Inverted papilloma of the conjunctiva is a rarely reported condition that, to the best of our knowledge, has been reported only in adults.1–5 We encountered a child in whom we diagnosed histopathologically an inverted papillomatous epithelial lesion of the nasal limbal conjunctiva, which was found in close proximity to a conjunctival compound nevus. We discuss the nature of these two lesions and their potential relationship.
A 9-year-old girl presented with a “spot” on her right eye that had been present for 7 years, but had tripled in size during the previous 9 months. The child was otherwise in good health. At the nasal limbus, an elevated, yellow-pink, amelanotic, smooth tumor measured 4 mm in diameter (Figure 1). A dilated conjunctival blood vessel extended from the medial canthus into the tumor’s medial substance. The lesion encroached less than 0.25 mm into the adjacent peripheral cornea. The remainder of the ocular examination was unremarkable. An excisional biopsy was performed.
Figure 1. (A) Elevated, yellow-pink bulbar conjunctival lesion adjacent to the nasal limbus in a 9-year-old girl. (B) A dilated blood vessel extends from the medial canthus into its medial substance.
Histopathologic examination revealed a conjunctival epithelial proliferation that extensively involved the substantia propria in an endophytic fashion with multiple lobules of benign-appearing, acanthotic conjunctival epithelium (Figure 2). Scattered, small epithelial-lined cystic structures were noted within the lesions, some of which contained desquamated epithelial debris, whereas others contained periodic acid-Schiff–positive material intermixed with degenerated cells. No goblet cells were identified and there was no evidence of dysplasia. Special stains revealed small amelanotic nests of benign nevus cells in the substantia propria and focally in close proximity to the junctional region of the epithelium and in the folds of the endophytic squamous proliferation, including some of the cysts (Figure 3). The substantia propria contained a focal, mild to moderate, predominantly chronic nongranulomatous inflammatory cell infiltrate around the nests of nevus cells (Figure 3B). The histopathologic diagnosis was an endophytic papillomatous lesion of the nasal bulbar and adjacent limbal conjunctiva of the right eye associated with an inflamed compound nevus.
Figure 2. (A) The superficial conjunctival epithelium (arrow) extends into the underlying substantia propria in an endophytic growth pattern. Several epithelial-lined cysts containing desquamated epithelial debris and a focal mild to moderate chronic inflammatory cell infiltrate are present in the substantia propria. (B) Lobules of acanthotic, nondysplastic squamous epithelium consistent with a diagnosis of inverted papilloma of the conjunctiva and sclera (S) (hematoxy-lin–eosin stain; original magnification [A] ×100 [B] ×200).
Figure 3. (A) The superficial epithelium, inverted lobules, and associated cysts in the substantia propria demonstrate a normal distribution of melanocytes. (B) Clusters of nevus cells both in opposition to surface epithelium (arrows) and within the substantia propria, lying within a moderate chronic inflammatory cell infiltrate, were found adjacent to the inverted papillomatous lesion (tyrosinase, melan-A, and S-100 vector red; original magnification [A and B] ×200).
Numerous conjunctival tumors can occur in children. In one large series examining pediatric conjunctival tumors, benign epithelial proliferative lesions (papilloma) accounted for 2% of cases and melanocytic lesions accounted for 67% of cases.1 Inverted papilloma is a benign neoplasm of mucous membrane, consisting of folds of epithelium inverting into the underlying stroma. This unusual morphological variant is in contrast to the exophytic pattern of branching fronds growing externally that is characteristic of typical conjunctival squamous papillomas.2–5 Inverted papillomas are more commonly encountered in the sinonasal areas and are the most frequent type of musocal neoplasm of the nose and paranasal sinuses.6,7 They are rarely seen in the conjunctiva, with only seven cases identified in the reviewed English literature (age range: 31 to 73 years).2–5 Our case is of interest because this lesion occurred in conjunction with a compound nevus in a child.
Inverted papillomas of the conjunctiva share some histological similarities with those found in the sinonasal tracts, but conspicuous cyst formation helps distinguish the conjunctival entity from its sinonasal counterpart.2 However, the two anatomic entities appear to have different natural histories. Inverted papillomas of the sinonasal tract may be locally aggressive, have a tendency to recur, and disclose malignant features in 7% of cases.5 In contrast, the reported cases of conjunctival inverted papilloma are not locally aggressive, have not recurred despite several years of follow-up, and are not thought to be precancerous.2–5
Squamous papillomas are documented to be associated with human papillomavirus (subtypes 6, 11, 16, and 18) infection of the conjunctiva, possibly acquired as the child passes through the birth canal.4,5 Histopathologically, inverted papillomas show folds of nonkeratinizing, acanthotic epithelium that invaginate into the stroma and have a benign appearance. Such a bland squamous proliferation may also be the predominant element in a nevus and, interestingly, immunohistochemical stains revealed inflamed nests of amelanotic nevus cells deep to and focally in contact with the inverted squamous component that had been missed by four pathologists independently. Reasons for this initially overlooked finding included that the nevus was totally amelanotic, it was intermixed with chronic inflammatory cells, and the proliferative epithelial lesion, which contained no goblet cells, was mostly not associated with the nevus (Figures 2–3). These findings converted our diagnosis of an inverted papilloma of the conjunctiva to an inflamed compound nevus associated with an inverted papillomatous epithelial lesion. Indeed, the inflamed compound nevus may account for the observed clinical growth with the progression of the melanocytic cells from the junctional region to the deeper stroma exerting a downward traction on the epithelium8 and thus contributing to this rare papillomatous configuration.
Our case is of interest because it simulates an inverted papilloma that has not previously been described in a child. Furthermore, we highlight the importance of immunohistopathological examination of unusual conjunctival lesions, which in our case aided in differentiating the amelanotic nevus cells from the chronic inflammatory infiltrate.
The spectrum of conjunctival tumors in children is broad, ranging from benign lesions such as nevus, papilloma, dermoid, and lymphangioma to malignancies such as squamous cell carcinoma, and melanoma.1 The lesion in our patient was a mixed diagnosis consisting of both an inverted papilloma together with an inflamed compound nevus. Given the uncertain prognosis of inverted papilloma of the conjunctiva, all conjunctival specimens should be sent for histopathologic examination and affected patients should be carefully observed after attempted complete excision.
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- Kalantzis G, Papaconstantinou D, Georgalas I, Tsitlidou A, Georgopoulos G. Different types of conjunctival papilloma presenting in the same eye. Orbit. 2010;29:266–268. doi:10.3109/01676831003739707 [CrossRef]
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- Myles WM, Brownstein S. Cystic subepithelial nevus of the caruncle. Ophthalmic Practice. 1990:8;160–162.