Posttransplantation lymphoproliferative disorder (PTLD) is a serious complication of solid organ transplantation and represents a spectrum of unregulated lymphoid proliferation that ranges from polyclonal hyperplasia to monoclonal malignant lymphoma (7
). The classification scheme of PTLD is constantly evolving and currently includes 4 major categories: hyperplastic (or early) lesions; polymorphic (generally monoclonal) lesions; monomorphic (lymphomatous, invariably monoclonal) lesions, which are further subcategorized along recognized lines of B-cell, T-cell, or natural killer cell neoplasia; and other lymphoproliferative disorders, including Hodgkin lymphoma (2
). Approximately 85% of cases are of B-cell origin and are related to EBV, as was the case with our patient (7
). The pathogenesis of EBV-related PTLD is considered to be the result of the failure of the host immune system to defend against EBV infection by limiting the T-cell responses that normally control the proliferation of infected B-cells (4
). In immunocompetent individuals, massive B-cell proliferation induced by EBV infection eventually subsides under the control of an equally massive cytotoxic T-cell reaction (2
). However, under conditions of immunosuppression, defective T-cell function may allow uncontrolled proliferation of EBV-infected B-cells, which express a set of viral genes known as "latency" genes. These genes make EBV-infected B-cells autonomously proliferate and form hyperplastic, polyclonal lesions. When polyclonal proliferation continues, the lesions progress to monoclonality, eventually forming a malignant lymphoma (1
). However, this hypothesis does not explain the existence of EBV-negative and T-cell or natural killer cell-derived PTLDs.
The frequency of PTLD has been reported to range from 1% to 10%, and it differs with the type of organ transplanted and the type and length of immunosuppression. The highest prevalence has been recorded in multivisceral transplant recipients (13-33% cases), followed by bowel (7-11%), heart-lung (9.4%), lung (1.8-7.9%), heart (3.4%), liver (2.2%), and kidney (1%) recipients (2
). The risk of PTLD is greater with primary EBV infection posttransplantation, an organ from an EBV-seropositive donor transplanted into an EBV-seronegative recipient, increased circulating levels of EBV genome, and the presence of cytomegalovirus infection (1
). The prevalence of PTLD is also greater in the pediatric population and in patients over 60 years of age. The site of occurrence of PTLD is also influenced by the organ allografts (2
), and lesions most commonly occur in the gastrointestinal tract, central nervous system, and allografted organs, and, less commonly, in the lymph nodes (8
). Involvement of the extracranial head and neck in PTLD is reportedly uncommon and is usually seen in association with disseminated extranodal disease (2
). Most commonly, the disease presents as a focal mass in the Waldeyer ring and cervical lymphadenopathy. Less commonly, the orbit and sinonasal tract can be involved (2
). Sinonasal disease mimics fungal sinusitis or nasal polyposis, manifesting as a bulky mass with bone erosion and invasion of the orbits. Orbital involvement may manifest as a soft-tissue mass with a propensity for the lacrimal gland fossa, often accompanied by bone destruction (2
Intraocular PTLD is rare, and to the best of our knowledge, less than 20 cases have been reported in the English literature (3
). Patients present with various clinical symptoms including decreased vision, a mass in the iris, uveitis/papillitis, eye discoloration, photosensitivity, diplopia, ophthalmoplegia, and corneal opacity. In a metaanalysis of 13 reported cases of intraocular PTLD, Fujita et al. (6
) found that most cases (12/13, 92%) involved pediatric patients and the lesion frequently involved the anterior chamber and iris. They also noted that liver transplant patients were more commonly affected (8/13, 62%). Although older than patients in previous studies, our patient also had a lesion in the iris and anterior chamber.
The most important differential diagnoses of adult ocular masses include ocular melanoma and metastasis. Ocular melanoma is the most common primary malignant intraocular tumor in adults, accounting for 80% of noncutaneous melanomas (11
). Like other melanin-containing tumors, ocular melanoma shows a high signal intensity on T1-weighted images and low signal intensity on T2-weighted images. However, since ocular lymphoma may have signal characteristics similar to those of uveal melanomas, MR signal characteristics may not be helpful for the differential diagnosis (11
). Instead, morphologic features may aid differential diagnosis, since iris melanoma tends to present as a discrete circumscribed lesion rather than a plaque-like thickening, as seen in iris lymphomas such as the present case (12
). Metastatic eye disease occurs most commonly from the lung and breast. Although metastases may produce solitary lesions, bilaterality and multicentricity usually suggest metastases. Other rare primary tumors to be differentiated from ocular lymphoma include medulloepithelioma, uveal leiomyoma, retinal pigment epithelial adenoma and adenocarcinoma, and optic disk melanocytoma. Medulloepithelioma and uveal leiomyomas tend to occur in the ciliochoroidal region and may be difficult to differentiate from the lymphoma seen in the present case on the basis of the imaging findings alone. Medulloepithelioma is a congenital tumor of the uvea, which presents as a mass behind the iris and pupil. Uveal leiomyoma is even rarer than other intraocular tumors and affects the ciliary body and the choroid overlying the posterior pole (12
As seen in the present case, the clinical diagnosis of ocular PTLD is often difficult, because it can masquerade as steroid-resistant uveitis (3
). In such situations, MR imaging may provide a diagnostic clue by revealing abnormal thickening of the uvea, especially in the anterior segment, with pathologic contrast enhancement. Although the imaging findings of uveitis are nonspecific, an inflamed uveal tract usually shows a high signal intensity on T2-weighted images in contrast to most ocular tumors, which present a low to intermediate signal intensity, as in the present case (13
). Although our patient died of heart and renal failure complicated by sepsis 11 months after the diagnosis of posttransplantation intraocular lymphoma, the clinical course of ocular PTLD is chronic and the reported prognosis is generally good (6
). Treatment includes reduction of immunosuppression, antiviral agents, and radiation therapy.
In summary, intraocular lymphoma can occur as a rare manifestation of PTLD. A high index of suspicion should be used for early diagnosis and treatment, when abnormal thickening of the uvea with contrast enhancement is seen on MR images in patients with a history of organ transplantation.