FP1626 : Study of Extensive Malignant Eyelid Tumors : A Teaching Hospital Based Study.

Dr. Maurya Rajendra Prakash, M05596, Dr. Anjali Singh, Dr. Mahendra Kumar Singh, Dr. Virendra Pratap Singh

INTRODUCTION:

The eyelid tumours are most frequent neoplasm in ophthalmic practice. Periocular skin and eyelids are common sites of neoplastic lesions of the head and neck. Approximately 5% of all cutaneous tumours occur in the eyelids^[1]. In developing countries eyelid malignancies are diagnosed late or misdiagnosed due to unawareness, illiteracy and ignorant care. The extensive eyelid malignancies requires more invasive surgeries and resulting in adverse functional and aesthetic effects^[2]. Advanced eyelid malignancies usually associated with recurrence and decreased survival rate. The incidence of different types of eyelid malignant tumours shows a geographical variation as a result of skin type and sun exposure. Basal cell carcinoma is the most frequent eyelid malignancy(80%-90%) worldwide^[3]. Frequency of sebaceous gland carcinoma is higher in Asian countries. The objective of this study is to report the clinico-pathological pattern of advanced malignant eyelid tumours, treatment, outcome and survival.

MATERIALS AND METHODS:

A prospective non-comparative interventional study was Performed in department of ophthalmology, S.S. Hospital, Institute of medical sciences, Banaras Hindu University, Varanasifrom February 2014 to march 2017. Each patient underwent a thorough history and detailed clinical examination (ocular, systemic and neck examination). Histopathological diagnosis was confirmed by biopsy, imprint cytology, and FNAC.Routine haematological tests, radiologicalinvestigation like X Ray Chest, USG Abdomen, and CT Scan Orbit were performed wherever clinicallyindicated.Management included primary surgical excision, neoadjuvant systemic chemotherapy(1.cis- platinum, bleomycin, methotrexate and 2. 5-FU,Cis-platinum ) followed by surgical excision with lid reconstruction.Clinical response of chemotherapy was assessed as per WHO criteria. Toxicity was monitored by blood counts, serum creatinine. All patients were kept for regular  follow up to observe the outcome, toxicity and recurrence.

RESULT:A total of 148 patients with eyelid tumours were studied in this prospective, non- comparative, interventional study.Out of 148 cases of eyelid tumours, 62[41.9%] were found to be malignant neoplasm. The mean age was 64.2 years with a range of 44-81 years. The majority were more than 60 years old. 24 patients (38.7%) were male rest were female. The site of tumour was defined as the area in which lesion first appeared. The sites of tumour were upper lid (48.39%), lower lid (35.48%), both eyelids (6.43%) and medial canthus and periocular areas (9.70%).

The size of tumour range from 15mm to 68mm. In gross morphology tumour were noduloulcerative(58.06%), nodular (25.81%) and ulcerative (16.13%) type. The most common histopathological diagnosis was sebaceous gland carcinoma(40.39%), involving 15 males and 10 females. The second most common type of malignancy was basal cell carcinoma (29.03%) affecting 8 males and 10 females. The squamous cell carcinoma was present in 16 cases (25.81%) and malignant melanoma affects 3 cases (4.84%). Histological examination showed well differentiated tumour in 21 (33.7%) cases, moderately differentiated 23 (37.10%), and poorly or undifferentiated carcinoma in 18 (29.03%) subjects. Microscopic perineural invasion was found within the lesion in 6 (9.68%) cases. Majority (25.80) were in advanced stage (stage II & III). Preauricular and cervical lymph node metastasis was detected in 6 (9.68%) patients at presentation. Orbital invasion was detected in 3 cases, by clinical, radiological and histological findings. None of the patients had distant metastasis. Tumour has complicated by inflammatory response orbital analysis in 4 (6.4%) cases. Primary treatment modality was neoadjuvant chemotherapy followed by surgical excision in 51.66% cases 35.48% patients underwent for primary surgical excision and lid reconstruction. Eyelid reconstruction was achieved by Cutler Beard technique (38.71%), Tenzel’s rotational flap (25.81%),Mustarde cheek rotational flap (22.55%). Orbital exentration was required in 3 patients. 32(51.66%) cases were managed by neoadjuvant chemotherapy (cis platinum, bleomycin and methotrexate in 41.93% patients and cis platinum and 5FU in 9.6%). Overall response (CR+PR) of chemotherapy was 74.19%, while in 25% cases no response was seen. Response of chemotherapy was better in poorly differentiated carcinoma. None of the patients had experienced any fatal side effect of chemotherapy. The mean follow up period was 14 months. Out of all malignancy cases 4 were lost in the follow up. At final follow up 82% patients were alive and well. Recurrence occurred in 13(20.97%) cases. One patient of malignant melanoma died during treatment.

DISCUSSION:

This study has one of the largest series of eyelid malignancies that includes commonly advanced cases, the study highlights the presentation pattern and challenges in the diagnosis and management of extensive eyelid carcinomas.

The present study revealed 38.7% males and 61.3% females. Other studies also reported predominance of female patients in malignant eyelid tumours^[4,5]. The three most common malignant tumour in our study were sebaceous gland carcinoma(40.39%), basal cell carcinoma (29.03%), squamous cell carcinoma (25.8%) and malignant melanoma (4.84%). Similar pattern was observed by Gosai etal were sebaceous gland carcinoma(46.34%), basal cell carcinoma (29.26%), squamous cell carcinoma (21.93%) cases^[4].Ramya et al sebaceous gland carcinoma(47.7%), basal cell carcinoma (26.8%), squamous cell carcinoma (21.9%)^[6]. Bogheri et al from Tehran reported different type and frequencies of malignant eyelid tumours, sebaceous gland carcinoma(6%), basal cell carcinoma (83%), squamous cell carcinoma (8%)^[7].

In most of the studies from other countries basal cell carcinoma is the most frequent malignant tumour of eyelid ^[8-10]. The mean duration of time since appearance of lesion and presentation was 28.4 months. The corresponding value 13.5 months in a Turkish study ^[10], 37.8 months in a Pakistani study ^[11]. The delayed presentation in developing countries may be due to socio-economic problem, self-neglect in old age and lack of proper referral system ^[11]. Delayed presentation may responsible for advanced stage and metastasis. The rate of lymph node metastasis in this study was 9.68%. The reported incidence of regional lymph node metastasis associated with squamous cell carcinoma ranges from 10% to 21.4% ^[10]. Orbital invasion was seen in 4.84% cases, similar to finding of Donaldson et al (5.9%) ^[12].In our study 51.61% patients were treated with neoadjuvant systemic chemotherapy. PMB regimen (cis-platinum, bleomycin and methotrexate) used for squamous cell carcinoma &basal cell carcinoma and 5 FU, cis-platinum was used for sebaceous gland carcinoma. In our study overall response (complete response + partial response) rate was 74.19% and there were no response in 19.35% cases while in 6.46% cases the disease progressed. Luxenberg and Guthrie use cis-platinum chemotherapy for BCC and SCC of eyelids found complete response in 62.5% and partial response in 37.5% patients [13]. While Michael Marley et al reported partial response in 100% cases of BCC of lid treated by cis-platinum based chemotherapy [14]. In this study response to chemotherapy was better in poorly and undifferentiated carcinoma as compare to well differentiatedcarcinoma. No serious side effects of chemotherapy was observed. After chemo reductionof tumour wide surgical excision with lid reconstruction were performed in 51.61% cases. Most common reconstructive technique used was Cutler Beard flap(38.71%). The tumour that are more aggressive and recurrent require wide surgical margin(5-10mm) while 2-4 mm surgical margin is recommended in less aggressive lesions[15].We observed microscopic perineural invasion in 9.68% cases, perineural invasion regarded as more aggressive and are associated with higher recurrence rates. In this study recurrence rate was 20.97%. The reported risk of recurrence of BCC after surgery was 5-15%[16]. The recurrence rate depends on the location, size, extent of infiltration, and histological type[17].

 CONCLUSION:

 In this part of country, delayed presentation leads to extensive eyelid carcinoma. Anterior chemotherapy reduces preoperative tumour bulk. It is better adjuvant therapy for advanced eyelid malignancies. Early detection of lesion can markedly reduces ocular morbidity, secondary orbital invasion and recurrence.

TABLE 1: Patient Characteristics

Characteristics		No	%
Gender
	Male	24	38.70
	Female	38	61.29
Duration of lesion at presentation
	0-1 year	22	35.48
	1-2 years	32	51.61
	>2 years	8	12.90
Localization
	Only Upper eyelid	30	48.39
	Only Lower eyelid	22	35.48
	Both eyelid	4	6.45
	Medial canthus	6	9.68
Types of Malignancy
	Sebaceous gland carcinoma	25	40.32
	Basal cell carcinoma	18	29.03
	Squamous cell carcinoma	16	25.81
	Malignant Melanoma	3	4. 84
Pathological Differentiation
	Well differentiated	21	33.87
	Moderately differentiated	23	37.10
	Poorly / undifferentiated	18	29.03
Type of Growth
	Nodular	16	25.81
	Ulcerative	10	16.13
	Ulcero-nodular	36	58.06

REFERENCES:

1. Cook BE Jr, Bartley EB. Treatment options and future prospects for the management of eyelid malignancies: An evident based update. Ophthalmology 2001;108;2088-98
2. Hilovsky JP. Lid lesion suspected of malignancy. J. Am optom Assoc1995; 66:510-5.
3. Diepgen TL, Mahler V. The epidemiology of skin cancer. Br. J. Dermatol 2002;146(supps 61)61-6
4. Gosai J, Mehta D, Pherwani K, Bhatt R, Agrawal K, Tandel D. clinical study of lid tumours in adults patients in western region of India. J-Evol med dent science2014:3(73):15364-15373.
5. Kumar R, Adhikari R, Sharma M, Pokharel D, Gautam N. pattern of ocular malignant tumours in bhairahwa Nepal. Int J Ophthal Vis Sci; 20087(1) 1-6.
6. Rammya BS, ChinmayeeDSb, Raghunatha AR. Tumours of eyelids- a Histopathological study of 86 cases in tertiary hospital. International journal of scientific and research publication 2014;4:1-5.
7. Bagheri A, Tarakoli M, Kanaanni A et al. eyelid masses: A 10 years survey from tertiary eye hospital in Tehran.
8. Chang CH, Chang SM, Lai YH, Huang J, Su My et al; eyelid tumour in southern Taiwan: A 5 year survey from medical university. Kaohsiung J Med Sci 2003; 19:549-51.
9. Cook BEJr, Bartky GB. Epidemiologic characteristic and clinical course of patients with malignant eyelid tumours, in an incidence cohort in olnosted country, Minnesota. Ophthalmology 1999;106:746-50.
10. Soysal GH, Markoc F, Invasive squamous carcinoma of eyelid and periocular region .Dr J ophthal 2007;91:325-9.
11. Hussain I, Khan FM, Alam M, Khan BS. Clinicopathological analysis of malignant eyelid tumour in north-west Pakistan 2013;63(1):25-27
12. Donaldson MJ, Suvillian TJ, White head KJ et al Squamous cell carcinoma of the eyelids. Dr J Ophthal.2002;866:1161-1165
13. Luxenberg MN, Guthrie TH, chemotherapy of eyelid and periorbital tumours. Trans am ophthalsoc 1985;83:162-180.
14. Morley M, Finger PT, Perlin M etal. Cisplatin chemotherapy for ocular basal cell carcinoma. Br J ophthal 1991;75:407-410.
15. Rossato LA, Carneiro RC etal. Diagnosis of aggressive subtypes of eyelid basal cell carcinoma by 2 mm punch biopsy, prospective and comparative study. Rev Col Bros Cir. 2016;43(4) :262-269
16. Szwczyk MP, Pazdrowski J, Dariczak- PazdrowskiA et al. Analysis of selected recurrence risk factors after treatment of headand neck basal carcinoma. PostepyDermatol Alergol.2014;31(3):146-151.
17. Yingyum Shi, RenbingJia, Xianqun Fan. Ocular basal cell carcinoma:A brief literature review of clinical diagnosis and treatment. Oncotargels therapy.2017;10:2483-2489.

 

 

Figure 1: A large multi-nodular sebaceous gland carcinoma involving left upper eyelid

 

 Figure 2: A huge ulcero-nodular squamous cell carcinoma that involved the both eyelids and orbit.