2.1.1. Clinical Findings

A thyroglossal duct cyst is the most common congenital neck mass and the second most common of all childhood cervical neck masses. Most are diagnosed at or before 10 years of age. They can occur anywhere along the thyroglossal duct tract but are most commonly found below the hyoid bone, displaying upwards displacement with tongue protrusion and swallowing. The cysts are usually a few centimeters in diameter and are round and smooth on palpation (Figure 2A).

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Figure 2

Thyroglossal duct cyst. (A) Clinical examination: typical picture of a non-infected thyroglossal duct cyst presenting as a midline neck mass. (B) Gross examination: cystic lumen filled with gelatinous and inflammatory material. (C) (H.E.S). Small cystic structure lined by ciliated pseudostratified columnar epithelium; mucous glands (*) on the left; hyoid bone (+) on the right, in close relation to the cyst. (D) (H.E.S), ectopic thyroid follicles in the cystic wall.

Thyroglossal duct cysts are often asymptomatic. If very large, dysphagia may be present. Infection may occur, often in conjunction with upper respiratory tract infections, and can cause painful cystic enlargement, abscess development or rupture with cutaneous sinus formation.

The main clinical differential diagnosis includes dermoid cyst, ectopic or lingual thyroid and lymphadenopathy. Ultrasonography is the first line radiological assessment tool, followed by magnetic resonance imaging (MRI).

Heterotopia-associated thyroid carcinoma, most often papillary thyroid carcinoma, may extremely rarely arise in thyroglossal duct cysts, with 27 case reports at a mean age of 12 years of age. The prognosis remains excellent. All carcinomas have been discovered after surgical excision.

2.1.2. Gross and Histopathological Features

A thyroglossal duct cyst usually corresponds to a single cyst, typically less than 2 cm in size, filled with mucoid, squamous or purulent material (Figure 2B). It may also be composed of several smaller cysts that are sometimes difficult to identify macroscopically. Occasionally, when inflammatory processes are prominent, no residual cystic space may be clearly identified.

In non-inflamed cysts, the cyst lining is ciliated pseudostratified columnar and/or squamous epithelium. Small cystic structures might only be noted in close relation to the hyoid bone, which must be sampled (Figure 2C). Ectopic normal thyroid tissue in the cyst wall can be found in 50 to 70% of cases, varying with sampling by the pathologist (Figure 2D). Inflammation and foreign body giant cell reaction are commonly noted. Mucous glands may also be present. C-cells are not present in thyroglossal duct cysts due to the different embryologic origin [5,6,7].

2.2.1. Clinical Findings

Classical branchial anomalies are usually isolated. Cysts present as nontender, fluctuant masses, which may become infected and lead to abscess formation. Sinuses and fistulas may be associated with discharge of mucoid and/or purulent secretions from the internal and/or external tract opening.

Differential diagnosis may be challenging between infected branchial cyst and a cervical lymphadenopathy. Anatomical localization should be carefully detailed. Moreover, recurrent or persistent cervical “nodal” mass should raise the question of an underneath branchial cleft cyst and US is usually helpful to clarify the diagnosis.

Precise topographic anatomical assessment allows to define which branchial arch is involved and therefore to diagnose the cyst type. As previously mentioned, first branchial cleft cysts are present in the preauricular or submandibular region, second branchial cleft cysts along the anterior border of the sternocleidomastoid muscle, and third/fourth branchial cleft cysts in the lower neck. Given the close association between third/fourth branchial cleft anomalies and the thyroid gland, an infection can present itself as acute suppurative thyroiditis.

In terms of imaging, US is the initial investigation of choice. CT scan and MRI scan can also aid in diagnosis and precise surgical mapping. When uncomplicated, they are typically visualized as well delineated cystic structures appearing centrally hypoechoic on US with posterior acoustic enhancement. Their US appearances can vary, however, sometimes appearing multilocular with septations, inhomogeneous or even solid. They are uniformly hypodense on CT and can demonstrate the ‘notch’ or ‘beak sign’ between the internal and external carotid arteries. MRI can help in determining the presence and path of sinus formation and presence of inflammatory changes within the adjacent soft tissues. Bilaterality is rare (only 2% to 3%) and often associated with familial predisposition [14].

Branchio-oto-renal syndrome (BOR) may be suspected based on family history, or when second branchial arch anomalies are clinically associated with deafness, pre-auricular pits, auricular malformation and/or renal anomalies (malformations or hypoplasia). If suspected, audiology workup and renal US should be performed. BOR syndrome is inherited in an autosomal dominant pattern, with a prevalence of 1/40,000 in Western countries and results from a mutation in the EYA1 gene [15,16].

2.2.2. Histopathological Features

Branchial cleft cysts are usually lined by squamous epithelium (90%) or ciliated columnar epithelium (8%) and rarely by both types of epithelia (2%) (Figure 3C,D). Occasionally, the cyst is denudated (Figure 3E) or lined by cholesterol clefts with a foreign body reaction (Figure 3F) due to inflammatory changes. Lymphoid tissue is generally identified (Figure 3G). Salivary tissue, sebaceous glands as well as thyroid tissue may be present (Figure 3H). An ectopic or undescended parathyroid gland may be associated with third/fourth branchial cleft anomalies, since parathyroid glands embryologically arise from these branchial arches. Parathyroid adenomas have also been reported in association with branchial cleft cysts.

2.3.1. Clinical Findings

The overwhelming majority (about 80–90%) are diagnosed by the time the patient turns 2 years old, the age of greatest lymphatic growth. No gender predilection is reported. Approximately 75–80% of lymphatic malformations involve the neck and the lower third of the face. In children, the most common location is the posterior cervical space, followed by the oral cavity.

These lesions are characteristically infiltrative in nature. Consequently, they may extend inferiorly from the posterior cervical triangle into the axilla and mediastinum or anteriorly into the floor of the mouth and the tongue. If the mass is very large, it may extend across the midline. Only 3–10% of cervical lymphatic malformations are associated with extension into the mediastinum.

Most patients are clinically asymptomatic. The lesion presents itself as a soft, painless and compressible mass in the neck. Size is extremely variable. Very large masses may cause dysphagia or dyspnea by extrinsic compression. The lesion may become painful or enlarge rapidly from acute spontaneous hemorrhage or infection. Disfigurement may also be a significant concern.

They may be associated with chromosomal defects, such as Turner’s syndrome, Trisomy 13, 18 and 21 as well as Noonan syndrome. Additional investigations by means of amniocentesis are therefore indicated when detected on antenatal US.

2.3.2. Histopathological Features

Lymphatic malformations are composed of multiple dilated cystic spaces separated by minimal intervening stroma (Figure 4A). The cysts vary in diameter from a few millimeters to more than 10 cm, and most contain chylous fluid, a variable number of lymphocytes and/or macrophages, and occasional erythrocytes. These thin-walled spaces are lined by endothelial cells and supporting connective tissue stroma. Focally disorganized smooth muscle is present in the wall of larger channels. Lesions may extend into adjacent soft tissues, invade into muscle, and surround vascular structures.

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Figure 4

Lymphatic malformation. (A), (H.E.S). Collection of large interconnected lymphatic cisterns. Small lymphoid aggregates are also present (at the upper left quarter). (B), (D2-40). Positive cytoplasmic immunostaining of endothelial cells. (C), (smooth muscle actin). Positive cytoplasmic immunostaining of disorganized smooth muscle in the wall of larger channels.

The macrocystic type is defined by collections of large interconnected lymphatic cisterns; some vessels may have a relatively thick but incomplete smooth muscular lining. Mural lymphoid aggregates are commonly present and help distinguish these lesions from venous malformations.

The microcystic type is comprised of smaller lymphatic channels that may interdigitate between local tissue elements. In superficial lesions, these often protrude into and expand dermal or mucosal papillae, forming lymph-filled vesicles.

An immunohistochemical panel consisting of D2-40 (more consistent staining of small versus large lymphatic channels), Prospero-related homeobox gene-1 (Prox-1), vascular endothelial growth factor receptor 3 (VEGFR3), CD31, and CD34 antibodies allows the differentiation of lymphatic malformations from venous ones in pathologic practice (Figure 4B,C) [17,18].

2.4.1. Clinical Findings

Dermoid cysts are present at birth and may grow slowly thereafter or remain stable in size. Most cysts are subcutaneous and recognized in children younger than 5 years old. Dermoid cysts may occur anywhere in the body, with 50% presenting in the head and neck area (30% face and 20% neck). Nasal and palpebral sites are most common in the face. In the neck, the midline location is very characteristic of the diagnosis and may be associated with a tuft of hair. Diagnosis is made by excisional biopsy.

Given the midline location, differential diagnosis includes thyroglossal duct cyst. In contrast to thyroglossal duct cysts, dermoid cysts are smaller in size, perfectly round, more superficial (subcutaneous, superficial to strap muscles) and do not move with swallowing. Submental localization raises specific differential diagnosis: ranula is usually developed on the buccal floor but can expand to posterior part of mylohyoid muscle. Anatomical localization and extension of the cyst should be finely analyzed in order not to ignore such lesion due to salivary retention [20].

2.4.2. Histopathological Features

At gross examination, the cyst has yellowish-white keratinous material and might reach 12 cm in size. They are lined by stratified squamous epithelium with associated small hair follicles and sebaceous glands (Figure 5A,B). Eccrine sweat glands and apocrine glands are less commonly present. The cavity contains laminated keratin and numerous vellus hairs oriented haphazardly (Figure 5C). Acute inflammation may result in the subsequent disruption of the cyst wall, with the development of an intense foreign body giant cell reaction (Figure 5D).

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Figure 5

Dermoid cyst. (A) (H.E.S). The cyst is lined by keratinizing stratified squamous epithelium. (B) (H.E.S). The cyst is deeply located in the subcutis. Small hair follicles and sebaceous glands are attached to the epithelium. (C) (H.E.S). The lumen contains numerous vellus hair shafts and lamellated keratin, and the epithelium has a granular layer. (D), (H.E.S). Several vellus hairs (arrowheads) are observed within the granuloma.

2.5.1. Clinical Findings

Cervical thymic cysts are painless neck masses that can present suddenly in children, or in association with cutaneous pharyngeal defects and ocular and facial anomalies as in branchio-oculo-facial syndrome (BOFS), an autosomal-dominant transmitted disorder with mutations in the TFAP2A gene. The presence of an ectopic thymus (dermal) can justify a BOFS diagnosis [25].

2.5.2. Histopathological Features

The cystic fluid may be clear, yellow, brown, green, or even purulent. The diagnosis is established by histologic demonstration of residual thymic tissue showing Hassall’s corpuscles and cortico-medullary differentiation (Figure 6A). The cyst wall lining may be spindle, cuboidal, or columnar, stratified or pseudostratified, ciliated or non-ciliated (Figure 6B). Cholesterol crystals, giant cells, histiocytes, inflammatory cells, and hemosiderin have also been described.

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Figure 6

Thymic cyst. (A), (H.E.S). Mature thymic tissue showing Hassall’s corpuscles (arrow) and cortico-medullary differentiation and arranged in lobules at the hypodermis. The overlying dermis is devoid of adnexa and replaced by scar-like fibrous tissue. (B), (H.E.S). Ductal-like structures (arrow) opening at the surface of the skin, lined by a columnar, pseudostratified epithelium (at the left, half part).

Congenital thymic cysts should be differentiated from multilocular thymic cyst, as the latter represents an acquired, multilocular, inflammatory lesion arising from cystic dilatation of the medullary duct and associated with autoimmune diseases, such as Sjogren’s syndrome and aplastic anemia. These acquired thymic cysts are lined by squamoid, cuboidal, columnar, micropapillary or mixed glandular epithelium, and can present with pseudo-epitheliomatous hyperplasia. Secondary inflammation is commonly found but no cartilage or smooth muscle can be identified [26].

2.6.1. Clinical Findings

Bronchogenic cysts are often incidentally found in children and later in life. The volume usually increases with age, with the diameter ranging from 1 to 4 cm in infants. Bronchogenic cysts are usually sporadic. They are encountered predominantly within the mediastinum or the lung parenchyma and, in few instances, within the neck. Symptoms secondary to infection may occur, such as fever, hemorrhage or perforation. Bronchogenic cysts may be compressive in infants and responsible for respiratory distress. They are, however, not connected to the respiratory tract. Clinical differential diagnosis includes esophageal and enteric duplication cysts and pericardial cysts [27,28]. Diagnosis is often performed with histological analysis because of poorly specific clinical presentation: midline cyst also raise differential diagnosis as thyroglossal duct cyst, dermoid cyst, vascular malformation or thymic cervical cyst.

2.6.2. Histopathological Features

The bronchogenic cyst presents itself as an extrapulmonary unilocular cyst. The lumen contains fluid, turbid, mucinous or purulent material. Its wall is lined by respiratory epithelium overlying fibromuscular connective tissue containing seromucinous glands and cartilage plates (Figure 7A,B). Squamous metaplasia may occur. The presence of cartilage tissue is important for establishing the final diagnosis and differentiating between bronchogenic cysts and other cysts of the neck [27,29].

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Figure 7

Bronchogenic cyst. (A), (H.E.S). unilocular cyst lined by respiratory epithelium overlying circular muscular tunic (arrow). (B), (H.E.S.). In the wall, seromucous glands (arrowheads) and cartilage plates (*).