Background
Branchial cleft anomalies are frequently encountered by otolaryngologists and constitute one of the uncommon anomalies of embryonic development [
1]. They arise from malformations occurring during development of the fetal branchial apparatus and formation of the epithelized tract, and these, in turn, may give rise to some congenital anomalies of the head and neck region [
2]. Approximately 17 % of all pediatric neck masses are related to branchial cleft anomalies [
1].
The third branchial cleft fistula is a rare type of branchial cleft anomaly that only accounts for 2–8 % of all the anomalies [
3,
4], with approximately 94 % of these anomalies found on the left side [
5]. Anatomical findings show that the third branchial cleft fistula passes along the carotid sheath and then travels between the glossopharyngeal and hypoglossal nerves. It pierces the thyrohyoid membrane and tracks above the superior laryngeal nerve ending at the internal opening in the cephalad location of the pyriform fossa, forming a sinus fistula. Sometimes it has an external opening in the lower neck or at the anterior border of the sternocleidomastoid muscle [
1,
6]. Due to the position of the common inner opening of third branchial cleft fistula [
7], it is susceptible to neck abscesses [
8].
Here, we present a fatal case involving a third branchial fistula followed by a severe neck abscess. To the best of our knowledge, reported cases of death due to this disease are rare. The autopsy, pathology, and diagnostic standards of third branchial fistula are discussed in this paper.
Discussion
Branchial cleft anomalies are due to aberrant embryonic development, and can result from different malformations of the branchial apparatus. These may present as a fistula, sinus tract, or cyst, and encompass four known specific types [
1]. First, branchial cleft anomalies are the rarest type, accounting for less than 1 % of the four types [
9]; while second branchial cleft anomalies are the most common types, accounting for approximately 95 %. Third branchial anomalies are also rare and they account for 2–8 % of all such cases [
3,
4,
10]. The prevalence of fourth cleft anomalies is low, at approximately 1–4 % [
11]. Although all four types of branchial cleft anomalies are able to give rise to neck abscesses [
1], they each have a unique anatomical appearance.
Pathologically, the presence of keratinizing and/or non-keratinizing squamous epithelial cells within neck tissue is thought to be a cytologic standard for diagnosing branchial fistulas [
12]. According to the standard referenced above, IHC examinations of P63 and PCK in neck tissue are recommended for a further pathologic diagnosis. P63 is a specific protein that is expressed in the nucleus of squamous epithelial cells, and PCK is a specific marker of keratinizing epithelial cells expressed in the cellular cytoplasm. In the present study, we found the pyriform fossa sinus to be surrounded by P63-expressing squamous epithelial cells. Numerous fistular structures surrounded by positive P63-expressing squamous epithelial cells and PCK-expressing keratinizing epithelial cells were also observed in the left cervical muscles.
The pathway taken by fourth branchial cleft fistulas has been described as being similar to that of third branchial cleft fistulas. This makes it difficult to differentiate the two types of branchial anomalies in clinical practice; and they are grouped as pyriform fossa sinus tracts by some authors [
5,
13]. A pyriform fossa sinus is most typically investigated with a CT scan [
14], and the manifestation of air within a left neck swelling is considered to be a characteristic finding of a lesion in a third and/or fourth branchial fistula [
15]. In a recent study on branchial anomalies, recurrent neck abscesses and suppurative thyroiditis are thought to be the primary clinical presentations of a pyriform fossa sinus [
14]. In our case, the features shown by neck CT and the inherent clinical syndromes conformed to the characteristic presentation of pyriform fossa sinus.
Third and fourth branchial cleft fistulas occupy a fine distinction in anatomy, although the two types of branchial anomalies have almost the same clinical presentation. Studies have shown that the internal opening of third branchial cleft fistulas is located at the cranial end of the pyriform fossa, and the tract passes above the superior laryngeal nerve; while the fourth branchial cleft fistulas originate at the caudal end of the pyriform fossa and pass through the cricothyroid membrane beneath the superior laryngeal nerve [
5,
16]. In our case, due to the patient’s operation 2 years ago and cryopreservation of the body, it was impossible to separate the tract and identify the pathway. However, the opening sinus in the cranial end of the pyriform fossa indicated that it was a third branchial cleft fistula. In a study of congenital branchial cleft anomalies, the recurrent rate of lateral neck abscess and suppurative thyroiditis induced by third branchial fistulas was reported to approach 42 and 45 %, respectively [
5]. Open-neck surgery with excision of the fistular tract (preceded by the administration of appropriate antibiotics), is most commonly performed to control neck infection [
7,
17]. In a study conducted by Nicoucar et al. [
7], endoscopic cauterization treatment was recommended to effect a radical cure (with limited complications) for third branchial cleft fistulas.
Branchial cleft fistulas are not associated with high mortality, as we found few fatal cases using PubMed, Google Scholar or other mainstream publication search engines. However, according to our findings in the present case, such a fistula becomes a potentially lethal disease if misdiagnosis or delayed/faulty treatment occurs. Collection of the neck CT scans is particularly valuable for observing the fistular tract, sinus, or infection [
14]. Histopathologic examination of neck tissue is critical for a correct diagnosis, and is considered to be the gold standard for branchial cleft fistulas [
12]. IHC can aid in confirming the common pathologic presentations, such as fistulas surrounded by squamous epithelial cells in cervical muscles and other neck organs [
1,
12]. In contrast, the fistular tract pathway should be confirmed because it is a key point in the diagnosis of the specific type of branchial cleft anomaly. The examination of the position of the fistular opening is a convenient method for a tentative diagnosis, and radiography of the fistula can provide a view of the pathway taken by the fistular tract. In practice, medical examiners should be made aware of this condition at autopsy if neck cysts or abscesses are found, as such information would be important in the diagnosis of the cause of death [
18].
Conclusions
This present analysis revealed that a proper histopathologic examination of the neck tissue along with a review of the medical history and examinations of CT and ultrasonographic images can provide a rapid and accurate diagnosis of third branchial cleft fistula. This commonly encountered and usually non-lethal disease can, however, potentially lead to death if the neck infection is not properly treated. In medico-legal practice, medical examiners need to make themselves aware of this condition, as this would be important in the diagnosis of the cause of death.