Where Do These Neck Masses, Fistulae and Sinuses Come From? Yoav Parag M.D., Kalliopi A Petropoulou M.D., Charles R Fitz M.D. Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA

Introduction The Clefts The Pouches

The pharyngeal pouches give rise to important structures in the adult. During the 3rd week of gestation the human embryo has The first pharyngeal (branchial) cleft and pouch participate in formation of the ear. Tongue The cleft elongates in a medial direction and the pouch invaginates laterally. These The first pouch forms the tubotympanic recess, eventually forming the adult middle 1 ear structures and the Eustachian tube. formed the 3 cell lineages (ectoderm, mesoderm and structures eventually come to lie in close apposition. The first pharyngeal cleft will The second pouch gives rise to the palatine tonsils. become the external auditory canal and the interface with the pouch will become endoderm) that will form all adult tissues and organs. The 2 The third pouch splits into a ventral portion that will become the thymus and a dorsal the tympanic membrane. portion that develops into the inferior parathyroid glands. The fourth pharyngeal pouch gives rise to the superior parathyroids. embryo at this stage can be likened to a hollow tube with Rarely a duplication of the first pharyngeal cleft occurs, resulting in formation of the The fifth pouch contains cells that differentiate into the calcitonin producing thyroid C a central cavity that represents the primitive gut. The first branchial cleft cyst. These cysts are typically located inferior or ventral to the cells. Structures of the third pouch: external acoustic meatus and may become apparent as periauricular swelling. Thyroid external surface of the embryonic tube is composed of Thymus By the fifth week of gestation the third pharyngeal pouch splits into a hollow ventral They may also drain externally through a fistulous tract, usually connecting to the portion that will give rise to the thymic primordia and a solid dorsal portion that will Figure 9: Coronal section through give rise to the inferior parathyroid glands. ectoderm, the internal surface is composed of endoderm external auditory canal. the developing neck showing the migration pathways of the thyroid from the foramen cecum, the The thymic primordia elongate inferomedially as thyopharygeal tubes. They detach and there is an intermediary layer of mesodermal cells. thymic primordia into the superior from the pouches and migrate to their resting position in the superior mediastinum. mediastinum and the superior and These tubes eventually involute. However, if they do not, thymic rests and cysts will inferior parathyroid glands. Notice be seen along the path of migration of the thymic primordia. (Fig 10a, b, c ) the formation of the palatine tonsils from the second pouch and the migration of thyroid C cells The inferior parathyroids detach from the pouches and migrate caudally to the Starting on day 22, six pairs of pharyngeal arches form on from the fifth pouch and into the inferior aspect of the thyroid gland. Any abnormal path of migration will result in center of the thyroid gland parathyroid ectopia.

either side of the foregut in the region of the future neck. Fig 4a,b,c,d: 14 mo old female presented with right neck mass. CHCT shows a cystic mass anterior to the sternocleidomastoid muscle anterolateral to the carotid space and posterior to the submandibular gland. The tongue begins to form by the 4th embryonic week from several mesodermal These arches are defined externally by ectodermal While this is atypical appearance of a becond branchial cleft byst (a,b), a eminences, arising from the medial aspect of the first pharyngeal arch. At the track was traced from the inferior aspect of the cyst to the lower neck skin Figure 6: Schematic representation of the adult neck showing intersection of these protuberances, there is a pit called the foramen cecum Fig 2a, b : CHCT of the neck reveals a multicystic structure in the left Fig 2c,d: Reformatted coronal images show extension of the cyst to the where a pit was present (arrows) the typical location of branchial cleft cysts and the typical where the thyroid primordium develops. infoldings known as the pharyngeal clefts and internally by parotid space (arrows) inferior wall of the left EAC as well as inferior extension to the skin draining locations of a cervical sinus. (arrows). The findings are consistent with first branchial apparatus fistula, During development the thyroid primordium descends caudally through the soft confirmed at surgery invaginations known as the pharyngeal pouches. After tissues of the neck forming a slender thyroglossal duct that eventually detaches from the foramen cecum and involutes. The thyroid continues to descent until it further differentiation 5 arches continue to develop with 5 comes to lie just inferior to the cricoid cartilage (Fig 11). The other pharyngeal clefts do not form adult structures. During the fourth and fifth Internal opening Occasionally a portion of the thyroglossal duct persists forming a thyroglossal complimentary pairs of clefts and pouches. weeks of life the second pharyngeal arch rapidly expands caudally and covers the duct cyst or a thyroglossal sinus if it communicates with the external surface of other arches and clefts, effectively enclosing the remaining clefts in a transient, the neck. Pharyngeal ( branchia)l arches ectoderm-lined cavity called the lateral cervical sinus. In normal development this Fig 11. 4 year old male 1 presented with paramedian left cavity disappears, however, if it persists it will become a lateral cervical cyst. If only neck mass. CECT shows a cystic 2 Fig 10 a,b,,c,. 9 year old male with a newly found right neck mass. Sagittal and axial FSET2W mass imbedded within the left one of the clefts persists as opposed to the whole sinus, it will be referred to as a sequences reveal cystic masses in both carotid spaces bilaterally (Fig 8a, b arrows). The right strap muscle consistent with mass extends down to the anterior superior mediastinum (Fig 8c arrow). The association with thyroglossal duct cyst branchial cleft cyst. the carotid space is suggestive of thymopharyngeal duct cysts, which was confirmed at surgery 3

4 Pharyngeal ( branchia)l arches Carotid bifurcation

Figure 7: Schematic illustration of the adult neck in coronal 1 section, demonstrating a fistulous connection between the 1rst Pharyngeal pouch Fig 5a,b,c,d. 4m0 old male; CHCT demonstrates Second Branchial Cleft palatine tonsil and the external skin surface through a remnant Cyst only on the left but bilateral pits in the lower neck (arrows) cervical sinus cyst.

Fig 10b 1a 1b Branchial Arches 2 Fig 10a Fig 10c

Figure 1: Schematic drawing of the embryonic tube at around 4 weeks of gestation (a). The pharyngeal arches are marked by the external 3 clefts and internal pouches. A coronal section through the embryonic tube (b) shows the mesenchymal core of each arch. Note the central prominence at the site of the future tongue primordium. Take Home Points 4 Clinical presentation may be pits or palpable masses.

The Arches Figure 3 a and b: Coronal section through the embryonic tube at 6 weeks (a) and 7 weeks (b) of gestation. Notice the overgrowth of If a mass lesion is found the images should be scrutinized the second pharyngeal arch that covers arches 3 to 5 and the intervening clefts (Fig 2a thick arrow) . Figure 2b (arrow) shows formation of the cervical sinus, a structure that will be obliterated in normal development for less conspicuous sinuses or fistulae Each arch contains a core of mesenchymal tissue that will give rise to the future muscles, bones and cartilages of the face and neck. Each Persistent cervical cysts are located just ventral to the sternocleidomastoid muscle. A completely enclosed cyst may expand to form a palpable lump as its ectodermal References arch is supplied by a solitary artery and innervated by a solitary lining desquamates, or becomes infected. Occasionally the cyst communicates Benson MT, Dalen K, Mancuso AA. Congenital anomalies of the branchial apparatus: embryology and pathologic anatomy. Radiographics. Sep 1992;12(5):943-60 nerve. These neurovascular associations continue throughout the externally through the skin or internally to the pharynx, usually to the embryonic Brown RL, Azizkhan RG. Pediatric head and neck lesions. Pediatr Clin North Am. Aug 1998;45(4):889-905 derivative of the second pharyngeal pouch, the palatine tonsils. Rarely lateral Koch BL. Cystic malformations of the neck in children. Pediatr Radiol. May 2005;35(5):463-77 development of the head and neck Mukherji SK, Fatterpekar G, Castillo M. Imaging of congenital anomalies of the branchial apparatus. Neuroimaging Clin N Am. Feb 2000;10(1):75-93 cervical cysts communicate both internally and externally. These types of fistulae Chandler JR, Mitchell B. Branchial cleft cysts, sinuses, and fistulas. Otolaryngol Clin North Am. Feb 1981;14(1):175-86 Fig 8a,b,c,d e, f,g: 24 mo old male presented with right lower neck pit (marked with fiducial). A fistulous track was traced from the pit to the right will be recognized by external drainage of mucous. Figures 1, 3, 6, 7 and 9 were adapted from KL Morre, TVN Persaud. The Developing Human; Clinically Oriented Embryology 6th Edition 1998 W.B. Saunders palatine tonsil (arrows). At surgery a Second Branchial apparatus fistula was found