Eyelid Tumours: A Clinicopathological Study

Transcription

1 Med. J. Cairo Univ., Vol. 80, No. 2, December: , Eyelid Tumours: A Clinicopathological Study LAILA H.M. ELSHAZLY, M.D. The Departments of Ocular and Pathology, Memorial Institute of Ophthalmology, Cairo, Egypt Abstract Purpose: This study was aimed at to determine the frequency of excised eyelid lesions in a patient population treated over a 10-year period. Material and Methods: The data of all excised eyelid lesions with tissue diagnoses from 2000 to 2010 in the pathology department were analyzed. Results: 167 eyelid specimens were examined; 68 (40.7%) obtained from male patients and 99 (59.3%) from female patients. The age range was years with a mean age of 35.67±20.72 years. The most frequent excised lesions were papilloma which represented 27.8% (45 cases). Cystic lesions in 34 cases were the second most common and represented 20.4%. These were mostly dermoid cysts in 21 cases (61.8%), occupying the upper temporal region of eyelids in 15 cases. Pigmented epithelial tumors were seen in 26 cases (16%). Out of these cases, compound nevus represented 69.2% (18 cases) and junctional nevus represented 3.8% (one case). Subepithelial nevi were reported in seven cases (26.9%). The premalignant and malignant tumors represented (4.8%,8 cases) with mean age ± years. These were one case of actinic keratosis, six cases of basal cell carcinoma and one case with sebaceous adenocarcinoma. Conclusion: Benign lesions were the most frequent histologically diagnosed eyelid lesions in Egyptian population. The true malignant lesions were lower than what has been described in many reports. Key Words: Eyelids Papilloma Nevus Basal cell carcinoma Adenocarcinoma. Introduction TUMOUR-LIKE masses in the eyelid are commonly encountered in clinical practice and a clinical diagnosis is often unreliable. The spectrum extends from a benign cyst to a highly malignant metastasising tumour [1]. The frequency of eyelids tumors has been varyingly reported. In one study in Japanese population, benign eyelid tumors represented 73% with com- Correspondence to: Dr. Laila Hassan Mohamad Elshazly, Laihasan@gmail. com mon nevocellular nevi (16%), seborrheic keratosis (10.3%), epidermoid cysts (8%), and papillomas (6.7%). Malignant eyelid tumors represented 27%, which included 10% basal cell carcinomas, 10% sebaceous gland carcinomas, 4.6% malignant lymphomas, and 2.3% metastatic tumors [2]. In one study, in Taiwan subtropical population, the most frequent benign eyelid tumors were nevus, papilloma, cysts and seborrheic keratosis, successively [3]. Similarly, Beak reported that melanocytic nevus was the most frequent benign tumor in Koreans (65.3%) followed by seborrheic keratosis (11.5%) and to a lesser extent squamous papilloma [4]. In another series in Singapore, Basal cell carcinoma (BCC) was found to be the most common eyelid malignancy, accounting for 84%, followed by sebaceous adenocarcinoma (10.2%), squamous cell carcinoma (SCC) (3.4%), and malignant melanoma (1.2%) [5]. In Switzerland, Benign tumors largely predominated over malignant ones, representing 84% of cases, and the five most frequent subtypes were squamous cell papilloma (26%), seborrheic keratosis (21%), melanocytic nevus (20%), hidrocystoma (8%), and xanthoma/xanthelasma (6%). Basal cell carcinoma was the most frequent malignant tumor (86%), followed by squamous cell carcinoma (7%) and sebaceous carcinoma (3%) [6]. The aim of this study was to determine retrospectively the frequency of commonly excised eyelids lesions in a population of patients identified with histopathologically confirmed diagnosis over a 10-year period. Also, correlation between clinical and histological diagnosis, and reference to previously published series were done. 95

2 96 Eyelid Tumours: A Clinicopathological Study Material and Methods The study was approved by the ethical committee. Informed consents were obtained routinely from patients undergoing any surgical removal and pathological examination. The data on eyelid masses diagnosed in the pathology department were retrospectively analyzed from 2000 to Age, sex distribution of patients, and location of lesions were evaluated according to Hospital pathological referral records. Hematoxylin and eosin stained sections from each biopsy specimen were examined. The final diagnosis in each case was established by a combination of history, ocular findings, and histopathology. The Students t-test and analysis of variance (ANOVA) test were used to analyze continuous variables such as age. Chi-square (X 2 ) test was used to analyze categorical variables such as sex and site of lesion. A p-value less than 0.05 was considered statistically significant. Results 167 eyelids specimens were examined in the pathology department in the decade spanning 2000 to Of these specimens, 68 (40.7%) were from males and 99 (59.3%) were from females. The specimens were referred to the pathology department due to rapid growth or suspicion of malignancy. The mean age of the cohort was 35.67±20.72 years (range, 87.34), with significant difference between patients ( p=0.0001, ANOVA). There was no significant difference in sex distribution (p=0.11., Chi-square test). The distribution of the lesions and differences in mean age between the lesions are shown in Table (1). Benign epithelial lesions represented 37.7% (63 cases) with mean age of ± 19.4 years. Papilloma was detected in 45 cases (27.8%). Correct clinical diagnoses were made in 37 cases. The clinical misdiagnoses included granuloma, molluscum contagiosum, basal cell carcinoma, hemangioma, and nevus. Papilloma was diagnosed mostly on the skin side of the eyelid in 32 cases (71.1%) and lid margin in 12 cases (26.7%) and inner canthus in one case (2.2%). It was clinically described as a pedunculated, papillary reddish lesion. The reason for excision was rapid growth and/or cosmetic in all cases, except one case which was recurrent. Histopathologically, it had a vascular connective tissue core lined by a hyperplastic epithelium (Fig. 1). Viral warts with vacuolated epithelial cells were diagnosed in 16 cases (35.6%). The subepithelial tissue was infiltrated with cells of acute inflammation (polymorphs and eosinophils) in two cases. One case showed excessive keratinization. Four cases were pigmented with clinical incorrect diagnosis as papillomatous nevus. Papilloma significantly affected middle-aged patients (40.42± 18.8 years) that significantly differed from cystic lesions (p=0.0001), and basal cell carcinoma (p=0.0120), with no significant difference from nevus, hemangiomas, seborrheic keratosis (p=0.49, 0.9, and 0.69, respectively, t-test) (Table 1). Other Benign epithelial lesions included seborrheic keratosis in nine cases (5.6%) with mean age 43.22±20.67 years. Four cases were misdiagnosed as papillomatous nevus and two cases as papilloma. Histologically, it showed intra-epidermal proliferation of benign basal cells with reticulated pattern in one case, deeply pigmented in five cases and frequent cystic accumulation of keratinous material in all cases (Fig. 2). Pilomatrixoma (benign calcifying epithelioma) was diagnosed in three cases with mean age 10.67± 1.15 years. Histologically, peripheral nucleated basophilic cells and central shadow cells were observed. Calcification was observed in one case and foreign body giant cell reaction was detected in another one. The second most common benign lesions were cystic lesions in 34 cases (20.4%). Of these, 21 cases (61.8%) were dermoid cysts occupying the upper temporal eyelids in most cases, upper nasal eyelid (one case) and brow (one case). Nine cases (26.5%) had epidermoid cysts involving the skin, lid margin, innercanthus and outercanthus. Two cases of sebaceous cysts and two cases of sweat glands retention cysts were located in the lid margin. Dermoid cysts were excised in young age patients (range from 8 months to 48 years) with significant difference from nevus, benign epithelial lesions, and malignant lesions (p=0.002, , and , respectively, t-test) (Table 1). Melanocytic nevi were the third most commonly excised benign eyelid lesion (26 cases, 16%). 23 cases (88.5%) were female and 3 cases (3%) were male. These nevi occurred most commonly on the lid margin (76.9%, 20 cases), followed by the skin (23.1%, 6 cases). Nevus excision was mostly due to rapid growth and/ or cosmetic. Histopathologically, 18 cases (69.2%) were diagnosed as compound nevi having nests of nevus cells with junctional activity in the epidermodermal junction and the dermis. Of these, seven cases showed papillomatous configuration and were mistakenly diagnosed as papilloma (Fig. 3). One subject (3.8%), aged 52 years had a junctional nevus with nests of nevus cells in the epidermodermal junction dating

3 Laila H.M. Elshazly 97 since birth. Subepithelial nevus was diagnosed in seven cases (26.9%) with one case had a concomitant sebaceous cyst. Rapid growth of compound nevi was attributed to cystic spaces in three cases. The growth of the remaining nevi could be explained by nevus cells proliferation. Nevi were excised in middle aged patients (37.38 ± years) with significant difference from cystic lesions and malignant lesions (p=0.002, and 0.001, respectively, t-test). Xanthelasma was diagnosed in five female patients. Foamy histiocytes laden with intracellular fat deposits primarily within the upper reticular dermis were detected (Fig. 4). Four cases (2.4%) of molluscum contagiosum, with mean age 38.5 ±23.2 years, were clinically described as multiple raised umblicated nodules involving the skin in three cases and lid margin in one case. Histopathologically, there were multiple lobules of acanthotic epithelium with intracytoplasmic eosinophilic inclusion bodies (molluscum bodies). The premalignant and malignant tumors were diagnosed in eight cases (4.8%) with mean age 59.25± years. They significantly affected old age patients as compared to benign lesions (p=0.001, t-test). One case (69 years old) had actinic keratosis with thickened, raised grayish white lesion at the lid margin. It was diagnosed clinically as a cutaneous horn. Microscopically, it showed acanthosis, hyperkeratosis, atypia of squamous cell layer and normal polarity. There was basophilic degeneration of dermal collagen with infiltrating inflammatory cells. Basal cell carcinoma (BCC) was diagnosed in six cases (3.6% of total eyelid lesions, 75% of malignant eyelid tumors) affecting old aged patients with mean age 61 ±8.94 years. Clinically, it was diagnosed as ulcerating rapidly enlarging lesion in the skin side of eyelids in four cases, and the lid margins in two cases. Lower eyelid was commonly reported in five cases. Microscopically, it showed epithelial nests with peripheral palisading of basal cells. It was accompanied with seborrheic keratosis in one case. Sebaceous gland adenocarcinoma was detected in one patient (12.5% of malignant tumors). It was diagnosed as a recurrent upper eyelid chalazion. Histologically, it showed masses of sebaceous cells with abundant cytoplasm and multiple mitotic figures. With respect to site of lesions, the skin side of the lid was the most common site in 79 cases (47.3%), followed by the lid margin in 44 cases (26.3%), upper angular area in 19 cases (11.4%), and the tarsus in 14 cases (8.4%). There was a significant difference in localization between excised lesions (p=0.0001, Chi-square test). The mean age for skin and lid margin lesions did not differ significantly (p=0.43, t-test). The upper angular lesions, which were mainly dermoid cysts, were significantly excised in young age (p=0.0001, t-test). Table (2) shows the distribution of excised lesions according to the site. Table (3) shows the correlation between clinical and pathological diagnoses. Table (1): The age and sex distribution of eyelid lesions. Eyelid lesions Numbe (%) Mean age±sd Male: Female Papilloma 45 (27.8) 40.42± :26 Nevus 26 (16.0) 37.39± :23 Dermoid 18 (11.1) 10.98± :10 Chalazion 12 (7.4) 32.50± :6 Seborrhic keratosis 9 (5.6) 43.22± :3 Epidermoid cyst. 8 (4.9) ± :5 Basal cell carcinoma 6 (3.7) 61.00±8.94 3:3 Trichofolliculoma 5 (3.1) 38.20± :4 Xanthelasma 5 (3.1) 52.00± :5 Pyogenic granuloma 4 (2.5) 36.00± :1 granloma Molluscum 4 (2.5) 38.50± :2 contagiosum Benign. Calcifying 3 (1.9) 10.67± :1 epithelioma Hemangioma 3 (1.9) 41.67± :1 Hamartoma 2 (1.2) 28.00± :2 Nerofibromatosis 2 (1.2) 36.50± :1 Sebaceous.Cyst 2 (1.2) 26.50± :1 Sweat duct cyst 2 (1.2) 53.50±6.36 1:1 Actinic keratosis 1 (0.6) :0 Fibrohisoma 1 (0.6) :0 Inverted follicular 1 (0.6) :1 keratosis Keratoacanthoma 1 (0.6) :0 Lymphoma 1 (0.6) 6.0 1:0 Sebaceous adenocarcinoma 1 (0.6) :0 Total 167 (100) 35.67± (40.7%): 99 (59.3%) p-value <0.0001* 0.11** * Significant difference in age between groups at p<0.05 (ANOVA). ** Significant difference in sex between groups at p<0.5 (Chi test). Table (2): The frequency of site distribution of eyelid lesions. Site Number (%) Skin 81 (48.5) Lid margin 41 (24.6) Upper angular 19 (11.4) Tarsus 14 (8.4) Inner canthus 6 (3.6) Brow 3 (1.8) Outer canthus 2 (1.2) Lid margin 1 (0.6) Total 167 (100%)

4 98 Eyelid Tumours: A Clinicopathological Study Table (3): Correlation between clinical and histopathological diagnoses. Papilloma Nevus Dermoid Chalazion Seborrhic keratosis Epidermoid cyst. Basal cell carcinoma Trichofolliculoma Xanthelasma Pyogenic granuloma Molluscum contagiosum Benign calcifying epithelioma Hemangioma Hamartoma Nerofibromatosis Sebaceous.Cyst Sweat duct cyst Actinic keratosis Fibrohisoma Inverted follicular keratosis Keratoacanthoma Lymphoma Sebaceous adenocarcinoma Correct clinical diagnosis 37 Cases 19 Cases Cases Three cases Two cases Three cases Five cases One case Four cases Three cases One case Two cases Two cases Clinical misdiagnoses Granuloma, molluscum contagiosum, bcc & hemangioma (one case each). pigmented nevi (four cases) Pigmented papilloma (seven cases) Nevus (4 cases) & papilloma (2 cases) Dermoid (4 cases), sebaceous cyst (one case), unspecified cyst (2 cases) Seborrheic keratosis (two cases), malignant melanoma (one case) Unspecified nodular lesion (5 cases) Papilloma (two cases), sebaceous adenoma (one case) Unspecified eyelid tumor (2 cases) or dermoid cyst (one case) Dermoid cyst (one case), unspecified eyelid tumor (one case) Dermoid cyst (one case) Cutaneous horn Papilloma Unspecified lid tumor Seborrheic keratosis Unspecified lid tumor Recurrent chalazion Table (4): Review of previous studies on eyelid tumors. Region Period Number of cases Histology Study Taiwan Benign (126;87.5%) nevi (38;30.2%), Papilloma Cheng et al., 2003 [22] (26;21%), cyst (13;10.3), seborrheic keratosis (10;8%) Malignant (18;12.5%) Bcc (14 case), sebaceous adenocarcinoma (three cases), Sqcc (one case) Singapore Malignant Bcc (84.0%) Lee et al., 1999 [5] Sebaceousadenocarcinoma (10.2%) Sqcc (3.4%) Mm (1.2) Romania Benign (216 cases); papilloma (84 cases,cystic Coroi et al., 2010 [23] (73 cases), seborrheic keratosis 11 case,navi (five cases). Malignant (225); bcc (185 cases), Sqcc (50 case), Sebaceous adenocarcinoma (five cases), Mm (15 cases). Hong Kong Malignant (36 cases) Bcc (27 cases), Sqcc (two cases), Sebaceous cell carcinoma (four cases). Mak et al., 2011 [24] Japan Benign (73%) nevus 14 cases, Seborrhieic keratosis nine cases, epidermoid cyst six cases, Papilloma six cases Malignant (27%), Bcc nine cases, Sebaceous adenocarcinoma, nine casaes, Malignant lymphomas,four cases Obata et al., 2005 [2] India Malignant Bcc (44%), Sebaceous adenocarcinoma Jahagirdar et al., 2007 [18] (37%), Sqcc (14.8%) Poland Benign (1262;62.2%). Papillomas (659;52.3%). Halon et al., 2005 [25 ] Malignant (21,3% (n=433). Basal cell carcinomas (314,72.5%). BCC = Basal cell carcinoma, SqCC = Squamous cell carcinoma, MM = Malignant melanoma

5 Laila H.M. Elshazly 99 Fig. (1): A case of papilloma involving the lid margin (A). Histopathologically, it had a vascular connective tissue core lined by a hyperplastic epithelium. (hematoxylin-eosin; original magnification, x25) (B). Fig. (2): A case of seborrheic keratosis with nodular lesion at the skin side of eyelids (A). Histologically, it showed intraepidermal proliferation of benign basal cells cells with reticulated pattern and frequent cystic accumulation of keratinous material (hematoxylin-eosin; original magnification, x25) (B). Fig. (3): Subepithelial nevus cells in the dermis with chronic inflammatory cells infiltration (hematoxylin-eosin; original magnification, x100). Fig. (4): A case of massive Xanthelasma palpebrum (A). Histologically, it showed xanthoma cells i.e. foamy histiocytes laden with intracellular fat deposits primarily within the upper reticular dermis (hematoxylin-eosin; original magnification, x100) (B).

6 100 Eyelid Tumours: A Clinicopathological Study Discussion This analysis of 167 eyelid lesions could be a representative sample of the Egyptian population. In this study, the most commonly excised benign lesions were benign epithelial papilloma. This was in accordance to Deprez et al., study on sweddish population [6]. On contrary, a previous study on Japanese subjects reported much lower incidence of papilloma (6.7%) (Table 4) [2]. The differences in sample size and innate characteristics might explain this difference between studies. Viral warts were diagnosed in 35.6% of our cases, which was consistent with earlier studies suggesting human papilloma virus (HPV1 and 2) as the major etiologic factor [7]. Herein, nevi were the third commonly excised tumors among middle aged patients with the majority involving the lid margin, which was previously reported [8]. In this study, majority of nevi were in females which suggested the role of hormones. Although no clear sex predilection was reported for the development of melanocytic nevi, melanocytes were postulated to exhibit some degree of sex hormone responsiveness [9]. Melanocytes were found to have cytosolic receptors for estrogens with responsive melanogenesis [10]. Some studies suggested that melanocytic nevi were stimulated by exposure to sunlight [11]. Sun exposure was found to induce DNA damage of superficial epithelial cells with activation of transcription factors that stimulated expression of melanin-producing enzymes causing increased pigmentation [11]. Malignant melanoma was not detected in this study, which emphasized the rarity of this lesion in dark skinned Egyptian population. As for xanthelasma cases, The exact cause was not known but several factors like lipid abnormalities, hormonal factors, local factors, and macrophages were attributed to play a role in its pathogenesis. Recently, the role of acetylated low density lipoproteins and macrophages with their scavenger receptors were observed [12]. Sex preponderance in Xanthelasma Palpebrarum was debatable [12,13], although majority of our patients were females. This could be explained by the fact that females were more conscious from cosmetic point of view. In general, BCC was mentioned to be commonest malignancy of the eyelid and it accounted for 80% to 90% of all eyelid cancers in one study [14]. In present study, BCC was the most frequent malignant tumor in old age with nearly equal sex distribution despite previous report of a fourfold higher incidence among white males than females [14]. BCC incidence was mentioned to be 726 per with geographic and ethnic variations [15]. Many factors were described to contribute to BCC including; ultraviolet light (UV-B) exposure, ocular trauma, predisposing genetic factors, and human papilloma virus (HPV) or human immune virus infection [14]. Although, the skin was the most commonly affected site in our study (47% of cases), the lid margin bears special attention being a transition between keratinized stratified epithelium into non keratinized epithelium (rich in stem cells). UV-B or HPV could induce stem cell gene p53 (tumor suppressor gene) mutations and transformation into malignancy [16]. In contrast to BCC, sebaceous cell carcinoma accounted for only 1.5% to 3.8% of all eyelid malignancies in USA and Australia, respectively [17]. The highest rate reported was about 37% in Indian population [18]. In present study, sebaceous cell carcinoma was the second after BCC, comprising 12.5% of all eyelid cancers. Neither squamous cell carcinoma (SCC) nor melanoma were recorded in our study. On contrary, the incidence of cutaneous SCC and melanoma was mentioned to rise, particularly among fair-skinned Caucasian populations [19,20]. The lower incidence rates of eyelid malignancies in Egyptians, in this study, could be explained by the innate skin types. According to Fitzpatrick's classification [21], the skin types of the Egyptian population usually belong to types III and IV, which were considered less susceptible to sun-related injuries than skin types I and II for fair-skinned Caucasians. Table (4) summarizes incidence rates of overall and individual histopathological types among various countries and ethnic groups. Incidence rates varied markedly in different parts of the world, with relatively higher rates being observed in fair-skinned populations. Limitations of the present study were the lack of follow-up, systemic evaluation was not possible due to the retrospective nature of the study and retrieval of data from previous records. As well as, the study was done in limited population who were examined in only one Hospital. In conclusion, this study showed that the most common lesions in an Egyptian cohort were papilloma, cystic lesions (mostly dermoid) and nevi (mostly compound nevus). Most benign eyelid tumors were excised at a young age; meanwhile precancerous actinic keratosis and malignant basal cell carcinoma were excised in older subjects. The skin and lid margins were the most frequent sites

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