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Table of Contents
ORIGINAL ARTICLE
Year : 2022  |  Volume : 4  |  Issue : 1  |  Page : 13

A novel histopathological classification of chalazion: A series of 540 cases


1 The MUHC-McGill University Ocular Pathology and Translational Research Laboratory, McGill University, Montreal, Canada; Diagnostic Pathology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
2 The MUHC-McGill University Ocular Pathology and Translational Research Laboratory, McGill University, Montreal, Canada
3 Department of Ophthalmology, McGill University, Montreal, Canada
4 Cancer Research Program, The Research Institute of the McGill University Health Centre, McGill University, Montreal, Canada

Date of Submission07-Oct-2021
Date of Decision03-Feb-2022
Date of Acceptance03-Feb-2022
Date of Web Publication23-Mar-2022

Correspondence Address:
Dr. Hiroaki Ito
The MUHC-McGill University Ocular Pathology and Translational Research Laboratory, 1001 Boulevard Decarie, Block E, E02-2389, Montreal, QC, H4A 3J1, 514-934-1934 (Ext. 38773)

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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/pajo.pajo_112_21

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  Abstract 


Introduction: A chalazion is a common localized lipogranulomatous inflammation of the eyelid. Histopathological diagnosis of chalazia is essential to rule out malignancy in particular sebaceous carcinoma. Our aim is to understand and classify the histopathological findings of chalazia and to determine any association with a patient's demographics.
Materials and Methods: H and E sections were reviewed and classified into four categories: (1) lipogranulomas only, (2) lipogranulomas with multinucleated giant cells, (3) lipogranulomas with abscess, and (4) fibrosis without lipogranulomas or granulomatous inflammation. Patients' sex, age, and location of the lesion were analyzed.
Results: Five hundred and forty cases included men (54.6%) and women (45.4%) with the mean age of 45.3 (13–89; standard deviation, 16.8). Five hundred and eight had information regarding location: left lower eyelid, 21.1%; right lower eyelid, 19.5%; left upper eyelid, 30.5%; and right upper eyelid, 28.9%. Category 1 accounted for 44.6%; category 2, 41.5%; category 3, 7.0%; and category 4, 6.9%. There was no significant correlation between classification and sex (P = 0.210) or age group (0–50 and > 50) (P = 0.369) nor between presence of giant cells and/or abscess and location (P = 0.826). Mean ages of category 1 (47.0) and 2 (43.1) were significantly different (P = 0.011).
Conclusion: Four histopathological subtypes were equally distributed across sexes and eyelid locations. Individuals in category 1 are older than category 2. Favoring a systematic way to analyze the histopathology of chalazia may result in fewer missed diagnoses of malignancy and other inflammatory or infectious diseases.

Keywords: Chalazion, classification, histopathological findings


How to cite this article:
Ito H, Nassrallah G, Bergeron S, Arthurs B, Burnier JV, Burnier MN. A novel histopathological classification of chalazion: A series of 540 cases. Pan Am J Ophthalmol 2022;4:13

How to cite this URL:
Ito H, Nassrallah G, Bergeron S, Arthurs B, Burnier JV, Burnier MN. A novel histopathological classification of chalazion: A series of 540 cases. Pan Am J Ophthalmol [serial online] 2022 [cited 2022 May 25];4:13. Available from: https://www.thepajo.org/text.asp?2022/4/1/13/340383




  Introduction Top


A chalazion is a common localized inflammatory condition characterized by lipogranulomas that results from obstruction of a sebaceous gland duct found in the eyelids.[1],[2] It is well known that neoplasia such as sebaceous carcinoma can mimic the clinical picture of a chalazion, a phenomenon described as masquerade syndrome.[3],[4],[5],[6],[7]

Sebaceous carcinoma is a highly malignant neoplasm that usually arises in the eyelid.[8],[9] It often masquerades as a benign or inflammatory lesion.[9],[10] In many patients, sebaceous carcinoma is very difficult to clinically distinguish from chalazion, resulting in delayed diagnosis.[9],[10] Duration of symptoms, particularly <6 months, prior to the treatment of sebaceous carcinoma correlates with higher mortality.[10] Therefore, it is imperative to refer excised chalazion for histopathological diagnosis in order to detect possible underlying malignancy as early as possible.

Elsewhere, excised chalazia are seldom analyzed and only the lesions with atypical clinical manifestations or recurrent chalazion are submitted for histopathological analysis: resulting in missed malignancies and late diagnosis.

Despite the common clinical manifestation of chalazion, histopathological review of chalazia is scant and the general pathologist may not be confronted with these lesions very often. No histopathological classification currently exists for chalazia to differentiate them from other inflammatory conditions.

Microscopic examination of chalazia shows zonal lipogranulomatous inflammation which is centered around clear spaces previously filled with lipids that have dissolved during tissue processing.[11] In addition to inflammatory cells (such as polymorphonuclear leukocytes, plasma cells, and lymphocytes), multinucleated giant cells (resembling foreign-body giant cells or Langhans giant cells) and even asteroid and Schaumann bodies can also be detected.[11] These granulomas without typical lipid droplets may resemble lesions of tuberculosis, sarcoidosis, or cat scratch disease.[1]

The present study was performed to further understand the histopathological findings of chalazia and systematically classify them. In addition, we aim to identify the distribution of different histopathological features in chalazia and to verify whether these histopathological features are associated with a specific patient's demographic. Our aim is to formulate recommendations for lesions that should be prioritized for histopathological evaluation.


  Materials and Methods Top


From January 2011 to December 2016, 562 excised cases of clinically suspicious chalazion were retrieved at the MUHC-McGill University Ocular Pathology and Translational Research Laboratory for histopathological review. The specimens included every case of clinically suspicious chalazion that was seen and excised at the MUHC by all ophthalmologists during the study period.

Among those, a total of 540 cases were histopathologically confirmed as chalazion; from each formalin-fixed paraffin-embedded block, one H and E section was obtained for review. First, the specimens were classified into two broad categories: those with lipogranulomas or granulomatous inflammation (category 1–3) and those without lipogranulomas or granulomatous inflammation (category 4). Each lesion was then subsequently assigned into one of four categories: (1) lipogranulomas only, (2) lipogranulomas with multinucleated giant cells, (3) lipogranulomas with abscess formation, and (4) fibrosis without lipogranulomas or granulomatous inflammation [shown in [Figure 1]].
Figure 1: The histopathological findings of chalazia. (a) Lipogranulomas containing epithelioid cells is centered around lipid droplets. (b) Multinucleated giant cells (foreign body giant cells) intermixed with inflammatory cells. (c) Abscess formation surrounded by granulomatous reaction. (d) Fibrous tissue without lipogranulomatous reaction. (a-d: H and E stain, scale bar = 100 μm)

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Patients' demographic data on sex, age, and lesion location were retrieved from pathology consults. A Chi-squared test was performed to assess correlations between histopathologic category and patient's sex, patient's age group, and location of the lesion. Age groups of 50 years or below and over 50 years were selected because of the higher rate of sebaceous cell carcinoma in the older group. An analysis of variance (ANOVA) and t-test were performed to assess correlations between mean ages of each category. Statistical analysis was performed using OriginPro 9, OriginLab Corporation, Northampton, MA, US and P < 0.05 was considered statistically significant.


  Results Top


A total of 540 biopsy-proven chalazion were included [Table 1]. These cases included 295 men (55%) and 245 women (45%), with a mean age of 45.3 years (range, 13–89; standard deviation, 16.8). Of the 540 cases, we included only the 508 that had information regarding the location of the lesion: left lower eyelid, 21.1% (n = 107); right lower eyelid, 19.5% (n = 99); left upper eyelid, 30.5% (n = 155); and right upper eyelid, 28.9% (n = 147). Of all cases, 59.4% (302/508) occurred on the upper eyelid.
Table 1: Relationship between histopathological subtypes (category 1-4) and sex, age, or location

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A histopathological review of the 540 slides revealed that 241 (44.6%) showed granulomas only (category 1), whereas 224 (41.5%) also had multinucleated giant cells (category 2). Of the remaining cases, 38 (7.0%) were classified as lipogranulomas with abscess formation (category 3) and 37 (6.9%) as fibrosis without lipogranulomas or granulomatous inflammation (category 4). Representative H and E images are shown in [Figure 1].

Chi-squared test revealed no significant correlation between histopathological classification and patient's sex (P = 0.210). Age above or below 50 also did not correlate with classification (P = 0.369). One-way ANOVA test was performed to compare mean ages of each category and revealed a significant difference among four categories (F (3, 536) = 3.227, P = 0.022). Following paired t-tests revealed a statistically significant difference between mean ages of category 1 (47.0 years) and 2 (43.1 years) (P = 0.011), and no significant differences between the other two categories. Moreover, there was no statistically significant relationship between the presence of giant cells and/or abscesses and the location of the lesion (P = 0.826). Results are shown in [Table 1].

Among the cases during the 6-year study period, 22 (3.9%) were clinically misdiagnosed cases that were histopathologically proven to be lesions other than chalazion. Among these, three (14%, or 0.5% of the total sample) were malignancies: two cases were proven sebaceous carcinoma and basal cell carcinoma. None of these three cases displayed a lipogranuloma. The histopathological images of one case of the sebaceous carcinomas are shown in [Figure 2].
Figure 2: The histopathological findings of sebaceous carcinoma. (a) An eyelid specimen shows multiple foci of invasive carcinoma without any lipogranulomatous reaction (H and E stain, ×10) (b) The neoplastic cells have large nuclei and nucleoli and show sebaceous differentiation (H and E stain, ×50)

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  Discussion Top


The aim of this present study was to histopathologically classify chalazion and, second, to determine whether histopathological features are associated with a specific patient's demographics. Our result shows that clinically suspicious chalazia can present under all four main histopathological subtypes: (1) lipogranulomas only, (2) lipogranulomas with multinucleated giant cells, (3) lipogranulomas with abscess formation, and (4) fibrosis without lipogranulomas or granulomatous inflammation. The three first categories, representing the majority of our study samples (93.1%, n = 503), show lipogranulomas or granulomatous inflammation. Of the cases that showed lipogranulomas, approximately half (52.1%, 262/503) presented as lipogranulomas with giant cells (category 2) or lipogranulomas with abscess (category 3).

In the present study, the four histopathological subtypes were equally distributed across sexes and eyelid locations. A slight predominance (60%) for upper eyelid location was observed, which is explained by a higher concentration of sebaceous glands in the upper eyelid when compared to the lower eyelid. For patients' age, t-test revealed a statistically significant difference of mean ages between category 1 (47.0 years) and 2 (43.1 years). Compared to the lesions with lipogranulomas only, we found lipogranulomas with multinucleated giant cells in younger patients. It might suggest a possibility that multinucleated giant cells are preferentially formed in younger patients or at different stages of the lesions. However, the present study does not include the delay between onset and excision, so we cannot conclude that there is a clear correlation between each category and mean ages. Moreover, classifying age into two groups, under 50 years and over 50 years, did not show any difference with regard to our classification system. While other clinical data are not available for this subset of cases, it would be of interest for future studies to assess a possible link between histopathological subtype of chalazion and clinical features of the lesion such as size, recurrence, and reported symptoms.

The fourth category was limited to 37 patients (6.9%), and in these biopsies, lipogranulomas could not be found even with deeper sections of the paraffin blocks. We decided to classify this case as chalazia for two reasons. First, they were diagnosed clinically as a typical chalazion. Second, we did not find any other features to diagnose other infections or inflammatory processes.

It is well known that some malignant neoplasms can mimic the clinical picture of a chalazion, a phenomenon described as the masquerade syndrome. Several reports have shown that chalazia can simulate various malignant tumors, such as sebaceous carcinoma,[3],[4],[7],[12] basal cell carcinoma,[12] squamous cell carcinoma,[5] and adenoid cystic carcinoma.[6] Among these neoplastic processes, sebaceous carcinoma is the greatest and most devastating mimicker of chalazion.

A previous study has reported that 1.1% of the clinically diagnosed chalazion cases were sebaceous carcinoma, which makes it the most commonly missed diagnosis of an eyelid malignancy.[12] Conversely, several studies have shown that the most common clinical misdiagnosis of sebaceous carcinoma was chalazia.[3],[13] Notably, 20%–44% of sebaceous carcinomas are clinically diagnosed as chalazia prior to the pathological diagnosis.[3],[4]

When addressing eyelid malignancies, two clinical key points are that sebaceous carcinomas are more frequently seen in the upper eyelid due to the abundance of sebaceous glands in this particular location (Meibomian gland)[13] and that sebaceous carcinomas are much more aggressive than other eyelid malignancies such as basal cell carcinomas or squamous cell carcinomas. It is also widely known that the most important clinical prognostic factor is associated with the length of time between initial presentation and the time of the diagnosis.[10] Several reports indicate that prognostic is greatly reduced if the lesion has been present over 6 months and it is particularly poor for lesions over 1 year old.[10] Given that sebaceous carcinoma of the upper eyelid is the lesion that most frequently mimics chalazion, it is imperative to histopathologically examine all chalazia in particular patients over 40 years of age or the so-called recurrent chalazia.

In the current study, three clinically presumed chalazia were histopathologically proven malignancies: two sebaceous carcinomas and one basal cell carcinoma. On clinical presentation, these patients did not display any atypical features. Had these lesions been excised without histopathological examination, several months would have elapsed before the lesion recurrent, ensuing a poorer prognosis. The masquerade syndrome has been well known: some tumors do not show lipogranulomatous reaction as in our three malignant cases [one of the cases is shown in [Figure 2]]; the other cases could occur in conjunction with a lipogranuloma as previously reported.[7] Given the severity of sebaceous carcinoma, all excised chalazion should be sent for histopathological analysis to achieve earlier and accurate diagnosis.


  Conclusion Top


This study is an extensive histopathological review of chalazion and the first attempt at classifying these lesions. A total of 562 lesions clinically suspicious of chalazion were carefully reviewed. A total of 3 malignancies were histopathologically confirmed, hence supporting the need for a systemic analysis of excised chalazia. By instigating a histopathological classification for chalazion, all pathologists will be able to confidently assess these lesions for potential malignancy and therefore reduce the delay in treatment of these patients.

The four subtypes of chalazion are equally distributed across all sex and eyelid locations. There is no clear correlation between the mean ages of each category. Further studies to determine associations between these categories and other clinical features are needed. Despite variable histopathological patterns, all chalazia are often deemed to be clinically equivalent, supporting the need for histopathological diagnosis to rule out any sign of malignancy in particular sebaceous carcinoma. Sebaceous carcinoma may present as a chalazion-like lesion; therefore, histopathological examination is crucial. In particular, histopathological examination of all chalazia should be performed particularly in adult patients, over 40 years of age, with upper eyelid and recurrent lesions, to avoid missing the diagnosis of sebaceous carcinoma. The pathological finding of fibrosis without typical lipogranuloma is consistent with the clinical diagnosis of chalazion; however, the absence of lipogranulomas should lead to an investigation by the ophthalmologists and pathologists of other causes of inflammatory or infectious diseases.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Sun MT, Huang S, Huilgol SC, Selva D. Eyelid lesions in general practice. Aust J Gen Pract 2019;48:509-14.  Back to cited text no. 2
    
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Zürcher M, Hintschich CR, Garner A, Bunce C, Collin JR. Sebaceous carcinoma of the eyelid: A clinicopathological study. Br J Ophthalmol 1998;82:1049-55.  Back to cited text no. 3
    
4.
Shields JA, Demirci H, Marr BP, Eagle RC Jr., Shields CL. Sebaceous carcinoma of the eyelids: Personal experience with 60 cases. Ophthalmology 2004;111:2151-7.  Back to cited text no. 4
    
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Vrcek I, Hogan RN, Mancini R. Cutaneous squamous cell carcinoma of the eyelid masquerading as a chalazion. Int Ophthalmol 2015;35:131-4.  Back to cited text no. 5
    
6.
Menon V, Deshmukh R, Mulay K. A rare masquerade of chalazion: Adenoid cystic carcinoma. Indian J Ophthalmol 2019;67:1371-3.  Back to cited text no. 6
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7.
Salimi A, Bergeron S, Arthurs B, Burnier MN. Sebaceous carcinoma masquerade syndrome: Importance of biopsy and histopathological examination. Hum Pathol Case Rep 2020;21:200410.  Back to cited text no. 7
    
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Dasgupta T, Wilson LD, Yu JB. A retrospective review of 1349 cases of sebaceous carcinoma. Cancer 2009;115:158-65.  Back to cited text no. 8
    
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Song X, Jia R, Fan X. An update on eyelid sebaceous cell carcinoma. Int Ophthalmol Clin 2019;59:1-11.  Back to cited text no. 9
    
10.
Rao NA, Hidayat AA, McLean IW, Zimmerman LE. Sebaceous carcinomas of the ocular adnexa: A clinicopathologic study of 104 cases, with five-year follow-up data. Hum Pathol 1982;13:113-22.  Back to cited text no. 10
    
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Yanoff M, Sassani JW. Ocular Pathology. 8th ed. Amsterdam; Netherlands: Elsevier; 2020. p. 177.  Back to cited text no. 11
    
12.
Ozdal PC, Codère F, Callejo S, Caissie AL, Burnier MN. Accuracy of the clinical diagnosis of chalazion. Eye (Lond) 2004;18:135-8.  Back to cited text no. 12
    
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Nelson BR, Hamlet KR, Gillard M, Railan D, Johnson TM. Sebaceous carcinoma. J Am Acad Dermatol 1995;33:1-15.  Back to cited text no. 13
    


    Figures

  [Figure 1], [Figure 2], [Figure 1], [Figure 2]
 
 
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