Masquerade is most often used in ophthalmology in reference to tumors that mimic intraocular inflammation. In this context, a masquerade is not always the result of a tumor, it can also be due to a degenerative process such as retinitis pigmentosa, siderosis, infection, or drugs. In the current context we will refer to intraocular tumors that are mistaken for other entities. Tumors can be mistaken for inflammatory processes the natural evolution of a long-standing ocular degeneration, or they can simulate a retinal process.
The incidence of malignant masquerade has been cited as comprising 2% of cases in a uveitis referral practice (as high as 8% in practices with mostly elderly patients).1 Although this figure is probably higher than what is seen in most practices, it should be considered in all cases where there is poor response to therapy, when the inflammatory process has atypical features, or when a picture compatible and more typical of a masquerade is present.
LYMPHOMAS AND LEUKEMIAS
In intraocular lymphoma (Figure 1), subretinal pigment epithelial infiltration of cells is typical. These well-circumscribed cream-colored cell collections varying in size from pinpoint to one-third to one-half disc diameter are not static and can move around over time. Zones of pigment alterations will form as the cellular infiltrates subside. The overall appearance may suggest a past viral infection, extensive drusen, or even retinitis pigmentosa.2-4 It is the combination of manifestations and the evolution that suggests the true diagnosis.
Leukemia is another good example. Ocular manifestations are present in up to 75% of patients.5-8 They are usually related to venous stasis developing as result of hyperviscosity caused by the large number of circulating white blood cells. Characteristic changes include retinal vascular sheathing, intraretinal hemorrhages, white-centered hemorrhages, cotton wool spots, and peripheral microaneurysms with capillary dropout. More extensive peripheral neovascularization, similar to those observed with sickle cell disease, is more commonly seen in association with chronic myelogenous lymphomas.5 Choroidal infiltration can lead to a compromised choriocapillaris and thereby lead to ischemia and the development of an exudative retinal detachment.9 Centrally located serous detachments are known to occur in recurrent cases and may be due to the steroids frequently used in such cases.
Central serous retinopathy is not uncommon in the context of malignancies. Commonly reported with leukemias, it is also seen with lymphomas, particularly while under treatment.10,11 It can develop as a results of steroid use in any chemotherapeutic regimen, or as a result of steroid-secreting tumors such as adrenal cortex carcinomas or adenomas. A centralized effusion is also possible in association with other retinal or choroidal processes from choroidal metastastasis to more benign processes such as hemangiomas, choroidal osteomas, or sclerochoroidal calcification.12,13 It has occasionally been seen with nevus and malignant melanomas.
Scleritis and episcleritis are rarely thought of as a masquerade, and yet several reports have documented them as a possible source. Masquerading tumors, as in other locations, are often initially misdiagnosed. Key features include lack of response or inadequate response to treatment, or the presence of a constellation of local or systemic symptoms that point to the neoplastic nature of the scleral inflammation. Bilateral episcleritis associated with open-angle glaucoma of recent onset has been observed with HTLV-1 T-cell leukemia.14,15 Diagnosis was made from blood count in one of these cases, and biopsy in the other. An occlusive vasculitis characterizes certain types of T-cell lymphomas, which manifest themselves as a diffuse scleritis. Unilateral disease unresponsive to even oral steroids should raise suspicion. Such T-cell lymphomas are often associated with upper respiratory mucosal involvement.10,16 Posterior scleritis may arise as a manifestation of a systemic lymphoma.10 Adenocarcinomas can mimic a nodular scleritis with infiltration of the angle or prominence on ultrasonography. A biopsy can confirm the diagnosis, but origin often remains unknown.17 Certain treatments for cancer also cause scleral inflammation; this is particularly the case with zoledronate used for breast and bone cancer18 and with erlotinib used in treating pancreatic cancer.19
OTHER MASQUERADE SYNDROMES
Masquerade can also arise in benign ocular lesions or in association with such lesions. Small pigmented nevi or nevus-like lesions are known to grow and possibly evolve into malignant melanomas over a number of years.20,21 Similarly, focal-pigmented hyperplastic lesions of the retinal pigment epithelium can become anaplastic in nature over several decades and become locally invasive.22 Toxoplasmic retinal lesions and the presence of toxoplasmosis gene products were found in patients with ocular lymphoma.23 Chronic recurrent inflammation can trigger or evolve into a neoplastic process, usually over several decades, and should always be considered in cases of patients whose response to treatment is less than adequate. Finally, tumors can act at a distance, and both carcinoma- associated retinopathy and diffuse uveal melanocytic proliferation (bilateral or unilateral) should in the appropriate context suggest the possibility of a distant tumor. The earlier the diagnosis is made or suspected, the more likely the patient will be able to maintain his/her vision. In the case of bilateral disease, small iris proliferations are sometimes seen, as the melanocytic cell proliferation may be dependent on higher levels of tyrosinase kinase (c-kit) and stem cell factor.24
Context, lack of response, and an appropriate dose of suspicion should allow the treating ophthalmologist to suspect, diagnose, and appropriately treat these masquerading tumors.
Marc D. de Smet, MDCM, PhD, FRCSC, is with the Center for Specialized Ophthalmology, Retinal Diseases and Inflammation at Clinique De Montchoisi, Lausanne, Switzerland. He states that he has no financial relationships to disclose. Dr. de Smet can be reached via e-mail at mddesmet1@mac.com.
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