First Reported Case of Primary Basal Cell Carcinoma of the Right Caruncle: a Case Report and Review of the Literature

in vivo 27: 535-540 (2013)

First Reported Case of Primary Basal Cell Carcinoma of the Right Caruncle: A Case Report and Review of the Literature

PASQUALE FINO, MARIA GIUSEPPINA ONESTI, PAOLO FIORAMONTI, ANDREA ROMANZI and NICOLÒ SCUDERI

Department of Plastic, Reconstructive and Aesthetic Surgery, University of Rome Sapienza, Umberto I Polyclinic, Rome, Italy

Abstract. Aim: The clinical and histopathological Basal cell carcinoma (BCC) is the most common human characteristics of a patient with a primary basal cell carcinoma malignant neoplasm, and accounts for nearly 80% of all non- (BCC) of the right caruncle without seeding of the tumor to the melanoma skin cancers. It is a slow-growing, locally invasive conjunctiva are described. Primary basal cell carcinoma of the epidermal tumor that rarely metastasizes. BCC has the caruncle is an extremely rare but distinct entity. Case Report: potential to cause death by invasion of the central nervous A 24-year-old female presented with a lesion of the medial system (3). Primary BCCs of mucous membranes is caruncle of the right eye. Clinical examination revealed a 5×2 extremely rare. Most caruncle/ conjunctival BCCs are skin mm, oval-shaped, brown coloured, lesion without local skin carcinomas, resulting from the local spread of adjacent involvement. No associated cutaneous lesion was present. The neoplasms. To our knowledge, only eleven primary BCCs of tumour was completely excised. One year later, no evidence of the caruncle (4-14) (Table I) and four primary BCCs of the recurrence has been noticed. Conclusion: This case describes conjunctiva have been reported to date (15-18). a primary BCC of the right caruncle without seeding to the conjunctiva. It represents the first case of right caruncle BCC Case Report documented in photographs. A 24-year-old woman was seen by an ophthalmologist The lacrimal caruncle is a small oval conjunctival relief because of a slowly-enlarging lesion on the caruncle of her nodule located in the lacrimal fossa, medial to the plica right eye. Neither myopia nor presbyopia were diagnosed. semilunaris along the eyelid inner canthus. It is covered by a Visual acuity was 20/20 OU. Extraocular movements were stratified epithelium similar to the skin, but without normal, the intraocular pressures normal, and the findings keratinization. Like the skin, it contains hair and sebaceous from the remainder of the ocular examination were glands and sweat glands. But unlike the skin, it also contains unremarkable. accessory lacrimal glands. Its function is to retain the tear, The medial interpalpebral lesion measured 5×2 mm and was and it forms part of the lacus lacrimalis, in passing through centered over the right caruncle (Figure 1). It was an oval- the puncta. Its balance is so delicate that small changes in shaped, brown-coloured lesion; limits were clear and edges the morphology of the lacus can cause epiphora, which may were regular. There was no involvement of adjacent also occur after the excision of lesions. The caruncle is also conjunctiva or skin. involved in mucus secretion (1). The patient had had no other previous cutaneous or visceral The caruncle is supplied by the superior medial palpebral malignant neoplasms, and showed no signs of skin, skeletal, arteries, its lymphatics drain into the submandibular lymph endocrine, or ophthalmic anomalies. There was no family nodes, and it is innervated by the infratrochlear nerve (2). history of skin cancer. The lesion had been noticed around six months earlier as a painless brown spot on the caruncle (2×1 mm). It slowly grew until it reached the volume noticed at the time of the ophthalmologist’s examination. Correspondence to: Pasquale Fino, MD, Department of Plastic, The lesion was excised under local anaesthesia and the Reconstructive and Aesthetic Surgery, University of Rome Sapienza, histopathological examination revealed a solid-type BCC, Policlinico Umberto I, Via Pantelleria, 35, Scala B, Interno 1/A, 00141, Rome, Italy. Fax: +39 06491525/+39 0664491523, e-mail: originating in the basal layer of the conjunctival epithelium: [email protected], [email protected] non-keratinized stratified squamous epithelium was found overlying solid lobules of basaloid cells (Figure 2). The Key Words: Basal cell carcinoma, caruncle, ocular tumor. tumour cells exhibited small round-to-ovoid hyperchromatic

0258-851X/2013 $2.00+.40 535 in vivo 27: 535-540 (2013) nuclei. The nuclei appeared relatively isomorphic. Mild mitotic activity was present. There was nuclear palisading at the periphery of the solid tumour. The BCC was resected with a margin of safety to guarantee complete removal, no complications were encountered. Our patient attended follow-up appointments every three months and there was no evidence of recurrence 24 months after surgical excision (Figure 3). An informed consent for the publication of these results was obtained from the patient.

Discussion

The exact origin of BCC is still controversial. The caruncle is the only part of the conjunctiva containing adnexal elements. The surface of the caruncle consists of a non- keratinized stratified squamous epithelium overlying a stroma that contains sebaceous glands, hair follicles, and, in some patients, modified lacrimal glands (of Krause), surrounded by a thin layer of fat in the center of the caruncle. Tumours can develop from both mucous membrane and skin structures. The presence of pilar, sebaceous, apocrine, and squamous elements in BCC support the hypothesis that a pluripotential stem cell gives rise to most BCCs (3). The embryology of the caruncle is also not well -understood. It is formed at the end of the third month of gestation after the eyelids have fused. It is believed to develop either secondary Figure 1. Preoperative view: the medial interpalpebral lesion measured to cutting-off of a portion of the lower eyelid with its 5×2 mm and was centered over the right caruncle. appendages by the ingrowth of the lower canaliculus, or it is formed independently of the canaliculus by cellular proliferation of the epithelium on the posterior surface of the nasal lower eyelid (10). studies confirm the low frequency of lesions of the caruncle Since 1854, when von Graefe reported the first series of and the wide variety of histological types; furthermore, lesions of the caruncle, only a few reviews have appeared, malignant lesions are very uncommon. Malignant tumours the majority of them were published more than 15 years ago that have been reported include lymphoma, melanoma, (10, 19-21) and, unfortunately, some of these do not contain sebaceous cell carcinoma and BCC (20, 22). However, most an accurate description of the clinical history of the caruncle BCCs are benign (92.5%). Cystic lesions also tend diagnosed patients (9-11, 13). to be benign. The most frequent lesion among caruncle tumours is the Caruncular tumors generally occur with clear gender nevus (40%) and the second is papilloma (30%). Out of predominance, being much more common in women than in these lesions, 92.5% are benign, 5% are pre-malignant and men (3:1). On the contrary, our review of the literature 2.5% are malignant(6). Papilloma is more common in highlights the opposite predominance existing for BCC younger people, and its importance is that it can achieve a caruncular histotype (men:women=2:1). In terms of location, degree of dysplasia (pre-malignancy) which would result in 55% of all the caruncular neoplasias were presented in the carcinoma in situ. Macroscopically, these kinds of lesions right eye and 45% in the left (14) but if we consider the are friable, non-pigmented and vascularized (red-coloured), previous 11 cases reporting carunclar BCC (Table I), to our histologically they appear as fibrovascular structures knowledge, this is the first time a BCC of the right caruncle surrounded by a squamous epithelium. It is not uncommon has been reported (six cases concerned the left caruncle, five to note local invasion. Larger lesions in height and length do not specify the exact location of the neoplasia). are granulomas and chronic inflammations including Caruncular neoplasias arise in a very wide age range (14-80 angioma, although BCC and amyloidosis can also occupy years), but BCC tends to occur in younger people (mean age 100% of the surface of the caruncle. All others are of 42.1 years); the BCC histotype presents a completely considerably less affected both in surface and height. Many different trend, being reported in 9/12 patients aged 60 years

536 Fino et al: First Case of Primary BCC of the Right Caruncle

Figure 2. Histological examination. Baso-squamous carcinoma: non-keratinized stratified squamous epithelium was found overlying solid lobules of basaloid cells (haematoxylin and eosin, original magnification, ×4).

or more (mean age of 61.8 years) (Table II). BCC in children or young adults tends to be associated with inherited predisposition, such as xeroderma pigmentosum, albinism, and nevoid BCC syndrome. Our patient had no clinical signs of these inheritable syndromes. It must be noted that 60% of patients with BCC of the eyelid may have other BCC foci elsewhere on the face, or associated ocular injuries (23). Most BCCs arise as lesions in sun-exposed areas of the body, particularly the face. In young adults, the eyelids and nose are the most common sites of BCCs (3). The location of all well-documented primary conjunctival BCC was in the actinically exposed interpalpebral conjunctiva (15). Long-term exposure to sunlight and thus to UV light was the only significant factor predisposing to BCC observed in our patient. The progressive growth or extent of the injury, along with increased pigmentation or colouration change is the most common reason for consultation. However, pigmentation is not a sign of malignancy. The average time of evolution prior to surgery was six months for the BCC. Most lesions have a red or brown-black colour and, although these are non- specific data, they can, together with clinical presentation, Figure 3. Postoperative view: 24 months after surgical excision. such as an increase in pigmentation or darkening, guide towards a correct clinical diagnosis.

Conclusion Keratinization, hypertrophy or retraction of the caruncle may significantly interfere with its function of mucus This case supports previous observations that BCCs can arise secretion, and may occur as a secondary dysfunction of the from the caruncle. Lesions of the caruncle are uncommon and lacrimal drainage system. Any change in colour, size, or very diverse, which makes clinical diagnosis very difficult. vascularization of a caruncular lesion should lead to excision Due to the enormous variety of reported cases, close to ensure an accurate clinical diagnosis. collaboration between eye pathologists, dermatopathologists, The average distance between the external surface of the surgical pathologists, and soft tissue pathologists may be caruncle and the common canaliculus has been reported to needed in selected difficult cases. be 0.85 mm, whereas the shortest distance measured is of

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Table I. Reported cases of caruncle primary basal cell carcinoma (BCC).

Source, Patient age Location, Size, Symptoms Clinical Histological Accurate Malignant Treatment Recurrence year (years), side mm appearance findings diagnosis neoplasm (follow-up) gender

Shields et al., 61, Female Caruncle - - - - Yes - Excision - 1986 (10) Poon et al., 74, Male Left 7×5 Growth Multilobulated Solid, microcystic Yes Patient: SCC, BCC Excision - 1997 (4) caruncle of lesion nodule, pattern, Family: Colonic (6 months) vascularized, peripheral and breast cancer pink palisading Hirsch et al., 72, Male Caruncle ------Excision - 1997 (11) Meier et al., 24, Male Left 3×5 Growth Nodule, Solid-cystic, Yes No Excision No 1998 (5) caruncle of lesion vascularized, hiperchromatic (14 months) (3 months) white, red nuclei, mitotic center activity, peripheral palisading Mencía- 80, Male Left 5×4 Growth Irregular, Solid nodule, Yes No Excision No Gutiérrez et al., caruncle of lesion brown-black, retraction (7 years) 2004 (6) (5 months) vascularized spaces, hiperchromatic nuclei, mitotic activity, peripheral palisading Østergaard 60, FemaleLeft 3×4 Growth Lobulated, Infiltrative Yes No Excision Yes et al., 2004 (7) caruncle of lesion, cystic islands of (5.5 years) discomfort nodule, basaloid tumour (weeks) vascularized, cells, scattered pale mitotic activity, peripheral palisading

Rossman et al., 82, Male Left 6×9 Growth Solid nodule, Nodular, Yes Patient: Excision, No 2006 (8) caruncle of lesion pale invasive epithelial Periauricular adjuvant (6 months) (2-3 months) lobules, peripheral skin cancer radiotherapy nuclei palisading Kaeser et al., 72, Female Caruncle - - Cystic nodule - Yes - Excision No (-) 2006 (9) Kaeser et al., 52, Male Caruncle - - Solid nodule, Pigmented Yes - Excision No (-) 2006 (9) black dendritic melanocytes and rounded melanophages, macronodules with peripheral palisading, surrounded by retraction cleft Levy et al., 67, Male Caruncle - - - Multiple islands of Yes - Excision - 2009 (13) neoplastic cells displaying both basaloid and squamous differentiation Lee et al., 73, Male Left 5×5 - Lobulated, - Yes No Excision, Yes 2010 (12) caruncle brown-black IA chemo- (22 months) therapy Fino, 2013 24, Female Right 5×2 Growth Lobulated, Solid, Yes No Excision No caruncle of lesion brown hyperchromatic (12 months) (6 months) and isomorphic nuclei, mild mitotic activity, periphery nuclear palisading

SCC, Squamous cell carcinoma; IA, intra-arterial; - , not described.

538 Fino et al: First Case of Primary BCC of the Right Caruncle

Table II. Epidemiological comparison between all caruncular 8 Rossman D, Arthurs B, Odashiro A, Saraiva V and Burnier M neoplasias and caruncular basal cell carcinoma. Jr: Basal cell carcinoma of the caruncle. Ophthal Plast Reconstr Surg 22(4): 313-314, 2006. All caruncle neoplasias* Caruncular BCC 9 Kaeser PF, Uffer S, Zografos L and Hamédani M: Tumors of the caruncle: A clinicopathologic correlation. Am J Ophthalmol Gender predominance Women Men 142(3): 448-455, 2006. Eye predominance Right Left** 10 Shields CL, Shields JA, White D and Augsburger JJ: Types and Mean age (years) 42.1 61.8 frequency of lesions of the caruncle. Am J Ophthalmol 102(6): 771-778, 1986. *Data from Perucho-Martínez (14). **A total of 5/12 case reports do 11 Hirsch C, Holz FG, Tetz M and Völcker HE: Clinical aspects not describe the exact location of the neoplasia. and histopathology of caruncular tumors. Klin Monbl Augenheilkd 210(3): 153-157, 1997. 12 Lee CL, Hsu SL and Chang CH: Primary ocular caruncular basal cell carcinoma in a Chinese patient. Kaohsiung J Med Sci 0.50 mm (1). Consequently, caution should be exercised 26(10): 562-566, 2010. when operations are performed on or near the caruncle to 13 Levy J, Ilsar M, Deckel Y, Maly A and Pe’er J: Lesions of the avoid inadvertent damage to the canalicular system. caruncle: A description of 42 cases and a review of the literature. Eye 23(5): 1004-1018, 2009. Mohs’ micrographic surgery in selected cases may 14 Perucho-Martínez S, Mencía-Gutiérrez E, Gutiérrez-Díaz E and preserve more normal tissue than conventional surgery, with Gómez-Ledesma MI: Neoplasms of the caruncle. lower reported rates of recurrence (24). Radiation can be Clinicopathologic study of 40 cases. Arch Soc Esp Oftalmol used as an adjuvant therapy to help reduce the chance of 79(10): 493-499, 2004. tumour recurrence or orbital invasion. 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