Non-Neoplastic Lesions of the Neck

Embryology

• Branchial apparatus appears around the fourth week of gestation and consists of a paired series of six arches, five pouches, and five clefts or grooves.

• Embryologic development of the head and neck structures can be classified through the development of the branchial apparatus, including arches (mesoderm), clefts (ectoderm), and pharyngeal pouches (endoderm) ( Table 12-1 ).

  TABLE 12-1

  Branchial Apparatus and Derivatives

  	Arches (Mesoderm)	Pharyngeal Pouches (Endoderm)	Clefts (Ectoderm)
  First	Cartilage bar (Meckel cartilage): Ramus and body of mandible Maxilla Incus (body) Malleus (head and neck) Part of pinna of ear Muscles and ligaments: Temporalis Masseter Pterygoids (medial and lateral) Digastric (anterior belly) Mylohyoid Tensor tympani Tensor veli palatini Anterior two thirds of tongue Sphenomandibular lig. Anterior malleolar lig. Innervation: Trigeminal (maxillary and mandibular divisions) Vasculature: Facial artery	Epithelial lining of the middle ear cavity, inner part of the tympanic membrane, eustachian tube, mastoid air cells	Epithelial lining of the external auditory canal, and outer part of the tympanic membrane
  Second	Cartilage bar (Reichert cartilage): Incus (long process) Malleus (manubrium) Stapes (long process) Styloid process Hyoid (lesser horn and upper body) Part of pinna of ear Muscles and ligaments: Facial (auricularis, buccinator, frontalis, occipitalis, orbicularis oculi, oris platysma) Digastric (posterior belly) Stapedius Stylohyoid Stylohyoid lig. Innervation: Facial Vasculature: Lingual branch of ext. carotid artery	Epithelial lining of the tonsillar fossa and palatine tonsil	None
  Third	Cartilage bar: Hyoid (lower body and greater horn) Muscles and ligaments: Stylopharyngeus Palatopharyngeus Posterior third (base or root) of tongue Innervation: Glossopharyngeal Vasculature: Internal carotid artery	Inferior parathyroid glands, thymus, pyriform sinus	None
  Fourth	Cartilage bar: Thyroid Muscles and ligaments: Cricothyroid Levator palatini Posterior third (base) of tongue Innervation: Vagus (superior laryngeal branch) Vasculature: Arch of aorta Right subclavian artery	Superior parathyroid glands C-cells of ultimobranchial body	None
  Fifth and sixth	Cartilage bar: Cricoid Arytenoids Muscles and ligaments: Intrinsic muscles of larynx Upper esophageal muscles Innervation: Vagus (recurrent laryngeal) Vasculature: Pulmonary arteries Ductus arteriosus	C-cells of ultimobranchial body (5th pharyngeal pouch) 6th pharyngeal pouch: none	None

• Branchial apparatus gives rise to most of the important structures of the head and neck, including the face, oral cavity, ears, and neck.

Clinical

• No gender predilection; occur at any age, but most commonly become evident in young adults

• Predominantly occur in the lateral neck along the anterior portion of the sternocleidomastoid muscle:

  • Also seen in the area around the external ear, in the external auditory canal, and in the parotid gland

• Generally, occur as an isolated phenomenon but may be familial or may rarely be associated with other congenital defects, including:

  • Malformed auricles

  • Hearing abnormalities

  • Patent ductus arteriosus

  • Tear duct atresia

Clinical

• Cysts present as nontender, fluctuant masses in appropriate locations; cysts may become inflamed and abscesses may develop, potentially associated with dysphagia, dyspnea, or stridor.

• Sinuses and fistulas are associated with discharge of mucoid and/or purulent secretions from the tract opening.

• Up to 10% of cases may be bilateral.

• Histogenesis of branchial cleft anomalies is controversial:

  • Among the structures proposed as the origins for these anomalies include the branchial apparatus (considered to represent the origin for these abnormalities), salivary gland inclusions, and thymic duct.

Clinical

• In comparison to second branchial anomalies, first branchial anomalies are uncommon, representing from 1% to 8% of all branchial apparatus defects.

• Typically occur in the area of the external ear and may include cysts, sinuses, and fistulas.

• First branchial anomalies may be identified in a variety of locations, including pre-, post-, or infra-auricular, at the angle of the jaw, associated with the earlobe, and in the external auditory canal or involving the parotid gland.

• Involvement of the external auditory canal may result in otalgia or otorrhea.

• Parotid involvement may result in an intra- or peri­parotid mass that may be mistaken for a parotid gland tumor.

Pathology

Differential Diagnosis

• Epidermoid cyst

• Dermoid cyst

Treatment and Prognosis

• Regardless of the histology, complete surgical excision is the preferred treatment:

  • Inadequate excision results in recurrence and increased risk of infection.

  • Incision and drainage are indicated in cases in which abscesses have developed, and in this situation complete surgical excision must wait until resolution of the infection.

  • Type II anomalies are often intimately associated with the parotid gland, necessitating a superficial parotidectomy to ensure complete excision.

  • Although there is no consistent relationship between the tract and the facial nerve as it courses through the parotid gland, exposure and dissection of the nerve and its branches are required in Work type II anomalies.

Clinical

• Accounts for the majority of the branchial apparatus anomalies, representing from 92% to 99% of all cases

• Equal gender predilection; typically occurs in the third through fifth decades of life:

  • Uncommon in patients older than 50 years of age:

    • –

      Less than 3% of cysts present after the age of 50

    • –

      Lateral neck cysts in patients 50 years of age and older should prompt diagnostic consideration for a metastatic cystic squamous cell carcinoma (see Chapter 13 ).

• Occur along the anterior border of the sternocleidomastoid muscle; most common at the level of the angle of the mandible

• Present as a painless, fluctuant neck mass that may increase in size in the face of an upper respiratory tract infection, at which time they may become painful

• Cysts are much more common than fistulas.

• Sinuses and fistulas are most often identified at birth or in early childhood, presenting as a small opening above the clavicle through which mucoid secretions may be expressed; these are divided into three types:

  • Incomplete external, with an external (cutaneous) but no internal (pharyngeal) opening

  • Incomplete internal, with a pharyngeal but no cutaneous opening

  • Complete, with pharyngeal and cutaneous openings:

    • –

      The cutaneous opening is seen anywhere along the anterior border of the sternocleidomastoid muscle from the hyoid bone to the sternum, with the epithelial tract coursing cephalad, between the internal and external carotid arteries, over cranial nerves IX and XII, deep to the posterior belly of the digastric muscle and terminating close to the middle constrictor muscle or with an internal opening in the pharyngeal wall and/or tonsillar region.

• Radiology:

  • Cysts appear as well-defined, low-density lesions surrounded by a thin, uniform wall.

  • Noninflamed cysts have no or minimal CT mural enhancement.

  • Infected cysts have increased CT density of the central fluid with rim enhancement and poorly defined cyst wall.

  • Fistulas or sinus tracts may extend either toward the skin surface, supratonsillar fossa, as well as between the internal and external carotid arteries.

• Histogenesis of second branchial cleft cysts is controversial:

  • Among the structures proposed as the origins for these anomalies include the branchial apparatus (considered to represent the origin for these abnormalities), salivary gland inclusions, and thymic duct.

Pathology

Differential Diagnosis

• Thymic cyst

• Thyroglossal duct cyst

• Metastatic cystic squamous cell carcinoma, including HPV-associated and non-HPV-associated:

  • Absence of cytologic features of malignancy excludes the diagnosis of a metastatic cystic squamous cell carcinoma

  • Some examples of cystic metastatic squamous cell carcinoma may be composed of relatively bland cytomorphologic features but even in such cases there are foci of cytologically atypical/malignant epithelial cells characterized by pleomorphic nuclei and increased mitotic activity:

    • –

      Increased proliferation rate as determined by Ki67 (MIB1) staining would be present in metastatic carcinoma and absent in branchial cyst.

    • –

      Diffuse and strong (nuclear and cytoplasmic) p16 immunoreactivity, representing a surrogate marker for HPV-16, would confirm the diagnosis of metastatic cystic HPV-associated carcinoma of oropharyngeal origin, differentiating it from a branchial cleft cyst, which should be nonreactive for p16.

    • –

      p16 may be overexpressed in almost 50% of benign branchial cleft cysts potentially limiting the diagnostic utility of p16 in this setting; in such an occurrence molecular testing (in situ hybridization, PCR) would be necessary to confirm presence of HPV and the malignant nature of the cyst.

  • Confusion and controversy exist between the diagnosis of metastatic cystic squamous cell carcinoma and that of a carcinoma arising in a branchial cleft cyst (so-called branchial cleft carcinoma or branchiogenic carcinoma); criteria for the diagnosis of a branchiogenic carcinoma include:

    • –

      The tumor occurs along the line extending from a point anterior to the tragus along the anterior border of the sternocleidomastoid muscle to the clavicle.

    • –

      Histology supports origin from a branchial cleft-derived structure (i.e., situated in the lateral aspect of the neck).

    • –

      Histology supports carcinoma arising in the wall of an epithelial-lined cyst.

    • –

      A minimum of 5-year follow-up demonstrates no evidence of a primary source for this neoplasm.

    • –

      Despite the fulfillment of these criteria, it is highly unlikely that carcinoma arises in a branchial cleft cyst; rather, these cystic squamous cell carcinomas take origin from a primary tumor in Waldeyer tonsillar ring:

      • ▪

        Primary (Waldeyer ring) neoplasm may be so small as to defy clinical detection but nevertheless is capable of metastasizing.

      • ▪

        Histology demonstrates partial or complete replacement of the lymph node by an epithelial-lined structure with central cystic change; the epithelium varies from areas that are bland, composed of uniform cells lacking pleomorphism, crowding, or loss of polarity, to overtly malignant-appearing epithelium composed of pleomorphic cells with increased cellularity, mitoses, and a loss of polarity.

• Metastatic papillary thyroid carcinoma:

  • Absence of architectural and cytomorphologic features associated with papillary thyroid carcinoma would differentiate metastatic papillary thyroid carcinoma from second BA.

  • Cystic metastatic papillary thyroid carcinoma to the neck may occur in the absence of a known history of a primary thyroid carcinoma and/or as an occult metastasis. Further, the primary thyroid-based carcinoma may be very small and clinically difficult to detect. Most often the metastasis originates from the ipsilateral thyroid lobe. Given the clinical scenario of unsuspected/unknown primary thyroid carcinoma, the histology of the neck mass may include a flattened/attenuated epithelial lining without papillary architecture histologically simulating the appearance of a branchial cleft cyst:

    • –

      Attention to the nuclear features may alert the pathologist to the possible presence of metastatic papillary thyroid carcinoma.

    • –

      In suspect cases, thyroglobulin, thyroid transcription factor 1 (TTF-1), and PAX8 reactivity would be present in metastatic papillary thyroid carcinoma and absent in BAs:

      • ▪

        Thyroglobulin reactivity is the single best marker for lesions of thyroid follicular epithelial cell origin and is generally absent in all other (nonfollicular epithelial cell origin) lesions.

      • ▪

        TTF-1 reactivity is not unique for follicular epithelial-derived lesions of the thyroid but can be present in other lesion types, including (but not limited to) medullary thyroid carcinoma and pulmonary adenocarcinoma; in contrast, thyroglobulin reactivity is a dedicated marker for lesions of thyroid follicular epithelial cell origin and represents the preferred immunomarkers in the evaluation for metastatic carcinomas of thyroid follicular epithelial cell origin.

      • ▪

        Regardless of the histologic (nuclear) features, thyroid tissue located in lymph nodes situated lateral to the great neck vessels represents metastatic thyroid carcinoma; see Section 8, Thyroid Gland, for more complete discussion.

Treatment and Prognosis

• Complete surgical excision is the preferred treatment.

  • Depending on the extent of the fistula tract, a tonsillectomy may be needed.

Pathology

Treatment and Prognosis

• Complete surgical resection of a third BA (cyst, sinus, fistula) is the preferred treatment and is necessary to prevent recurrence:

  • Surgical procedure may require a subtotal thyroidectomy.

Embryology

• The thyroid gland is the first endocrine gland to appear during embryonic development.

• Thyroid gland derives from three primordium, the median anlage, and lateral anlages:

  • Median anlage develops around the 24th day of gestation as a small, median endodermal thick­ening on the primitive pharynx; this thickening forms a diverticulum, which is attached to the tongue by a narrow tube, the thyroglossal duct; its opening in the base of the tongue constitutes the foramen cecum.

  • Proximal opening persists as the foramen cecum of the tongue

• As a result of further cellular proliferations, the hollow thyroid diverticulum obliterates and divides into the right and left lobes, connected by the isthmus around the seventh week of gestation.

• During development the thyroid descends and assumes a definitive position in the anterior neck; by this time the thyroglossal duct degenerates.

Clinical/Pathology

• See Section 8, Thyroid Gland, for a more complete discussion including illustrations.

• Majority of cases occurs in the midline of the neck above the thyroid isthmus but below the level of the hyoid bone:

  • Thyroglossal duct cysts are nearly always connected to the hyoid bone.

  • Uncommonly, thyroglossal duct cysts may occur lateral to midline but do not occur in the lateral portion of the neck (i.e., lateral to the jugular vein).

• Clinical presentation of an uninfected thyroglossal duct cyst is usually that of an asymptomatic midline neck mass:

  • Mass typically moves upward on swallowing.

  • Inflamed or infected thyroglossal duct cysts may be associated with tenderness and pain.

  • Extrinsic airway compression in neonates with apnea, cyanosis, and respiratory compromise may uncommonly occur.

• Thyroglossal duct cysts are smooth-walled, cystic structures that usually measure less than 2 cm.

• In noninflamed cysts, the cyst lining is respiratory (columnar) epithelium but may also include squamous epithelium.

• Presence of thyroid tissue in the cyst wall varies and may be dependent on the extent of specimen sampling; in generally, thyroid tissue can be found in more than 60% of the cases.

• Thyroid tissue may be normal, hyperplastic, and nodular or neoplastic (see below).

• Surgery is the preferred treatment; en bloc surgical resection of the cyst, the middle third of the hyoid bone (Sistrunk procedure), and the suprahyoid tract up to the foramen cecum; this extended surgery prevents recurrence:

  • Adequate surgery results in cure with low, if any, recurrences.

• Benign and malignant neoplasms may occur in the setting of a thyroglossal duct cyst.

• C-cell–related lesions, including medullary carcinoma, do not occur in thyroglossal duct cysts due to the different embryologic derivation of the C-cells.

Embryology and Anatomy

• Thymus develops in the sixth week of gestation, arising primarily from the third branchial pouch (mesoderm); the fourth branchial pouch may provide minimal contribution to the development of the thymus.

• Thymic primordia descend in the neck along the course of the carotid sheath.

• Connection of the paired primordia to the pharynx is retained by the thymopharyngeal ducts.

• During the eighth week of gestation the thymic primordia fuse in the midline of the neck and then descend into the mediastinum.

• Failure of descent or failure to involute results in thymic abnormalities, including cervical thymic cyst.

• Cervical thymic cysts are considered to be congenital, although mediastinal thymic cysts are thought to be acquired.

Clinical

• Cervical thymic cysts are uncommon.

• Occur slightly more often in men; the majority of cervical thymic cysts (67%) occurs during the first decade of life with the rest occurring in the second to third decades:

  • Rarely, cervical thymic cysts occur in adults.

• Found anywhere between the angle of the mandible and the sternum, including the lateral and midline neck

• Majority of patients presents with a slow-growing, painless neck mass that may transiently increase in size during a Valsalva movement; uncommonly, the clinical presentation may include dyspnea, dysphagia, hoarseness, or pain.

• Rarely (if ever) associated with a sinus or fistula

• May represent an isolated cystic lesion in the neck, may extend into the mediastinum, or may be in continuity with an intrathoracic thymus gland:

• Radiology:

  • Connections to intrathoracic structures result in abnormal radiologic findings.

  • Appearance of cervical thymic cyst on CT can be characteristic:

    • –

      The course of the descent of embryologic thymic tissue in the neck to the mediastinum indicates the potential site of deposition of an ectopic cervical thymic cyst.

    • –

      In a child, a cystic lesion that has an intimate relationship to the carotid sheath is likely to be a thymic cyst.

Pathology