being the preferred modality] and positron emission tomography-computed tomography (PET-CT) prior to pan-endoscopy and tissue biopsy. Occult papillary thyroid cancer is also a recognised cause of cystic metastases and may also seen seen in children. Fluid aspiration in association with thyroglobulin levels may aid the distinction [11].

On ultrasound (US) imaging, second branchial cleft cysts are typically well-circumscribed, thin-walled and anechoic with evidence of compressibility and posterior acoustic enhancement [12]. They may contain internal echoes compatible with internal debris. On CT imaging, they are well-circumscribed, low-density cystic masses with a thin wall [8]. If they become infected, this may become thick-walled with evidence of mural enhancement, localised inflammatory change and peri-lesional fat stranding. The mural thickening is attributed to the response of lymphoid tissue. MRI is better suited in the assessment of deep tissue involvement. On T1-weighted imaging, they may turn from low to high signal depending on the proteinaceous content of the cyst, but are typically hyperintense on T2-weighted imaging, as seen in Fig. 2 [13]. As with CT imaging, mural thickening and enhancement varies with inflammatory change and typically occurs in the setting of infection. A tissue ‘beak’ between the internal and external carotid arteries is pathognomonic of Bailey type III cysts. Surgical management involves complete surgical excision encompassing the external sinus opening with dissection of the sinus tract [14].

First branchial cleft anomalies can occur anywhere along the course of the first branchial arch tract. This extends from a cutaneous opening in the submandibular triangle, supero-lateral to the hyoid bone, ascending to the region of the parotid salivary gland to terminate at the cartilaginous/bony junction of the external auditory canal. The tract may pass above or below the facial nerve [4].

Work in 1972 subdivided first branchial cleft anomalies into two groups, Type I and Type II, based on presumed pathogenesis with limited applicability from an imaging perspective;

Type I anomalies are purely ectodermal in origin and present as cystic masses adjacent to the external auditory canal. They are duplications of the membranous external auditory canal and contain squamous epithelium but no skin adnexa or cartilage.

Type II anomalies may present as cysts, sinuses or fistulae in the region of the angle of the mandible. They are ectodermal and mesodermal in origin, hence they contain squamous epithelium, skin adnexa (hair follicles, sweat and sebaceous glands) and cartilage.

First branchial cleft anomalies are often misdiagnosed and often inadequately treated before they are surgically excised. They are more common in females and typically present as cyst/sinus/fistula between the external auditory canal and submandibular area. They may present with cervical symptoms and drainage from a pit-like depression at the angle of the mandible. If infected, the drainage may be purulent and there may be associated adenitis in the submandibular area. First branchial cleft anomalies can also present with an inflammatory mass in the parotid region or present with auricular symptoms and drainage of mucus or pus from the external auditory canal (Figs. 5 and 6) [15].

On CT imaging, first branchial cleft anomalies usually present as a cystic mass superficial/within/deep to the parotid salivary gland [16]. As with other branchial cleft anomalies, cyst wall thickness and enhancement vary with the degree of inflammation.

First branchial cleft anomalies, as with other branchial cleft anomalies, typically do not regress spontaneously and have a propensity for recurrent infections; hence, surgical excision is advised for definitive treatment [14]. This involves complete resection with preservation of normal structures and utilises a superficial parotidectomy approach with potential risk of injury to the facial nerve. The extent of the anomaly is typically underestimated and a significant cutaneous tract may be present and necessitate excision of involved skin and cartilage of the external auditory canal. Pre-operatively, a sinogram may be performed in order to delineate the extent of the tract, although this is not routinely performed in our institution (Fig. 7).

Third and fourth branchial cleft anomalies may appear similar to second branchial cleft anomalies externally with a cutaneous opening in the supraclavicular area; however, internally, they enter the pharynx through the pyriform sinus below the hyoid bone. Third and fourth branchial cleft anomalies are distinguished anatomically by their relationship to the superior laryngeal nerve with third pharyngeal cleft anomalies above and fourth pharyngeal cleft anomalies below. The internal opening helps to determine their origin and a third branchial cleft sinus arises from the rostral end of the pyriform fossa [2]. Third branchial cleft fistulae/sinus tracts typically present earlier than third branchial cleft cysts. Most third branchial cleft cysts present in the posterior cervical space, posterior to the sternocleidomastoid muscle as a painless, fluctuant mass that may enlarge and become tender if infected. An infected third branchial cleft cyst should be considered if a patient presents with an abscess in the posterior triangle of the neck.

A fourth branchial cleft fistula/sinus tract arises from the pyriform sinus apex and descends inferiorly to the mediastinum in the path of the tracheo-oesophageal groove [13, 17]. They are commonly left-sided for reasons that are yet to be established and most often present as a sinus tract coursing from the apex of the pyriform fossa to the upper aspect of the left thyroid lobe (Fig. 8). As a result, patients can present with a recurrent abscess in the low anterior neck and/or recurrent suppurative thyroiditis. It can be difficult to determine the exact tract on imaging and this can be achieved with a barium swallow test that can also be combined with a CT neck study after the barium swallow. Due to the anatomical course, complete resection with open neck surgery is difficult and new endoscopic techniques that involve treatment with cauterisation have been developed with success [14].

There are no pathognomonic clinical or imaging features of branchial arch anomalies; therefore, diagnosis is dependent upon the radiologist having a sound knowledge of the types of branchial arch malformations and their typical location. The diagnosis should be considered when persistent cysts or fistulae are present in the head and neck and correlate this with appropriate clinical history and examination. Differential diagnoses for cysts and sinus tracts in the head and neck should be considered (Table 2).