Benign Fibrous Histiocytoma of the Corneoscleral Limbus: Unique Clinicopathologic Features

A benign fibrous histiocytoma (BFH) involving the limbus is a rare type of tumor. We describe 2 patients with unique clinicopathologic features that, to our knowledge, have not previously been described.

Case 1. A 26-year-old white woman was referred to us because of an enlarging mass in the left inferonasal limbus. The lesion had been excised at another institution but recurred 6 weeks postoperatively. On examination, her best-corrected visual acuity was 20/20 OD and 20/60 OS due to irregular astigmatism. The right eye was normal. The left eye revealed a yellow limbal mass between the 7:30 and 10-o'clock meridians, with marked corneal involvement(Figure 1A). Gonioscopy showed no intraocular involvement; however, the lesion reached the deep corneal stroma without breaching the Descemet membrane. The patient was systemically well. A 10-mm-diameter en bloc excision with a tectonic corneoscleral graft was performed. After more than 9 years of follow-up, there has been no recurrence of the tumor, and the visual acuity is stable at 20/60 OS (Figure 1B).

Light microscopic examination of the lesion showed a hypercellular tumor consisting of oil red O–positive histiocytes and fibrocytes in a matted or storiform arrangement and invading deep corneal stroma and superficial sclera. Occasional giant cells of the Touton type were evident. No mitoses were seen (Figure 1C and D). Immunohistochemical analysis showed that both histiocytes and fibroblasts were positive for vimentin but negative for S100 protein and CD68 antigen (reactive macrophages). Electron microscopic studies disclosed that most cells were histiocytic, with an indented nucleus and reticulated nucleolus (results not shown). A scattered inflammatory infiltrate consisting predominantly of lymphocytes and plasma cells was observed.

Case 2. A 12-year-old white girl had a 6-month history of an increasing corneolimbal mass. A biopsy was performed at another institution, and the patient was referred to us for treatment. On examination, her best-corrected visual acuity was 20/20 OU. The left eye was normal. The right eye revealed a yellow mass involving the inferior third of the cornea and the limbal conjunctiva between the 4:30 and 8:30 clock positions (Figure 2A). Gonioscopy showed no intraocular involvement. The patient was systemically well. Light microscopic review of the biopsy revealed a tumor consisting of lipidized histiocytes and occasional fibroblasts in a matted arrangement. The nuclei had a bland appearance (Figure 2D). Immunohistochemical analysis showed that histiocytes were positive for CD68 and that both histiocytes and fibroblasts were negative for S100 protein. A scanty lymphocytic infiltrate was observed. The patient and her family declined surgery, and the patient was prescribed 1% topical rimexolone to be used twice daily in the right eye, with regular review of compliance and intraocular pressure. After 16 weeks of therapy, the lesion had thinned, resulting in a translucent scar (Figure 2B and C). The treatment was ceased after 12 months, and the scar and vision remained stable during 18 months of follow-up.

To our knowledge, there are only 12 well-documented reports of BFH involving the conjunctiva or limbus.^1,2 The age of patients has ranged from 3 to 65 years, with a female predominance(3:1). The history of the lesions has been less than 6 months, on average. Clinically, the lesions in our patients resembled those reported, in view of the yellow coloration, lesion size (maximal diameter, 1.5-9.0 mm), and prominent superficial vessels (Table 1).² Important clinical differential diagnoses include malignant FH, amelanotic melanoma, lymphomas, and juvenile xanthogranuloma. Rare differential diagnoses should include Gaucher disease, Niemann-Pick disease, histiocytosis X tumors, and reticulohistiocytoma.^3,4 As many limbal lesions may have a similar clinical appearance, a biopsy is required to obtain a definitive diagnosis.

The histopathologic features of the lesions were consistent with the diagnosis of BFH, with an admixture of histiocytic cells (characteristically lipid laden with foamy cytoplasm) and fibrocytic cells arranged in a matted or storiform pattern and with bland nuclear features. Giant cells (including Touton cells) may occasionally be observed as well as a variable inflammatory infiltrate consisting primarily of lymphocytes and plasma cells (Table 1).^1-4 Of particular interest was the immunohistochemical demonstration of variable CD68 expression and, in the first case, vimentin expression in both histiocytes and fibroblasts, which would support the concept of a primitive mesenchymal cell origin with variable capacity to differentiate along either or both cell lines.⁴ Benign fibrous histiocytoma may be difficult to distinguish histologically from juvenile xanthogranuloma; however, the cellular uniformity of the latter combined with a lack of fibrocytes, an inflammatory infiltrate containing eosinophils, and the distinctive clinical setting usually differentiate these entities. The tumors failed to express S100 protein, which has been demonstrated in histiocytes of Langerhans cell histiocytosis. Also, the lack of tissue eosinophils argues against the latter condition as well as reticulohistiocytosis.^4,5

Previous reports of recurrent BFH do not describe the recurrent tumor cells as being infiltrative. In the first case, the tumor had diffuse, poorly defined margins, and extensively infiltrated the surrounding tissues, including the conjunctiva, deep corneal stroma, and sclera. Invasion of deeper structures, including the corneal stroma, has been reported in other benign limbal lesions, such as nodular fasciitis, dermoids, neurofibromas, fibromas, and juvenile xanthogranulomas, and is associated with recurrence after incomplete excision.^3,4 Although the overall recurrence rate of the primary lesion after excision would appear to be low (Table 1), ^1-4 a tendency for an infiltrative growth pattern suggests that the surgical management should include complete excision of all identifiable disease using intraoperative clinical biomicroscopic control. The need for close follow-up in the early postoperative period is also highlighted, as the recurrent lesion appeared within a few weeks after the original surgery and grew rapidly. Because the recurrent lesion appeared to have had more aggressive clinical features, and infiltrated the surrounding tissues quite markedly in these cases, en bloc excision to obtain tumor-free histologic margins should be considered in cases that fail superficial resection.

There are 2 brief reports involving a trial of topical steroid therapy for primary BFH of the limbus. In one of the cases, the lesion continued to grow during therapy, which was ceased after 3 months.⁶ The other case was reported to be successfully treated with topical steroid therapy, although no details are described.⁷ The second case is the first detailed description of successful management of limbal BFH using tissue biopsy and topical corticosteroid therapy alone. Variable responses to glucocorticoids may be related to differences in the level of expression of the glucocorticoid receptors within the tumor. A high frequency of expression of glucocorticoid receptors has been reported in malignant FH; however, to our knowledge, there are no reports that have examined the expression of receptors in BFH.⁸ More cases need to be accumulated to verify the usefulness of this treatment; however, on the basis of our observations, in selected cases with careful monitoring, a therapeutic trial of topical glucocorticoid therapy may be a reasonable option.

This study was supported in part by the Alexander von Humboldt Foundation, Bonn, Germany, and the Royal Australian and New Zealand College of Ophthalmologists and Sydney Eye Hospital, Sydney (Dr Conway).

The authors have no relevant financial interest in this article.

We acknowledge the excellent technical assistance of Carmen Hofmann-Rummelt.

Corresponding author and reprints: R. M. Conway, MD, PhD, Department of Ophthalmology and Eye Hospital, University Erlangen-Nürnberg, Schwabachanlage 6, D-91054 Erlangen, Germany (e-mail: rmaxconway@hotmail.com).