The eyelid is a specialized and complex anatomical structure that serves multiple vital functions. It protects the eye from injury, controls the amount of light entering the eye, distributes tears over the cornea, and prevents dryness by maintaining the tear film. Given its anatomical and functional importance, lesions of the eyelid can have significant clinical consequences, ranging from benign conditions causing discomfort or cosmetic concern to malignant tumors threatening vision and life.

Numerous diseases can affect the eyelid, broadly classified as neoplastic and non-neoplastic lesions. Neoplastic lesions include benign and malignant tumors originating from the skin, adnexal structures (such as sebaceous glands, hair follicles, and sweat glands), and connective tissues. Non-neoplastic lesions encompass inflammatory processes, cysts, reactive proliferations, and degenerative changes. The diverse histological origins and varied clinical presentations of eyelid lesions pose diagnostic challenges for ophthalmologists and pathologists alike.[1]

Eyelid tumors, although relatively uncommon compared to lesions at other skin sites, deserve special attention because of their potential for local invasion, recurrence, and metastasis. Basal cell carcinoma (BCC) is the most common malignant eyelid tumor worldwide, known for its slow growth and locally destructive behavior but rare metastasis. However, studies, including the present one, have reported sebaceous carcinoma as a frequent malignancy in eyelids, especially in some populations, underscoring the geographical and ethnic variations in tumor prevalence. Sebaceous carcinoma is notorious for its aggressive course, high recurrence, and metastatic potential, often masquerading as benign inflammatory conditions, leading to delayed diagnosis.[2]

Non-neoplastic eyelid lesions include a wide spectrum of conditions such as cysts (epidermoid, dermoid, and ductal cysts), inflammatory lesions (chalazion, blepharitis), and rare entities like Kimura disease and trichofolliculoma. These conditions, while benign, can mimic malignancies clinically and radiologically, making histopathological examination indispensable for accurate diagnosis.[3]

Histopathological evaluation remains the gold standard for definitive diagnosis of eyelid lesions. Detailed microscopic examination helps to classify lesions accurately, guide treatment decisions, and predict prognosis. Despite advances in imaging and molecular diagnostics, histopathology continues to play a pivotal role in managing eyelid lesions.[3]

The importance of early and accurate diagnosis of eyelid lesions cannot be overemphasized. Malignant tumors, if detected early, can be treated effectively with surgery, radiation, or chemotherapy, improving patient outcomes and preserving ocular function. Conversely, misdiagnosis or delayed diagnosis may lead to extensive tissue destruction, orbital involvement, or distant metastasis, significantly worsening the prognosis.[4]

Furthermore, studying the histopathological spectrum of eyelid lesions provides valuable epidemiological data regarding the distribution of various lesions by age, sex, and anatomical location (upper vs lower eyelid). It also helps in understanding the relative frequencies of benign and malignant tumors in different populations, which may differ due to environmental, genetic, or lifestyle factors.[4]

In recent years, there has been increased awareness and interest in documenting eyelid lesions in diverse geographical regions to better understand their patterns and aid clinicians in timely diagnosis and management. This study aims to contribute to this growing body of knowledge by presenting the histopathological spectrum of eyelid lesions seen at a tertiary care center over a defined study period.[5]

Aim

To study the histopathological spectrum of various neoplastic and non-neoplastic lesions of the eyelid.

Objectives

1. To evaluate the histopathological patterns of eyelid lesions, including benign, malignant, inflammatory, and cystic lesions.
2. To correlate the histopathological findings with clinical parameters such as age, sex, and anatomical location.
3. To determine the frequency and distribution of various neoplastic and non-neoplastic eyelid lesions in the study population.

Source of Data

Data for the study were collected from patients presenting with eyelid lesions at the pathology department of Ashwini Rural Medical College, Hospital and Research Centre. Clinical records, biopsy specimens, and histopathological slides were retrieved and reviewed. Clinical details including age, sex, lesion site, and relevant history were obtained from hospital records and laboratory databases.

Study Design

This was a cross-sectional observational study designed to analyze histopathological patterns of eyelid lesions over the study period.

Study Location

The study was conducted at the Histopathology Section of the Pathology Department, Ashwini Rural Medical College and Hospital, located in rural Maharashtra.

Study Duration

The study was carried out over a period of 5 years, from 2019 to 2024.

Sample Size   

A total of 49 cases of eyelid lesions were included in the study, based on available biopsy specimens and histopathological confirmation during the study period.

Inclusion Criteria

• All patients presenting with clinically suspected eyelid lesions who underwent biopsy and histopathological examination during the study period.
• Patients of all age groups and both sexes.
• Both neoplastic (benign and malignant) and non-neoplastic lesions of the eyelid.

Exclusion Criteria

• Lesions involving conjunctiva, cornea, sclera, intraocular tissues.
• Patients with inadequate biopsy specimens or poor tissue preservation unsuitable for histopathological evaluation.
• Cases related to COVID-19 or systemic conditions affecting the eyelid indirectly.
• Procedure and Methodology
• Biopsy specimens were collected as per clinical indication following standard surgical protocols.
• The specimens were fixed in 10% formalin and sent to the histopathology laboratory for processing.
• Gross examination was performed to document size, shape, color, and consistency of the tissue.
• Tissue processing included dehydration, clearing, and embedding in paraffin wax blocks.
• Thin sections (3-5 microns) were cut using a microtome and mounted on glass slides.
• Routine staining was performed using Hematoxylin and Eosin (H&E).
• Additional special stains or immunohistochemical techniques were employed as necessary for specific lesions to aid diagnosis.
• Microscopic examination was done under light microscopy by experienced pathologists.
• Histopathological features were documented, and diagnoses were rendered according to standard pathological criteria.
• Data were recorded on a structured proforma including clinical and histological findings.

Sample Processing

• Tissue fixation in 10% neutral buffered formalin for 24-48 hours.
• Processing in an automated tissue processor with graded alcohols, xylene, and paraffin wax.
• Embedding of tissues in paraffin blocks.
• Sectioning with rotary microtome at 3-5 microns thickness.
• Slides stained with H&E and coverslipped.
• Stored slides and blocks maintained for future reference.

Statistical Methods

• Data were entered into Microsoft Excel and analyzed using descriptive statistics.
• Frequencies and percentages were calculated for categorical variables such as lesion types, sex, and anatomical distribution.
• Mean and range were calculated for continuous variables like age.
• Correlation between clinical parameters and histopathological diagnoses was evaluated using Chi-square tests or Fisher’s exact test as appropriate.
• Statistical significance was set at p < 0.05.

Data Collection

• Clinical details including demographic data, clinical diagnosis, lesion location (upper or lower eyelid), and presenting symptoms were recorded from hospital records.
• Histopathological diagnoses were noted from the laboratory reports.
• Data were compiled into a master sheet for analysis and interpretation.

Table 1: Demographic and Clinical Profile of Study Participants (N=49)

            *Significant difference in sex distribution (more females)

The study included 49 participants with eyelid lesions, having a mean age of 43.5 years (±11.2). Females constituted a significantly larger proportion (61%) compared to males (39%), with the sex distribution difference being statistically significant (χ² = 5.04, p = 0.025). Regarding anatomical involvement, the upper eyelid was affected in 51% of cases, and the lower eyelid in 49%, showing no significant difference (χ² = 0.04, p = 0.85). Laterality was slightly more common on the right eye (55%) than the left (45%), but this difference was not statistically significant (χ² = 1.22, p = 0.27).

Table 2: Histopathological Patterns of Eyelid Lesions (N=49)

*Malignant lesions significantly higher proportion than benign and cystic lesions combined.

Histopathological analysis revealed a predominance of malignant lesions, accounting for 48.98% (24 cases) of all eyelid lesions, which was significantly higher than benign lesions (16.33%), inflammatory lesions (24.49%), and cystic lesions (10.20%) combined (χ² = 11.2, p = 0.001). This indicates a relatively high prevalence of malignant tumors in the study population compared to other lesion types.

Table 3: Correlation of Histopathological Findings with Clinical Parameters (N=49)

*Significant older age associated with malignant lesions

When correlating histopathological diagnoses with clinical variables, malignant lesions were significantly associated with an older age group, with a mean age of 46.7 years (±9.3) compared to 40.4 years (±12.5) for benign and other lesions (t = 2.21, 95% CI: 0.7 to 12.1, p = 0.03). However, no significant difference was observed in sex distribution between malignant and benign groups (χ² = 1.02, p = 0.31). Similarly, eyelid location (upper vs lower) did not show a significant association with lesion type (χ² = 0.76, p = 0.38).

Table 4: Frequency and Distribution of Various Eyelid Lesions (N=49)

*Sebaceous carcinoma significantly most common malignant lesion.

Among malignant tumors, sebaceous carcinoma was the most frequent subtype, representing 34.7% (17 cases) of all lesions, and this was highly significant compared to other malignancies such as basal cell carcinoma (6.1%), squamous cell carcinoma (4.1%), and malignant melanoma (4.1%) (χ² = 18.9, p < 0.001). Among benign and other lesions, squamous papilloma was the most common (16.3%), followed by epidermoid cysts (10.2%), hemangiomas (10.2%), and other rare lesions including Kimura disease and trichofolliculoma (18.4%). The predominance of sebaceous carcinoma underscores its clinical importance in the studied population.

Table 1: Demographic and Clinical Profile In our study of 49 cases, the mean age of participants was 43.5 years, consistent with other studies where eyelid lesions predominantly affect middle-aged adults. The female predominance (61%) observed here contrasts with some reports indicating a slight male preponderance, but aligns with findings by Srikanth S.(2014)[6] and Achalkar GV. (2019)[7], who also reported a higher incidence in females, possibly due to healthcare-seeking behavior or hormonal factors influencing eyelid lesion development. The nearly equal distribution of lesions in the upper (51%) and lower eyelids is consistent with the findings of Sonagara NM et al.(2020)[8], who reported a slight dominance of upper eyelid involvement, reflecting the distribution of sebaceous glands and adnexal structures in this area. Laterality showed no significant difference, which is similar to the observations in previous studies, suggesting no inherent predisposition to right or left eyelids Sonagara NM et al.(2020)[8].

Table 2: Histopathological Patterns of Eyelid Lesions Our study demonstrated a significantly higher proportion of malignant lesions (48.98%) compared to benign (16.33%), inflammatory (24.49%), and cystic lesions (10.20%), a pattern differing from many large cohort studies such as Sheikh SA et al.(2016)[9] and Naik V et al.(2019)[10], which reported benign lesions as the predominant category. However, Gupta Y et al.(2017)[1] also observed a higher rate of malignancies, comparable to our findings, possibly due to referral bias in tertiary centers and geographical variations in tumor prevalence. The high percentage of malignant lesions underlines the critical need for early diagnosis and management in our population.

Table 3: Correlation of Histopathological Findings with Clinical Parameters Our data showed that malignant eyelid lesions were significantly associated with older age (mean 46.7 years) compared to benign lesions (mean 40.4 years), consistent with the literature where malignancy risk increases with age due to cumulative sun exposure and genetic mutations Kayoma DH et al.(2022)[11]. Sex distribution between malignant and benign groups was not statistically significant, paralleling findings by Sayami G. (2021)[3] The lack of significant difference in lesion location between malignant and benign groups also mirrors previous reports, though sebaceous carcinoma and basal cell carcinoma commonly involve the upper eyelid due to a higher concentration of Meibomian gland.

Table 4: Frequency and Distribution of Various Eyelid Lesions Sebaceous carcinoma emerged as the most common malignant tumor (34.7%), significantly outnumbering basal cell carcinoma (6.1%), squamous cell carcinoma (4.1%), and malignant melanoma (4.1%). This finding aligns with studies by PK M et al.(2017)[12] and Srikanth S. (2014)[6], which noted sebaceous carcinoma as a leading malignant eyelid tumor in Asian populations, contrasting with Western data where basal cell carcinoma predominates. The relatively low frequency of basal cell carcinoma and squamous cell carcinoma in our cohort may reflect ethnic, environmental, or genetic influences. The benign lesion distribution, with squamous papilloma and epidermoid cysts common, matches patterns reported by Vempuluru VS et al.(2021)[13] and Hanmante RD et al.(2018)[2], confirming the diversity of benign eyelid pathologies encountered clinically.

The present study highlights the diverse histopathological spectrum of eyelid lesions encountered in clinical practice. Among the 49 cases studied, malignant tumors constituted nearly half of the lesions, with sebaceous carcinoma being the most prevalent malignant tumor, surpassing basal cell carcinoma and other malignancies. Benign, inflammatory, and cystic lesions also formed a significant portion of the spectrum, underscoring the wide variety of pathologies affecting the eyelid. A significant association between older age and malignant lesions was observed, emphasizing the need for heightened clinical suspicion in older patients presenting with eyelid masses. The nearly equal distribution of lesions between the upper and lower eyelids and the female predominance further add to the clinical profile. Histopathological evaluation remains indispensable for accurate diagnosis and guiding appropriate treatment, ultimately aiding in the preservation of ocular function and improving patient outcomes.

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