Opthalmopathology laboratory, department of Pathology, ErasmusMC University, PO-Box 2040, 3000CA, Rotterdam the Netherlands

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1 Survey of the histopathological and clinical characteristics of caruncular lesions; lessons from a retrospective case series over 25 years completed with an extensive review of literature. Robert M. Verdijk 1, Tanya Luschyk 2, Olga Weijtens 2, Willem van den Bosch 2 and Dion Paridaens 2 Opthalmopathology laboratory, department of Pathology, ErasmusMC University, PO-Box 2040, 3000CA, Rotterdam the Netherlands Department of Oculoplastic and Orbital Surgery, Rotterdam Eye Hospital, Rotterdam, The Netherlands. Corresponding author: Dr. Robert M. Verdijk, MD, PhD, Opthalmopathology laboratory, department of Pathology, ErasmusMC University, PO-Box 2040, 3000CA, Rotterdam the Netherlands. The authors have no conflicts of interest to declare

2 Outline Lesions of the lacrimal caruncle are rare and vary widely due to its unique composition. Correct clinical preoperative diagnosis is very difficult and is reached only in about half of the cases Rarely, general pathologists and even specialized ophthalmic pathologists encounter lesions taken from this location. The anatomy and histology of the lacrimal caruncle is unique in its composition of both dermal and conjunctival structures that may all be involved in pathological change 15. The aim of this presentation is to introduce the lesions of the caruncle based on a retrospective review of caruncular lesions of the eye examined at the largest tertiary ophthalmic pathology laboratory of the Netherlands. A retrospective search of all lesions of the caruncle examined at the laboratory of ophthalmopathology from 1987 to 2012 was performed. One hundred and sixty lesions of the caruncle were identified. The classical textbooks often only depict oncocytoma of the caruncle which is the classical lesion for this site, but is only sixth in occurrence in our experience. Nevi (36.25%) were the most common lesions observed, squamous papillomas were the second most common entity (15.25%). Together these two entities represented 51.5% of the lesions found in the caruncle. A total of 25 different classifying histopathological diagnostic entities were identified reflecting the complex composition of the caruncle and fifteen more diagnoses can be added by a review of the literature on caruncular lesions Fourteen lesions in our series were malignant (9%). Most lesions present in the caruncle are benign. We present an educative series of clinical and histopathological photographs of the lesions encountered in our practice. We will emphasise the difficulty of clinical identification of histopathologically confirmed lesions and the need for confirmation

3 Table: Diagnosis categories, frequency and clinical information on 160 caruncular lesions Diagnosis N % age sex min max m f Melanocytic lesions Naevus 58 36, PAM mild atypia 3 1, PAM severe atypia (melanoma in situ) 1 0, Melanoma 2 1, Pigmentation 2 1, Epithelial lesions Papilloma 26 16, Basal cell carcinoma 3 1, Squamous cell carcinoma 2 1, Conjunctival intraepithelial neoplasia (CIN) 2 1, Sebhorrheic Keratosis 1 0, Sebaceous tumors Sebaceous hyperplasia 9 5, Sebaceous carcinoma 2 1, Sebaceous adenoma 1 0, Vascular lesions Pyogenic Granuloma 2 1, Capillary hemangioma 2 1, Cavernous hemangioma 1 0,

4 Hyperplasia Hyperplastic caruncle 1 0, Cysts Conjunctival or epidermal inclusion cyst 13 8, Apocrine hidrocystoma 1 0, Inflammation Chronic inflammation 9 5, Myeloproliferative lesions Follicullar lymphoïd hyperplasia 5 3, Lymphoma 4 2, Other tumors NSCLC (metastasis) 1 0, Pleiomorphic adenoma 1 0, Oncocytoma (oxyphilic adenoma) 8 5, Follicular lymphoid hyperplasia

5 Sebaceous hyperplasia Sebaceous carcinoma Inclusion cyst

6 Capillary hemangioma Cavernous hemangioma Melanoma

7 Reference list 1. Evans WH. Tumor of the lacrimal caruncle: A study of 200 collected cases. Arch Ophthalmol. 1940;24: Luthra CL, Doxanas MT, Green WR. Lesions of the caruncle: a clinicohistopathologic study. Surv Ophthalmol. Nov-Dec 1978;23(3): Levy J, Ilsar M, Deckel Y, Maly A, Pe'er J. Lesions of the caruncle: a description of 42 cases and a review of the literature. Eye (Lond). May 2009;23(5): Gomez Cabrera CG, Cabrera Arias JG, Ramirez Garcia LK. Clinical and histological characteristics of caruncle tumors. Revista Cubana de Oftalmologia. 2009;22(sup): Kapil JP, Proia AD, Puri PK. Lesions of the lacrimal caruncle with an emphasis on oncocytoma. Am J Dermatopathol. May;33(3): Ostergaard J, Prause JU, Heegaard S. Caruncular lesions in Denmark : a histopathological study with correlation to clinical referral diagnosis. Acta Ophthalmol Scand. Feb 2006;84(1): Ash JE. Epibulbar tumors. Am J Ophthalmol. Aug 1950;33(8): Solari HP, Ventura MP, Orellana ME, Novais GA, Cheema DP, Burnier MN, Jr. Histopathological study of lesions of the caruncle: a 15-year single center review. Diagn Pathol. 2009;4: Kaeser PF, Uffer S, Zografos L, Hamedani M. Tumors of the caruncle: a clinicopathologic correlation. Am J Ophthalmol. Sep 2006;142(3): Santos A, Gomez-Leal A. Lesions of the lacrimal caruncle. Clinicopathologic features. Ophthalmology. May 1994;101(5): Shields CL, Shields JA, White D, Augsburger JJ. Types and frequency of lesions of the caruncle. Am J Ophthalmol. Dec ;102(6): Shields CL, Shields JA, White D, Augsburger JJ. Survey of lesions of the caruncle. Trans Pa Acad Ophthalmol Otolaryngol. 1986;38(2): Bowyer J, Sullivan T, Whitehead K. Steatocystoma simplex of the caruncle. Br J Ophthalmol. Feb 2003;87(2): Wilson RP. Tumours and cysts of the lacrimal caruncle. Trans Ophthalmol Soc N Z. 1959;11: Kathuria SS, Howarth D, Hurwitz JJ, Oestreicher J. An anatomic and histologic study of the caruncle. Ophthal Plast Reconstr Surg. Nov 1999;15(6): Pappalardo J, Lee GA, Whitehead K. Actinomycotic granule of the caruncle: a case report. Ophthal Plast Reconstr Surg. Jul-Aug;27(4):e Nylander AG, Atta HR. Adenosquamous carcinoma of the lacrimal caruncle: a case report. Br J Ophthalmol. Nov 1986;70(11): Poon A, Sloan B, McKelvie P, Davies R. Primary basal cell carcinoma of the caruncle. Arch Ophthalmol. Dec 1997;115(12): Dhir SP, Shishku MN, Krewi A. Ocular horn. Br J Ophthalmol. Apr 1989;73(4): Ghafouri A, Rodgers IR, Perry HD. A caruncular dermoid with contiguous eyelid involvement: embryologic implications. Ophthal Plast Reconstr Surg. Sep 1998;14(5): Bradfield YS, Kulkarni A, Potter HD, Warner T, Albert DM. Eyelid fibrous hamartoma with conjunctival angioma in an infant. Arch Ophthalmol. Jun 2007;125(6): Evans M, Chang E, Yu DL, Rao NA. Granular cell tumour: a rare caruncle lesion. Br J Ophthalmol. Feb 2006;90(2): Kiratli H, Kocabeyoglu S, Saglam A, Soylemezoglu F. Langerhans cell histiocytosis of the caruncle. Clin Experiment Ophthalmol. Sep-Oct 2007;35(7):

8 24. Heegaard S, Prause JU. Leiomyoma of the caruncle. Acta Ophthalmol Scand. Dec 1998;76(6): Bianciotto C, Demirci H, Shields CL, Eagle RC, Jr., Shields JA. Metastatic tumors to the eyelid: report of 20 cases and review of the literature. Arch Ophthalmol. Aug 2009;127(8): Vannas S, Lapinleimu K. Molluscum contagiosum in the skin, caruncle, and conjunctiva: detection of a cytopathic agent in tissue culture. Acta Ophthalmol (Copenh). 1967;45(3): Rennie IG, Parsons MA, Benson MT. Neurilemoma of the caruncle: a clinicopathological report. Br J Ophthalmol. Dec 1991;75(12): Freedman KA, Tran RM. Neurofibroma involving the caruncle. Arch Ophthalmol. Feb 2004;122(2): Koo L, Chang EL. Methicillin-resistant Staphylococcus aureus caruncle abscess. Ophthal Plast Reconstr Surg. Mar-Apr 2007;23(2): Lam DS, To KF, Fan DS, Cheuk W. An uncommon malignant neoplasm of the caruncle: report of a case of undifferentiated carcinoma. Arch Ophthalmol. Mar 1998;116(3):

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