On examination, corrected visual acuity was 20/150 OD. A papillomatous conjunctival tumor was at the limbus, extending from the 9-o’clock position to the 3-o’clock position (Figure 1). The anterior chamber was normal. Other than cataract, the remainder of the examination was noncontributory. There was no regional adenopathy.

View larger version (97K): [in this window] [in a new window] [as a PowerPoint slide]   Figure 1. Recurrent tumor wraps around the limbus from the 9-o’clock position to the 3-o’clock position and has a papillary pattern of growth. The contiguous corneal epithelium has a frosted appearance.

The tumor was excised under local anesthesia with a visibly normal margin, and abnormal epithelium was removed from the cornea mechanically. The surgical bed and surrounding conjunctival margin were treated with cryotherapy.

When the tumor recurred 6 months later in the same location, it was excised with a partial sclerectomy; additional cryotherapy was applied. The patient died of heart disease 4 years later but never showed signs of local or regional recurrence.

The slides obtained from the primary tumor showed conjunctival intraepithelial neoplasia with scattered clear cells. The tumor had a papillary pattern of growth. Slides from the next 2 recurrences were not available.

The third recurrence had a papillary pattern of growth and showed full-thickness dysplasia (Figure 2A). In many areas, the cytoplasm of the dysplastic cells was vacuolated (Figure 2B). The clear cells stained negative with mucicarmine, alcian blue at pH 2.5, periodic acid–Schiff, and S-100 protein and positive for epithelial membrane antigen.

View larger version (542K): [in this window] [in a new window] [as a PowerPoint slide]   Figure 2. Third tumor recurrence in 12 years. A, Biopsy of the recurrent tumor reveals full-thickness dysplasia. A single layer of flattened epithelium rests on the surface. Cells within the upper third of the epithelium show no signs of cellular maturation. The substantia propria is filled with clear cells, many of which have a signet ring appearance (hematoxylin-eosin, original magnification x200). B, In another area of the papilliform growth, the overlying epithelium is dysplastic and contains scattered clear cells. The connective tissue making up the core of the papillae contains suspicious clear cells (hematoxylin-eosin, original magnification x200). C, The last biopsy consists of moderately pleomorphic clear cells that stain negative for mucin, glycogen, and lipid. There is considerable variation in the size and shape of individual cells and their nuclei (hematoxylin-eosin, original magnification x160).

The fourth recurrence consisted almost entirely of moderately pleomorphic clear cells (Figure 2C). The cells stained negative with alcian blue at pH 2.5, periodic acid–Schiff, and HMB-45. Results of a frozen section with oil red O performed at the time of surgery were negative.

Comment
The phenomenon of cytoplasmic clearing is found in a variety of tumors arising from the epithelium, most of which demonstrate positive histochemical evidence indicating eccrine, follicular, melanocytic, or sebaceous cell lineage.^2-6 The diagnosis of primary clear cell carcinoma is made by excluding these specific entities as well as metastatic carcinoma.² The relationship of the clear cells to neoplastic conjunctival epithelium in our patient was evident in the first biopsy and became more evident in the third recurrence as the proportion of clear cells increased.

Too few cases of clear cell carcinoma of the skin have been reported to draw firm conclusions about its clinical behavior. Four of the 6 initially described tumors from the skin displayed rapid growth, and 1 patient died of metastatic disease.¹ The tumor in our patient demonstrated a propensity for local recurrence, had few mitotic figures, and during a 16-year period never showed any evidence of regional or distant spread. Until more information on the behavior of primary clear cell carcinoma of skin or mucous membranes is available, it should be regarded as locally aggressive and possibly lethal.

AUTHOR INFORMATION
Correspondence: Dr Margo, PO Box 46218, Tampa FL 33646 (cmargo{at}hsc.usf.edu).

Financial Disclosure: None reported.