TUMORS OF THE CONJUNCTIVA 1 AND CARUNCLE ANATOMY AND HISTOLOGY resemble apocrine cells due to the presence The conjunctiva, a mucous membrane com- of eosinophilic cytoplasm and apical snouts. posed of epithelium and substantia propria, Goblet cells are abundant toward the fornix covers and connects the anterior surface of and at the nasal side of the bulbar conjunctiva. the eye and the inner surface of the eyelids. Other cells present in the conjunctival epithe- Although the conjunctiva is a continuous layer, lium include melanocytes, Langerhans cells, for descriptive purposes it is divided into a pal- and wandering intraepithelial lymphocytes. pebral portion (tarsal) lining the undersurface The limbal conjunctiva is the anular area that of the eyelid, a forniceal portion or intermediate extends from the cornea to about 3 mm on the part forming a conjunctival cul de sac where it bulbar portion. The basal epithelial layers of the reflects onto the surface of the globe, a bulbar limbal conjunctiva contain the stem cells that portion covering the exposed part of the eyeball repopulate the corneal epithelium. Branching to the cornea (fig. 1-1), and associated elements, dendritic melanocytes are abundant in this the plica semilunaris and the caruncle. region and are often associated with melanin- The epithelium of the conjunctiva is con- containing basal epithelial cells. tinuous with the corneal epithelium and with The substantia propria of the bulbar conjunc- the epidermis of the eyelid margin through tiva is composed of loose connective tissue and a a transition zone of nonkeratinized stratified deeper dense collagenous layer. The connective squamous epithelium. The conjunctival epi- tissue is composed of haphazardly arranged col- thelium is composed of cuboidal and cylindri- lagen fibers, loosely intermixed fibroblasts, blood cal cells arranged in two to five layers, with vessels, lymphatic vessels, scattered mast cells, the addition of mucus-secreting goblet cells macrophages, lymphocytes, plasma cells, poly - (fig. 1-2). The superficial epithelial cells may morphonuclear leukocytes, and eosinophils. Figure 1-1 Figure 1-2 NORMAL CONJUNCTIVA BULBAR CONJUNCTIVAL EPITHELIUM The different appearances of the bulbar, forniceal, and The stratified cuboidal or cylindrical conjunctival palpebral portions of the conjunctiva are illustrated. epithelium shows prominent mucus-secreting goblet cells (arrow) in different stages of maturation, from the base to the surface layer. 1 Tumors of the Eye and Ocular Adnexa Figure 1-3 Figure 1-4 CONJUNCTIVAL CUL DE SAC NORMAL CARUNCLE A collection of lymphocytes resembling a lymph follicle is The caruncle has a nodular configuration and is covered seen in the loose substantia propria of the forniceal conjunctiva. by stratified squamous epithelium. Goblet cells, pilo- sebaceous units, and adnexal glandular structures are seen. Lymphatic Drainage The substantia propria of the palpebral conjunc- tiva is more uniform, and is closely attached to Superficial, radial, and deep lymphatic vessels the tarsus. Inner buddings of the surface epithe- comprise the lymphatic channels that are lo- lium extend into the subepithelial connective cated in the substantia propria. Large lymphatic tissue to form tubular and cystic structures, vessels merge into major nasal and temporal “pseudoglands of Henle,” whose epithelium is trunks. The nasal trunk drains into the subman- made up of cuboidal cells and goblet cells. The dibular lymph nodes, and the temporal one blood vessels of the substantia propria (arterioles drains into the preauricular and parotid lymph and venules) support and drain a complex cap- nodes. The submandibular lymph nodes receive illary network. The connective tissue contains the lymphatic drainage from the caruncle. myelinated and unmyelinated branches of the trigeminal nerve. Close to the fornices are lym- CLASSIFICATION AND FREQUENCY phocytic aggregates, with or without reactive Conjunctival tumors are classified as benign, follicles and plasma cells, similar to those found premalignant, and malignant. Tumors and in other mucosal-associated lymphoid tissues tumor-like lesions of the conjunctiva, together (MALT) (fig. 1-3). Acini and ducts of the acces- with eyelid tumors, are among the most fre- sory lacrimal glands of Wolfring and Krause quently excised ophthalmic lesions that a pa- are observed in the subepithelial tissues of the thologist encounters. The overall frequency of palpebral conjunctiva, at the upper edge of the tumors in both locations varies among different tarsus and close to the fornices, respectively. series (1–4). The most frequent conjunctival tu- Nasally, a fold of loose conjunctiva forms the mors are epithelial, melanocytic, and lymphoid plica semilunaris, where smooth muscle cells proliferations, and choristomas (Table 1-1). and cartilage may occasionally be found. Among the epithelial tumors, intraepithelial neo- The caruncle, which is a transition zone be- plasia and squamous cell carcinoma are mainly tween the skin and the conjunctiva, is located encountered in adults, and papilloma and cho- at the inner canthus; it measures 5 x 3 mm (fig. ristoma are mostly found in children. Forty-four 1-4). The surface of the caruncle is composed percent of the excised pigmented lesions are nevi, of columnar and nonkeratinized squamous and approximately 36 percent are melanomas epithelium. The subepithelial connective tis- (Table 1-2). A precursor of melanoma, primary sue may contain pilosebaceous units, accessory acquired melanosis, is a distinctive melanocytic lacrimal gland tissue, smooth muscle fibers, and lesion of the conjunctiva that has characteris- adipose tissue. tic clinical features and microscopic findings. 2 Tumors of the Conjunctiva and Caruncle Table 1-1 Table 1-2 TUMORS OF THE CONJUNCTIVAa CONJUNCTIVAL TUMORS OF MELANOCYTIC ORIGINa Number of Cases (%) Type of Tumor Number of Cases (%) Doheny AFIP Nevus 145b (44.3) Type of Tumor 1970-2000 1984-1989 Primary acquired melanosis 42 (12.8) Epithelial 522 (48.3) 509 (40.5) without atypia Melanocytic 327 (30.3) 542 (43.1) Primary acquired melanosis 18 (5.5) Soft tissue 67 (6.0) 29 (2.3) with atypia Lymphocytic and hem- 113 (10.5) 117 (9.3) Melanoma 120 (36.7) atopoietic Metastatic melanoma 2 (0.6) Adnexal glands 22 (2.0) 24 (1.9) aFrequency distribution of 327 melanocytic lesions from Choristomatous 29 (2.7) 37 (2.9) the pathology files of the Doheny Eye Institute collected between 1970 and 2000. Total 1080 1258 bThirty-nine were associated with inflammation. aFrequency distribution of conjunctival tumors and tumor- like lesions from the pathology files of the Doheny Eye Institute and the Armed Forces Institute of Pathology (AFIP) Registry of Ophthalmic Pathology. Lymphoid proliferations are less frequent in the conjunctiva than in the orbit. A wide variety of soft tissue tumors may arise from the substantia propria of the conjunctiva; they are similar to their counterparts in other locations, and will be only briefly discussed. EPITHELIAL NEOPLASMS Papilloma Definition. Conjunctival papilloma is a benign Figure 1-5 acquired papillary lesion. It is composed of branching fibrovascular cores covered by acan- PAPILLOMA thotic, nonkeratinized squamous epithelium Conjunctival papilloma contains fibrovascular cores that contains a variable number of mucus- covered by squamous or columnar epithelium. secreting cells (fig. 1-5). Synonyms include squamous cell papilloma, conjunctival papilloma, infectious papilloma, and conjunctival wart. multilayered, nonkeratinized squamous cells; Clinical Features. Papillomas may develop at occasionally, oval or spindle-shaped cells confer any age but are more frequent in children. They a transitional appearance. Most papillomas in are solitary or multiple, unilateral or bilateral. children have a variable number of mucus-se- They arise mainly from the region of the caruncle creting goblet cells. Acute inflammatory cells of- and the semilunar fold at the inner canthus or ten permeate the exposed epithelium. Although from the fornix. There may be secondary or mul- HPV has been demonstrated in these lesions, ticentric involvement of the bulbar and palpebral the presence of koilocytosis is uncommon. conjunctivae. In adults they may originate from Papillomas arising from the limbal region often the limbus and adopt a sessile appearance (fig. are sessile and covered by acanthotic squamous 1-6). Human papilloma virus (HPV) serotypes 6, epithelium (fig. 1-7). Some cells have larger and 11, and 16 have been demonstrated in 50 to 92 more hyperchromatic nuclei, suggesting a mild percent of the lesions (5–8). degree of dysplasia. Conjunctival papil lomas Microscopic Findings. Squamous papillomas with dysplasia have no risk of malignant trans- are exophytic lesions that are often covered by formation in children. 3 Tumors of the Eye and Ocular Adnexa Figure 1-6 Figure 1-7 CLINICAL APPEARANCE OF A LIMBAL PAPILLOMA SESSILE PAPILLOMA The flat circumscribed lesion has multiple arborizing Arborizing fibrovascular cores are covered by acanthot ic blood vessels, giving it a raspberry-li ke appearance. squamous epithelium. Figure 1-8 INVERTED PAPILLOMA Left: The fibrovascular cores and acanthotic epithelium are growing within the substantia propria. Right: The epithelium contains a number of mucus-secreting cells. An endophytic variant of the papilloma, in- Treatment and Prognosis. Symptomatic verted mucoepidermoid papilloma, is characterized conjunctival papillomas are surgically excised by invaginated lobules of proliferating, nonker- by