Continuing Education Activity

Branchial cleft cysts, also known as branchial cleft anomalies, are congenital anomalies arising from the first through fourth pharyngeal pouches. These anomalies can exist as true fistulae, as cysts, or as sinus tracts, depending on the degree of incomplete obliteration during embryogenesis. This activity describes the pathophysiology, evaluation, and management of branchial cleft anomalies.

Objectives:

• Describe the epidemiology and pathophysiology of patients with branchial cleft cysts.
• Outline the clinical presentations and evaluation of patients with branchial cleft cysts.
• List the treatment options available for patients with branchial cleft cysts.
• Explain interprofessional team strategies for enhancing care coordination to facilitate the evaluation and management of patients with branchial cleft cysts.

Introduction

Branchial cleft cysts are congenital anomalies arising from the first through fourth pharyngeal clefts. The most common type of branchial cleft cyst arises from the second cleft, with anomalies derived from the first, third, and fourth clefts being rarer. As this is a congenital anomaly it is present at birth, though may not be obvious or symptomatic until later. The majority of lesions present in childhood as a visible punctum on the skin, though may present as cysts or neck masses, occasionally being mistaken for neck abscesses. Branchial cleft anomalies present in one of three forms: cysts, sinuses or fistulae. Cysts have an epithelial lining without external openings, and as such may be asymptomatic and only noticed incidentally. Such cysts may not present until adulthood. Sinus tracts may communicate either externally with skin as a visible punctum, or internally with the pharynx or larynx, where the punctate opening will be visible only on endoscopy. Branchial cleft fistulae are true communications connecting the pharynx or larynx with the external skin.[1][2][3][4][5]

Etiology

Branchial cleft anomalies form due to the incomplete involution of branchial cleft structures. Around the fourth week of gestation, neural crest cells migrate into the future head and neck region where the 6 pairs of branchial (pharyngeal) arches begin to develop. The mesoderm is covered externally by ectoderm and internally lined by endoderm. Normally there are 5 branchial arches, with the arches are separated by depressions known as clefts on the ectodermal surface and corresponding pouches on the endodermal surface, yielding four pharyngeal clefts. The second arch develops caudally and then covers the third and forth arches. These buried clefts become ectoderm-lined cavities that normally involute completely by 7 weeks of gestation. If the clefts do not involute, or incompletely involute, these pathological remnants will form cysts, sinuses, or fistulae in predictable locations according to their branchial cleft of origin.[6][7][8][9]

• First Branchial Cleft Cyst
  • First cleft cysts makeup approximately 5-25% of all branchial cleft anomalies and are subclassified via the Work classification system. Work type I contain ectoderm only and on physical exam show preauricular masses or sinuses that track anterior and medial to the external auditory canal. These typically present lateral to the facial nerve and end within the external auditory canal, or connect to the umbo of the middle ear, essentially as a duplication of the external auditory canal. Work type II cysts are more common, and contain both ectoderm and mesoderm. These classically present at the angle of the mandible or within the submandibular region. They can be course either lateral or medial to the facial nerve and pass superficial (57%), deep (30%), or between (13%) branches of the facial nerve. [10]
• Second Branchial Cleft Cyst
  • This is the most common branchial cleft cyst, representing approximately 40-95% of branchial anomalies.  The external punctum is found anterior and medial to the sternocleidomastoid (SCM) on the neck skin. Bilateral second branchial cleft cysts can be associated with branchio-oto-renal syndrome. The course of a second branchial cleft sinus is as follows: the external opening is located on the neck skin as described above, with the fistula traveling deep to platysma then passing in between the internal and external carotids, coursing superficial to both glossopharyngeal and hypoglossal nerves before connecting to the tonsillar fossa. Cysts or sinuses of the second branchial cleft can exist anywhere along this course. [11][12]
• Third Branchial Cleft Cyst
  • Third branchial cleft cysts are estimated to represent 2-8% of all branchial cleft anomalies. When present, the external skin opening is seen over the middle to lower third of the anterior SCM. The coursde of the third branchial cleft sinus is as follows: from the skin opening described above the tract courses deep to platysma and course posterior to the internal carotid artery. It will pass between the glossopharyngeal and hypoglossal nerves, and maybe intimately associated with superior laryngeal nerve (classically coursing superior to it). It then connects to the pyriform sinus in the larynx.[13]
• Fourth Branchial Cleft Cyst
  • Fourth cleft cysts are extremely rare, representing approximately 1% of all branchial cleft anomalies. They are reported more commonly on the left, with the skin opening near the medial lower border of the SCM. The exact course of the fourth branchial cleft remnant is not as well characterized owing to its rarity, however, it classically passes deep to the common carotid and can loop around either the aortic arch (in a left-sided anomaly) or the subclavian (in a right-sided anomaly). These run superficial to the recurrent laryngeal nerve and hypoglossal nerve terminating in the apex of the pyriform sinus in the larynx.[13]

Epidemiology

The true incidence of branchial cleft anomalies in the United States is unknown despite their relative frequency. This is likely due to the variety of both the anomalies and their presentations complicating accurate reporting. There is no ethnic or gender predilection. Most branchial cleft anomalies arise from the second pouch, while the first, third, and fourth pouches are rare, and 10% of branchial cleft anomalies are bilateral. These typically present in the first decade of life, but if no external communication is present presentation may be delayed into adulthood. [5]

Pathophysiology

Branchial cleft cysts are embryologic anomalies, and are defined by the internal opening of the branchial sinuses arising from incomplete obliteration in embryogenesis. They may present as fistulae, cysts, sinus tracts, or cartilaginous remnants and clinically encountered on the anterior neck and upper chest. Lesions presenting below the clavicles are more likely epidermoid or dermoid cysts rather than branchial remnants. Branchio-oto-renal (BOR) and branchio-oculo-facial (BOF) syndromes should be suspected when a patient presents with preauricular pits or multiple branchial cleft anomalies, including bilateral anomalies. These syndromes are autosomal dominant conditions associated with hearing loss, ear malformations, and renal anomalies in the BOR syndrome, while BOF includes eye anomalies, such as microphthalmia and obstructed lacrimal ducts, and facial anomalies, such as cleft lip and palate.[5]

Histopathology

Branchial cleft cysts are lined with stratified squamous epithelium and may contain keratinous debris inside the cyst. In some cases, the cyst wall is lined by ciliated columnar epithelium resulting in more mucoid contents. Lymphoid tissue is typically present surrounding the epithelial lining. If the cyst is infected or ruptured, inflammatory cells can be identified in the cavity or stroma.[5]

History and Physical

Branchial cleft cysts are often asymptomatic, but can often become tender, enlarged, or inflamed with superinfection or abscess formation during episodes of upper respiratory tract infections. The patient can present with purulent drainage of the sinus to skin or pharynx in such situations. The most concerning symptoms include dysphagia, dyspnea, and stridor due to cyst compression of the upper airway.[14] Cystic lesions are more common than fistulae, but they usually present later, usually in the second decade of life. Cysts most often present as non-tender soft-tissue masses beneath the sternocleidomastoid muscle. However, they may present with acute infection. Change in size during upper respiratory infections is noted in up to 25%. 

The physical examination will differ depending on the location of the branchial cleft cyst.

• A first branchial cleft cyst is typically smooth, non-tender, fluctuant mass found between the external auditory canal and submandibular area and frequently will have a cutaneous punctum from which fluid may be expressed. It is variably involved with the parotid gland and facial nerve, and there may be a connection to the middle or external ear so an otologic exam is crucial in these patients.[15]

• A second branchial cleft cyst is typically identified by a pit or punctum of the skin at the lower anterior border of the sternocleidomastoid and may connect to the tonsillar fossa of the pharynx. It can be in proximity to the glossopharyngeal and hypoglossal nerve as well as carotid vessels. The cysts are tender if secondarily infected, and in severe cases may lead to airway compromise. If it is associated with a sinus tract, mucoid or purulent discharge may be present on the skin or into the pharynx.[16][17]

• Third and fourth branchial cleft cysts are rare. They are normally on the left side of the neck or the suprasternal notch/clavicular area. Typically they present as a firm mass or infected cyst draining to the piriformis sinus or external neck skin. These fistulae are more likely to present when infected and they may have undergone repeated incision and drainage procedures owing to incorrect diagnosis and subsequent recurrence.[18]

Evaluation

There is no specific laboratory test needed for evaluation. [17][19][20]

Imaging Studies

• If a sinus tract present, a sinogram can be obtained by injecting radiopaque dye to delineate the course and determine the size of the cyst.
• Ultrasonography can be obtained to determine the cystic characteristics of the cyst.[1][19]
• Contrast-enhanced CT will depict a cystic and enhanced mass in the neck.[20]
• MRI can be used for a finer resolution.[21]

Fine-needle aspiration is helpful to distinguish a branchial cleft cyst from malignant neoplasm.[16]

Treatment / Management

The treatment of a branchial cleft cyst is elective excision due to the risk of infection, further enlargement, or an extremely low risk of malignancy. So long as there is no airway compromise or frank abscess, there is typically no urgency; clinicians can defer excision beyond 3 to 6 months of age or allow treatment of an acute infection.[5] However, in the event of airway compromise or large abscess emergent surgery may be required [22][23]. Systemic antibiotics and aspiration are generally preferable to incision and drainage which might produce more distortion of the surgical planes.[24]

The incision is planned to optimize cosmesis, placing it within a natural skin crease whenever possible. If a fistula or sinus is present then identifying the tract by gentle insertion of a probe or catheter is important in order to ensure complete excision and decrease chance of recurrence. Methylene blue can be used by dipping a lacrimal probe in the solution and inserting it into the tract to make it easier to identify intraoperatively. Dissection should be performed carefully over the surface of the lesion as the tract can be thin-walled. If the track is long, then exposure should be obtained by using a second "stepladder" incision placed within a skin crease cephalad to the primary incision. In first branchial cleft cysts, initial exposure of the main trunk of the facial nerve and branches should be performed with a superficial parotidectomy approach to reduce the risk of facial nerve injury, as the anomaly can be intimately associated with the nerve. Preoperative fistulograms can also be useful.[9][25] In the event that a patient cannot undergo surgery, ethanol ablation has been used as an alternative in this patient population, though is not usually recommended as a primary treatment.[9][26]

Third and fourth branchial cleft cysts are treated with a standard transverse cervical incision to identify the recurrent laryngeal nerves, occasionally requiring thyroid lobectomy to completely excise the tract to the piriform sinus. Before the trans-cervical portion of the surgery is begun, direct laryngoscopy is performed to confirm diagnosis, and to allow endoscopic cannulation of the opening into the piriform sinus to facilitate dissection during excision.[5][27]

Differential Diagnosis

Differentials include:[1]

• Lymphadenopathy
• Hemangioma
• Carotid Body Tumor
• Cystic Hygroma
• Ectopic Thyroid/Salivary Tissue
• Vascular Neoplasm/Malformation
• Thyroglossal Duct Cysts
• Cat Scratch Disease
• Atypical Mycobacterial Infections
• Cystic Squamous Cell Carcinoma

Prognosis

Patients and families should be educated that branchial cleft cysts are typically benign, and with treatment, patients generally recover without complications or recurrence. 

Complications

Once branchial cleft cysts are excised, recurrence is relatively uncommon. There is an estimated risk of 3%. However, if previous surgery or recurrent infection has occurred, recurrence can be as high as 20%.[5]

Consultations

An otolaryngologist or pediatric otolaryngologist should be consulted in these cases depending on the age of the patient.

Deterrence and Patient Education

Branchial cleft anomalies are congenital malformations and currently, there are no preventative measures to reduce the likelihood of presentation. Patients and physicians should be educated on the symptomatology and physical exam findings that could lead to the early diagnosis of these lesions. This could reduce the cost of care for the patient, which would otherwise consist of future physician visits, multiple courses of antibiotics, and diagnostic imaging. 

Enhancing Healthcare Team Outcomes

The management of patients with branchial cleft cysts is interprofessional. The surgery is usually performed by an otolaryngologist or, rarely, by a pediatric surgeon. However, the follow up may be required by a nurse practitioner, pediatrician, or primary care provider. Surgery is the only treatment for branchial cleft cysts. Two well-known complications are recurrence and infection. Specialty trained nurses in the fields of otolaryngology are involved in family education, patient monitoring, and patient feedback. In rare cases, injury to the facial nerves may also occur., which could require further surgery. The outcomes after branchial cleft cysts are excellent with a recurrence rate of about 3% to 7% (Level V). [24][25]