Cysts of the Neck, Unknown Primary Tumor, and Neck Dissection

Embryogenesis

Structural malformations, including lateral cysts, sinuses, and fistulas, are related to the abnormal persistence of pharyngeal grooves and/or pharyngeal pouches. The postnatal location of these structures indicates the location of their embryonic precursors. External fistula openings are usually noted in the neck anterior to the sternocleidomastoid muscle. Fistulas arising from remnants of pharyngeal grooves II or III are thought to result from incomplete closure of the cervical sinus by tissue from the hyoid arch. Cervical cysts, although present from birth, are often clinically inapparent until after puberty, when they expand because of increased epithelial secretions from the inner cyst surface caused by maturational changes. Preauricular sinuses or fistulas, which are usually found in a triangular shaped preauricular region, are also common. These structures are thought to represent persistent clefts between preauricular hillocks on the first and second arches. Cervicoaural fistulas represent persisting ventral portions of the first pharyngeal groove, which extend from a pharyngeal opening to somewhere along the auditory tube or the external auditory meatus. The branchial apparatus undergoes this complex development and differentiation during the third through seventh embryonic weeks. Many anatomic structures develop completely or in part within the branchial apparatus ( Table 11.4 ).

A number of theories have been proposed to explain the genesis of branchial cleft anomalies. The most widely accepted theory is that the remnants result from incomplete obliteration of the branchial clefts, arches, and pouches. Lesions may take the form of cysts, sinuses (internal or external), or fistulas. Cystic lesions presumably develop as the result of buried epithelial cell rests. Sinus anomalies have, by definition, a communication with either the external skin surface or the pharyngeal mucosa, and they end as a blind tubular or saccular anomaly within mesenchymal tissue. These anomalies likely arise from incomplete obliteration of part of a branchial groove. Fistulas suggest complete communication from the ectodermal surface to the endodermal surface and presumably relate to an incompletely closed or ruptured branchial plate.

Despite this seemingly simple embryogenic concept, agreement has not been reached on a wholly acceptable hypothesis of the origin of branchial anomalies. Most theories center on the idea that they originate in pharyngeal-tonsillar epithelium, salivary gland inclusions in lymph nodes, or the branchial apparatus. However, most authorities still favor the branchial duct theory.

Clinical Features

Branchial cleft cysts, fistulas, and sinuses occur with equal frequency in males and females. The precise location and course of these anomalies depend on the particular branchial pouch or cleft from which they are derived. They are bilateral in 2% to 10% of patients, and some may be familial, the mode of inheritance being an autosomal dominant gene, with reduced penetrance and variable expressivity. They generally exist as an isolated phenomenon, but in rare instances may be associated with other defects, such as patent ductus arteriosus, tear duct atresia, hearing abnormalities, preauricular pits, or malformed auricles. A recent report suggested a link between increased estrogen in pregnancy and growth of branchial cleft cysts. Salivary duct fistulas can mimic branchial cleft fistula, clinically. A malignancy may develop rarely in ectopic salivary tissue associated with these pharyngocervical tracts.

Differential diagnosis of a branchial cleft cyst arising in an adult always includes a cystic metastasis of a squamous cell carcinoma, especially if cytologic atypia is noted. P16 immunohistochemistry may be helpful if this differential diagnosis arises; however, a significant number of benign branchial cleft cysts may also show diffuse p16 positive staining. In these latter cases, additional human papilloma virus (HPV) molecular testing (in situ hybridization, polymerase chain reaction [PCR], etc.) should be done to confirm the presence of HPV and the diagnosis of metastatic squamous cell carcinoma. Also there is a recent description of three well-differentiated squamous cell carcinomas having areas of columnar epithelium, with surface cilia presenting as cystic neck masses. One of these was originally diagnosed as a branchial cleft cyst. Some observers have previously interpreted the presence of cilia as equating with a benign process; however, as these cases indicate, the presence of cilia in a cystic lesion, by itself, is insufficient to rule out a metastatic carcinoma. One needs to consider the possibility of any cystic neck mass, involving a lymph node, with a high index of suspicion for metastatic carcinoma, for all patients over the age of 30 years. Evaluation of HPV status is useful in this situation, as branchial cleft cysts have not been found to harbor biologically active high-risk HPV.

First Branchial Cleft Anomalies

One of the most comprehensive review of these anomalies was by Olson and colleagues. They reviewed 460 branchial cleft anomalies at the Mayo Clinic; 38 (8%) were of first branchial cleft origin. Of these, 68% were cysts, 16% were sinuses, and 16% were fistulas. These anomalies occurred predominantly in females and were found in persons of every age from newborn to elderly. Clinically, they may masquerade as parotid tumors, otitis with ear drainage or as ear canal cholesteatoma.

First branchial cleft disorders are classified into two types. Type I defects are those that embryologically duplicate the membranous external auditory canal and contain only ectodermal elements. They often are confused on histologic examination with ordinary epidermoid cysts because they are lined only with keratinized stratified squamous epithelium unassociated with adnexal structures (hair follicles, sweat glands, sebaceous glands) or cartilage ( Fig. 11.3 ). Characteristically, they are located medially, inferiorly, or posteriorly to the concha and pinna. Drainage from the cyst or fistula may occur in any of these sites. The fistula (or sinus tract) often parallels the auditory canal and ends in a blind cul-de-sac at the level of the mesotympanum. In some instances, parotid tissue may be associated with the tract. The external auditory canal, both membranous and bony, is intact, and hearing is normal.

Type II deformities are composed of both ectodermal and mesodermal elements and therefore contain, in addition to skin, cutaneous appendages and cartilage ( Fig. 11.4 ). This type of defect is thought to represent an embryologic duplication of both the auditory canal and the pinna. Patients with a type II defect usually present with an abscess or fistula at a point just below the angle of the mandible. The tract extends upward over the angle of the mandible through the parotid gland, toward the external auditory canal. The tract may end short of or drain into the auditory canal, usually along the anteroinferior border near the cartilaginous-bony junction. Communication of the tract with the middle ear is distinctly uncommon. Type II defects are therefore more intimately associated with the parotid gland thcytoplasmic stainingn are type I defects; however, both may mimic a parotid tumor.

In some instances, because of the histology and/or location, a distinction between type I and II lesions cannot be made. Olson and colleagues therefore suggested that first cleft abnormalities be classified only as to whether the lesion is a cyst, sinus, or fistula. First branchial cleft abnormalities must be differentiated pathologically from epidermoid cysts (especially type I), dermoids (especially type II), and cystic sebaceous lymphadenomas. Rarely a “hybrid” first and second branchial cleft cyst may occur.

Second Branchial Cleft Anomalies

These are by far the most common branchial cleft anomalies, accounting for as many as 90% of such anomalies in some series. The external opening, when present, is usually located along the anterior border of the sternocleidomastoid muscle at the junction of its middle and lower thirds. The tract, if there is one, follows the carotid sheath; it crosses over the hypoglossal nerve, courses between the internal and external carotid arteries, and ends at the tonsillar fossa.

Cysts of the second cleft are three times more common than fistulas. There is no sex predominance. Most patients (75%) are 20 to 40 years old at the time of diagnosis. Because less than 3% of cysts are found in patients older than 50 years of age, pathologists must be careful in making such a diagnosis in this age group; a metastatic squamous cell carcinoma in a cervical lymph node, with cystic degeneration, may masquerade as a branchial cleft cyst. Looking for atypical squamous epithelium will help separate these two entities and confirm the latter diagnosis (see “Clinical Features” earlier).

The cysts are usually 2 to 6 cm in diameter and are lined with stratified squamous epithelium (90%), respiratory epithelium (8%), or both (2%). Repeated infections cause the wall to become fibrotic, and the epithelium may then be partially replaced by granulation or fibrous tissue. Lymphoid tissue, either nodular or diffuse, occurs in the wall of 97% of the cysts and often contains germinal centers and subcapsular or medullary sinuses, or both ( Fig. 11.5 ). Ectopic salivary gland tissue has been identified in the cyst wall. The contents of the cysts may be cheesy, mucoid, serous, or, if infected, purulent. Rarely a “hybrid” first and second branchial cleft cyst may occur.

Third Branchial Cleft Anomalies

Disorders of this cleft are rare. Cysts, when they occur, present in the region of the laryngeal ventricle and are lined with stratified squamous epithelium. Fistulas open externally along the anterior margin of the lower third of the sternocleidomastoid muscle. If complete, the tract should ascend in relation to the carotid sheath, pass superior to the hypoglossal nerve and inferior to the glossopharyngeal nerve, course behind the internal carotid artery, penetrate the thyrohyoid membrane, and open into the pyriform sinus. Cysts lying deep to the internal carotid artery and intimately associated with the vagus nerve are probably remnants of the third cleft or pouch.

The third branchial anomalies, similar to the fourth, are usually found on the left side of the neck but may also arise on the right side. Patients have various clinical presentations, including acute suppurative thyroiditis, a neck abscess, a fistulous opening in the lower neck, or a retropharyngeal abscess or fistula. In addition, a third branchial cleft fistula passes over both the superior and recurrent laryngeal nerves, but a fourth branchial cleft fistula passes under the superior laryngeal nerve and over the recurrent laryngeal nerve. This anatomic difference may be useful in establishing whether one is dealing with a third or fourth branchial cleft anomaly.

Fourth Branchial Cleft Anomalies

These anomalies are extremely uncommon, with slightly fewer than 50 cases reported between 1972 and 2003. These anomalies might have external openings along the anterior border of the sternocleidomastoid muscle in the lower neck, and the tracts would typically descend along the carotid sheath into the chest, passing under either the arch of the aorta on the left or the subclavian artery on the right (both vessels are derived from the fourth branchial arch). They would then ascend in the neck, and their internal openings would be in the esophagus, a fourth bronchial pouch derivative. Anomalies in this area of the body might be confused with thymic cysts. In addition, a third branchial cleft fistula passes over both the superior and recurrent laryngeal nerves, but a fourth branchial cleft fistula passes under the superior laryngeal nerve and over the recurrent laryngeal nerve. This anatomic difference may be useful in establishing whether one is dealing with a third or fourth branchial cleft anomaly. Salivary fistulas arising from ectopic salivary gland tissue may also clinically mimic a branchial cleft fistula.

The fourth branchial anomalies, similar to the third, are usually found on the left side of the neck but may also involve the right side. Their clinical presentation varies from no symptoms to acute suppurative thyroiditis, a neck abscess, a cutaneous fistula and rarely a neck mass which may have suddenly enlarged. One case has also been associated with ipsilateral thyroid agenesis. Neonatal cases account for only 8.7% of the fourth branchial anomalies.

Treatment

Complete surgical excision is the only satisfactory method of treatment for branchial cleft anomalies. The lesions are prone to recurrent infection and scarring, rendering dissection tedious and difficult. Any infection should be treated with antibiotics and the area drained before surgical excision is attempted. Aspiration of an uninfected cyst is not indicated because this may predispose the patient to infection and make dissection more hazardous and increase recurrence rates. The wall of the cyst and the tract may be extremely adherent to adjacent nerves and vessels.

The surgical principles are similar, regardless of whether one is dealing with a first, second, third or fourth cleft remnant, although the approaches are different. Confirming the extent of the tract is mandatory preoperatively, as these lesions are closely associated to some of the most vital structures of the neck. Injection of dye intraoperatively to delineate the course of the embryonal tract, as much as possible, and careful microscopic dissection and removal of the tract, along with surrounding tissue, is very important in preventing recurrences. All first branchial cleft abnormalities appear to be associated with external ear canal abnormalities (all 41 patients with type I had an abnormality in the posterior wall of the external ear canal, and 96.6% of 29 patients with type II had an abnormality in the inferior wall). Therefore the abnormal skin and cartilage of the external ear canal should be excised together with the other branchial cleft abnormalities to avoid recurrence.

Recurrence rates with careful dissection should be less than 3%. If patients are ineligible for surgery or refuse surgery, ethanol ablation treatment appears to be a safe alternative.

Embryogenesis

Multiple explanations have been given for development of CMCC. The most commonly accepted embryopathogenic explanation is that the facial processes of the first and second branchial arches fail to fuse during intrauterine life, either because of mechanical factors or vascular anomalies, which gives rise to ischemia and necrosis and results in a CMCC.

Clinical Features

This lesion most commonly affects white females and usually presents at birth with a ventral midline vertical defect of the skin of the neck. The more characteristic findings include a vertical weeping strip of atrophic skin that may occur at any level between the chin and the sternal notch. Often there is a nipple-like projection at the cephalic end of the fissure and an associated sinus tract at the caudal aspect that may discharge mucoid material. A subcutaneous fibrous cord associated with the cleft is usually present. Other associated defects include a cleft lower lip, tongue, and mandible; cleft sternum; ectopia cordis with intracardiac anomalies; thyroglossal duct cyst; ectopic bronchial cysts; a midline cleft from mandible to sternum; an atrophic kidney; and one patient with undescended testes.

Pathologic Features

Histologically, the most consistent finding is a thin atrophic epidermis with absence of skin appendages in the dermis of the cleft tissue. The cephalic skin tag shows normal epidermis, and the central core exhibits bundles of skeletal muscle abnormally arranged and occasionally fibrofatty tissues. A central fibrous cord can be seen beneath the squamous epithelium. A sinus tract lined with both nonkeratinizing squamous epithelium and pseudostratified ciliated columnar epithelium is often present, as are seromucinous glands.

Treatment and Prognosis

The treatment of a CMCC is surgical. Early intervention is required to correct this anomaly. If left untreated, it can result in neck webbing with contractures and mandibular deformities. It is important that all pathologic tissue, including the fibrous cord, be removed. If portions of the cleft remain, subcutaneous inclusion cysts will promptly recur.

Embryogenesis

Beginning during the fourth week as an endodermal thickening just caudal to the median tongue bud (tuberculum impar), the thyroid primordium elongates forming a prominent downgrowth called the thyroid diverticulum . The pathway of the bilobed thyroid diverticulum extends caudally as determined by the pattern of cervical arteries and continues to extend during pharyngeal development. As it migrates caudally, the tip of the thyroid diverticulum expands and bifurcates forming the thyroid gland, consisting of its two main lobes with a connecting isthmus. For a while, the thyroid remains connected to its original site of origin (foramen cecum) by a narrow thyroglossal duct.

Around the seventh week, after the thyroid gland has reached its final location, the thyroglossal duct has mostly regressed. Nevertheless, in almost half the population, the distal portion of the thyroglossal duct persists as the pyramidal lobe of the thyroid. The original site of the thyroid primordium persists as the foramen cecum, a small pit at the base of the tongue. If involution fails to take place, cysts or sinuses may occur anywhere along the pathway of descent.

Clinical Features

Approximately 90% of TGDCs occur in the midline of the neck, although some occur paramedially, most often to the left. Overall, 73.8% occur below the hyoid bone, 24.1% are suprahyoidal, and 2.1% are intralingual. In two series of 1316 and 685 TGDCs analyzed by Allard , Thompson and Heffner respectively, no sex predominance was found; however, in the latter series, pediatric patients had a male predominance, while adults, a female predominance. In the literature review, children younger than 10 years of age accounted for 31.5% of patients, 20.4% occurred in patients in their second decade, patients in their 20s made up 13.5% of the total, and those 30 years or older made up the remaining 34.6%. In the largest community-based practice series, 26% of patients presented in the first decade, 12% in the second decade, 9% in the third decade, 13% in the fourth decade, 15% in the fifth decade, and 24% of patients were 50 years of age or older. At the time of presentation, 60% of patients had a cyst and 40% a sinus or fistula or both. Most patients (>99%) presented with a mobile, midline mass with very occasional patients presenting with a lateral neck mass. Seventy-six percent of patients had an infrahyoid presentation and 24% were suprahyoid. Five patients had a fixed mass, of which three were associated with thyroid carcinomas and 23% had pain or tenderness. The exact incidence of a TGDC is unknown, but is estimated to be 2.23/100,000 population. Rarely, TGDCs are familial.

Cysts may fluctuate in size. Often there are no symptoms except the presence of the mass, unless the cyst becomes infected. Rare TGDCs (1.6%) developed within the thyroid gland. Intralingual cysts may cause choking spells, dysphagia, and cough. Fistulas may occur spontaneously or may be secondary to trauma, infection, drainage, or inadequate surgery. These occur in 10% to 34% of patients.

Thyroid radiographic studies should probably be obtained on all patients undergoing surgical excision of a thyroglossal duct cyst. Despite the fact that a small amount of functioning thyroid tissue is associated with the tract in 30% of cases, it rarely, if ever, represents the only functioning thyroid tissue, as is often true with lingual thyroid cyst.

Pathologic Features

TGDCs have a mean diameter of 2.6 cm, but cysts up to 10 cm in diameter have been reported. They are lined with respiratory (38%) or squamous epithelium (10%) or both (51%) or, if infection has occurred, with granulation tissue or scar tissue ( Fig. 11.6 ). Fistulas are almost invariably secondary to infection.

The incidence of finding ectopic thyroid tissue in association with TGDC varies in different series and likely varies according to the diligence with which it is sought. It ranges from 31% to 83% of specimens (measuring 0.01-5 cm in greatest dimension) and may be located in the cyst wall, adjacent skeletal muscle and/or adjacent fat. Seromucous glands (possibly ectopic salivary gland tissue) were identified in 60% of cases studied by Sade and Rosen and in 15% of patients in Thompson and Heffner series. Skin adnexal structures, cartilage and gastric mucosa have also been noted in the wall of the cysts. A thyroid carcinoma, all papillary carcinomas, was identified in 22 cysts from this latter series (3.2%), ranging in size from 0.1 to 3.8 cm in greatest dimension (see next section).

Treatment and Prognosis

The treatment of thyroglossal duct remnants, whether cyst, sinus, or fistula, is complete surgical excision using the Sistrunk operation. This consists of an en bloc excision of the entire thyroglossal tract to the foramen cecum, as well as removal of the central 1 to 2 cm of the hyoid bone. If this procedure is used, the rate of disease recurrence is approximately 3%. If the central hyoid bone is not removed, a recurrence rate as high as 45% may be expected.

Rare reports of malignancy in thyroglossal duct remnants are found in the literature. Eighty percent to 92% of such neoplasms are papillary thyroid carcinomas with the remaining neoplasms being predominantly follicular carcinomas or squamous cell carcinomas with a rare adenosquamous or anaplastic carcinoma. Medullary carcinoma does not appear to arise from TCDCs as there are no parafollicular C cells in TGDCs. Criteria for diagnosis include demonstration of a thyroglossal remnant and a normal thyroid gland. Because of the paucity of cases and the fact that the malignancy is not recognized until after complete pathologic examination of the remnant, it is difficult to delineate treatment and prognosis. If there is a history of sudden increase in size or clinical presentation of a fixed, hard mass, then the possibility of a malignancy arising in a TGDC needs to be considered. Most researchers agree, however, that: (1) total thyroidectomy is not routinely indicated, as long as there are no palpable abnormalities in the gland, the carcinoma is not high grade or aggressive and no significant radiographic findings are found; and (2) that the Sistrunk operation offers a reasonable chance of cure. In a recent literature review of 164 patients with thyroglossal duct cyst carcinoma, there was a 4.3% recurrence rate with a mean time to recurrence of 42.1 months from initial treatment. Only one patient died of TGDC carcinoma, while all other patients were disease free at the time of last follow-up (mean follow-up was 46.1 months).

Embryogenesis

Originating in third pharyngeal pouch, the paired endodermal thymic primordia begin to migrate during the sixth week. Early in migration, they separate from the parathyroid primordia and migrate through a substrate of mesenchymal cells, until reaching the region of the future mediastinum behind the sternum. By the end of their migration, the two closely apposed thymic lobes are still epithelial structures but are surrounded with a capsule of neural crest–derived connective tissue, which also forms septa among the endodermal epithelial cords and contributes to the thymic vasculature. Lymphocyte precursors first invade the thymic primordia during migration before they have become vascularized. This is followed by a refractory period, which persists until the thymic primordia have completed their migration and have become vascularized. By 14 to 15 weeks of gestation, blood vessels grow into the thymus, and a week later, epithelial cells aggregate into Hassall’s corpuscles. It is believed that most cervical thymic cysts arise from the persistence of tissue rests (ectopic thymus) along the pathway of migration of the thymic primordia.

Clinical Features

Cervical thymic cysts are virtually never recognized as such, clinically; most are confused with a branchial cleft cyst or, less often, a TGDC or laryngocele. The most common presenting symptom is a slowly enlarging mass that may or may not be painful; rarely a patient may present with increasing swelling, while phonating. The cysts occur more often on the left side; they rarely are familial, and males are affected twice as often as females. Sixty-seven percent occur in the first decade of life. The remainder occur in the second and third decades of life. Cervical thymic cysts characteristically occur adjacent to or within the carotid sheath and therefore present in or near the anterior cervical triangle. They can be found anywhere from the angle of the mandible to the sternum, paralleling the sternocleidomastoid muscle and the normal embryologic pathway of the thymus. Cysts containing both thymus and parathyroid may be referred to as third pharyngeal pouch cysts . Rarely thymic cysts can present intrathyroidal or as a subglottic mass.

Pathologic Features

The cysts are round to tubular, are unilocular or multilocular, and can measure more than 9 cm in greatest dimension. The epithelial lining may be composed of columnar, cuboidal, or stratified squamous cells ( Fig. 11.7 ). In some areas, it may be replaced by granulation or fibrous tissue, and occasionally cholesterol clefts are present. Thymic tissue found in the cyst wall qualifies the cyst as a thymic cyst. Numerous sections may be required, however, to identify the thymic tissue ( Fig. 11.8 ). In addition, the cyst may have a fibrous cord tracking inferiorly to the superior mediastinum. Parathyroid tissue may or may not be present. Moran and colleagues reported three patients with carcinoma arising in a multilocular cervical thymic cyst.

Treatment

Complete surgical excision is the treatment of choice. To date, no cases with postoperative recurrence have been reported.

Embryogenesis

Bronchial cysts are derived from small buds of diverticula that separate from the foregut during formation of the tracheobronchial tree. When they occur outside the thoracic cavity, the cysts presumably arise from erratic migration of sequestered primordial cells.

Clinical Features

Most cervical bronchial cysts are present in the skin and the subcutaneous tissue of the suprasternal notch. Rarely, they are found in the lower anterior neck, chin, shoulder, intraorally, posterior pharyngeal wall, thyroid gland, and cervical spinal canal. Cervical bronchial cysts may also extend into the mediastinum. They are more common in males than in females (ratio, 3:1). The cysts usually become clinically apparent at or soon after birth and appear as asymptomatic nodules that slowly increase in size. They are less common in adults. Draining sinuses that exude mucoid material are present in approximately one-third of cases. The cyst frequently becomes more conspicuous when the patient performs the Valsalva maneuver.

Pathologic Features

Noninfected cysts are grossly tubular rather than of an ovoid configuration and are filled with either clear serous or thick mucoid material. The cyst wall is thin, and the inner surface is smooth or trabeculated.

The bronchial cyst is lined with ciliated, pseudostratified, or columnar epithelium ( Fig. 11.9 ). Squamous stratified epithelium often makes up the lining of the sinus, but this epithelium rarely lines the cyst, unless the cyst is infected. The cyst wall contains smooth muscle, elastic fibers, and mucoserous glands. Cartilage is seldom present in cervical cysts, although it is common in their intrathoracic counterparts. Lymphoid tissue, when present, is scanty and focal, never diffuse or excessive.

Differential Diagnosis

A bronchial cyst can be distinguished from a teratoma by the complete absence of tissues, other than those that can be explained based on a malformation of the respiratory tract. A dermoid cyst can be excluded by the lack of hair and skin appendages and the absence of squamous epithelium. The presence of smooth muscle, mucoserous glands, and cartilage (should it be found), and paucity of lymphoid tissue, eliminates the possibility of a branchial cleft cyst. A TGDC can be differentiated from a bronchogenic cyst by the presence of thyroid follicles. Furthermore, a TGDC does not contain smooth muscle and almost never cartilage. A lack of ciliated epithelium distinguishes lateral cervical cysts containing gastric mucosa from cervical bronchogenic cysts.

Treatment

Complete surgical excision of the cyst along with its sinus tract is usually curative. Malignancies arising in cervical bronchial cysts are exceedingly rare but they do occur.

Embryogenesis

The parathyroid/thymus primordium develops early from the third pouch endoderm; by 5 weeks of gestation, cells identifiable as parathyroid tissue can be recognized in the endoderm. The primordia of the thymus and the parathyroid glands lose their connection with the third pharyngeal pouch and they migrate caudally. Although the parathyroid III primordia initially migrates with the thymic primordia, they separate and the parathyroid primordia ultimately continue to migrate toward the midline, where they join with the thyroid gland and pass the parathyroid primordia of the fourth pouch to form the inferior parathyroid glands. As with their counterparts from the third pouch, the parathyroid IV primordia lose their connection with the fourth pouch and migrate toward the thyroid gland as superior parathyroid glands.

The cause of parathyroid cysts is not clear, and a variety of theories have been proposed. The suggestion that the cysts are embryologic remnants of the third or fourth branchial cleft or result from coalescence of multiple microscopic cysts, degeneration of a parathyroid adenoma, and retention of glandular secretions has been put forth. No single theory adequately explains all cases. It may be that those cysts with clear, colorless fluid are developmental in origin, whereas the cysts with bloody or straw-colored fluid may result from infarction or cystic degeneration of a parathyroid adenoma. These latter lesions tend to be functioning cysts.

Clinical Features

Most patients with parathyroid cysts present with an asymptomatic low anterior neck mass. Tracheal and esophageal compression, hoarseness secondary to recurrent laryngeal nerve compression, and pain secondary to hemorrhage into the cyst have been reported. Approximately 95% of the cysts occur below the inferior thyroid border, and 65% are associated with the inferior parathyroid glands. Cysts have been identified everywhere from the angle of the mandible to the mediastinum; however, they can occur in the thyroid lobe or posterior to it. They are more common on the left side and may be multiple.

Nonfunctioning cysts make up the majority of cases and are approximately two to three times more common in women than in men. The mean age of patients with this cyst is 43.3 years. Nonfunctioning cysts occur almost exclusively in the inferior parathyroid glands. Functioning cysts account for 11.5% to 30% of the cases, are more common in men (ratio, 1.6:1), and tend to occur in sites other than the inferior parathyroid glands, from the angle of the mandible to the mediastinum. The mean age of these patients is 51.9 years. Most patients with a functioning cyst have signs and symptoms of hyperparathyroidism, but the disease can be clinically occult and may be discovered incidentally by abnormal serum calcium and phosphorus levels or an elevated serum parathyroid hormone level. Multiple parathyroid cysts have been reported in patients with hyperparathyroidism, and rarely a multiloculated cyst occurs.

Fine-needle aspiration is the principal diagnostic tool. Aspiration of clear fluid with an elevated parathyroid hormone level is a definite indication of a parathyroid cyst. The C-terminal/midmolecule of the parathyroid hormone should be assayed because the N-terminal–specific assay is frequently associated with false-negative results.

Pathologic Features

Parathyroid cysts vary from <1 to 10 cm in diameter, but the mean diameter is approximately 3 to 5 cm. They are usually grayish-white, translucent, and unilocular, with a thin membranous capsule. The inner surface is smooth and may contain small light brown areas.

Histologic studies show that a parathyroid cyst’s wall is usually formed by a solitary layer of compressed cuboidal or low columnar epithelium, with either chief cells or oxyphil cells present in the fibrous wall ( Fig. 11.10 ). Some cysts have no identifiable parathyroid tissue. Even in these cases, however, a diagnosis can be established by testing the cyst fluid or doing immunohistochemistry stains for parathyroid hormone on the cyst lining cells.

The presence of lymphoid tissue and the stratified squamous epithelium, lining the cyst, help distinguish those unusual branchial cleft cysts with parathyroid tissue from parathyroid cysts.

Treatment

Aspiration may be curative, but persistence or recurrence of the cyst is common and a sign that surgical removal is needed. Functional cysts are associated with a higher risk of other parathyroid gland abnormalities, such as hyperplasia or adenoma; therefore the other glands may need to be explored if intraoperative plasma parathyroid (PTH) levels do not drop appropriately after removal of the cystic parathyroid gland.

Embryogenesis

The positions of these dermoid cysts at the midline and along the lines of embryonic fusion of the facial processes are consistent with origin by inclusion of ectodermal tissue. Such inclusions would take place along lines of closure at junctions of bone, soft tissue, and embryonic membranes.

Clinical Features

Dermoid cysts of the head and neck occur at almost any age. More than 50% are detected by the time the patient is 6 years old, and approximately one-third are present at birth. The distribution between sexes is approximately equal. The cysts range from a few millimeters to 12 cm in diameter. Dermoid cysts in the neck are rare but can account for close to one-fourth (22%) of midline or near-midline neck lesions. They have been reported in the upper neck, near the thyroid cartilage, and as low as the suprasternal notch. They may occasionally present in the lateral neck and also arise in the submandibular and parotid glands. These cysts usually grow slowly and do not cause pain. On palpation, the cysts are soft to fluctuant.

Pathologic Features

Microscopic examination reveals that this developmental cyst is lined with keratinizing stratified squamous epithelium supported by a fibrous connective tissue wall. Numerous ectodermal derivatives may be seen, including dermal adnexa, such as hair follicles, sebaceous glands, and less commonly sweat glands (eccrine glands) ( Fig. 11.11 ).

Treatment

Complete surgical excision is required, after which there is little risk of recurrence.

Clinical Features

These lesions are uncommon in children younger than 10 years of age. A painless, soft, ballotable neck mass is the most common clinical presentation of a deep ranula. Parapharyngeal extension may be present. Cervical ranulas have varied considerably in size at the time of treatment. Usually located above the hyoid bone and in the submental or submandibular region, these lesions may extend deeply into the neck to the supraclavicular region and upper mediastinum or posteriorly to the skull base. The etiology of plunging ranula is still unknown, but an association with trauma, congenital anomalies, such as an imperforate salivary gland duct or ostial stenosis, and sublingual glandular diseases have been described.