Solitary Epithelioid Histiocytoma (Reticulohistiocytoma) of the Eyelid

Solitary epithelioid histiocytoma of the dermis (and rarely of the mucosae but not the viscera) was previously designated as a reticulohistiocytoma.¹ There are reports of 2 solitary corneoscleral lesions² and 1 small recurrent lesion in an eyelid.³ Among the rarest of histiocytic disorders, it typically affects the truncal region of young men (uncommonly the face and digits) and is unassociated with any systemic disease. Among 12 of 44 noneyelid lesions of solitary epithelioid histiocytoma with follow-ups, none recurred despite incomplete excision.¹ Multicentric reticulohistiocytoma, on the other hand, has a predilection for the face and digits of middle-aged women and displays an associated disabling multifocal arthropathy and internal carcinoma in approximately 27% of patients.^1,4,5 It has been described in all 4 eyelids.⁵ Current opinion holds that both unicentric and multicentric epithelioid histiocytomas are nonneoplastic, arising from the macrophagic rather than the dendritic histiocytic compartment.

A healthy 39-year-old woman was referred for evaluation of a 3-month-old lesion on her left lower eyelid. The patient had no other skin lesions. The examination of the eyelids revealed a smooth, 10-mm-elevated, flesh-colored, firm lesion (Figure, A) in the lateral one-third of the eyelid. Most of the eyelashes were missing. Visual acuity was 20/20 OU. There was no head and neck lymphadenopathy. Computed tomographic results of the neck, chest, and abdomen/pelvis were negative. A full-thickness eyelid resection was performed with 2-mm margins. The patient has experienced no recurrence after 9 months.

The excised mass measured 0.4 × 0.5 cm at its base and 1.0 cm in height (Figure, B). Microscopically, a mass of grouped, large epithelioid histiocytes (Figure, C) began beneath a mildly parakeratotic epidermis and a narrow band of collagen; they were usually mononucleated but occasionally multinucleated, subdivided by fine collagen strands, and accompanied by a mixture of lymphocytes, polymorphonuclear leukocytes, and eosinophilic leukocytes. The tumor evinced incursion into the orbicularis muscle and tarsus (Figure, B). The principal polygonal cells were endowed with abundant eosinophilic or amphophilic cytoplasm (Figure, D) without periodic acid–Schiff–positive inclusions. Their nuclei were round and possessed small nucleoli; mitotic figures were not identified. Acid fast and methenamine silver stains did not detect organisms. The large tumor cells were strongly positive for vimentin (Figure, E), sporadically positive for S-100 protein, strongly positive for CD163, and more weakly positive for CD68 (Figure, F) and α1-antitrypsin. Staining results for lysozyme, factor XIIIa, and AE1/AE3 (for keratin), HMB-45, melan A, and Mitf (for melanocytes), desmin and smooth muscle actin (for myoid cells), and CD1a (for Langerhans cells) were negative in the principal tumor cells. Ki-67 nuclear staining for cells in S-phase was absent in the round cells but present among the dispersed inflammatory cells.

Zak⁶ called attention to the round ganglionlike aspect of the principal cells in solitary epithelioid histiocytoma. Their capacious, often partially xanthomatized cytoplasm with a deeply eosinophilic or amphophilic character, their large nuclei with a distinct and sometimes large nucleolus, the absence of a desmoplastic stroma, and frequent surrounding lacunae permitting definition of the cell borders set the lesion apart. Granulocytes and T lymphocytes (but not B lymphocytes) are admixed within the lesion. The tumor cells are CD163, CD68, and α1-antitrypsin positive (histiocytic markers) with erratic and focal staining for S-100 protein and Mitf (the last feature being absent in our case).¹ They are negative for keratin, CD1a (Langerhans cells), melan A, and HMB-45 (melanoma or Spitz nevus) and have a very low Ki-67 index (<1%); mitotic figures can occasionally be observed.^1,4 The differential diagnosis should focus on sarcoidosis (which has a tuberculoid pattern), Rosai-Dorfman disease (strongly S-100 protein positive) with emperipolesis, elevated tuberous xanthoma, juvenile and adult xanthogranulomas with Touton giant cells, Erdheim-Chester disease with Touton cells and marked fibrosis, necrobiotic xanthogranuloma, Langerhans cell histiocytosis, and epithelioid sarcoma.¹

Correspondence: Dr Jakobiec, Department of Ophthalmology, David G. Cogan Laboratory of Ophthalmic Pathology, 243 Charles St, Room 321, Boston, MA 02114 (fred_jakobiec@meei.harvard.edu).

Author Contributions: Dr Jakobiec had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.