Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 
  • Users Online: 1083
  • Home
  • Print this page
  • Email this page

   Table of Contents      
ORIGINAL ARTICLE
Year : 2020  |  Volume : 68  |  Issue : 11  |  Page : 2466-2470

Malignant tumors of the eyelid in India: A multicenter, multizone study on clinicopathologic features and outcomes


1 Department of Orbit, Oculoplasty and Ocular Oncology, Narayana Nethralaya, Bangalore, Karnataka, India
2 Department of Orbit, Oculoplasty and Ocular Oncology, Calcutta Medical Research Institute, Kolkata, West Bengal, India
3 Department of Orbit, Oculoplasty and Ocular Oncology, Hinduja Hospital, Mumbai, Maharashtra, India
4 Department of Orbit Oculoplasty and Ocular Oncology, Shroff Charity Eye Hospital, New Delhi, India
5 Department of Orbit, Oculoplasty and Ocular Oncology, Center for Sight, New Delhi, India

Date of Submission03-Jan-2020
Date of Acceptance23-May-2020
Date of Web Publication26-Oct-2020

Correspondence Address:
Dr. Roshmi Gupta
Orbit, Oculoplasty and Ocular Oncology Services, Narayana Nethralaya, 121/C Chord Road, Rajajinagar 1st R Block, Bangalore - 560 010, Karnataka
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijo.IJO_2306_19

Rights and Permissions
  Abstract 


Purpose: To analyze data on eyelid malignancy in India, clinical and pathologic features, and outcomes. Methods: A multicentre study, from oculoplastic practices in four geographic zones in India. The centers perform similar documentation and protocol-based management for eyelid tumors. Clinical features, pathology, American Joint Committee on Cancer (AJCC) class, management, and the outcomes were analyzed. Results: The study included 129 patients, with slight female preponderance and mean age 62.7 years. The median delay to the consultation was 9 months. Rural patients traveled a mean distance of 115.2 km; there was no difference between the city and outstation patients in the delay to consultation or follow up. Pathology included 55/129 (42.6%) sebaceous gland carcinoma (SGC), 47/129 (36.4%) basal cell carcinoma (BCC), squamous cell carcinoma (SCC) in 15 (11.6%), and 12 (9.3%) other tumors. Commonest AJCC class was T2b/T3a in 80/111 (72%), invasion of the orbit was present in 16 (12.4%). Surgery with margin clearance was performed in 103. With a mean follow-up of 21.44 months, local recurrence and/or metastasis were seen in 12%. The diagnosis of SGC was strongly associated with adverse outcomes (odds ratio: 7.36). On multiple logistic regression analysis, diagnosis of SGC (P = 0.011) was significant in having adverse outcomes. Conclusion: The multicenter Indian data shows the highest prevalence of SGC, with the commonest AJCC class T2b. Most tumors were locally resectable at presentation. The histopathologic diagnosis of SGC is the factor strongly associated with adverse outcomes.

Keywords: Basal cell carcinoma, eyelid malignant tumors, India, sebaceous gland carcinoma, squamous cell carcinoma


How to cite this article:
Gupta R, Bhaduri A, Desai S, Das S, Menon V. Malignant tumors of the eyelid in India: A multicenter, multizone study on clinicopathologic features and outcomes. Indian J Ophthalmol 2020;68:2466-70

How to cite this URL:
Gupta R, Bhaduri A, Desai S, Das S, Menon V. Malignant tumors of the eyelid in India: A multicenter, multizone study on clinicopathologic features and outcomes. Indian J Ophthalmol [serial online] 2020 [cited 2020 Nov 24];68:2466-70. Available from: https://www.ijo.in/text.asp?2020/68/11/2466/299051



Basal cell carcinoma (BCC) is held to be the commonest eyelid malignancy worldwide.[1],[2] Sebaceous gland carcinoma (SGC) is seen more frequently in the Asian and Asian Indian population and known to have the second-worst prognosis among eyelid malignancies.[3],[4]

The outcome of eyelid malignancies depends on the histopathologic diagnosis and the extent. The American Joint Committee for Cancer (AJCC) classification is used for documentation of disease severity. The Indian literature on eyelid malignancies includes several series with contradictory data. No reporting of the extent of disease or AJCC classification of eyelid malignancies in India is available.

In a country with a large geographic extent and diverse population, there is a need for representative data on clinicopathologic features and outcomes on eyelid malignancy in India. This study presents data on eyelid malignancies in India across zones (North, East, West, and South).


  Methods Top


The study was a retrospective interventional multicenter study, from five centers located in four geographic zones in India. All the participating ophthalmologists are trained similarly in principles of oculoplastic surgery and ocular oncology. At the time of this study, they had experience between 10 to 15 years and had single-surgeon sub-specialty practices. The duration of the series included in the study ranged from 5 to 12 years; the shortest from 2014–2019, longest from 2008–2019. All authors practice protocol-based management of eyelid malignancies. Only patients with biopsy-proven malignancy were included in this study.

All authors follow similar criteria for clinical diagnosis: Unexplained, rapidly progressive mass lesion, ulceration, loss of lid margin architecture and madarosis, unexplained unilateral blepharoconjunctivitis. The greatest dimension and perpendicular are measured, and a clinical photograph is documented [Figure 1]a, [Figure 1]b, [Figure 1]c, [Figure 1]d. Orbital imaging is advised when the posterior margin of the tumor cannot be determined on clinical examination, presence of proptosis, ptosis, or limitation of ocular movement [Figure 1]d. Draining lymph nodes are examined clinically. The authors also follow a similar procedure for excision—minimal touch technique with 5 mm margins, margins sent for histopathology marked for orientation, and map biopsy in all SGC. The pathologist confirms the diagnosis and absence of tumor on the margins, and the defect is reconstructed.
Figure 1: (a) Sebaceous carcinoma (white arrow), stage T2a. (b) Basal cell carcinoma, stage T2b. (c) Basal cell carcinoma, stage T3a. (d) Sebaceous carcinoma, stage T3b. Inset: Computed tomography shows the orbital extension

Click here to view


Histopathology included hematoxylin–eosin stain on tissue embedded in paraffin sections. The patients from the East zone underwent Oil Red O stain on fresh tissue when there was a suspicion of SGC. Patients underwent immunohistochemistry for other tumors such as eccrine carcinoma, lymphoma, mucinous carcinoma, and so on.

All patients were managed by surgical excision with tumor-free margins verified on histopathology, either on frozen or on the permanent section. Orbital exenteration was performed for orbital extension of the tumor or for SGC with an extensive pagetoid spread. The excision was followed by reconstruction. All patients had a pathologist confirm the diagnosis on permanent section histopathology, and were reviewed at 1 week, 6 weeks, and advised reviews 3 monthly for the first year, and after that yearly.

The data entry was done from medical records, clinical drawings, and clinical photographs. A common data collection form was used, which included the following: Age, gender, referral diagnosis, distance to the clinic, laterality, involvement of upper lid/lower lid/canthus/margin/contiguous conjunctiva, orbital extension, regional lymph nodes, pathology details, AJCC class, treatment, both planned and performed, and outcome (whether recurrence, locoregional spread, or metastasis).

We included all patients with available histopathologic diagnoses for the classification and categories of tumors. This also included patients who did not undergo definitive treatment. For outcome analysis, we included only patients with a follow-up of 3 months or greater.

AJCC 7th edition classification was applied retrospectively based on the recorded dimensions and extent. Some patients had undergone partial excision elsewhere and were categorized as Tx.

Analysis

Descriptive data were compiled using MS Excel (MS Office 2018). Statistical analysis was done using MedCalc v19.0.5. We assessed clinical and pathologic features as risk factors for locoregional spread and recurrence, using odds ratio and logistic regression analysis.

Patients from the city and outstation patients were compared for the delay to diagnosis and duration of follow-up using the Student's T-test.


  Results Top


The final analysis included a total of 129 patients, with 68 (52.3%) female patients. The mean age of patients was 62.7 years (range 5–92 years). From the first appearance of signs, the median delay to the first consultation was 9 months (mean 17.26 months, range 1–120). The mean distance from home to hospital was 115.2 km (range 0–738 km). Forty-eight patient records showed a referral diagnosis, of which nine (18.7%) had been misdiagnosed as benign. Thirty-one (24%) patients had a history of intervention elsewhere, including incision biopsy, incision and curettage, or excision without margin clearance.

[Table 1] shows the clinical characteristics of the tumors. Among the clinical features, 120/129 (93%) patients presented with a mass lesion, 6/55 (10.9%) of the SGC patients presented with blepharoconjunctivitis, 25/129 (19.3%) of all patients had bleeding on presentation, and 17/129 (13%) patients presented with ptosis. One patient who presented with an orbital extension of SGC had a history of treatment for 'ocular cicatricial pemphigoid' for 8 years.
Table 1: Clinical details of eyelid malignancies

Click here to view


Histopathology revealed [Table 2] SGC to be the commonest. The distribution included BCC, squamous cell carcinoma (SCC), and others. Among the SGC, 22.7% were well-differentiated, 54.5% were moderately differentiated, and 22.7% were poorly differentiated. Pagetoid spread was seen in 23 (41%) patients of SGC. The miscellaneous tumors included 6 (4.6%) cases of eccrine carcinoma and mucinous carcinoma of sweat gland, 2 (1.5%) cases of lymphoma, 1 case of embryonal rhabdomyosarcoma, 1 case of angiosarcoma, 1 case of adenoid cystic carcinoma, and 1 case of adenosquamous carcinoma. [Table 3] shows the comparative distribution of the different malignancies in the various zones of the country.
Table 2: Histopathologic diagnosis and AJCC classification

Click here to view
Table 3: Distribution of tumor diagnoses in the different zones of India

Click here to view


Commonest AJCC classes were T2b and T3a, accounting for 80/111 (72%) lesions. Positron emission tomography (PET) scan was advised at the time of diagnosis to all patients of SGC, all orbital extension, and patients other than BCC [Table 2]. However, due to financial constraints, it was performed in 21 patients, and one showed positive lesions elsewhere in the body at initial assessment. None of our patients underwent sentinel node biopsy. None underwent pre-emptive lymphatic dissection.

Surgery with tumor-free margin was done in 112 eyes, with other patients lost to follow-up after advice [Table 4]. The mean follow-up was 21.44 months, with metastasis and/or recurrence in 14 patients (11.3%). All the recurrences were SGC or SCC. SGC patients showed a 9% recurrence and 14.5% metastasis in spite of histopathologic margin clearance at surgery [Table 4]. One patient underwent neoadjuvant chemotherapy and orbital exenteration and was lost to follow-up.
Table 4: Management and outcome, n=98 for outcome

Click here to view


There was no difference between metro (37%) and outstation (63%) patients in the mean delay to first consultation (18.73 months versus 18.74 months) or the loss to follow-up (22% versus 26%).

Analysis of adverse outcome (distal metastasis, lymphatic spread, or recurrence) was performed for 98 patients with more than 3 months of follow-up after surgical excision. This included both cases with eyelid lesion excision with clear margins, and with orbital exenteration [Table 4]. On logistic regression analysis [Table 5], the diagnosis of SGC was more likely to have an adverse outcome such as recurrence or metastasis (odds ratio 7.36, P = 0.0115). The involvement of canthus, greatest dimension, and duration of disease did not seem to affect the outcome. On further analysis of SGC versus other tumors, the mean greatest dimension was similar in both categories: 17.3 mm in SGC, 16.5 mm in others, P value = 0.82. The duration of disease was significantly more in non-SGC tumors (mean 12.9 months in SGC, 25.8 months in others, P = 0.05). Involvement of canthus was significantly less in SGC (34% in SGC versus 54.6%, P = 0.02).
Table 5: Analysis of factors influencing adverse outcome (recurrence, lymph node metastasis or distant metastasis)

Click here to view



  Discussion Top


BCC is the commonest eyelid malignancy worldwide. Studies from Japan and China show an equal incidence of SGC and BCC [Table 6].[3],[4] It has long been the impression that the pattern of eyelid malignancies in India differs from that in the Western population. However, the Indian reports have been variable, with different studies describing different distributions of tumors.[7],[8],[9],[10],[11]
Table 6: Comparative proportion of eyelid malignancies in various studies

Click here to view


Of the Indian studies, three are from plastic surgery or pathology services.[7],[8],[9] All three find BCC to be the commonest eyelid malignancy. They may not reflect the picture seen by ophthalmologists. There are two studies from referral eye institutes.[10],[11] These differ significantly in the distribution of the different diagnoses. Sihotaet al. found BCC, SCC, and SGC to be almost equally common, whereas Kaliki et al. found SGC to vastly outnumber BCC.[10],[11] Due to these contradictory results, one cannot generalize about eyelid malignancy patterns in India from the previous reports. A recent editorial on ocular oncology elaborates on the pitfalls of drawing conclusions for eyelid malignancy for the entire country from retrospective data of a single referral center.[12] Our study aims to address the need for a data set, which is more truly representative of the country.

The incidence of cutaneous cancers has been associated with skin color, sun exposure, or a location closer to the equator. The Indian mainland spans 8°4′N to 37° 6 ′N latitudes and a wide variety of climate. The Indian population also shows diversity in skin pigmentation.[13],[14],[15] Thus, a multizone study such as ours yields the most representative data on eyelid malignancies in India.

The AJCC classification [Table 7] is increasingly commonly used. In SGC and SCC, higher T grading in the AJCC classification is predictive of nodal metastasis, systemic metastasis, and mortality.[16],[17],[18] These existing studies use the AJCC 7th edition. Our series also uses AJCC 7th edition classification in a retrospective fashion and allows comparison to current literature. The largest number of patients presented to the oncology service with tumor Group 2a to Group 3a, permitting surgical resection and sparing the globe.[19] The AJCC 8th edition is in use from January 2018. It will be useful to prospectively stage eyelid malignancies as per the 8th edition.
Table 7: AJCC TNM classification of eyelid malignancies

Click here to view


SGC is known for aggressive behavior, with 12–40% loco-regional spread and mortality.[20],[21] Our study shows that the prevalence of SGC is the commonest in Indian population. We also see an Odds ratio of 7.36, that SGC will lead to a worse outcome than non-SGC.

Canthal involvement and the greatest dimension of tumor were not found significant for adverse outcomes. We did not analyze the greatest dimension and AJCC classification separately since the latter incorporates the size of the tumor. Delay from the onset of disease to diagnosis was not significant for adverse outcomes [Table 5]. These results are unexpected since each of these factors has been shown to influence prognosis. We hypothesize that this result comes from a combined analysis of the different kinds of tumors. The SGC outcomes were much worse compared to any other tumor. SGC had a significantly shorter duration of disease than others and fewer canthal involvement. The greatest dimension of SGC was similar to that of other categories, but with worse outcomes. Overall, the prognosis of SGC was so serious as to supersede the other known risk factors in this series.

When comparing the use of frozen section versus permanent section for margin clearance, we found no significant difference in the outcome. The authors emphasize that tumor-free margins must be obtained on the excision of an eyelid malignancy, whether by frozen section or by permanent section [Table 5]. A permanent section histopathology may require the surgeon to excise more tissue at a second sitting before reconstruction is done. A recent study shows that while the frozen section closely approximates the results of the permanent section, the sensitivity of the permanent section is better than that of the frozen section in SGC.[22] There is also data to show that delayed reconstruction after paraffin section margin clearance gives good results.[23] However, wherever the facility is available, a single-stage procedure with on-table frozen section margin clearance and reconstruction would be preferable.

Logistic and financial difficulties are a hurdle in seeking timely help for malignancies. Before referral to subspeciality practitioners, there had been misdiagnoses in 19% and inappropriate management in 24%. We found that the delay to first consultation and loss to followup were similar in patients from within the city versus out-station patients. Patients were motivated to travel a mean of 115.2 km for specialty treatment. This knowledge can help future planning of subspecialty services in ophthalmology.

The strength of the study is that it is a multi-zonal, multicentric study, including both urban and rural patients, and including AJCC classification. The authors follow similar patterns of evaluation, documentation, management, and follow-up protocol as mentioned in the methods section. This permits homogeneity in data collection. The weakness of the study is that the pathologic evaluations of the tumors were performed at different locations, and may not have been uniform. This study is a retrospective, hospital-based study, and subject to the limitations of design. We cannot comment on the incidence or prevalence of the disease conditions from this study. In future, a national registry of ocular oncology-pathology may help in a prospective study of such disease.


  Conclusion Top


In conclusion, this study offers a representative look at the mix of eyelid malignancies in India, the severity of presentation and outcome. The proportion of SGC is high, and this is the single largest risk factor for poor outcome.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Margo CE, Waltz K. Basal cell carcinoma of the eyelid and periocular skin. Surv Ophthalmol 1993;38:169-92.  Back to cited text no. 1
    
2.
Deprez M, Uffer S. Clinicopathological features of eyelid skin tumors. A retrospective study of 5504 cases and review of literature. Am J Dermatopathol 2009;31:256-62.  Back to cited text no. 2
    
3.
Takamura H, Yamashita H. Clinicopathological analysis of malignant eyelid tumor cases at Yamagata university hospital: Statistical comparison of tumor incidence in Japan and in other countries. Jpn J Ophthalmol 2005;49:349-54.  Back to cited text no. 3
    
4.
Ni Z. [Histopathological classification of 3,510 cases with eyelid tumor]. Zhonghua Yan Ke Za Zhi 1996;32:435-7.  Back to cited text no. 4
    
5.
Lee SB, Saw SM, Au Eong KG, Chan TK, Lee HP. Incidence of eyelid cancers in Singapore from 1968 to 1995. Br J Ophthalmol 1999;83:595-7.  Back to cited text no. 5
    
6.
Ho M, Liu DT, Chong KK, Ng HK, Lam DS. Eyelid tumours and pseudotumours in Hong Kong: A ten-year experience. Hong Kong Med J 2013;19:150-5.  Back to cited text no. 6
    
7.
Jahagirdar SS, Thakre TP, Kale SM, Kulkarni H, Mamtani M. A clinicopathological study of eyelid malignancies from Central India. Indian J Ophthalmol 2007;55:109-12.  Back to cited text no. 7
[PUBMED]  [Full text]  
8.
Abdi U, Tyagi N, Maheshwari V, Gogi R, Tyagi SP. Tumours of eyelid: A clinicopathologic study. J Indian Med Assoc 1996;94:405-9.  Back to cited text no. 8
    
9.
Kale SM, Patil SB, Khare N, Math M, Jain A, Jaiswal S. Clinicopathological analysis of eyelid malignancies - A review of 85 cases. Indian J Plast Surg 2012;45:22-8.  Back to cited text no. 9
[PUBMED]  [Full text]  
10.
Sihota R, Tandon K, Betharia SM, Arora R. Malignant eyelid tumors in an Indian population. Arch Ophthalmol 1996;114:108-9.  Back to cited text no. 10
    
11.
Kaliki S, Bothra N, Bejjanki KM, Nayak A, Ramappa G, Mohamed A. Malignant eyelid tumors in India: A study of 536 Asian Indian patients. Ocul Oncol Pathol 2019;5:210-9.  Back to cited text no. 11
    
12.
Patel BCK. Epidemiology of eyelid malignancies in Indian Asians: The importance of being earnest. Ocul Oncol Pathol 2019;5:205-9.  Back to cited text no. 12
    
13.
Verma SB. Redefining colour of Indian skin. J Eur Acad Dermatol Venereol 2008;22:1263-4.  Back to cited text no. 13
    
14.
Hourblin V, Nouveau S, Roy N, de Lacharrière O. Skin complexion and pigmentary disorders in facial skin of 1204 women in 4 Indian cities. Indian J Dermatol Venereol Leprol 2014;80:395-401.  Back to cited text no. 14
[PUBMED]  [Full text]  
15.
Mukherjee M, Mukerjee S, Sarkar-Roy N, Ghosh T, Kalpana D, Sharma AK. Polymorphisms of four pigmentation genes (SLC45A2, SLC24A5, MC1R and TYRP1) among eleven endogamous populations of India. J Genet 2013;92:135-9.  Back to cited text no. 15
    
16.
Nasser QJ, Roth KG, Warneke CL, Yin VT, El Sawy T, Esmaeli B. Impact of AJCC'T' designation on risk of regional lymph node metastasis in patients withsquamous carcinoma of the eyelid. Br J Ophthalmol 2014;98:498-501.  Back to cited text no. 16
    
17.
Esmaeli B, Nasser QJ, Cruz H, Fellman M, Warneke CL, Ivan D. American joint committee on cancer T category for eyelid sebaceous carcinoma correlates with nodal metastasis and survival. Ophthalmology 2012;119:1078-82.  Back to cited text no. 17
    
18.
Kaliki S, Gupta A, Ali MH, Ayyar A, Naik MN. Prognosis of eyelid sebaceous gland carcinoma based on the tumor (T) category of the American joint committee on cancer (AJCC) classification. Int Ophthalmol 2016;36:681-90.  Back to cited text no. 18
    
19.
Ainbinder DJ, Esmaeli B, Groo SC, Finger PT, Brooks JP. Introduction of the 7th edition eyelid carcinoma classification system from the American joint committee on cancer–International union against cancer staging manual. Arch Pathol Lab Med 2009;133:1256-61.  Back to cited text no. 19
    
20.
Kaliki S, Ayyar A, Dave TV, Ali MJ, Mishra DK, Naik MN. Sebaceous gland carcinoma of the eyelid: Clinicopathological features and outcome in Asian Indians. Eye (Lond) 2015;29:958-63.  Back to cited text no. 20
    
21.
Raza Rizvi SA, Alam MS, Akhtar K. Eyelid sebaceous gland carcinoma: Varied presentations and reconstruction outcome. Oman J Ophthalmol 2018;11:21-7.  Back to cited text no. 21
    
22.
Alam MS, Tongbram A, Krishnakumar S, Biswas J, Mukherjee B. Sensitivity and specificity of frozen section diagnosis in orbital and adnexal malignancies. Indian J Ophthalmol 2019;67:1988-92.  Back to cited text no. 22
[PUBMED]  [Full text]  
23.
While B, Salvi S, Currie Z, Mudhar HS, Tan JH. Excision and delayed reconstrution with paraffin section histopathological analysis for periocular sebaceous carcinoma. Ophthalmic Plast Reconstr Surg 2014;30:105-9.  Back to cited text no. 23
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]



 

Top
 
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
Abstract
Methods
Results
Discussion
Conclusion
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed409    
    Printed0    
    Emailed0    
    PDF Downloaded66    
    Comments [Add]    

Recommend this journal