Unusual Development of Second Branchial Cleft Cyst in an Adult after URTI: Diagnosis and Detailed Approach

First Branchial Cleft Cyst

First cleft cysts contribute to the formation of about 5-25% of all branchial cleft anomalies and are subclassified by the Work classification system. On physical examination, work type I shows preauricular masses or sinuses that track medial and anterior to the external auditory canal and contains ectoderm only. They classically appear lateral to the facial nerve and end within the external auditory canal, or attach to the umbo of the middle ear, as a duplication of the external auditory canal. Work type II cysts contain both ectoderm and mesoderm, and are more common. Classically they present in the submandibular area or at the angle of the mandible. They can appear either medial or lateral to the facial nerve and cross superficial to it in 57% of cases, 30% are deep, or between branches of the facial nerve in 13% of them [8].

Second Branchial Cleft Cyst

It forms approximately 40-95% of branchial anomalies making it the most common type. The external opening is found anterior and medial to the sternocleidomastoid (SCM) on the skin of the neck. Branchio-oto-renal syndrome is associated with bilateral second branchial cleft cysts. Its’ sinus has an external opening that is located on the neck skin as described above, with the fistula running deep to the platysma then passes in between the internal and external carotids, being superficial to both glossopharyngeal and hypoglossal nerves before attaching to the tonsillar fossa. Cysts or sinuses of this branchial cleft can appear anywhere along this tract [2, 9]. Second branchial cleft cysts have been classified into subtypes by Bailey back in 1929 [10]

• Type I: Most superficial and lies along the anterior surface of sternocleidomastoid deep to the platysma, but not in contact with the carotid sheath.
• Type II: Most common type where the branchial cleft cyst lies anterior to the sternocleidomastoid muscle, posterior to the submandibular gland, adjacent and lateral to the carotid sheath.
• Type III: Extends medially between the bifurcation of the internal and external carotid arteries, lateral to the pharyngeal wall.
• Type IV: Lies deep to the carotid sheath within the pharyngeal mucosal space and opens into the pharynx.

Intraoperatively our patient’s branchial cleft cyst was pushing the glossopharyngeal and the hypoglossal nerve superio-medially and the internal jagular vein inferio- medially, extending to the accessory nerve inferiorly and ending in the pyriform fossa.

Third Branchial Cleft Cyst

These cysts approximately form 2-8% of all branchial cleft anomalies. The external skin opening is located over the middle to lower third of the anterior SCM in the case of third branchial cleft cysts. Its’ sinus has a skin opening as described above then the tract runs deep to the platysma and course posterior to the internal carotid artery. It then passes between the glossopharyngeal (IX) and hypoglossal (XII) nerves, and can be closely associated with the superior laryngeal nerve, classically passing superior to it. After that it connects to the pyriform sinus in the larynx [11].

Fourth Branchial Cleft Cyst

These cysts represents around 1% of all branchial cleft anomalies, making them very rare and the rarest out of them all. It is more common to appear on the left, with the skin opening close to the medial lower border of the SCM. The exact path of the fourth branchial cleft remnant is not very well established due to its rarity, however, it typically runs deep to the common carotid and can curve around either the aortic arch in a left-sided anomaly or the subclavian in a right-sided anomaly. These pass superficial to the recurrent laryngeal nerve and hypoglossal nerve ending in the apex of the pyriform sinus in the larynx [11].

Ruling out other conditions that may present similarly is essential. Some of the differential diagnosis that should be kept in mind in such presentation include lymphadenopathy (reactive, neoplastic, lymphoma, metastasis), hemangioma, carotid body tumor, cystic hygroma, ectopic thyroid or salivary tissue, vascular neoplasm or malformation thyroglossal duct cysts, cat scratch disease, atypical mycobacterial infections, and cystic squamous cell carcinoma. Since our patient is an adult, it is beyond important to rule out cancer as early as possible. As it has been said time is money and a neck swelling in this age group is cancer until proven otherwise. Hence, proper investigations should be done starting from basic laboratory tests, ultrasound, fine needle aspiration is essential, and CT/MRI should be done. Open biopsy is indicated if there is high suspicion of malignancy and FNAC is negative.

Oropharyngeal HPV-associated squamous cell carcinoma (SCC) can metastasize to a cervical lymph node as a cystic squamous cell carcinoma. Literature suggests the importance of carefully ruling out this differential as the presentation and imaging can look almost identical to a branchial cleft cyst. Not considering HPV-associated SCC can lead to delayed diagnosis of disease hence delayed treatment. It is more common in young male adults and non-smokers. It has a good prognosis with chemoradiotherapy. It is still to be determined in the next several years by public health officials whether adolescent boys should be vaccinated against HPV, in comparison to young sexually active girls who are getting vaccinated [12]. There are different methods to detect human papilloma virus. For example, Nicolas F Schlecht, et al. and colleagues [13] had the highest estimates obtained for oropharyngeal tumors by in-situ hybridization using the Ventana Fam16 probe cocktail. However, other studies, such as Agoston, et al. [14] have reported higher detection rates in oropharyngeal tumors using in-situ hybridization with the Ventana Fam16 probe cocktail, and PCR using L1 and E7 DNA primers, but did not provide analogous estimates of test performance as comparisons were made to combined test results assuming no false positives [13].

On histopathology, branchial cleft cysts usually appear as a cyst with lining epithelia categorized into stratified epithelium without keratinization, columnar epithelium with or without cilia, or a mixture of both. In about 90% of cases branchial cleft cysts are usually lined by squamous epithelium. Two percent of cysts show both types of epithelium, squamous and columnar. On the other hand, 8% are made of ciliated columnar epithelium [15]. There is usually lymphoid tissue under the epithelium, commonly with germinal centers and subcapsular lymph sinuses. A branchial cleft cyst itself is usually encircled by lymphoid tissue also. It is common to have marked inflammatory changes and the epithelium superimposing the lymphoid tissue is attenuated or absent [16].

Treatment of branchial cleft cysts consists of antibiotics if there is active infection, with avoiding of incision and drainage as it might cause alteration of surgical planes. After resolution of the infection, full excision of the cyst is the gold standard management. Excision of a branchial cleft cyst by itself is not considered as an emergent procedure. Due to recurrent infections and the low risk of malignancy, it is usually done. However, emergent surgery may be required in case of airway compromise or large abscess [17, 18]. The incision is usually made within the line of a natural skin crease to make the wound look as cosmetic as possible. Recurrence is usually uncommon once branchial cleft cysts are excised. There is an approximated recurrence risk of 3%. However, recurrence can be as high as 20% if previous surgery or recurrent infection has occurred [19, 20].