The eyelid contains various histological components including eyelid skin squamous epithelium, subcutaneous tissue (comprising eccrine and apocrine glands), the tarsal plate (consisting of meibomian glands) and palpebral conjunctiva. Cystic lesions are a type of benign eyelid tumor arising in the subcutaneous tissues of the eyelid, the tarsus and beneath the palpebral conjunctiva (1). Common eyelid cystic lesions may be characterized as epidermal or intratarsal keratinous cysts (IKC), eccrine hidrocystoma, milia or steatocystoma (1–3). The pathogenesis of eyelid cystic lesions may be associated with the occlusion of ducts within the tarsal plate or with the aberrant invagination of the epithelium (1,4). Chalazion is also a common inflammatory disease arising in the eyelid, which histologically presents with lipogranuloma without cyst formation. Although cystic lesions are benign, they can be clinically confused with malignant tumors such as sebaceous carcinoma, which possibly manifest clinical features including blepharitis or chalazion (5). IKC arising in the meibomian gland has been described (1). IKC is a non-inflammatory intratarsal cyst which is considered to arise from the meibomian gland duct (1). It is important to understand the clinical features of IKC, and differentiate IKC from other eyelid diseases, as IKC requires a total excision with partial tarsectomy. Otherwise, IKC can easily relapse if removed by simple incision and/or curettage (1,2). Indeed, cases of IKC have been frequently misdiagnosed as chalazia or epidermal cysts, and recurred following incomplete resection of the cysts' wall and/or curettage (1,2). The incidence of IKC among cystic lesions of the eyelid, however, remains unknown. If the incidence and clinicopathological features are clearly provided, these results may contribute to the better treatment of eyelid cystic lesions and tumors. The aim of the present study was to investigate the clinicopathological features of cystic lesions in the eyelid including IKC.

Primarily, the current study determined that the upper eyelid was the most frequent site of the cystic lesions in the studied patients. Although the reason remains unknown, the longitudinal length of eyelid skin and tarsus being longer in the upper eyelid than the lower eyelid, and the number of meibomian glands and hair follicles being anatomically greater in the upper eyelid than the lower eyelid may be causes. These known facts mean that the upper eyelid possess a greater volume and area, thus resulting in a greater number of cystic lesions in the upper eyelid than the lower eyelid.

Deprez and Uffer (3) reported that among 5,504 eyelid skin tumors excluding chalazion and tumors of the palpebral conjunctiva, benign tumors made up 84% of the cases, and the frequency of the subtypes was squamous cell papilloma (23% in benign tumors), seborrheic keratosis (19%), melanocytic nevus (18%), epidermal cyst (11%) and hidrocystoma (7%). Out of 849 cystic lesions, the most frequent subtypes were epidermal cyst (58% in cystic lesions), followed by hidrocystoma (38%) and dermoid cyst (4%) (3). Epidermal cysts typically form a smooth dome-shaped elevation of varying size that may have an opening site to the eyelid surface (4). Epidermal cysts histologically have their wall constituted by keratinized stratified squamous epithelium with a granular layer, in which the content is laminated layers of keratin (4). In the current study, epidermal cysts were the most common lesions in the eyelid cystic lesions as reported previously (3).

Interestingly, IKCs were the second most common lesion in our cohort. IKC is characterized by localization of the cystic lesion in the tarsus. Clinically, an IKC presents as a lump under the eyelid skin or beneath the conjunctiva that is stationary and does not move with manipulation of the overlying eyelid skin (1,6). Histologically, the cyst contains an undulating surface lined by 4–5 layers of polygonal keratinocytes that exhibit abrupt keratinization without keratohyalin granules (trichilemmal keratinization) (1,7). The lumen of the cysts is filled with abundant, eosinophilic, refractile and string-like keratin (7). By contrast, neither goblet cells nor sebaceous cells are intermixed in the wall of IKC (1). As IKCs are among the more recent cysts to be characterized (1), and are likely to mimic the histological findings of epidermal cysts, IKCs may have been classified as epidermal cysts in previous years. Indeed, IKCs have been reported as the third most common lesions following chalazia and sebaceous tumors among the lesions originating from the tarsal plates (1). Collectively, the present findings indicated that IKCs were also a fairly common histological subtype among cystic lesions of the eyelid in the test population.

Previous studies reported that sporadic IKCs presented with a single nodule (95%), and could occur in the upper eyelids (95%), were slightly more frequent in men (56%) and were more frequent in older individuals (mean age, 56 years) (6). By contrast, eyelid cysts, typically IKCs, tended to occur bilaterally as multiple eyelid cysts (80%) and were observed at earlier ages (mean age, 40 years) in Gorlin (nevoid basal cell carcinoma) syndrome (6). In the current study, all of the IKCs were sporadic, and the mean age was 68±14 years. All of these lesions involved the upper eyelid as a single cyst, and there was no obvious gender predilection (two males and three females).

In the current study, 6 cysts were not classified. Of these, 4 out of 6 cases were unclassifiable because they lacked epithelium and/or the contents of the cysts, possibly due to dropout during the process of obtaining pathological sections. The other 2 cases were initially considered an apocrine hidrocystoma and an IKC. However, the former was atypical as an apocrine hidrocystoma since the cyst exhibited an eosinophilic amorphous structure with cholesterol cleft in the lumen, which is not commonly found in an apocrine hidrocystoma (4). The latter was morphologically atypical as an IKC because the epithelium exhibited melanin. Jakobiec et al (1) reported that immunostaining of cytokeratin (CK)17, carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA) may distinguish IKCs from epidermal cysts; CK17, CEA and EMA are positive for IKCs, and negative for epidermal cysts. Further immunopathological studies would have been required to elucidate the origin of the cystic lesions.

There were limitations to the current study. Firstly, the number of patients with cystic lesions was relatively small due to it being a single-center study. Therefore, the study did not include other eyelid cystic lesions such as eccrine hidrocystoma, milia and steatocystoma that were not encountered in our center. Secondly, because it was a retrospective study, the follow-up periods, and the amount of information obtained from the medical records differed for each patient. Therefore, the location of cysts in certain patients was unknown, and some cysts may have recurred after the follow-up period.

In conclusion, the upper eyelid was the most frequent site of cystic lesions in the eyelid in the studied cohort. The most common diagnoses were epidermal cysts followed by IKCs, though unclassifiable cysts were intermixed with the total lesions studied. The current study indicates that the incidence and differential diagnosis of eyelid cystic lesions may contribute to the implementation of appropriate treatment for patients with eyelid tumors.