Head and Neck Cystic Lesions: A Cytology Review of Common and Uncommon Entities

Cystic lesions of the head and neck are a diagnostic challenge since they are the clinical presentation for a wide range of conditions. Neoplastic and non-neoplastic lesions may present as a cystic mass. Cystic lesions may be seen in either primary or secondary malignancies. Non-neoplastic lesions can be infectious, inflammatory, congenital, or developmental. Fine-needle aspiration (FNA) is a cost-effective and minimally invasive technique that is commonly used to diagnose head and neck lesions. It is performed by palpation or under image guidance including ultrasound and computed tomography [1, 2]. Clinical history and anatomical site of the lesion are valuable in terms of narrowing down the differential diagnosis of a cystic neck mass. Herein, cytomorphology of common and uncommon entities that present as a cystic mass in the head and neck are reviewed.

The PubMed, Google, Google Scholar, and Scopus were searched for peer-reviewed cytology articles written about head and neck cystic lesions. It was searched for key words like cyst and specific organs or specific neck sites. For example, key words searched were “thyroid and cyst,” “parotid and cyst,” or “anterior neck and cyst.” Combining the pathologic condition and cyst type was another way of looking for articles, for example, “medullary thyroid carcinoma and cyst” or “schwannoma and cyst.” We searched for articles about developmental cysts by looking for each entity such as “thyroglossal duct cyst.” The scope of this review was wide so the criteria for including papers were defined as (1) all cited papers were peer-reviewed; (2) including sound published papers globally and from different authors, different institutions, and different countries; (3) including experts’ published findings; (4) looking for the papers that were published in the last 10 years first and then extend the search beyond that date only if there were key papers needed to be included; and (5) the papers with more case numbers were preferred to case reports. We reviewed 413 papers and 71 papers met the criteria. The entities were discussed based on anatomic site and the origin of the lesion.

Cystic thyroid nodules are referred to as thyroid nodules that are filled with fluid. Thyroid nodules can be cystic or partially cystic. Approximately, 15–25% of thyroid nodules are cystic and mostly benign [3]. Cysts are formed after spontaneous hemorrhage occurs within the solid nodule. Spontaneous or cystic degeneration of adenomatoid nodules is what gives rise to most thyroid cysts. On cytology, adenomatoid nodules with cystic degeneration have macrophages in the background (shown in Fig. 1a). The cyst-lining cells are follicular cells that have undergone reactive changes including spindle- or elongated-shaped morphology, large round to oval nuclei with distinct nucleoli, fine chromatin, smooth nuclear contour, distinct cytoplasmic borders, and occasional exaggerated unipolar/bipolar cytoplasmic processes [3, 4]. Rarely, aspirates from the FNA may exclusively consist of benign-appearing, mature squamous cells [5]. It is worth noting that about 10–15% of thyroid nodules represent malignancy [6]. Papillary thyroid carcinoma (PTC) is the most common form of thyroid cancer comprising up to 80% of thyroid malignancies [7]. It is more frequent in women and patients under the age of 40 years. PTC typically is an indolent tumor [7]. The cytologic features seen in PTC are elongated, enlarged nuclei with hyperchromatic chromatin, nuclear grooves, and intranuclear pseudoinclusions (shown in Fig. 1b). The neoplastic cells can be seen arranged in clusters or as single cells in a background of thick colloid, nuclear, or calcific debris; macrophages; and stromal fragments. Bubble gum colloid, ropy colloid, and colloid attached to the malignant cells is a useful diagnostic clue in PTC in a cystic background [7, 8]. Medullary thyroid carcinoma (MTC) accounts for approximately 5% of all thyroid malignant neoplasms, and 20% of MTC occur as part of familial disorders [9, 10]. Cystic MTC is a very uncommon clinical presentation with rare reported cases [11]. FNA shows cellular pleomorphism, including small cells, elongated cells, and plasmacytoid cells characterized by eccentric nuclei. The nuclei are small and round to elongated, occasionally binucleated, with finely granular chromatin patterns characteristic of neuroendocrine tumors. The cytoplasm is granular with distinct cell borders. Measurement of needle washout calcitonin level, elevated serum calcitonin, procalcitonin, and CEA, and immunoexpression of calcitonin on aspirated cells are diagnostic clues [10, 11]. Immunohistochemistry can also be used to aid in the diagnosis of thyroid cysts. In both PTC and adenomatoid nodule, there is positivity for TTF-1, thyroglobulin, and PAX8 [12]. Besides these entities, a cystic mass of the thyroid can also represent more rare conditions. One of these examples is an epidermal inclusion cyst [13, 14]. The aspirated material shows benign mature squamous cells in addition to follicular cells in a background of debris and scattered anucleate squamous cells [13, 15]. A case of epidermal inclusion cyst was reported to be adjacent to the thyroid mimicking a thyroid nodule [6]. Cystic echinococcosis, also known as hydatid cyst, is a parasitic disease that can present as a thyroid nodule in reported cases. It can involve multi-organs or the thyroid only. On cytology, large single hooklets, characteristic of cysticercosis, can be found in a background of thick colloid, mixed inflammatory cells, and occasional granulomas [16‒18]. Ultrasound imaging is routinely used to assess the characteristics of the thyroid nodules, which can detect a cystic versus solid thyroid nodule. Cysts are detected as anechoic with thin walls and smooth margins. Lesions that appear more hypoechoic relative to the thyroid gland have an increased likelihood of malignancy. Using imaging and FNA can yield the proper diagnosis, which in turn determines the type of treatment for the thyroid nodule [7].

Parathyroid cysts (PCs) are rare lesions that account for 1–5% of neck masses and 0.5% of parathyroid glands’ pathologies. PCs are more common in females (male:female of 1:1.85), typically appearing in ages 40s and 60s [19]. The most common location of PCs is near the left thyroid lobe (31.6%), and the cyst diameter ranges from 0.5 to 15 cm [20]. They are divided into two main categories, depending on their hormonal activity: functional and nonfunctional. Functional PCs are associated with increased levels of parathyroid hormone (PTH) unlike nonfunctional PCs. Most PCs are nonfunctional and can be mistaken for other neck masses, such as thyroid cysts [21]. Although females are most likely to have a PC, functional ones tend to be most common in men [22]. The most common clinical presentation of a PC is an asymptomatic neck mass; however, it may present with compressive symptoms in up to 20% of cases [20]. Cytologic examination shows clusters of epithelial cells and fibroblasts. FNA cellularity varies from scant to abundant. The cellular arrangement varies from lattice-like sheets, sheets of parathyroid cells, poorly formed rosette formation to compact clusters. Occasional naked nuclei are seen. The cells are characterized by mildly variable in size, round, and slightly eccentric nuclei with smooth to stippled chromatin; inconspicuous nucleoli; and delicate, indistinct blue to gray cytoplasm in Diff-Quik Smears. Fine cytoplasmic vacuolization is noted in high magnification [23].

Cytologically, nonfunctional PCs are lined by thin-walled cuboidal or columnar epithelium. Functional PCs lack this epithelium [20]. Other tissues such as thyroid and thymic tissue can be found in the cyst wall along with parathyroid tissue [19]. Immunohistochemistry can be used to aid in the diagnosis. There is positivity for chromogranin-A, synaptophysin, and PTH. TTF-1 and thyroglobulin are both negative [24]. In general, the most useful diagnostic tool for detecting PCs is ultrasound-guided FNA. The aspiration sample from FNA, consisting of cystic fluid, can be tested for elevated PTH levels to confirm the diagnosis of PCs [19].

Thyroglossal duct cyst is the most common congenital/developmental anomaly presenting as an anterior cervical mass. It affects both genders equally. Thyroglossal cysts are mainly found in the pediatric population and rarely in elderly patients, with the mean age of 26–55 years. It is predominantly located midline and less commonly left para-midline and right para-midline [25‒27]. The size of the cyst varies from 0.5 cm to 5 cm. Embryologically, the thyroglossal duct is a remnant of the thyroid anlage that fails to descend from the foramen cecum of the tongue to final peritracheal position [26]. The general presentation of a thyroglossal cyst is painless swelling in front of the neck moving with protrusion of the tongue since the cyst is attached to the base of the tongue or the hyoid bone [27]. A painful infected thyroglossal duct cyst or a discharging sinus can be the initial presentation following an upper respiratory tract infection [26]. FNA of thyroglossal duct cyst shows abundant macrophages, inflammatory cells including lymphocytes and neutrophils, and occasional multinucleated giant cells. The epithelial component is predominantly ciliated columnar epithelium, mature and immature squamous epithelium, parakeratotic squamous cells, and rarely thyroid follicular epithelium (shown in Fig. 1c). The background component can be watery, granular, proteinaceous, mucinous, or colloid. Cholesterol crystals can be seen in a subset of cases [27]. The differential diagnosis includes a branchial cleft cyst, epidermal inclusion cyst, lymphoepithelial cyst (LEC), thyroid gland cyst, PTC, and metastatic squamous cell carcinoma [27]. A thyroglossal-associated PTC is reported in small subsets of cases. This is often the classic form of PTC compared to the follicular variant or PTC with tall cell features. This diagnosis should be rendered after exclusion of PTC of the pyramidal lobe of thyroid (present in 50% of cases) or metastatic PTC of the Delphian node of midline (prelaryngeal lymph node located anterior to the cricothyroid membrane and superior to the isthmus) [26]. Clinical differential diagnosis of thyroglossal duct cyst includes thyroid malignancy, multinodular goiter, dermoid cyst, lymphadenopathy, and lipoma. Macrophages consistently appear to be the dominant cell type in aspirated material and cholesterol crystals, and stratified squamous epithelial cells enable differentiation of thyroglossal duct cysts from thyroid gland cystic nodules [28].

Thymic cysts rarely occur in the neck area. They affect females more commonly than males (M:F; 4:5) with the mean age of 36 years. They are more common on the left side than right and midline. They can be unilocular or multilocular with variable sizes. Most cases are asymptomatic, painless, and present as a slow-growing mobile neck mass. Cough, dyspnea, hoarseness, sore throat, and odynophagia are the most common symptoms reported in patients. Surgical excision shows thymic tissue consists of cuboidal or flat epithelium and Hassall’s corpuscle. Cytology shows epithelial cells and lymphocytes in a background of macrophages and cyst fluid [29]. The findings for anterior neck cysts are summarized in Table 1.

Lateral neck cysts typically present as a lump or mass near the anterior sternocleidomastoid muscle on the lateral sides of the neck. Due to the anatomical locations of the carotid artery and jugular vein, vascular or lymphatic lesions may present as solitary cystic lateral neck mass. In patients under 40 years old, benign branchial anomalies are the most common diagnosis of lateral neck masses [30]. With increasing age, differentiating between branchial cleft cysts and cystic lymph node metastasis becomes challenging. Malignancy is a key component that must be considered in a lateral neck cyst in patients over 40 years of age [30, 31]. Malignancy has been reported to be as high as 56% in adults over 40 compared to 1.6% for those under the age of 40 years. The proportion of malignancy is greater than 80% in patients over the age of 70 years and is most commonly found in female patients [32].

Common differential diagnoses for patients with malignant cystic lesions include malignant lymphoma (Hodgkin’s lymphoma, non-Hodgkin’s lymphoma), and carcinoma (PTC, squamous cell carcinoma). Metastatic diseases can be characterized cytologically and based on immunophenotype. Cytology and immunohistochemistry for PTC and squamous cell carcinoma are described in the thyroid cyst and head and neck carcinoma sections, respectively. The differential diagnoses for nonmalignant cystic lesions include branchial cleft cysts, granulomatous infection, epithelioid-cystic lymphadenitis, Warthin’s tumor, and thyroid cysts [32].

Squamous cell carcinoma is among the most common types of head and neck cancers. Squamous cell carcinoma can be divided into human papilloma virus (HPV)- related and non-HPV-related sub-groups. HPV-related squamous cell carcinomas typically originate in regions of the oropharynx including the oral cavity, oropharynx, hypopharynx, and larynx. HPV-related squamous cell carcinoma is associated with high-risk HPVs. HPV16 and HPV18 encounter almost 90–96% of all HPV-related squamous cell carcinomas [33].

FNA is a routinely used procedure for the diagnosis of HPV-related head and neck carcinoma. Cytologically, cells from HPV-related carcinoma have a high nuclear to cytoplasmic ratio and are usually minimally keratinized, small, monomorphic, and spindle-shaped compared to non-HPV related SCCs [33, 34].

Both HPV and non-HPV SCC are immunoreactive for p53 and cytokeratin. Additionally, HPV SCC is positive for p16. Since p16 is a tumor suppressor protein that is overexpressed in all types of HPV infected cells, immunostaining against p16 is a very sensitive surrogate marker [35].

In situ hybridization (ISH) is the most sensitive method to detect HPV infection [36]. Using DNA ISH, the infected cells present with “punctuate” nuclear pattern, which consists of discrete signals in the nucleus. A diffuse pattern implies an extrachromosomal “bystander” DNA. Using RNA ISH, “punctuate” patterns in either the nucleus or cytoplasm are considered positive. RNA probes are often complementary to E6/E7 mRNA. Since it only targets transcriptionally active viruses, it does not detect bystander viruses [36‒38].

HPV-negative squamous cell carcinoma is mostly associated with excessive consumption of alcohol and tobacco. The chance of head and neck squamous cell carcinoma in smokers is about ten times greater than that of nonsmokers [39]. Unlike the HPV-positive head and neck SCC, the cells of HPV-negative head and neck SCC are often moderately or well-differentiated, with preservation of stratification and keratinization [40]. The HPV-negative squamous cell carcinoma shows null or minimal staining with p16 immunostaining, and it is negative for HPV studies [35, 40]. Both HPV-related and non-HPV related squamous cell carcinomas commonly present as a cystic mass or a cystic lymph node (shown in Fig. 2a–e). Branchial cleft cyst and epidermal inclusion cyst (shown in Fig. 2f) remain the most important differential diagnoses with squamous cell carcinomas. In patients younger than age of 40 years, branchial cleft cyst is a more likely diagnosis, while squamous cell carcinoma and branchial cleft cyst should be considered in patients older than 40 years of age [41]. Table 2 summarizes the common entities with cystic presentations in the lateral neck.

Parapharyngeal space (PPS) tumors are rare lesions that comprise less than 0.5% of head and neck masses [42]. The majority of the lesions, 66.4% up to 87.3% of the cases, are benign and 18% are malignant [42, 43] (Table 3). The PPS is a complex space located in the suprahyoid neck resembling a pyramid with the base formed by the skull base and the apex pointing to the greater cornu of the hyoid bone, mainly divided pre- and poststyloid space [44]. They present as a cervical mass (50%) or an intraoral mass (47%). Salivary gland tumors (45%) were the most common neoplasms followed by neurogenic lesions (41%) in a systematic review of 1,143 cases of PPS tumors [42]. Pleomorphic adenoma is the most common benign salivary gland neoplasm of prestyloid area, and paraganglioma and schwannoma are common neurologic neoplasms located in poststyloid area, respectively [43, 45]. Cytology examination of a pleomorphic adenoma typically shows an admixture of epithelial and myoepithelial cells with a fibrillary myxoid and chondroid matrix. Paragangliomas may be solid or cystic and are typically hypervascular. They have variable cellularity with epithelioid, plasmacytoid, or spindled morphology. They are immunoreactive for chromogranin A and synaptophysin, while negative for cytokeratin [46]. Yet, given the placement of these masses, they can compress vital structures that run through the PPS which can be life-threatening [45]. Paragangliomas can be mistaken for malignant neoplasms such as thyroid carcinomas due to their plasmacytoid or spindle cell morphology, nuclear inclusions, and cystic background [46]. The more common primary malignant tumors are adenoid cystic carcinoma, squamous cell carcinoma, and malignant peripheral nerve sheath tumors. Synovial sarcoma is a rare malignant neoplasm of the head and neck in pediatrics, which may present as a cystic mass [47]. Metastatic thyroid carcinoma and metastatic squamous cell carcinoma are among secondary lesions involving this anatomic site [42]. Developmental cysts such as branchial cleft cyst, epidermoid cyst, and dermoid cyst can occur in the PPS [42]. Schwannoma is the most common type of peripheral nervous system tumor seen in this area and is almost entirely composed of Schwann cells on aspirated material.

It affects both males and females, although it is slightly more common in females (23:35). The mean age is 49.6 years (range 6–82 years) [48]. It presents with palpable superficial masses. The head and neck area is a common site for presentation of schwannoma comprising 25–45% of all schwannoma cases [49]. The reported sites are the tongue, hard palate, lower lip, buccal mucosa, floor of the mouth, mandible, parotid gland, maxilla, and cheek [49].

The aspirates of schwannomas are moderate to highly cellular. The cells are arranged in cohesive fragments or scattered single cells with bipolar cytoplasmic processes. The tissue fragments are small or large. A fibrillary stroma is seen in majority of the cases. The cells are arranged in fascicles in most cases, while others showed random distribution of nuclei. The nuclei are oval to pointed with smooth nuclear membrane and fine chromatin. Mitotic figures are not seen. Nucleoli are absent or small and indistinct when they are present. Fishhook-like nuclei, intranuclear inclusions, and marked nuclear pleomorphism are other features that can be seen in schwannoma. Degenerative changes are characterized by smudged hyperchromatic nuclei and loss of chromatin details. Occasionally, hemosiderin and scattered lymphocytes are seen in the background [48]. Schwannoma is composed of two tissue patterns: Antoni A and Antoni B. Antoni A are hypercellular regions characterized by elongated cells and palisading nuclei that are tightly packed together, and a basement membrane rich in laminin, a glycoprotein produced by Schwann cells, known as Verocay bodies. Antoni B regions are loosely organized tissue with myxomatous and cystic changes frequently found adjacent to Antoni A regions. Antoni B tissue may contain inflammatory cells such as lymphocytes and histiocytes and they may represent degenerated Antoni A tissue [50]. Cystic formation and hemorrhage may cause diagnostic challenges [49]. Immunohistochemical staining of schwannomas is particularly useful in the differentiation of schwannoma from other spindle cell neoplasms of the head and neck. Immunohistochemical positivity for S-100 is very useful in differentiating schwannoma from neurofibroma, squamous cell carcinoma, fibrosarcoma, or neuroendocrine carcinoma [51]. In addition to the S-100 protein, schwannoma demonstrates immunohistochemical positivity for CD68 and SOX10 [52]. FNA is commonly used in the diagnosis of head and neck tumors and cysts, including schwannomas. However, it is important to note that FNA has its own limitations for a definitive diagnosis of schwannoma in absence of immunohistochemistry and presence of cystic changes [48, 53].

Branchial cleft cysts are formed during embryonic development. They appear as a painless, compressible lump in the neck or just below the mandible [54]. They occur equally in both males and females [55]. Branchial cleft cysts, while typically present in young patients, can be found in any age demographic. Branchial cleft cysts are seen in different anatomical locations: deep to the platysma, anterior to the sternocleidomastoid, abutting the internal carotid artery and adherent to the internal jugular vein (most common), extending between the internal and external carotid arteries, and abutting the pharyngeal wall and potentially extending superiorly to the skull base [56]. Branchial cleft cysts are classified as below:

• First branchial cleft cyst: epidermoid cyst, dermoid cyst, cystic sebaceous lymphadenoma.

• Second branchial cleft cyst: lateral thyroglossal duct cyst.

• Third branchial cleft cyst: ectopic thyroid.

• Fourth branchial cleft cyst: thymic cyst.

The etiology of branchial cleft cysts is still debated. Differential diagnoses besides a branchial cleft cyst to consider are metastatic squamous cell carcinoma, tuberculosis-related lymphadenitis, HIV-related lymphadenopathy, sarcoidosis, cat-scratch disease, lymphoma, and PTC metastasis [56]. The location and cytomorphology of branchial cyst are important factors to yield the correct diagnosis. The aspirated material appears yellow, pus-like fluid. The aspirates consist of keratinized anucleate cells, squamous epithelium, and a matrix of amorphous debris [57]. Atypical features such as high nuclear to cytoplasmic ratio, irregular nuclear membranes, and small cell clusters raise the possibility for a malignant process [58]. LECs, also known as branchial cysts, are non-neoplastic cysts that typically appear in the head and neck. These cysts grow in either a unilocular or multilocular lesion. Possible etiologies for LECs include lymphocyte-induced cystic ductal dilatation and entrapment of salivary epithelium during embryogenesis. Although they are typically seen in adults, they have also been seen in children. Ranging from 0.5 to 5.0 cm in greatest dimension, if left untreated, the cyst rarely transforms into a malignant lesion.

Cytologically, LEC consists of dense polymorphous lymphocytes with predominantly squamous or less commonly glandular or cilicated epithelium (shown in Fig. 3a). A confirmatory diagnosis is made on histologic examination of the excised cyst. Surgical excision is the conventional treatment for LECs, which includes the enucleation of the cyst or resection. If the cyst is in the salivary gland, the entire gland may be removed as well.

Epidermal inclusion cysts (EICs) also known as epidermoid cysts, infundibular cysts, keratin cysts, inclusion cysts, and epidermal cysts, are developmental cysts. These cysts are typically benign, slow-growing with variable size, and can occur anywhere on the body, although most often they occur on the back, neck, and head [59]. They typically manifest as a small nodule with visible punctum, located in the mid and lower dermis. They are thought to be derived from the infundibular portion of the hair follicle [60].

It is unclear whether EICs will enlarge, become infected, or remain dormant; however, infected EICs become erythematous, filled with pus, and painful or noticeable to patients. FNA aspirate is typically thick and non-liquidus. It shows both anucleate squamous and nucleated squamous epithelial cells, as well as extracellular keratinous material. Aspirate from infected EICs shows additional features including inflammatory cell infiltrate, including lymphocytes and neutrophils [61]. A surgical resection confirms the diagnosis [59].

Salivary gland neoplasms constitute approximately 6% of all head and neck neoplasms [62]. Cystic salivary gland lesions are even more rare and account for up to 8% of all salivary gland lesions [63] (Table 4). Both non-neoplastic and neoplastic lesions may clinically present as cystic [64]. Cystic salivary gland lesions may pose diagnostic challenges due to low cellularity, and the presence of mucoid or nonspecific watery background [63]. Developmental and congenital cysts may occur in salivary glands including epidermal inclusion cysts, branchial cleft cysts, and LECs [64]. Mucocele, duct ectasia, salivary duct cyst, squamous lined cyst, and retention cysts are non-neoplastic conditions presenting as cysts [65, 66]. Occasionally, chronic sialadenitis may present as a cystic mass [64]. Warthin tumor is the most common benign neoplasm presenting as a cyst. It is characterized by clusters and fragments of oncocytic epithelium admixed with small mature lymphocytes, occasional epithelioid histiocytes forming germinal centers in a dirty watery background on cytology. Pleomorphic adenoma, apocrine hidrocystoma, sebaceous lymphadenoma, cystadenoma, hemangioma, and lymphadenoma are other benign neoplasms that rarely present as a cyst. Presence of atypical metaplastic squamous cells may cause a diagnostic pitfall in cystic benign neoplasms [67]. Malignant salivary gland neoplasms may also present as a cystic lesion including mucoepidermoid carcinoma, squamous cell carcinoma, secretory carcinoma, and acinic cell carcinoma [64]. Mucoepidermoid carcinomas are low-grade or high-grade tumors. Abundant mucin is associated with low-grade mucoepidermoid carcinomas (Shown in Fig. 3b–d). FNA of large cystic low-grade mucoepidermoid carcinomas may show abundant mucin with rare mucin containing epithelial cells and can be misinterpreted as a retention cyst [67]. Other neoplasms can rarely present as cystic lesions such as lymphoma [64]. A study evaluated the risk of malignancy in 178 cystic salivary lesions, applying the Milan System for Reporting Salivary Gland Cytology. Non-neoplastic (44.9%), nondiagnostic (29.2%), and atypia of undetermined significance (19.6%) were the most common categories, respectively. The risk of malignancy was 22.2% for nondiagnostic category, 19% for non-neoplastic category, 29.4% for atypia of undetermined significance, 50% for salivary gland neoplasm of uncertain malignant potential, and 100% for suspicious for malignancy category.

Additionally, ranula or mucocele may also appear as a cystic neck mass. Aspirated material consists of mucin and occasional macrophages (Shown in Fig. 3e).

The enlarged lymph nodes may present as a cystic mass. Cystic lymphadenopathy can be the clinical presentation of a group of benign and malignant conditions. The French Society of Otolaryngology- Head and Neck Surgery proposed a diagnostic procedure for cervical lymphadenopathy with cystic changes [47]. A study of 196 patients presenting with supposedly benign cystic cervical lymphadenopathy showed that 3.6% were malignant including 3.1% metastatic squamous cell carcinoma and 0.5% were metastatic PTC. Head and neck squamous cell carcinoma including oropharyngeal and nasopharyngeal followed by PTC were the most common causes of cystic lymphadenopathy reported in two different studies on 136 and 67 cases, respectively. Metastatic lung cancer, cutaneous squamous cell carcinoma, melanoma, and rarely lymphoma can present as a cystic lymphadenopathy. Non-neoplastic lymphadenopathy can be due to infectious agents. Tuberculosis can present as cystic lymphadenopathy and it is more frequently seen in endemic areas (up to 40% of cervical masses) [68]. Caseating granulomas are cytologic findings on FNA, and PCR can confirm mycobacterium tuberculosis. Atypical mycobacteria, Bartonellosis (caused by Bartonella henselae), and Tularemia (Francisella Tularensis) are examples of other infectious agents that can cause cystic lymphadenopathy [47, 69‒71].

Abscesses can present as a cyst in any areas of the head and neck. FNA shows pus consists of numerous neutrophils and necrotic debris (shown in Fig. 3f). ROSE is diagnostic, and the aspirated material can be sent to the microbiology laboratory for bacterial studies.

Diagnosis of cystic lesions in the head and neck is challenging due to the diversity of entities that can present as cysts. We have reviewed the common and uncommon entities presenting as head and neck cysts. FNA remains a cost-effective and minimally invasive method that is commonly used for the diagnosis of head and neck cysts. However, it is important to note that the diagnostic accuracy of FNA is variable for different conditions. Ultrasound guidance and sampling from representative sites are common practices to improve the diagnostic accuracy of FNA. Ancillary studies such as immunostains on cell blocks or core biopsies are other modalities to improve diagnostic accuracy. Age of greater than 40 years may raise the possibility of a malignant process. Squamous cells can pose diagnostic dilemmas and they should be evaluated very carefully.

The authors have no conflicts of interest to declare.

The authors have no funding sources to disclose.

Sandra Vazquez Salas, Katie Pedro, Amrita Balram, Sarah Syed, Kent Kotaka, Ana Kadivar, Benjamin Eke, Madison McFarland, Michelle Sung, Niranjan Behera, and Benjamin G. Dunber: writing – original draft, data curation, investigation, resources, and writing–review and editing. Zahra Maleki: conceptualization, data curation, formal analysis, investigation, methodology, project administration, resources, software, supervision, validation, visualization, writing – original draft, and writing – review and editing.