J.D. Schoen, M.D.
J.L. Edmonds, M.D.
The differential diagnosis is extensive but can generally be divided into lymphadenopathy, malignant masses and congenital lesions. A number of possibilities exist in the workup of a congenital neck mass
This article will serve to elucidate the etiology, diagnosis and treatment of one of these interesting entities—namely, the branchial anomalies. A review of embryologic structures in the head and neck is in order to begin.
After closure of the neural tube and gut, with the outer surface of the embryo invested with ectoderm, development of the external body form begins. The body is flexed in a cranio-caudal direction and the result of this flexing and bending is the movement of the prochordal plate to a level beneath the developing brain. In this new position, the prochordal plate (now referred to as the buccopharyngeal membrane) is covered with ectoderm and lined with endoderm and is contiguous with the developing foregut and gut. A depression in the bucco-pharyngeal membrane, called the stomodeum, is the developing mouth. This level of development corresponds to the 4-week embryo. Other developing structures include the nasal placodes and the heart. (Fig. 1a, 1b)2
Externally, the branchial apparatus is marked by 4 ectodermal branchial clefts. Internally, the embryonic pharynx is marked by 5 lateral, endodermally lined, pharyngeal pouches. The first four pouches correspond to the external clefts. Between each pouch and cleft is a mesodermal branchial arch. (Fig. 2)3 These typically contain a skeletal element, a vascular element, and the primordia of nerves and muscles. Of the 4 clefts and 5 pouches identifiable in the 5th week of development, only the first cleft and first pouch are not normally obliterated by the 8th week. A number of adult structures are derived from the embryonic branchial clefts, pouches and arches.
Before considering specific branchial anomalies, a simple review of nomenclature is in order. A cyst is a mucosal or epidermal lined structure without any external opening. A sinus usually refers to a tract, with or without a cyst, that communicates to either the skin or the gut. Some texts further delineate sinuses as either external or internal. An external sinus is a blindly ending space extending inward from an opening in the skin, thought to represent a nonobliterated branchial cleft. An internal sinus is a blindly ending space extending outward from an opening in the pharynx, thought to represent a nonobliterated branchial pouch. A fistula is a patent duct-like structure having both an external (cutaneous) and internal (pharyngeal) orifice. The pharyngeal orifice is often tiny and difficult to identify. Clinically, almost all of these fistulas are lateral cervical fistulas, originating from the second pouch and cleft. Of these anomalies, the cyst is more common than the sinus or fistula, typically located in the anterior triangle of the neck.
First Arch, Cleft and Pouch
The first (or mandibular) arch divides into two parts, the maxillary process and mandibular process. The cartilage of the maxillary process disappears while the mandibular process persists as Meckels Cartilage. The mesoderm of the first arch gives rise to: the muscles of mastication, the anterior belly of the digastric and the tensor tympani; the mandibular process, malleus, incus and sphenomandibular ligament; dentine and cementum; the tragus and crus of the helix; and the first aortic arch derivative, the facial or external maxillary artery.
Maldevelopment of the first branchial arch derivatives result in various congenital malformations of the eyes, ears, palate, and mandible, which constitutes the first arch syndrome. This constellation of symptoms is a result of insufficient migration of cranial neural crest cells into the first branchial arch during the fourth developmental week. The two main manifestations of the first arch syndrome are recognized as Treacher Collins Syndrome and Pierre Robin Syndrome. Other anomalies consistent with these derivatives include: agnathia, micrognathia and macrognathia associated with abnormal development of the mandibular process; anotia, microtia, macrotia and synotia related to faulty development of the ear; accessory tragus; malformed/absent malleus or incus; anodontia, polydontia and supernumary teeth; and astomia, microstomia and macrostomia associated with abnormal development of the stomodeum.
The ectoderm of the first branchial cleft develops into: the epidermis of the cheeks, mandible and rostral half of auricle; cranial nerve V; salivary gland parenchyma of the parotid, submaxillary and sublingual glands; enamel of the teeth; the epithelial lining of the lips and tongue to the foramen cecum; and the epidermis of the external auditory canal and tympanic membrane (T.M.).
The most common abnormality related to the first branchial cleft is associated with the external auditory canal (EAC). These can generally be classified as aplasia, atresia, stenosis, and duplication. The common diagnosis of recurrent purulent draining otitis media with lymphadenopathy should alert the clinician to investigate a possible first branchial cleft duplication anomaly, classified by Work as Type I or Type II anomalies.4 Tracts arising from (Type I) or paralleling (Type II) the external auditory canal can lead to a cystic cavity, which will become recurrently infected and often drain in or near the ear. These tracts are often intimately associated with the facial nerve.5 Other anomalies associated with faulty first cleft development include: pits of the lower lip; clefts of the middle chin and ear lobe; preauricular sinuses and tags; cervical tags and dermoid cysts; atretic, stenosed or malformed external auditory canals; and double or congenitally perforated T.M. Sinus tracts paralleling the EAC, or arising from it, are also well recognized first branchial cleft anomalies.
Endoderm of the first branchial pouch gives rise to the covering of the first arch and pouch (which persists as the eustachian tube, tympanic cavity, mastoid antrum and cells), and the epithelial lining of the sides and floor of the mouth. Anomalous development thus produces atretic eustachian tubes (common in children with recurrent otitis media), diverticula of eustachian tubes, absence of tympanic cavity or mastoid antrum and cells, double or perforated tympanic membrane, bifid/trifid tongue and branchiogenic nasopharyngeal cysts.
Table 2 - First Branchial Arch, Cleft and Pouch Derivatives 6
Second Arch, Cleft and Pouch
The second or hyoid arch mesoderm gives rise to "Reichert’s Cartilage", the precursor to part of the body and lesser horns of the hyoid, the stapes superstructure, styloid process and stylohyoid ligament. The helix and antehelix are other connective tissue structures derived from the 2nd mesodermal arch. Muscular derivatives include the muscles of facial expression, the stapedius, stylohyoid, and posterior belly of digastric. The second arch artery, often vestigial, may persist as the stapedial or lingual arteries, which is significant when encountered during stapes surgery. Anomalies of the second arch consist of absent or malformed auricle (commonly seen) or ossicles (resulting in conductive hearing loss) and muscular asymmetry of the face.
Ectoderm of the second cleft gives rise to the epidermis of the dorsal half of the auricle and the upper neck, as well as cranial nerves VII and VIII. Second cleft cysts, sinuses and fistulas result from the anomalous failure to obliterate the second cleft by the inferior extension of the second arch (creating a putative temporary structure, the cervical sinus of His). Ectodermally derivded, epithelial lined cysts of this derivation are typically below the mandible. If infected, these may drain to the skin anterior to the sternocleidomastoid muscle, now referred to as a second branchial cleft sinus. If a complete congenital fistula exists, this is a result of faulty development of the second branchial cleft and pouch. Fistulas of the second cleft/pouch (the most common) take a cervical origin and traverse along the carotid sheath between the bifurcation, behind the posterior belly of the digastric up to the tonsillar area (entering the pharynx as a slit on the anterior aspect of the cephalic half of the posterior pillar of the faucial tonsil).7 The diagnosis of such a fistula should be suspected in a patient with recurrent tonsillitis with lymphadenopathy or neck swelling. Careful inspection of the pharyngeal tonsil may reveal a sinus opening which leads to a neck cyst or neck fistula.
Second pouch endodermal epithelium lines the root of the tongue and part of the pharynx, as well as the palatine tonsil surface and crypts, the foramen cecum and the thyroid stalk. Faulty development of these derivatives results in thyroglossal cysts, sinuses and fistulas as well as lingual thyroid. Lateral tonsillar fossa sinuses opening into the tonsillar crypts likewise develop. A complete fistula, as previously described, is a combined second cleft/pouch anomaly.
Table 3 - Second Branchial Arch, Cleft and Pouch Derivatives
Third Arch, Cleft and Pouch
Mesodermal derivatives of the third branchial arch include: muscles, comprised of the superior constrictors and stylopharyngeus; skeletal structures represented by part of the body and the greater horns of the hyoid bone; and the third aortic arch components apparently forming the common/internal carotid arteries and descending aorta. Anomalies attributed to maldevelopment in this region include hyoid bone deformities and aneurysms of the carotid artery system.
The ectoderm of the third branchial cleft gives rise to the epidermis of the middle cervical area (anterior cervical triangle), the cervical sinus, and the neural elements of the glossopharyngeal nerve. Abnormal development of these derivatives manifests as thymic stalk, accessory thymus, thymic cyst, cervical cyst, and cervical fistula. Cervical cyst remnants of this origin typically lie deep to the internal carotid in intimate association with the vagus nerve.
Third pouch endoderm forms the epithelium of the root of the tongue, hypopharynx, and part of the epiglottis. In addition, the inferior parathyroids, thymic reticulum and pyriform fossa derive from this layer. Thus, undescended/accessory parathyroid glands, thymicomegaly and/or thymic cysts, and diverticulum or sinus tract of the pyriform fossa result from aberrant development in this area. A sinus tract leading from the left piriform sinus to this cystic space is an uncommon malformation. A sinus tract from the piriform can also lead to the thyroid and may result in suppurrative thyroiditis. A complete congenital fistula, an anomaly of the third cleft and pouch, would route caudal to the glossopharyngeal nerve, over the superior laryngeal nerve, posterior to the internal carotid artery, opening through the thyrohyoid membrane into the pharynx near the pyriform sinus. 8
Recurrent neck swelling with identified or suspected neck cyst in a child, or recurrent neck swelling with thyroiditis in a child should alert the clinician to the possibility of a third branchial pouch anomaly. These sinus tracts arise in the left piriform and communicate to the thyroid or a left neck cyst. They never occur on the right, for unclear reasons. Suspicion of such a lesion can be investigated with a barium swallow or endoscopy. Ideally, both should be performed if the first investigation fails to yield a diagnosis.
Table 4 - Third Branchial Arch, Cleft and Pouch Derivatives
Fourth Arch, Cleft and Pouch
Mesodermal muscles of the fourth arch include the inferior constrictors and the laryngeal musculature while connective tissue components consist of the thyroid cartilage, cuneiforms, and part of the epiglottis. Arterial derivatives include the left aortic arch and the right subclavian. Acknowledged anomalies of this arch include asymmetric or stenotic larynx, laryngoptosis, chondromalacia, and double arch aorta.
Fourth cleft ectoderm apparently gives rise only to the neural elements of the vagus nerve, the abnormal development of which manifests as a cyst, often producing a cough if in close proximity to the nerve.
Fourth pouch endodermal development is responsible for formation of the superior parathyroid glands, the ultimobranchial body (which ultimately becomes the parafollicular C-cells of the thyroid), and a portion of the pyriform sinus. Failure of development of the third and fourth branchial pouches and their derivatives results in DiGeorge’s Syndrome. This syndrome is characterized by absence of the thymus and parathyroid glands resulting in neonatal tetany and impaired cellular immunity. A complete fistula of the 4th pouch has not yet been described in humans; cysts, however, of the hypopharynx, larynx and thyroid are not uncommon. In addition, laryngocele, posterior mediastinal thyroid and internal sinuses of the 4th branchial pouch have been reported. Some texts describe the piriform sinus malformations as fourth branchial pouch anomalies, but it seems likely that these more correctly are categorized as third branchial anomalies.9
Table 5 - Fourth Branchial Arch, Cleft and Pouch Derivatives
Principles of Treatment
In approaching anomalies heretofore described, one should avoid techniques such as incision and drainage, sclerosis, and radiation therapy. Definitive management entails complete surgical excision, often involving removal of a small amount of normal tissue analagous to the Sistrunk maneuver in the management of thyroglossal duct cyst. Sinus and fistulous tracts should be preoperatively delineated with radiopaque dyes or endoscopy, or other more practical when possible. In the face of acute infection, the patient should be stabilized and the infectious process treated prior to any invasive procedure.10
Complete surgical excision is curative.