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Corneal limbal xanthogranuloma in Erdheim-Chester disease

Published:October 26, 2021DOI:https://doi.org/10.1016/j.jcjo.2021.09.015
      Adult orbital xanthogranulomatous disease is a rare non-Langerhans cell histiocytic condition with 4 clinical subtypes: adult‐onset xanthogranuloma, adult‐onset asthma with periocular xanthogranuloma, necrobiotic xanthogranuloma (NBX), and Erdheim–Chester disease (ECD). We report, to our knowledge, the first case of ECD with limbal infiltration.
      A 52-year-old woman presented with xanthomatous cutaneous lesions around her eyes and flexural folds of submammary skin. Subsequent full body imaging revealed sclerotic lesions in her sternum, left rib, and bilateral femurs and tibias. There were no intracranial or orbital lesions. Bone biopsy of the sternal lesions confirmed ECD. The patient was treated with oral steroids and then cladribine by hematology. Two-monthly interval imaging with positron emission tomography showed stable systemic disease.
      The patient was referred to the eye clinic with a progressively enlarging left ocular lesion that had been present since her initial diagnosis. Ocular examination revealed a 5 mm well-defined yellow deposit along the superonasal limbus (Fig. 1). There were multiple yellow deposits along her nasal lower eyelid bilaterally. She did not have any optic neuropathy, and her orbital examination was normal.
      Fig 1
      Fig. 1Clinical photograph showing xanthomatous lesion on limbus in left eye and multiple lower lid xanthelasmas.
      Biopsy of the lesion showed a subepithelial stromal deposit of foamy macrophages with bland nuclear features (Fig. 2). The cells showed pale eosinophilic cytoplasm with indistinct cytoplasmic borders and ovoid nuclei on highest magnification. Strong and diffuse immunoreactivity for CD68 and CD163 confirmed a histiocytic nature. The lesion also was positive for factor XIIIa but negative for Langerin, CD1A, S100, and BRAF V600E. These identical immunohistochemical features were demonstrated in a previous sternal bone biopsy for this patient.
      Fig 2
      Fig. 2Corneal limbus lesion biopsy (H&E stain, × 400 magnification) showing bland cells (black arrows) in the stroma. These cells show eosinophilic cytoplasm with indistinct cytoplasmic borders and ovoid nuclei.
      Systemic ECD manifestations typically involve the metadiaphysis of lower extremity bones, skin, heart, lungs, kidneys, large blood vessels, and retroperitoneal space.
      • Mazor RD
      • Manevich-Mazor M
      • Shoenfeld Y.
      Erdheim–Chester disease: a comprehensive review of the literature.
      Ocular involvement of ECD has been reported in the orbit, lacrimal gland, recti muscles, lids, and conjunctiva.
      • Mazor RD
      • Manevich-Mazor M
      • Shoenfeld Y.
      Erdheim–Chester disease: a comprehensive review of the literature.
      In general, xanthogranulomatous epibulbar lesions are rare and may appear as yellow, elevated lesions with irregular borders showing fixation to sclera and extension to the plica semilunaris.
      • Satchi K
      • Loughnan M
      • McKelvie PA
      • et al.
      Bilateral epibulbar xanthomas: a case report.
      Our case is the first documentation of an ECD xanthogranulomatous lesion with limbal involvement.
      Histologically, ECD typically shows foamy histiocytes with small nuclei and surrounding fibrosis, multinucleated giant cells, and Touton giant cells.
      • Mazor RD
      • Manevich-Mazor M
      • Shoenfeld Y.
      Erdheim–Chester disease: a comprehensive review of the literature.
      Immunohistochemistry shows histiocytes that are positive for CD68, CD163, factor XIIIa, and fascin and negative for CD1a and CD207 (Langerin).
      • Mazor RD
      • Manevich-Mazor M
      • Shoenfeld Y.
      Erdheim–Chester disease: a comprehensive review of the literature.
      S100 is usually negative but can be weakly or focally positive in 20%–30%.
      • Goyal G
      • Heaney M
      • Collin M
      • et al.
      Erdheim-Chester disease: consensus recommendations for evaluation, diagnosis, and treatment in the molecular era.
      The BRAF V600E mutation is present in over half of ECD cases.
      • Haroche J
      • Charlotte F
      • Arnaud L
      • et al.
      High prevalence of BRAF V600E mutations in Erdheim-Chester disease but not in other non-Langerhans cell histiocytoses.
      Our case of corneal limbus ECD demonstrated a majority of typical pathologic and immunohistochemical features in keeping with the diagnosis.
      A pooled study of case series has previously been performed to assess clinical and immunohistochemical features of adult orbital xanthogranulomatous disease subtypes.
      • Sivak-Callcott JA
      • Rootman J
      • Rasmussen SL
      • et al.
      Adult xanthogranulomatous disease of the orbit and ocular adnexa: new immunohistochemical findings and clinical review.
      Periocular skin lesions are present in 95% of of adult‐onset asthma with periocular xanthogranuloma cases, 85% of NBX cases, 50% of adult‐onset xanthogranuloma cases, and 42% of ECD cases. These conditions are generally positive for CD68, CD163, and factor XIIIa. Necrobiosis with palisading epithelioid histiocytes is most commonly seen in NBX.
      Differential diagnoses for xanthogranulomatous epibulbar lesions include juvenile xanthogranuloma, xanthoma disseminatum, Langerhans cell histiocytosis, limbal amyloidosis, fibrous histiocytoma, and Rosai-Dorfman disease.
      • Satchi K
      • Loughnan M
      • McKelvie PA
      • et al.
      Bilateral epibulbar xanthomas: a case report.
      These diagnoses may be distinguished from ECD by their clinical features and histologic characteristics.
      In conclusion, we report the first known case of ECD involving the corneal limbus. For patients with known ECD who present with corneal lesions, it may be a manifestation of their disease and may be appropriately managed with excisional biopsy. In patients with no known disease, ophthalmologists should consider ECD as a differential diagnosis for corneal lesions.

      Footnotes and Disclosure

      The authors have no proprietary or commercial interest in any materials discussed in this correspondence.

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