Large Cell Acanthoma of the Conjunctiva: Clinicopathologic and Immunohistochemical Features

Abstract

Large cell acanthoma (LCA) was first described as a lesion on sun-exposed skin. All LCAs feature keratinocytes twice the size of normal cells (cytomegaly). Although infrequently diagnosed in the skin, it has been even more rarely described by ophthalmic pathologists in the eyelid skin and the conjunctiva. This report describes the third case of a conjunctival epithelial LCA, with the first published clinical photograph highlighting its leukoplakic and well-circumscribed character, as well as the most thorough analysis of the immunohistochemical features of this lesion. It is contrasted with squamous dysplasias and papillomas of the conjunctiva. A review of previous conjunctival LCA lesions discloses frequent recurrences after initial surgery and the remote but real potential for squamous dysplastic transformation. Immunohistochemical stains for certain cytokeratins, p53, and Ki-67 (proliferation index) will in the future be particularly helpful in establishing an early and accurate diagnosis of conjunctival LCA.

Keywords: Conjunctiva; Cytokeratins; Ki-67; Large cell acanthoma; Mucous membranes; Skin; p53.

Fig. 1

Clinicopathologic features of conjunctival large cell acanthoma. a A 70-year-old woman developed a sharply circumscribed, white, “leukoplakic” lesion in the left lower palpebral and forniceal conjunctiva that had caused a foreign body sensation with tearing. b Medium-power photomicrograph of the central portion of the lesion reveals substantial thickening of the epithelium. The lower half is eosinophilic, while the upper half appears pale and swollen. Note the absence of a papillary architecture (periodic acid-Schiff [PAS], ×2). c The basal region is composed of large eosinophilic cells (cytomegaly) with centrally placed, round, vesicular nuclei possessing prominent nucleoli. No atypical cells with nuclear hyperchromasia are seen (hematoxylin and eosin [H&E], ×40). d The superficial and surface cells display more intense cytoplasmic eosinophilia indicating incipient nuclear pyknosis and parakeratosis (H&E, ×40). e More advanced nuclear pyknosis with delamination of dyscohesive, marginally vital surface cells (H&E, ×20). f The PAS stain discloses a zone of PAS-positive glycogen-rich cells (between arrows) and an absence of glycogen in the pale surface cells. The glycogen disappeared with diastase predigestion (PAS, ×10).

Fig. 2

Histochemical and immunohistochemical features of large cell acanthoma (LCA) cells. a The periodic acid-Schiff (PAS) stain clearly demonstrates an abrupt interface between the LCA cells on the left and normal conjunctival epithelial cells on the right. The LCA cells are at least twice the size of the normal keratinocytes, mostly due to their abundant cytoplasm. Note that the LCA cells have a low nuclear-to-cytoplasmic ratio. The arrows indicate a non-violated basement membrane. Chronic inflammation is present in the subepithelial substantia propria (PAS, ×40). b Left panel: CK-7 immunohistochemical staining, normally positive in conjunctival epithelium, is negative in the LCA cells. Right panel: CK-10 discloses scattered positivity in the LCA cells. There is negativity in normal epithelium. Chronic inflammation is present in the subepithelial substantia propria (×10). c CK-14 immunostains the full thickness of the LCA cells with more intense staining of the surface parakeratotic cells. Normal conjunctiva displays CK-14 staining that is restricted to the basal and parabasal keratinocytes (×10). d CK-17 is full thickness positive in the LCA cells, whereas it is totally negative in normal epithelium. The arrows indicate unstained basal cells (×20). e p53 nuclear immunostaining is limited to the basal and parabasal cells, in contrast to the higher-level staining observed in dysplasias. The extent of the upward staining depends on the severity of the dysplastic process (×10). f Nuclear Ki-67 staining is tightly restricted to the base epithelial cells as in normal epithelium. In dysplasias, the Ki-67 positivity is found at higher levels according to the severity of the lesion (×10).