TITLE: Branchial Anomalies
SOURCE: Grand Rounds Presentation, University of Texas Medical Branch (UTMB= ),
Dept. of Otolaryngology
DATE: September 30, 2011
RESIDENT PHYSICIAN: David Gleinser, MD
FACULTY PHYSICIAN: Harold Pine, MD, MD
SERIES EDITOR: Francis B. Quinn, Jr., MD
ARCHIVIST: Melinda Stoner Quinn, M= SICS

"This material was prepared by resident physicians in partial fulfillment of educational requirements established for the Postgraduate Training Program of the UTMB Department of Otolaryngology/Head and Neck Sur= gery and was not intended for clinical use in its present form. It was prepared = for the purpose of stimulating group discussion in a conference setting. No warranties, either express or implied, are made with respect to its accurac= y, completeness, or timeliness. The material does not necessarily reflect the current or past opinions of members of the UTMB faculty and should not be used for purposes= of diagnosis or treatment without consulting appropriate literature sources and informed professional opinion."

The study of branchial ano= malies covers a wide variety of pathological conditions. Each condition is the result of abnorma= lities in embryologic development. For th= is reason, the treating clinician should be familiar with the normal developme= ntal process.

Between the 2^nd and 6^th week of gestation, the branchial apparatus undergoes development. At that time, the neck is shaped like a hollow tube with circumferential ridges (arches). Between the arches are other ridges ter= med clefts and pouches. The clefts are= on the outside (ectoderm) and the pouches are on the inside (endoderm). Each arch leads to the development of a specific cartilage, artery, muscle component, and cranial nerve, all of whi= ch are neural crest in origin. Althou= gh there are six arches, only five form structures (I-IV and VI); the 5^th= arch fails to develop in humans.

The first arch is referred to as the “mandibular arch”= as it lays the framework for the development of the mandible through Meckel’s cartilage. It also gives rise to t= he malleus head and neck as well as the incus body and short process. The muscles that are associated with th= e 1^st arch are the muscles of mastication, anterior belly of the digastric, mylohyoid, tensor tympani, and tensor veli palatini. The cranial nerve is the trigeminal ner= ve (CN V), and the arteries are the maxillary and internal carotid arteries.

The second arch is the “hyoid arch.” Its cartilage is Reichert’s cartilage w= hich gives rise to the stapes, malleus manubrium, incus long process, styloid process, and part of the hyoid bone (lesser horn and upper body). The muscles that this arch gives rise t= o are the muscles of facial expression, buccinator, platysma, stapedius, stylohyo= id, and posterior belly of the digastric. The cranial nerve is the facial nerve (CN VII), and the artery is the stapedial artery.

The third arch gives rise to the remainder of the hyoi= d bone (greater horn and lower body), stylopharyngeus, glossopharyngeal nerve (CN = IX), and the common carotid artery. The fourth arch gives rise to the thyroid, epiglottic, and cuneiform cartilages= as well as the cricothyroid and inferior constrictor muscles. In addition, the fourth arch leads to t= he development of the superior laryngeal nerve and the subclavian artery and aortic arch. The sixth arch gives = rise to the cricoid, arytenoid, and corniculate cartilages. The muscles are all the intrinsic muscl= es of the larynx except the cricothyroid. The nerve associated with the sixth arch is the recurrent laryngeal nerve while= the artery is the pulmonary artery.

The branchial pouches also= give rise to various structures with the clefts usually providing the covering f= or those structures. There are four c= lefts and four pouches in human development. The first pouch gives rise to the eustachian tube, middle ear, masto= id, and the inner layer of the tympanic membrane. The second pouch gives rise to the tonsils, root of the tongue, fora= men cecum, and part of the pharynx. The third pouch is divided into two wings; ventral and dorsal. The ventral wing gives rise to the thym= us while the dorsal wing gives rise to the inferior parathyroid glands. The fourth pouch gives rise to the supe= rior parathyroid glands and the parafollicular C-cells of the thyroid gland.

One can see that when abnormalities in the development= of the branchial apparatus occur, numerous pathologic conditions can arise. When the first branchial arch is involv= ed in abnormal development, the resulting abnormalities are termed “First Arch Syndrome.” These abnormalities in= volve the eyes, ears, palate, and mandible. Two main syndromes associated with “First Arch Syndrome” are Treacher Collins and Pierre Robin.

Treacher Collins Syndrome,= also termed mandibulofacial dysostosis, is a syndrome typically inherited in an autosomal dominant fashion. Featur= es include midface and mandibular hypoplasia, cleft palate, and multiple ear a= nd eye anomalies. The ear anomalies c= an include microtia, anotia, stenotic or atretic external auditory canals, and= a malformed malleus and incus. The e= ye anomalies include coloboma of the lower eyelids and down-slopping palpebral fissures. Pierre Robin syndrome is characterized by three main features; a u-shaped cleft palate, micrognathia= , and glossptosis (posterior displacement or retraction of the tongue).

When abnormalities occur in the development of the sec= ond branchial arch, a malformed auricle (microtia) and ossicles (stapes, malleus, and inc= us) may be the result. In addition, hy= oid malformation and muscular asymmetry of the face may also be seen. Third arch anomalies typically involve = hyoid malformations and carotid artery aneurysms. Fourth branchial arch anomalies mainly involve the larynx and include laryngeal stenosis, laryngoptosis (low position of the larynx), chondromala= cia, double aortic arch, and pulmonary artery sling.

Abnormalities involving the first branchial pouch incl= ude atresia and diverticuli of the eustachian tube, both of which can lead to recurrent bouts of otitis media. In addition= , one may see a bifid tongue, perforated tympanic membrane and branchiogenic nasopharyngeal cysts. The mastoid antrum and tympanic cavities may also be absent.

When there are errors in the development of the second branchial pouch, a thyroglossal duct cyst may occur. Thyroglossal duct cysts result from the failed involution of the thyroglossal duct and thus a cyst may be seen anyw= here from the base of the tongue to the upper mediastinum. They occur in roughly 7% of the populat= ion, and are best noted as midline neck masses that are closely associated with = the hyoid bone. They will typically mo= ve with tongue protrusion and swallowing. The treatment of a thyroglossal duct cyst is surgical resection thro= ugh a Sistrunk procedure.

Another anomaly that may be noted with errors in the development of the second branchial pouch is a lingual thyroid. This anomaly results from the failed de= cent of the thyroid gland during development. In 90% of cases, the atopic thyroid remains at the base of the tongue. In most cases, the lingual thyroid is not noted until early adulthood given the fact that most are asymptomatic. In other cases, the lingual thyroid may cause dysphagia or even airway compromise. The lingual thyroid usually appears as= a reddish mass at the base of the tongue due to the fact that it is very vascular. In 2/3^rd of c= ases, this is the only functional thyroid tissue, thus thyroid function studies should be performed in order to determine if there is other functioning thy= roid tissue prior to treatment. If the = patient is asymptomatic, close observation may be all that is required. If symptoms are present, treatment opti= ons include surgical resection or radioablative therapy. In 70% of cases, the patient will be hypothyroid and thus will require lifelong thyroid replacement therapy.

DiGeorge Syndrome is the m= ost notable syndrome involved with developmental anomalies of the third and fou= rth branchial pouches. This syndrome involves a partial deletion of chromosome 22, and is most notable for the congenital absence of the thymus and parathyroid glands. This leads to hypocalcemia and tetany a= s well as impaired cellular immunity. Oth= er features of this syndrome as well as the chromosome involved can be remembe= red by the acronym CATCH-22: Cardi= ac anomalies, Abnormal facies, Thymic aplasia, Cleft palate, and Hypocalcemia. Other anomalies associated with the thi= rd and fourth branchial pouches include accessory parathyroid glands and thymic cy= sts.

When errors occur in branchial cleft development, the = most notable outcome is a branchial cleft cyst. However, other anomalies may result as well. For instance, when errors occur with the development of the first branchial cleft, external auditory canal stenosis = or atresia as well as preauricular skin tags and pits may result. When the second branchial cleft is invo= lved, cervical sinuses may result. Error= s in the development of third branchial cleft could yield a thymic cyst.

As stated previously, the most notable anomaly involve= d with improper development of the brachial cleft is the branchial cleft cyst. There are four recognized types, and mo= st are unilateral in presentation. Howeve= r, 2-3% of cases may present with bilateral cysts.

The first branchial cleft cyst can be broken down into= two types by the Work classification. = A type I cyst is of ectoderm origin and usually involves the preauricular area. The sinus tract associated with this ty= pe of cyst starts in the preauricular area, parallels the external auditory canal while typically staying lateral to the facial nerve, and ends either in the external auditory canal or the middle ear. A type II cyst is more common than the type I cyst, and is made up of ectoderm and mesoderm. This cyst w= ill typically appear around the angle of the mandible or in the submandibular r= egion. The tract its sinus takes is from the a= ngle of the mandible or submandibular region into the substance of the parotid g= land going medial or lateral to the facial nerve, and ending in the conchal bowl= or at the bony-cartilaginous junction of the external auditory canal.

A second branchial cleft cyst is the most common type = of branchial cleft cyst, representing roughly 95% of all cases. This cyst typically appears as a mass j= ust anterior and medial to the Sternocleidomastoid muscle in the neck. The tract that the sinus takes goes fro= m this region of the neck, along the carotid sheath and between the external and internal carotid arteries. It then passes superficial to the 9^th and 12^th cranial nerves before piercing the tonsillar fossa.

The third branchial cleft cyst is rarer than a first o= r second branchial cleft cyst, and typically only occurs on the left side of the neck. These cysts appear in a simi= lar location as the second branchial cleft cyst, but their sinus tract differs. Instead of passing throug= h the internal and external carotid arteries, the sinus tract will go behind the two. It will also run deep to the = 9^th nerve while staying superficial to the hypoglossal, superior and recurrent laryngeal nerves. It will then ope= n into the apex of the pyriform sinus.

The fourth branchial cleft cyst is the rarest of all, = with roughly 200 cases reported in the literature.   This cyst is usually lower in the neck than the second and third cys= t, with its tract taking a much different course than the other cysts. The sinus tract will go deep to the com= mon carotid before looping around the aorta on the left or subclavian on the right. At this point, the tract wi= ll go deep to the superior laryngeal nerve while staying superficial to the recur= rent laryngeal nerve. At this point, it pierces the thyrohyoid membrane and enters the pyriform sinus at is apex. Of note, both third and fourth branchial cleft cysts may be closely associated with the thyroid gland. For this reason, if a patient is suffer= ing from recurrent thyroid infections/abscesses, a third or fourth branchial cl= eft anomaly must be considered.

When working up a branchial cleft cyst, one must of co= urse start with a detailed history and physical examination.   Following this, imaging studies are us= ually obtained. There are multiple modal= ities, but typically a CT scan is ordered. On CT, a branchial cleft cyst appears as a homogeneous mass with a central are= a of low attenuation and a smooth enhancing rim. Although CT does provide for a good radiographic evaluation of the c= yst, it does have some drawbacks. It is= more expensive than an ultrasound, and results in more radiation exposure. In addition, children may require sedat= ion in order to obtain the exam. On ultrasonography, branchial cleft cysts will appear as a lesion with an area= of low echogenicity and lack of internal septations. This is the easiest and most cost effec= tive imagining modality. However, it is= not as helpful with surgical planning and thus is typically not ordered alone.<= span style=3D'mso-spacerun:yes'>   MRI is another option available for im= aging, although is not commonly obtained due to its high cost and need for sedatio= n in children. On MRI, a branchial clef= t cyst will appear hypointense on T1 and hyperintense on T2. Other imagining modalities include fluo= roscopic fistulography and barium esophagoscopy. Both of these can help with delineating the path of the sinus tract, which will aid in surgical planning.

Treatment of the branchial cleft cyst is dependent on whether an infection is present or not. If the cyst is infected, antibiotics should be given for 2-4 weeks i= n an attempt at clearing the infection prior to surgical resection of the cyst.<= span style=3D'mso-spacerun:yes'> If an abscess has formed, it will usual= ly require drainage. If possible, the= least invasive procedure should be attempted to drain these abscesses because the= more dissection that is performed, the harder it will be to completely remove the cyst at a future operation secondary to scar formation. For this reason, needle aspiration shou= ld be considered first. If the abscess persists, then an incision and drainage should be performed.

The definitive treatment of a branchial cleft cyst is complete surgical excision of the tract and cyst. For first branchial cleft cysts, the fa= cial nerve must be identified as the tracts are usually closely associated with = the nerve.   It has been recommended by= some surgeons to wait until the patient is two years of age to allow for a more favorable anatomic location of the facial nerve. However, this is controversial as this = could lead to more infections and more scaring, making it more difficult to remove the cyst and tract in the future.

When a third or fourth branchial cleft cyst is suspect= ed, one should start by examining the pyriform sinus with a direct laryngoscopy, looking for a sinus opening. If th= ere is one, a Fogarty vascular catheter could potentially be threaded through the sinus and into the tract, greatly aiding in the identification of the tract when the neck is entered. For both= of these cysts, the surgeon should also identify the recurrent laryngeal nerve= in order to avoid injuring it during dissection because both of these cysts’ tracts are usually closely associated with it.

Another treat= ment option available for fourth branchial cleft cysts comes in the form of endoscopic cauterization of the sinus opening through the pyriform sinus du= ring a direct laryngoscopy. This has be= en described in multiple studies and case reports with good results. For instance, Verret et al performed endoscopic cauterization on 10 patients without surgical excision of the cy= st and tract. Seven patients showed no recurrence of the disease after 3 years of follow-up. The other three patients in their study= were lost to follow-up.

Branchial anomalies are nu= merous and can involve multiple areas of the head and neck. An understanding of the embryology and pathology associated with these anomalies will greatly aid the clinician in= the treatment of these patients.

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SOURCES

Branste= tter BF, Davis LM, Coombs BD, et al. Branchial Cleft= Cysts Imaging. eMedicine by WebMD. 2011 May. Available from: http://emedi= cine.medscape.com/article/382803-overview.

Schoen JD and Edmonds JL. Branchial Anomalies. Children’s ENT of Houston. 2011 = Sept. Available from: http://www.childrensenthouston.com/branchial-anomalies.

Rodriguez-Vazquez JF, Merida= -Velasco JR, Verdugo-Lopez S, et al. Morphogenesis of the second pharyngeal arch cartilage (Reichert’s cartilage) in human embryos. J Anat. 2006 February; 208(2): 179–189.

Marino TA. Development and Fate of the Primitive Pharynx, Branchial Arches, and the Tongue. Temple University. 2011 Sept. Available from: htt= p://isc.temple.edu/marino/embryology/parch98/parch_text.htm.

Verret<= /span> DJ, McClay J, Murray A, et al. Endoscopy Cauterization of Fourth Branchial Cleft Sinus Tracts. Arch Otolaryngol Head Neck Surg. 2004 April; 130: 465-468.

Bawle EV, Jyonouchi H, Park CL, et al. DiGeorge Sy= ndrome. eMedicine by WebMD. 2010 Aug. Available from: http://emedi= cine.medscape.com/article/886526-overview.

Propst<= /span> EJ, Willging JP, and Alessandro de Alarcon. Branchial Arch An= omaly. Otolaryngology Cases. New York: Thieme, 2010.
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